My research interests encompass the physics and mathematics of imaging with Magnetic Resonance (MR). My research is directed in part towards exploration of rapid MRI scanning methods using spiral and other non-Cartesian k-space trajectories for dynamic imaging of function. Using spiral techniques, we have developed MRI pulse sequences and processing methods for mapping cortical brain function by imaging the metabolic response to various stimuli, with applications in the basic neurosciences as well as for clinical applications. These methods develop differential image contrast from hemodynamically driven increases in oxygen content in the vascular bed of activated cortex (Blood Oxygen Level Dependent, or BOLD contrast), using pulse sequences sensitive to the paramagnetic behavior of deoxyhemoglobin or to the blood flow changes. Other interests include multimodal imaging using fMRI in conjunction with EEG, fPET, fNIRS, and neuromodulation with tDCS, tACS, TMS and HiFU. Investigating viscoelasticity of human brain using MR Elastography is of interest as an alternative to BOLD contrast for depicting brain activation.

Academic Appointments

Honors & Awards

  • Steinmetz Award, General Electric Company (1985)
  • Fellow, American Institute for Medical and Biological Engineering (1997)
  • Fellow, ISMRM (2000)
  • Gold Medal, ISMRM (2000)
  • Outstanding Researcher Award, RSNA (2001)
  • Member, National Academy of Engineering (2013)
  • Lauterbur Lecture: MRI in Yon Tines of Yore, International Society of Magnetic Resonance in Medicine (2018)

Boards, Advisory Committees, Professional Organizations

  • Member, Eta Kappa Nu (1964 - Present)
  • Member, IEEE (1965 - 1980)
  • Member, American Physical Society (1969 - 1977)
  • Member, ISMRM (International Society for Magnetic Reonance in Medicine (1985 - Present)
  • Subcommittee on MR nomenclature and phantom development, American College of Radiology (1988 - 1996)
  • Member, American Association of Physicists in Medicine (AAPM) (1990 - 1996)
  • Nominator, Nobel Prize in Physiology and Medicine (1992 - 2002)
  • Member, Organization for Human Brain Mapping (2003 - Present)
  • Advisory Board, Tsinghua University Center for Biomedical Imaging (2011 - Present)
  • Member, National Academy of Engineering (2013 - Present)

Professional Education

  • PhD, University of Minnesota, Electrical Engineering (1969)


  • Gary Glover. "United StatesApproximately 50 issued in Biomedical Imaging"

Current Research and Scholarly Interests

My research is devoted to the advancement of imaging sciences for applications in diagnostic radiology. We collaborate closely with departmental clinicians and with others in the school of medicine, humanities, and the engineering sciences.

Presently my research is directed in part towards exploration of rapid scanning methods using spiral and other non-Cartesian k-space trajectories. Using spiral techniques, we have developed MRI pulse sequences and processing methods for mapping cortical brain function by imaging the metabolic response to various stimuli, with applications in the basic neurosciences as well as for clinical applications. These methods develop differential image contrast from hemodynamically driven increases in oxygen content in the vascular bed of activated cortex, using pulse sequences sensitive to the paramagnetic behavior of deoxyhemoglobin or to the blood flow changes. Multimodal imaging and neuromodulation combines fMRI with EEG, fPET, fNIRS, TES (TACS, TDCS, TMS) and HIFU.

Clinical Trials

  • Magnetic Resonance Imaging of Breast Cancer Recruiting

    To compare magnetic resonance imaging (MRI) with more well established diagnostic imaging techniques to determine which method best finds and defines breast cancer.

    View full details

2023-24 Courses

Stanford Advisees

Graduate and Fellowship Programs

All Publications

  • Histologic safety of transcranial focused ultrasound neuromodulation and magnetic resonance acoustic radiation force imaging in rhesus macaques and sheep. Brain stimulation Gaur, P., Casey, K. M., Kubanek, J., Li, N., Mohammadjavadi, M., Saenz, Y., Glover, G. H., Bouley, D. M., Pauly, K. B. 2020; 13 (3): 804–14


    BACKGROUND: Neuromodulation by transcranial focused ultrasound (FUS) offers the potential to non-invasively treat specific brain regions, with treatment location verified by magnetic resonance acoustic radiation force imaging (MR-ARFI).OBJECTIVE: To investigate the safety of these methods prior to widespread clinical use, we report histologic findings in two large animal models following FUS neuromodulation and MR-ARFI.METHODS: Two rhesus macaques and thirteen Dorset sheep were studied. FUS neuromodulation was targeted to the primary visual cortex in rhesus macaques and to subcortical locations, verified by MR-ARFI, in eleven sheep. Both rhesus macaques and five sheep received a single FUS session, whereas six sheep received repeated sessions three to six days apart. The remaining two control sheep did not receive ultrasound but otherwise underwent the same anesthetic and MRI procedures as the eleven experimental sheep. Hematoxylin and eosin-stained sections of brain tissue (harvested zero to eleven days following FUS) were evaluated for tissue damage at FUS and control locations as well as tissue within the path of the FUS beam. TUNEL staining was used to evaluate for the presence of apoptosis in sheep receiving high dose FUS.RESULTS: No FUS-related pre-mortem histologic findings were observed in the rhesus macaques or in any of the examined sheep. Extravascular red blood cells (RBCs) were present within the meninges of all sheep, regardless of treatment group. Similarly, small aggregates of perivascular RBCs were rarely noted in non-target regions of neural parenchyma of FUS-treated (8/11) and untreated (2/2) sheep. However, no concurrent histologic abnormalities were observed, consistent with RBC extravasation occurring as post-mortem artifact following brain extraction. Sheep within the high dose FUS group were TUNEL-negative at the targeted site of FUS.CONCLUSIONS: The absence of FUS-related histologic findings suggests that the neuromodulation and MR-ARFI protocols evaluated do not cause tissue damage.

    View details for DOI 10.1016/j.brs.2020.02.017

    View details for PubMedID 32289711

  • Note: this list and vitae are not complete. Instead, please see
  • Efficacy of Ketamine in Unmedicated Adults With OCD: A Randomized Controlled Trial Rodriguez, C., Chen, C., Glover, G., Jo, B., Spielman, D., Williams, L., van Roessel, P., DeBattista, C., Wintermark, M., Lombardi, A., Pinto, A., Valentine, K., Filippou-Frye, M., Hawkins, J., McCarthy, E., Mukunda, P., Varias, A., Wilson, J., Wright, B. ELSEVIER SCIENCE INC. 2023: S83
  • An Electrostatically Actuated Gecko Adhesive Clutch ADVANCED MATERIALS TECHNOLOGIES Hajj-Ahmad, A., Han, A., Lin, M. A., Glover, G. H., Cutkosky, M. R. 2023
  • Exploring Corticospinal Functional Connectome Using Resting-State Functional Magnetic Resonance Imaging Kaptan, M., Law, C. W., Weber, K., Pfyffer, D., Zhang, X., Maronesy, T., Glover, G., Mackey, S. CHURCHILL LIVINGSTONE. 2023: 17-18
  • Imaging Noxious Thermal Intensity Encoding Along The Neuraxis Using Simultaneous Spinal Cord-Brain Functional Magnetic Resonance Imaging Pfyffer, D., Law, C. W., Weber, K. A., Kaptan, M., Maronesy, T., Glover, G. H., Mackey, S. CHURCHILL LIVINGSTONE. 2023: 76
  • Differential Association Of Pain Catastrophizing, Resilience And Interoceptive Awareness With Resting-State Functional Connectivity In Chronic Low Back Pain Patients Jarrahi, B., Huang, C., Glover, G., Mackey, S. CHURCHILL LIVINGSTONE. 2023: 75
  • Confounds in neuroimaging: A clear case of sex as a confound in brain-based prediction. Frontiers in neurology Weber, K. A., Teplin, Z. M., Wager, T. D., Law, C. S., Prabhakar, N. K., Ashar, Y. K., Gilam, G., Banerjee, S., Delp, S. L., Glover, G. H., Hastie, T. J., Mackey, S. 2022; 13: 960760


    Muscle weakness is common in many neurological, neuromuscular, and musculoskeletal conditions. Muscle size only partially explains muscle strength as adaptions within the nervous system also contribute to strength. Brain-based biomarkers of neuromuscular function could provide diagnostic, prognostic, and predictive value in treating these disorders. Therefore, we sought to characterize and quantify the brain's contribution to strength by developing multimodal MRI pipelines to predict grip strength. However, the prediction of strength was not straightforward, and we present a case of sex being a clear confound in brain decoding analyses. While each MRI modality-structural MRI (i.e., gray matter morphometry), diffusion MRI (i.e., white matter fractional anisotropy), resting state functional MRI (i.e., functional connectivity), and task-evoked functional MRI (i.e., left or right hand motor task activation)-and a multimodal prediction pipeline demonstrated significant predictive power for strength (R 2 = 0.108-0.536, p ≤ 0.001), after correcting for sex, the predictive power was substantially reduced (R 2 = -0.038-0.075). Next, we flipped the analysis and demonstrated that each MRI modality and a multimodal prediction pipeline could significantly predict sex (accuracy = 68.0%-93.3%, AUC = 0.780-0.982, p < 0.001). However, correcting the brain features for strength reduced the accuracy for predicting sex (accuracy = 57.3%-69.3%, AUC = 0.615-0.780). Here we demonstrate the effects of sex-correlated confounds in brain-based predictive models across multiple brain MRI modalities for both regression and classification models. We discuss implications of confounds in predictive modeling and the development of brain-based MRI biomarkers, as well as possible strategies to overcome these barriers.

    View details for DOI 10.3389/fneur.2022.960760

    View details for PubMedID 36601297

    View details for PubMedCentralID PMC9806266

  • Efficacy of Ketamine in Unmedicated Adults With Obsessive-Compulsive Disorder: A Randomized Controlled Trial Rodriguez, C., Chen, C., Glover, G., Jo, B., Spielman, D., Williams, L., van Roessel, P., DeBattista, C., Flood, P., Ringold, A., Wintermark, M., Anderson, K., Linkovski, O., Lombardi, A., Millen, A., Pinto, A., Raila, H., Valentine, K., Filippou-Frye, M., Hawkins, J., McCarthy, E., Mukunda, P., Varias, A., Wilson, J., Wright, B. SPRINGERNATURE. 2022: 302-303
  • Efficacy of Ketamine in Unmedicated Adults With Obsessive-Compulsive Disorder: A Randomized Controlled Trial Rodriguez, C., Chen, C., Glover, G., Jo, B., Spielman, D., Williams, L., Van Roessel, P., DeBattista, C., Flood, P., Ringold, A., Wintermark, M., Anderson, K., Linkovski, O., Lombardi, A., Millen, A., Pinto, A., Raila, H., Valentine, K., Filippou-Frye, M., Hawkins, J., McCarthy, E., Mukunda, P., Varias, A., Wilson, J., Wright, B. SPRINGERNATURE. 2022: 302-303
  • Morphological Component Analysis of Functional MRI Brain Networks IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING Nguyen, H. M., Chen, J., Glover, G. H. 2022; 69 (10): 3193-3204


    Sparse representations have been utilized to identify functional connectivity (FC) of networks, while ICA employs the assumption of independence among the network sources to demonstrate FC. Here, we investigate a sparse decomposition method based on Morphological Component Analysis and K-SVD dictionary learning - MCA-KSVD - and contrast the effect of the sparsity constraint vs. the independency constraint on FC and denoising.Using a K-SVD algorithm, fMRI signals are decomposed into morphological components which have sparse spatial overlap. We present simulations when the independency assumption of ICA fails and MCA-KSVD recovers more accurate spatial-temporal structures. Denoising performance of both methods is investigated at various noise levels. A comprehensive experimental study was conducted on resting-state and task fMRI.Validations show that ICA is advantageous when network components are well-separated and sparse. In such cases, the MCA-KSVD method has modest value over ICA in terms of network delineation but is significantly more effective in reducing spatial and temporal noise. Results demonstrate that the sparsity constraint yields sparser networks with higher spatial resolution while suppressing weak signals. Temporally, this localization effect yields higher contrast-to-noise ratios (CNRs) of time series.While marginally improving the spatial decomposition, MCA-KSVD denoises fMRI data much more effectively than ICA, preserving network structures and improving CNR, especially for weak networks.A sparsity-based decomposition approach may be useful for investigating functional connectivity in noisy cases. It may serve as an efficient decomposition method for reduced acquisition time and may prove useful for detecting weak network activations.

    View details for DOI 10.1109/TBME.2022.3162606

    View details for Web of Science ID 000856133100024

    View details for PubMedID 35358040

  • Inconsistencies in mapping current distribution in transcranial direct current stimulation. Frontiers in neuroimaging Jwa, A. S., Goodman, J. S., Glover, G. H. 2022; 1: 1069500


    tDCS is a non-invasive neuromodulation technique that has been widely studied both as a therapy for neuropsychiatric diseases and for cognitive enhancement. However, recent meta-analyses have reported significant inconsistencies amongst tDCS studies. Enhancing empirical understanding of current flow in the brain may help elucidate some of these inconsistencies.We investigated tDCS-induced current distribution by injecting a low frequency current waveform in a phantom and in vivo. MR phase images were collected during the stimulation and a time-series analysis was used to reconstruct the magnetic field. A current distribution map was derived from the field map using Ampere's law.The current distribution map in the phantom showed a clear path of current flow between the two electrodes, with more than 75% of the injected current accounted for. However, in brain, the results did evidence a current path between the two target electrodes but only some portion ( 25%) of injected current reached the cortex demonstrating that a significant fraction of the current is bypassing the brain and traveling from one electrode to the other external to the brain, probably due to conductivity differences in brain tissue types. Substantial inter-subject and intra-subject (across consecutive scans) variability in current distribution maps were also observed in human but not in phantom scans.An in-vivo current mapping technique proposed in this study demonstrated that much of the injected current in tDCS was not accounted for in human brain and deviated to the edge of the brain. These findings would have ramifications in the use of tDCS as a neuromodulator and may help explain some of the inconsistencies reported in other studies.

    View details for DOI 10.3389/fnimg.2022.1069500

    View details for PubMedID 37555148

    View details for PubMedCentralID PMC10406311

  • Transcranial ultrasound neuromodulation of the thalamic visual pathway in a large animal model and the dose‐response relationship with MR‐ARFI Scientific Reports Mohammadjavadi, M., Ash, R. T., Li, N., Gaur, P., Kubanek, J., Saenz, Y., Glover, G. H., Popelka, G. R., Norcia, A. M., Butts Pauly, K. 2022; 12: 19588
  • Ruminative reflection is associated with anticorrelations between the orbitofrontal cortex and the default mode network in depression: implications for repetitive transcranial magnetic stimulation. Brain imaging and behavior Ehrlich, T. J., Bhat, J., Horwege, A. M., Mathalon, D. H., Glover, G. H., Roach, B. J., Badran, B. W., Forman, S. D., George, M. S., Scott, J. C., Thase, M. E., Yesavage, J. A., Yurgelun-Todd, D. A., Rosen, A. C. 2021


    Patients with depression who ruminate repeatedly focus on depressive thoughts; however, there are two cognitive subtypes of rumination, reflection and brooding, each associated with different prognoses. Reflection involves problem-solving and is associated with positive outcomes, whereas brooding involves passive, negative, comparison with other people and is associated with poor outcomes. Rumination has also been related to atypical functional hyperconnectivity between the default mode network and subgenual prefrontal cortex. Repetitive pulse transcranial magnetic stimulation of the prefrontal cortex has been shown to alter functional connectivity, suggesting that the abnormal connectivity associated with rumination could potentially be altered. This study examined potential repetitive pulse transcranial magnetic stimulation prefrontal cortical targets that could modulate one or both of these rumination subtypes. Forty-three patients who took part in a trial of repetitive pulse transcranial magnetic stimulation completed the Rumination Response Scale questionnaire and resting-state functional magnetic resonance imaging. Seed to voxel functional connectivity analyses identified an anticorrelation between the left lateral orbitofrontal cortex (-44, 26, -8; k=172) with the default mode network-subgenual region in relation to higher levels of reflection. Parallel analyses were not significant for brooding or the RRS total score. These findings extend previous studies of rumination and identify a potential mechanistic model for symptom-based neuromodulation of rumination.

    View details for DOI 10.1007/s11682-021-00596-4

    View details for PubMedID 34860349

  • Response to Scholkmann Commentary: "Effect of Wearing a Face Mask on fMRI BOLD Contrast". NeuroImage Law, C. S., Lan, P. S., Glover, G. H. 2021: 118773

    View details for DOI 10.1016/j.neuroimage.2021.118773

    View details for PubMedID 34864152

  • Investigating mechanisms of fast BOLD responses: the effects of stimulus intensity and of spatial heterogeneity of hemodynamics. NeuroImage Chen, J. E., Glover, G. H., Fultz, N. E., Rosen, B. R., Polimeni, J. R., Lewis, L. D. 2021: 118658


    Recent studies have demonstrated that fast fMRI can track neural activity well above the temporal limit predicted by the canonical hemodynamic response model. While these findings are promising, the biophysical mechanisms underlying these fast fMRI phenomena remain underexplored. In this study, we discuss two aspects of the hemodynamic response, complementary to several existing hypotheses, that can accommodate faster fMRI dynamics beyond those predicted by the canonical model. First, we demonstrate, using both visual and somatosensory paradigms, that the timing and shape of hemodynamic response functions (HRFs) vary across graded levels of stimulus intensity-with lower-intensity stimulation eliciting faster and narrower HRFs. Second, we show that as the spatial resolution of fMRI increases, voxel-wise HRFs begin to deviate from the canonical model, with a considerable portion of voxels exhibiting faster temporal dynamics than predicted by the canonical HRF. Collectively, both stimulus/task intensity and image resolution can affect the sensitivity of fMRI to fast brain activity, which may partly explain recent observations of fast fMRI signals. It is further noteworthy that, while the present investigations focus on fast neural responses, our findings suggest that a revised hemodynamic model may benefit the many fMRI studies using paradigms with wide ranges of contrast levels (e.g., resting or naturalistic conditions) or with modern, high-resolution MR acquisitions.

    View details for DOI 10.1016/j.neuroimage.2021.118658

    View details for PubMedID 34656783

  • Prediction of Cognitive Function with Multimodal Brain MRI Weber, K., Wager, T. D., Rosen, A., Ashar, Y. K., Law, C. S., Gilam, G., Upadhyayula, P. A., Zhu, S., Banerjee, S., Glover, G. H., Hastie, T. J., Mackey, S. WILEY. 2021: S42
  • Effect of Wearing a Face Mask on fMRI BOLD Contrast. NeuroImage Law, C. S., Lan, P. S., Glover, G. H. 2021: 117752


    International spread of the coronavirus SARS-CoV-2 has prompted many MRI scanning facilities to require scan subjects to wear a facial covering ("mask") during scanning as a precaution against transmission of the virus. Because wearing a mask mixes expired air with the subject's inspired air stream, the concentration of inspired carbon dioxide [CO2] is elevated, resulting in mild hypercapnia. Changes in the inspired gas mixture have been demonstrated to alter R2*-weighted Blood Oxygen Dependent (BOLD) contrast. In this study, we investigate a potential for face masking to alter BOLD contrast during a sensory-motor task designed to activate visual, auditory, and sensorimotor cortices in 8 subjects. We utilize a nasal cannula to supply air to the subject wearing a surgical mask in on-off blocks of 90s to displace expired CO2, while the subject performs the sensory-motor task. While only a small fraction (2.5%) of the sensory-motor task activation is related to nasal air modulation, a 30.0% change in gray matter BOLD signal baseline is found due to air modulation. Repeating the scan with mask removed produces a small subject-specific bias in BOLD baseline signal from nasal air supply, which may be due to cognitive influence of airflow or cannula-induced hypoxia. Measurements with capnography demonstrate wearing a mask induces an average increase in ETCO2 of 7.4%. Altogether, these results demonstrate that wearing a face mask during gradient-echo fMRI can alter BOLD baseline signal but minimally affects task activation.

    View details for DOI 10.1016/j.neuroimage.2021.117752

    View details for PubMedID 33460795

  • Brain Strength: Multi-Modal Brain MRI Predicts Grip Strength Weber, K. A., Wager, T. D., Upadhyayula, P. A., Law, C. S., Ashar, Y. K., Prabhakar, N. K., Zhu, S., Gilam, G., Banerjee, S., Delp, S. L., Glover, G. H., Hastie, T. J., Mackey, S. WILEY. 2020: S223–S224
  • Finding the neural correlates of collaboration using a three-person fMRI hyperscanning paradigm. Proceedings of the National Academy of Sciences of the United States of America Xie, H., Karipidis, I. I., Howell, A., Schreier, M., Sheau, K. E., Manchanda, M. K., Ayub, R., Glover, G. H., Jung, M., Reiss, A. L., Saggar, M. 2020


    Humans have an extraordinary ability to interact and cooperate with others. Despite the social and evolutionary significance of collaboration, research on finding its neural correlates has been limited partly due to restrictions on the simultaneous neuroimaging of more than one participant (also known as hyperscanning). Several studies have used dyadic fMRI hyperscanning to examine the interaction between two participants. However, to our knowledge, no study to date has aimed at revealing the neural correlates of social interactions using a three-person (or triadic) fMRI hyperscanning paradigm. Here, we simultaneously measured the blood-oxygenation level-dependent signal from 12 triads (n = 36 participants), while they engaged in a collaborative drawing task based on the social game of Pictionary General linear model analysis revealed increased activation in the brain regions previously linked with the theory of mind during the collaborative phase compared to the independent phase of the task. Furthermore, using intersubject correlation analysis, we revealed increased synchronization of the right temporo-parietal junction (R TPJ) during the collaborative phase. The increased synchrony in the R TPJ was observed to be positively associated with the overall team performance on the task. In sum, our paradigm revealed a vital role of the R TPJ among other theory-of-mind regions during a triadic collaborative drawing task.

    View details for DOI 10.1073/pnas.1917407117

    View details for PubMedID 32843342

  • Imaging brain function with simultaneous BOLD and viscoelasticity contrast: fMRI/fMRE. NeuroImage Lan, P. S., Glaser, K. J., Ehman, R. L., Glover, G. H. 2020: 116592


    Magnetic resonance elastography (MRE) is emerging as a new tool for studying viscoelastic changes in the brain resulting from functional processes. Here, we demonstrate a novel time series method to generate robust functional magnetic resonance elastography (fMRE) activation maps in response to a visual task with a flashing checkerboard stimulus. Using a single-shot spin-echo (SS-SE) pulse sequence, the underlying raw images inherently contain blood-oxygen-level dependent (BOLD) contrast, allowing simultaneous generation of functional magnetic resonance imaging (fMRI) activation maps from the magnitude and functional magnetic resonance elastography (fMRE) maps from the phase. This allows an accurate comparison of the spatially localized stiffness (fMRE) and BOLD (fMRI) changes within a single scan, eliminating confounds inherent in separately acquired scans. Results indicate that tissue stiffness within the visual cortex increases 6-11% with visual stimuli, whereas the BOLD signal change was 1-2%. Furthermore, the fMRE and fMRI activation maps have strong spatial overlap within the visual cortex, providing convincing evidence that fMRE is possible in the brain. However, the fMRE temporal SNR (tSNRfMRE) maps are heterogeneous across the brain. Using a dictionary matching approach to characterize the time series, the viscoelastic changes are consistent with a viscoelastic response function (VRF) time constant of 12.1 s ± 3.0 s for a first-order exponential decay, or a shape parameter of 8.1 s ± 1.4 s for a gamma-variate.

    View details for DOI 10.1016/j.neuroimage.2020.116592

    View details for PubMedID 32014553

  • On the analysis of rapidly sampled fMRI data NEUROIMAGE Chen, J. E., Polimeni, J. R., Bollmann, S., Glover, G. H. 2019; 188: 807–20
  • On the analysis of rapidly sampled fMRI data. NeuroImage Chen, J. E., Polimeni, J. R., Bollmann, S., Glover, G. H. 2019


    Recent advances in parallel imaging and simultaneous multi-slice techniques have permitted whole-brain fMRI acquisitions at sub-second sampling intervals, without significantly sacrificing the spatial coverage and resolution. Apart from probing brain function at finer temporal scales, faster sampling rates may potentially lead to enhanced functional sensitivity, owing possibly to both cleaner neural representations (due to less aliased physiological noise) and additional statistical benefits (due to more degrees of freedom for a fixed scan duration). Accompanying these intriguing aspects of fast acquisitions, however, confusion has also arisen regarding (1) how to preprocess/analyze these fast fMRI data, and (2) what exactly is the extent of benefits with fast acquisitions, i.e., how fast is fast enough for a specific research aim? The first question is motivated by the altered spectral distribution and noise characteristics at short sampling intervals, while the second question seeks to reconcile the complicated trade-offs between the functional contrast-to-noise ratio and the effective degrees of freedom. Although there have been recent efforts to empirically approach different aspects of these two questions, in this work we discuss, from a theoretical perspective accompanied by some illustrative, proof-of-concept experimental in vivo human fMRI data, a few considerations that are rarely mentioned, yet are important for both preprocessing and optimizing statistical inferences for studies that employ acquisitions with sub-second sampling intervals. Several summary recommendations include concerns regarding advisability of relying on low-pass filtering to de-noise physiological contributions, employment of statistical models with sufficient complexity to account for the substantially increased serial correlation, and cautions regarding using rapid sampling to enhance functional sensitivity given that different analysis models may associate with distinct trade-offs between contrast-to-noise ratios and the effective degrees of freedom. As an example, we demonstrate that as TR shortens, the intrinsic differences in how noise is accommodated in general linear models and Pearson correlation analyses (assuming Gaussian distributed stochastic signals and noise) can result in quite different outcomes, either gaining or losing statistical power.

    View details for PubMedID 30735828

  • Dynamic per slice shimming for simultaneous brain and spinal cord fMRI MAGNETIC RESONANCE IN MEDICINE Islam, H., Law, C. W., Weber, K. A., Mackey, S. C., Glover, G. H. 2019; 81 (2): 825–38

    View details for DOI 10.1002/mrm.27388

    View details for Web of Science ID 000462086300010

  • Striatal dopamine deficits predict reductions in striatal functional connectivity in major depression: a concurrent 11C-raclopride positron emission tomography and functional magnetic resonance imaging investigation. Translational psychiatry Hamilton, J. P., Sacchet, M. D., Hjornevik, T., Chin, F. T., Shen, B., Kampe, R., Park, J. H., Knutson, B. D., Williams, L. M., Borg, N., Zaharchuk, G., Camacho, M. C., Mackey, S., Heilig, M., Drevets, W. C., Glover, G. H., Gambhir, S. S., Gotlib, I. H. 2018; 8 (1): 264


    Major depressive disorder (MDD) is characterized by the altered integration of reward histories and reduced responding of the striatum. We have posited that this reduced striatal activation in MDD is due to tonically decreased stimulation of striatal dopamine synapses which results in decremented propagation of information along the cortico-striatal-pallido-thalamic (CSPT) spiral. In the present investigation, we tested predictions of this formulation by conducting concurrent functional magnetic resonance imaging (fMRI) and 11C-raclopride positron emission tomography (PET) in depressed and control (CTL) participants. We scanned 16 depressed and 14 CTL participants with simultaneous fMRI and 11C-raclopride PET. We estimated raclopride binding potential (BPND), voxel-wise, and compared MDD and CTL samples with respect to BPND in the striatum. Using striatal regions that showed significant between-group BPND differences as seeds, we conducted whole-brain functional connectivity analysis using the fMRI data and identified brain regions in each group in which connectivity with striatal seed regions scaled linearly with BPND from these regions. We observed increased BPND in the ventral striatum, bilaterally, and in the right dorsal striatum in the depressed participants. Further, we found that as BPND increased in both the left ventral striatum and right dorsal striatum in MDD, connectivity with the cortical targets of these regions (default-mode network and salience network, respectively) decreased. Deficits in stimulation of striatal dopamine receptors in MDD could account in part for the failure of transfer of information up the CSPT circuit in the pathophysiology of this disorder.

    View details for PubMedID 30504860

  • Dynamic per slice Shimming for Simultaneous Brain and Spinal Cord fMRI. Magnetic resonance in medicine Islam, H., Law, C. S., Weber, K. A., Mackey, S. C., Glover, G. H. 2018


    PURPOSE: Simultaneous brain and spinal cord functional MRI is emerging as a new tool to study the central nervous system but is challenging. Poor B0 homogeneity and small size of the spinal cord are principal obstacles to this nascent technology. Here we extend a dynamic shimming approach, first posed by Finsterbusch, by shimming per slice for both the brain and spinal cord.METHODS: We shim dynamically by a simple and fast optimization of linear field gradients and frequency offset separately for each slice in order to minimize off-resonance for both the brain and spinal cord. Simultaneous acquisition of brain and spinal cord fMRI is achieved with high spatial resolution in the spinal cord by means of an echo-planar RF pulse for reduced FOV. Brain slice acquisition is full FOV.RESULTS: T2*-weighted images of brain and spinal cord are acquired with high clarity and minimal observable image artifacts. Fist-clenching fMRI experiments reveal task-consistent activation in motor cortices, cerebellum, and C6-T1 spinal segments.CONCLUSIONS: High quality functional results are obtained for a sensory-motor task. Consistent activation in both the brain and spinal cord is observed at individual levels, not only at group level. Because reduced FOV excitation is applicable to any spinal cord section, future continuation of these methods holds great potential.

    View details for PubMedID 30284730

  • MR Performance in the Presence of a Radio Frequency-Penetrable Positron Emission Tomography (PET) Insert for Simultaneous PET/MRI IEEE TRANSACTIONS ON MEDICAL IMAGING Lee, B. J., Grant, A. M., Chang, C., Watkins, R. D., Glover, G. H., Levin, C. S. 2018; 37 (9): 2060–69


    Despite the great promise of integrated positron emission tomography (PET)/magnetic resonance (MR) imaging to add molecular information to anatomical and functional MR, its potential impact in medicine is diminished by a very high cost, limiting its dissemination. An RF-penetrable PET ring that can be inserted into any existing MR system has been developed to address this issue. Employing optical signal transmission along with battery power enables the PET ring insert to electrically float with respect to the MR system. Then, inter-modular gaps of the PET ring allow the RF transmit field from the standard built-in body coil to penetrate into the PET fields-of-view (FOV) with some attenuation that can be compensated for. MR performance, including RF noise, magnetic susceptibility, RF penetrability through and $B_{1}$ uniformity within the PET insert, and MR image quality, were analyzed with and without the PET ring present. The simulated and experimentally measured RF field attenuation factors with the PET ring present were -2.7 and -3.2 dB, respectively. The magnetic susceptibility effect (0.063 ppm) and noise emitted from the PET ring in the MR receive channel were insignificant. $B_{1}$ homogeneity of a spherical agar phantom within the PET ring FOV dropped by 8.4% and MR image SNR was reduced by 3.5 and 4.3 dB with the PET present for gradient-recalled echo and fast-spin echo, respectively. This paper demonstrates, for the first time, an RF-penetrable PET insert comprising a full ring of operating detectors that achieves simultaneous PET/MR using the standard built-in body coil as the RF transmitter.

    View details for DOI 10.1109/TMI.2018.2815620

    View details for Web of Science ID 000443877100010

    View details for PubMedID 29993864

  • Towards a new approach to reveal dynamical organization of the brain using topological data analysis NATURE COMMUNICATIONS Saggar, M., Sporns, O., Gonzalez-Castillo, J., Bandettini, P. A., Carlsson, G., Glover, G., Reiss, A. L. 2018; 9: 1399


    Little is known about how our brains dynamically adapt for efficient functioning. Most previous work has focused on analyzing changes in co-fluctuations between a set of brain regions over several temporal segments of the data. We argue that by collapsing data in space or time, we stand to lose useful information about the brain's dynamical organization. Here we use Topological Data Analysis to reveal the overall organization of whole-brain activity maps at a single-participant level-as an interactive representation-without arbitrarily collapsing data in space or time. Using existing multitask fMRI datasets, with the known ground truth about the timing of transitions from one task-block to next, our approach tracks both within- and between-task transitions at a much faster time scale (~4-9 s) than before. The individual differences in the revealed dynamical organization predict task performance. In summary, our approach distills complex brain dynamics into interactive and behaviorally relevant representations.

    View details for PubMedID 29643350

  • PET Imaging Stability Measurements During Simultaneous Pulsing of Aggressive MR Sequences on the SIGNA PET/MR System JOURNAL OF NUCLEAR MEDICINE Deller, T. W., Khalighi, M., Jansen, F. P., Glover, G. H. 2018; 59 (1): 167–72


    The recent introduction of simultaneous whole-body PET/MR scanners has enabled new research taking advantage of the complementary information obtainable with PET and MRI. One such application is kinetic modeling, which requires high levels of PET quantitative stability. To accomplish the required PET stability levels, the PET subsystem must be sufficiently isolated from the effects of MR activity. Performance measurements have previously been published, demonstrating sufficient PET stability in the presence of MR pulsing for typical clinical use; however, PET stability during radiofrequency (RF)-intensive and gradient-intensive sequences has not previously been evaluated for a clinical whole-body scanner. In this work, PET stability of the GE SIGNA PET/MR was examined during simultaneous scanning of aggressive MR pulse sequences. Methods: PET performance tests were acquired with MR idle and during simultaneous MR pulsing. Recent system improvements mitigating RF interference and gain variation were used. A fast recovery fast spin echo MR sequence was selected for high RF power, and an echo planar imaging sequence was selected for its high heat-inducing gradients. Measurements were performed to determine PET stability under varying MR conditions using the following metrics: sensitivity, scatter fraction, contrast recovery, uniformity, count rate performance, and image quantitation. A final PET quantitative stability assessment for simultaneous PET scanning during functional MRI studies was performed with a spiral in-and-out gradient echo sequence. Results: Quantitation stability of a 68Ge flood phantom was demonstrated within 0.34%. Normalized sensitivity was stable during simultaneous scanning within 0.3%. Scatter fraction measured with a 68Ge line source in the scatter phantom was stable within the range of 40.4%-40.6%. Contrast recovery and uniformity were comparable for PET images acquired simultaneously with multiple MR conditions. Peak noise equivalent count rate was 224 kcps at an effective activity concentration of 18.6 kBq/mL, and the count rate curves and scatter fraction curve were consistent for the alternating MR pulsing states. A final test demonstrated quantitative stability during a spiral functional MRI sequence. Conclusion: PET stability metrics demonstrated that PET quantitation was not affected during simultaneous aggressive MRI. This stability enables demanding applications such as kinetic modeling.

    View details for PubMedID 28747522

  • MR-Compatible Haptic Display of Membrane Puncture in Robot-Assisted Needle Procedures. IEEE transactions on haptics Han, A. K., Bae, J. H., Gregoriou, K. C., Ploch, C. J., Goldman, R. E., Glover, G. H., Daniel, B. L., Cutkosky, M. R. 2018


    Multilayer electroactive polymer films actuate a small hand-held device that can display tool tip forces during MR-guided interventions. The display produces localized skin stretch at the thumb and index fingertips. Tests confirm that the device does not significantly affect MR imaging and produces detectable stimuli in response to forces measured by a biopsy needle instrumented with optical fibers. Tests with human subjects explored robotic and teleoperated paradigms to detect when the needle contacted a membrane embedded at variable depth in a tissue phantom that approximated the properties of porcine liver. In the first case, naive users detected membranes with a 98.9% success rate as the needle was driven at fixed speed. In the second case, users with experience in needle-based procedures controlled the needle insertion and detected membranes embedded in tissue phantoms with a 98% success rate. In the second experiment, some users detected membranes with very light contact forces, but there was greater subject-to-subject variation.

    View details for DOI 10.1109/TOH.2018.2816074

    View details for PubMedID 29993819

  • Dissociated patterns of anti-correlations with dorsal and ventral default-mode networks at rest. Human brain mapping Chen, J. E., Glover, G. H., Greicius, M. D., Chang, C. 2017


    Previous studies of resting state functional connectivity have demonstrated that the default-mode network (DMN) is negatively correlated with a set of brain regions commonly activated during goal-directed tasks. However, the location and extent of anti-correlations are inconsistent across different studies, which has been posited to result largely from differences in whether or not global signal regression (GSR) was applied as a pre-processing step. Notably, coordinates of seed regions-of-interest defined within the posterior cingulate cortex (PCC)/precuneus, an area often employed to study functional connectivity of the DMN, have been inconsistent across studies. Taken together with recent observations that the DMN contains functionally heterogeneous subdivisions, it is presently unclear whether these seeds map to different DMN subnetworks, whose patterns of anti-correlation may differ. If so, then seed location may be a non-negligible factor that, in addition to differences in preprocessing steps, contributes to the inconsistencies reported among published studies regarding DMN correlations/anti-correlations. In this study, they examined anti-correlations of different subnetworks within the DMN during rest using both seed-based and point process analyses, and discovered that: (1) the ventral branch of the DMN (vDMN) yielded significantly weaker anti-correlations than that associated with the dorsal branch of the DMN (dDMN); (2) vDMN anti-correlations introduced by GSR were distinct from dDMN anti-correlations; (3) PCC/precuneus seeds employed by earlier studies mapped to different DMN subnetworks, which may explain some of the inconsistency (in addition to preprocessing steps) in the reported DMN anti-correlations. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

    View details for DOI 10.1002/hbm.23532

    View details for PubMedID 28150892

  • Nuisance Regression of High-Frequency Functional Magnetic Resonance Imaging Data: Denoising Can Be Noisy. Brain connectivity Chen, J. E., Jahanian, H., Glover, G. H. 2017; 7 (1): 13-24


    Recently, emerging studies have demonstrated the existence of brain resting state (RS) spontaneous activity at frequencies higher than the conventional 0.1 Hz. A few groups utilizing accelerated acquisitions have reported persisting signals beyond 1 Hz, which seems too high to be accommodated by the sluggish hemodynamic process underpinning blood-oxygen-level dependent contrasts (the upper limit of the canonical model is ~ 0.3 Hz). It is thus questionable whether the observed high-frequency (HF) functional connectivity (FC) originates from alternative mechanisms (e.g., inflow effects, proton density changes in or near activated neural tissue), or rather is artificially introduced by improper preprocessing operations. Here, we examined the influence of a common preprocessing step - whole-band linear nuisance regression (WB-LNR) - on resting state functional connectivity (RSFC), and demonstrated via both simulation and analysis of real dataset that WB-LNR can introduce spurious network structures into the HF bands of fMRI signals. Findings of present study call into question whether published observations on HF-RSFC are partly attributable to improper data preprocessing instead of actual neural activities.

    View details for DOI 10.1089/brain.2016.0441

    View details for PubMedID 27875902

  • MR Performance Comparison of a PET/MR System Before and After SiPM-Based Time-of-Flight PET Detector Insertion IEEE TRANSACTIONS ON NUCLEAR SCIENCE Khalighi, M. M., Delso, G., Maramraju, S. H., Deller, T. W., Levin, C. S., Glover, G. H. 2016; 63 (5): 2419-2423
  • Thalamo-Cortical Dysconnectivity in Schizophrenia Ferri, J. M., Ford, J. M., Roach, B. J., Turner, J. A., van Erp, T. M., Voyvodic, J., Preda, A., Belger, A., Bustillo, J. R., O'Leary, D., Mueller, B. A., Lim, K. O., McEwen, S. C., Calhoun, V. D., Diaz, M. T., Glover, G. H., Greve, D., Wible, C. G., Vaidya, J. G., Potkin, S. G., Mathalon, D. H. ELSEVIER SCIENCE INC. 2016: 44S
  • Influence of the cortical midline structures on moral emotion and motivation in moral decision-making. Behavioural brain research Han, H., Chen, J., Jeong, C., Glover, G. H. 2016; 302: 237-251


    The present study aims to examine the relationship between the cortical midline structures (CMS), which have been regarded to be associated with selfhood, and moral decision making processes at the neural level. Traditional moral psychological studies have suggested the role of moral self as the moderator of moral cognition, so activity of moral self would present at the neural level. The present study examined the interaction between the CMS and other moral-related regions by conducting psycho-physiological interaction analysis of functional images acquired while 16 subjects were solving moral dilemmas. Furthermore, we performed Granger causality analysis to demonstrate the direction of influences between activities in the regions in moral decision-making. We first demonstrate there are significant positive interactions between two central CMS seed regions-i.e., the medial prefrontal cortex (MPFC) and posterior cingulate cortex (PCC)-and brain regions associated with moral functioning including the cerebellum, brainstem, midbrain, dorsolateral prefrontal cortex, orbitofrontal cortex and anterior insula (AI); on the other hand, the posterior insula (PI) showed significant negative interaction with the seed regions. Second, several significant Granger causality was found from CMS to insula regions particularly under the moral-personal condition. Furthermore, significant dominant influence from the AI to PI was reported. Moral psychological implications of these findings are discussed. The present study demonstrated the significant interaction and influence between the CMS and morality-related regions while subject were solving moral dilemmas. Given that, activity in the CMS is significantly involved in human moral functioning.

    View details for DOI 10.1016/j.bbr.2016.01.001

    View details for PubMedID 26772629

  • Effects of salience-network-node neurofeedback training on affective biases in major depressive disorder PSYCHIATRY RESEARCH-NEUROIMAGING Hamilton, J. P., Glover, G. H., Bagarinao, E., Chang, C., Mackey, S., Sacchet, M. D., Gotlib, I. H. 2016; 249: 91-96


    Neural models of major depressive disorder (MDD) posit that over-response of components of the brain's salience network (SN) to negative stimuli plays a crucial role in the pathophysiology of MDD. In the present proof-of-concept study, we tested this formulation directly by examining the affective consequences of training depressed persons to down-regulate response of SN nodes to negative material. Ten participants in the real neurofeedback group saw, and attempted to learn to down-regulate, activity from an empirically identified node of the SN. Ten other participants engaged in an equivalent procedure with the exception that they saw SN-node neurofeedback indices from participants in the real neurofeedback group. Before and after scanning, all participants completed tasks assessing emotional responses to negative scenes and to negative and positive self-descriptive adjectives. Compared to participants in the sham-neurofeedback group, from pre- to post-training, participants in the real-neurofeedback group showed a greater decrease in SN-node response to negative stimuli, a greater decrease in self-reported emotional response to negative scenes, and a greater decrease in self-reported emotional response to negative self-descriptive adjectives. Our findings provide support for a neural formulation in which the SN plays a primary role in contributing to negative cognitive biases in MDD.

    View details for DOI 10.1016/j.pscychresns.2016.01.016

    View details for Web of Science ID 000372526600012

    View details for PubMedCentralID PMC4803612

  • Effects of salience-network-node neurofeedback training on affective biases in major depressive disorder. Psychiatry research Hamilton, J. P., Glover, G. H., Bagarinao, E., Chang, C., Mackey, S., Sacchet, M. D., Gotlib, I. H. 2016; 249: 91-96


    Neural models of major depressive disorder (MDD) posit that over-response of components of the brain's salience network (SN) to negative stimuli plays a crucial role in the pathophysiology of MDD. In the present proof-of-concept study, we tested this formulation directly by examining the affective consequences of training depressed persons to down-regulate response of SN nodes to negative material. Ten participants in the real neurofeedback group saw, and attempted to learn to down-regulate, activity from an empirically identified node of the SN. Ten other participants engaged in an equivalent procedure with the exception that they saw SN-node neurofeedback indices from participants in the real neurofeedback group. Before and after scanning, all participants completed tasks assessing emotional responses to negative scenes and to negative and positive self-descriptive adjectives. Compared to participants in the sham-neurofeedback group, from pre- to post-training, participants in the real-neurofeedback group showed a greater decrease in SN-node response to negative stimuli, a greater decrease in self-reported emotional response to negative scenes, and a greater decrease in self-reported emotional response to negative self-descriptive adjectives. Our findings provide support for a neural formulation in which the SN plays a primary role in contributing to negative cognitive biases in MDD.

    View details for DOI 10.1016/j.pscychresns.2016.01.016

    View details for PubMedID 26862057

    View details for PubMedCentralID PMC4803612

  • Reduced field of view imaging using a static second-order gradient for functional MRI applications. Magnetic resonance in medicine Islam, H., Glover, G. H. 2016; 75 (2): 817-822


    Imaging using reduced FOV excitation allows higher resolution or signal-to-noise ratio (SNR) per scan time but often requires long radiofrequency pulses. The goal of this study was to improve a recent reduced field of view (FOV) method that uses a second-order shim gradient to decrease pulse length and evaluate its use in functional MRI (fMRI) applications.The method, which was initially limited to excite thin disc-shaped regions at the isocenter, was extended to excite thicker regions off the isocenter and produced accurate excitation profiles on a grid phantom. Visual stimulation fMRI scans were performed with full and reduced FOV. The resolution of the time series images and functional activation maps were assessed using the full-width half-maxima of the autocorrelation functions (FACFs) of the noise images and the activation map values, respectively.The resolution was higher in the reduced FOV time series images (4.1% ± 3.7% FACF reduction, P < 0.02) and functional activation maps (3.1% ± 3.4% FACF reduction, P < 0.01), but the SNR was lower (by 26.5% ± 16.9%). However, for a few subjects, the targeted region could not be localized to the reduced FOV due to the low Z2 gradient strength.The results of this study suggest that the proposed method is feasible, though it would benefit from a stronger gradient coil.

    View details for DOI 10.1002/mrm.25650

    View details for PubMedID 25809723

    View details for PubMedCentralID PMC4583326

  • NEURAL CIRCUITS Prefrontal cortical regulation of brainwide circuit dynamics and reward-related behavior SCIENCE Ferenczi, E. A., Zalocusky, K. A., Liston, C., Grosenick, L., Warden, M. R., Amatya, D., Katovich, K., Mehta, H., Patenaude, B., Ramakrishnan, C., Kalanithi, P., Etkin, A., Knutson, B., Glover, G. H., Deisseroth, K. 2016; 351 (6268): 41-U59


    Motivation for reward drives adaptive behaviors, whereas impairment of reward perception and experience (anhedonia) can contribute to psychiatric diseases, including depression and schizophrenia. We sought to test the hypothesis that the medial prefrontal cortex (mPFC) controls interactions among specific subcortical regions that govern hedonic responses. By using optogenetic functional magnetic resonance imaging to locally manipulate but globally visualize neural activity in rats, we found that dopamine neuron stimulation drives striatal activity, whereas locally increased mPFC excitability reduces this striatal response and inhibits the behavioral drive for dopaminergic stimulation. This chronic mPFC overactivity also stably suppresses natural reward-motivated behaviors and induces specific new brainwide functional interactions, which predict the degree of anhedonia in individuals. These findings describe a mechanism by which mPFC modulates expression of reward-seeking behavior, by regulating the dynamical interactions between specific distant subcortical regions.

    View details for DOI 10.1126/science.aac9698

    View details for Web of Science ID 000367364200035

    View details for PubMedCentralID PMC4772156

  • The Function Biomedical Informatics Research Network Data Repository. NeuroImage Keator, D. B., van Erp, T. G., Turner, J. A., Glover, G. H., Mueller, B. A., Liu, T. T., Voyvodic, J. T., Rasmussen, J., Calhoun, V. D., Lee, H. J., Toga, A. W., McEwen, S., Ford, J. M., Mathalon, D. H., Diaz, M., O'Leary, D. S., Jeremy Bockholt, H., Gadde, S., Preda, A., Wible, C. G., Stern, H. S., Belger, A., McCarthy, G., Ozyurt, B., Potkin, S. G. 2016; 124: 1074-1079


    The Function Biomedical Informatics Research Network (FBIRN) developed methods and tools for conducting multi-scanner functional magnetic resonance imaging (fMRI) studies. Method and tool development were based on two major goals: 1) to assess the major sources of variation in fMRI studies conducted across scanners, including instrumentation, acquisition protocols, challenge tasks, and analysis methods, and 2) to provide a distributed network infrastructure and an associated federated database to host and query large, multi-site, fMRI and clinical data sets. In the process of achieving these goals the FBIRN test bed generated several multi-scanner brain imaging data sets to be shared with the wider scientific community via the BIRN Data Repository (BDR). The FBIRN Phase 1 data set consists of a traveling subject study of 5 healthy subjects, each scanned on 10 different 1.5 to 4 T scanners. The FBIRN Phase 2 and Phase 3 data sets consist of subjects with schizophrenia or schizoaffective disorder along with healthy comparison subjects scanned at multiple sites. In this paper, we provide concise descriptions of FBIRN's multi-scanner brain imaging data sets and details about the BIRN Data Repository instance of the Human Imaging Database (HID) used to publicly share the data.

    View details for DOI 10.1016/j.neuroimage.2015.09.003

    View details for PubMedID 26364863

  • Multisite, multimodal neuroimaging of chronic urological pelvic pain: Methodology of the MAPP Research Network. NeuroImage. Clinical Alger, J. R., Ellingson, B. M., Ashe-McNalley, C., Woodworth, D. C., Labus, J. S., Farmer, M., Huang, L., Apkarian, A. V., Johnson, K. A., Mackey, S. C., Ness, T. J., Deutsch, G., Harris, R. E., Clauw, D. J., Glover, G. H., Parrish, T. B., Hollander, J. d., Kusek, J. W., Mullins, C., Mayer, E. A. 2016; 12: 65-77


    The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network is an ongoing multi-center collaborative research group established to conduct integrated studies in participants with urologic chronic pelvic pain syndrome (UCPPS). The goal of these investigations is to provide new insights into the etiology, natural history, clinical, demographic and behavioral characteristics, search for new and evaluate candidate biomarkers, systematically test for contributions of infectious agents to symptoms, and conduct animal studies to understand underlying mechanisms for UCPPS. Study participants were enrolled in a one-year observational study and evaluated through a multisite, collaborative neuroimaging study to evaluate the association between UCPPS and brain structure and function. 3D T1-weighted structural images, resting-state fMRI, and high angular resolution diffusion MRI were acquired in five participating MAPP Network sites using 8 separate MRI hardware and software configurations. We describe the neuroimaging methods and procedures used to scan participants, the challenges encountered in obtaining data from multiple sites with different equipment/software, and our efforts to minimize site-to-site variation.

    View details for DOI 10.1016/j.nicl.2015.12.009

    View details for PubMedID 27408791

    View details for PubMedCentralID PMC4925887

  • Prefrontal cortical regulation of brainwide circuit dynamics and reward-related behavior. Science Ferenczi, E. A., Zalocusky, K. A., Liston, C., Grosenick, L., Warden, M. R., Amatya, D., Katovich, K., Mehta, H., Patenaude, B., Ramakrishnan, C., Kalanithi, P., Etkin, A., Knutson, B., Glover, G. H., Deisseroth, K. 2016; 351 (6268)


    Motivation for reward drives adaptive behaviors, whereas impairment of reward perception and experience (anhedonia) can contribute to psychiatric diseases, including depression and schizophrenia. We sought to test the hypothesis that the medial prefrontal cortex (mPFC) controls interactions among specific subcortical regions that govern hedonic responses. By using optogenetic functional magnetic resonance imaging to locally manipulate but globally visualize neural activity in rats, we found that dopamine neuron stimulation drives striatal activity, whereas locally increased mPFC excitability reduces this striatal response and inhibits the behavioral drive for dopaminergic stimulation. This chronic mPFC overactivity also stably suppresses natural reward-motivated behaviors and induces specific new brainwide functional interactions, which predict the degree of anhedonia in individuals. These findings describe a mechanism by which mPFC modulates expression of reward-seeking behavior, by regulating the dynamical interactions between specific distant subcortical regions.

    View details for DOI 10.1126/science.aac9698

    View details for PubMedID 26722001

  • The Function Biomedical Informatics Research Network Data Repository NEUROIMAGE Keator, D. B., van Erp, T. G., Turner, J. A., Glover, G. H., Mueller, B. A., Liu, T. T., Voyvodic, J. T., Rasmussen, J., Calhoun, V. D., Lee, H. J., Toga, A. W., McEwen, S., Ford, J. M., Mathalon, D. H., Diaz, M., O'Leary, D. S., Bockholt, H. J., Gadde, S., Preda, A., Wible, C. G., Stern, H. S., Belger, A., McCarthy, G., Ozyurt, B., Potkin, S. G. 2016; 124: 1074-1079


    The Function Biomedical Informatics Research Network (FBIRN) developed methods and tools for conducting multi-scanner functional magnetic resonance imaging (fMRI) studies. Method and tool development were based on two major goals: 1) to assess the major sources of variation in fMRI studies conducted across scanners, including instrumentation, acquisition protocols, challenge tasks, and analysis methods, and 2) to provide a distributed network infrastructure and an associated federated database to host and query large, multi-site, fMRI and clinical data sets. In the process of achieving these goals the FBIRN test bed generated several multi-scanner brain imaging data sets to be shared with the wider scientific community via the BIRN Data Repository (BDR). The FBIRN Phase 1 data set consists of a traveling subject study of 5 healthy subjects, each scanned on 10 different 1.5 to 4 T scanners. The FBIRN Phase 2 and Phase 3 data sets consist of subjects with schizophrenia or schizoaffective disorder along with healthy comparison subjects scanned at multiple sites. In this paper, we provide concise descriptions of FBIRN's multi-scanner brain imaging data sets and details about the BIRN Data Repository instance of the Human Imaging Database (HID) used to publicly share the data.

    View details for DOI 10.1016/j.neuroimage.2015.09.003

    View details for Web of Science ID 000366151000003

    View details for PubMedID 26364863

    View details for PubMedCentralID PMC4651841

  • Successful demonstration of simultaneous PET/MR Imaging with a RF-penetrable PET insert. EJNMMI physics Lee, B., Grant, A., Chang, C., Glover, G., Levin, C. 2015; 2: A17-?

    View details for DOI 10.1186/2197-7364-2-S1-A17

    View details for PubMedID 26956272

    View details for PubMedCentralID PMC4798708

  • Relating Intrinsic Low-Frequency BOLD Cortical Oscillations to Cognition in Schizophrenia NEUROPSYCHOPHARMACOLOGY Fryer, S. L., Roach, B. J., Ford, J. M., Turner, J. A., van Erp, T. G., Voyvodic, J., Preda, A., Belger, A., Bustillo, J., O'Leary, D., Mueller, B. A., Lim, K. O., McEwen, S. C., Calhoun, V. D., Diaz, M., Glover, G., Greve, D., Wible, C. G., Vaidya, J., Potkin, S. G., Mathalon, D. H. 2015; 40 (12): 2705-2714


    The amplitude of low-frequency fluctuations (ALFF) in the blood oxygenation level-dependent (BOLD) signal during resting-state fMRI reflects the magnitude of local low-frequency BOLD oscillations, rather than interregional connectivity. ALFF is of interest to studies of cognition because fluctuations in spontaneous intrinsic brain activity relate to, and possibly even constrain, task-evoked brain responses in healthy people. Lower ALFF has been reported in schizophrenia, but the cognitive correlates of these reductions remain unknown. Here, we assess relationships between ALFF and attention and working memory in order to establish the functional relevance of intrinsic BOLD oscillatory power alterations with respect to specific cognitive impairments in schizophrenia. As part of the multisite FBIRN study, resting-state fMRI data were collected from schizophrenia subjects (SZ; n=168) and healthy controls (HC; n=166). Voxelwise fractional ALFF (fALFF), a normalized ALFF measure, was regressed on neuropsychological measures of sustained attention and working memory in SZ and HC to identify regions showing either common slopes across groups or slope differences between groups (all findings p<0.01 height, p<0.05 family-wise error cluster corrected). Poorer sustained attention was associated with smaller fALFF in the left superior frontal cortex and bilateral temporoparietal junction in both groups, with additional relationships in bilateral posterior parietal, posterior cingulate, dorsal anterior cingulate (ACC), and right dorsolateral prefrontal cortex (DLPFC) evident only in SZ. Poorer working memory was associated with smaller fALFF in bilateral ACC/mPFC, DLPFC, and posterior parietal cortex in both groups. Our findings indicate that smaller amplitudes of low-frequency BOLD oscillations during rest, measured by fALFF, were significantly associated with poorer cognitive performance, sometimes similarly in both groups and sometimes only in SZ, in regions known to subserve sustained attention and working memory. Taken together, these data suggest that the magnitude of resting-state BOLD oscillations shows promise as a biomarker of cognitive function in health and disease.

    View details for DOI 10.1038/npp.2015.119

    View details for Web of Science ID 000362836700006

    View details for PubMedID 25944410

    View details for PubMedCentralID PMC4864646

  • Functional Magnetic Resonance Imaging Methods NEUROPSYCHOLOGY REVIEW Chen, J. E., Glover, G. H. 2015; 25 (3): 289-313


    Since its inception in 1992, Functional Magnetic Resonance Imaging (fMRI) has become an indispensible tool for studying cognition in both the healthy and dysfunctional brain. FMRI monitors changes in the oxygenation of brain tissue resulting from altered metabolism consequent to a task-based evoked neural response or from spontaneous fluctuations in neural activity in the absence of conscious mentation (the "resting state"). Task-based studies have revealed neural correlates of a large number of important cognitive processes, while fMRI studies performed in the resting state have demonstrated brain-wide networks that result from brain regions with synchronized, apparently spontaneous activity. In this article, we review the methods used to acquire and analyze fMRI signals.

    View details for DOI 10.1007/s11065-015-9294-9

    View details for PubMedID 26248581

  • Erratum to: Functional Magnetic Resonance Imaging Methods. Neuropsychology review Chen, J. E., Glover, G. H. 2015; 25 (3): 314-?

    View details for DOI 10.1007/s11065-015-9298-5

    View details for PubMedID 26319138

  • Subcortical volumes differentiate Major Depressive Disorder, Bipolar Disorder, and remitted Major Depressive Disorder JOURNAL OF PSYCHIATRIC RESEARCH Sacchet, M. D., Livermore, E. E., Iglesias, J. E., Glover, G. H., Gotlib, I. H. 2015; 68: 91-98


    Subcortical gray matter regions have been implicated in mood disorders, including Major Depressive Disorder (MDD) and Bipolar Disorder (BD). It is unclear, however, whether or how these regions differ among mood disorders and whether such abnormalities are state- or trait-like. In this study, we examined differences in subcortical gray matter volumes among euthymic BD, MDD, remitted MDD (RMD), and healthy (CTL) individuals. Using automated gray matter segmentation of T1-weighted MRI images, we estimated volumes of 16 major subcortical gray matter structures in 40 BD, 57 MDD, 35 RMD, and 61 CTL individuals. We used multivariate analysis of variance to examine group differences in these structures, and support vector machines (SVMs) to assess individual-by-individual classification. Analyses yielded significant group differences for caudate (p = 0.029) and ventral diencephalon (VD) volumes (p = 0.003). For the caudate, both the BD (p = 0.004) and the MDD (p = 0.037) participants had smaller volumes than did the CTL participants. For the VD, the MDD participants had larger volumes than did the BD and CTL participants (ps < 0.005). SVM distinguished MDD from BD with 59.5% accuracy. These findings indicate that mood disorders are characterized by anomalies in subcortical gray matter volumes and that the caudate and VD contribute uniquely to differential affective pathology. Identifying abnormalities in subcortical gray matter may prove useful for the prevention, diagnosis, and treatment of mood disorders.

    View details for DOI 10.1016/j.jpsychires.2015.06.002

    View details for Web of Science ID 000359956100015

    View details for PubMedID 26228406

  • Prototype positron emission tomography insert with electro-optical signal transmission for simultaneous operation with MRI PHYSICS IN MEDICINE AND BIOLOGY Olcott, P., Kim, E., Hong, K., Lee, B. J., Grant, A. M., Chang, C., Glover, G., Levin, C. S. 2015; 60 (9): 3459-3478


    The simultaneous acquisition of PET and MRI data shows promise to provide powerful capabilities to study disease processes in human subjects, guide the development of novel treatments, and monitor therapy response and disease progression. A brain-size PET detector ring insert for an MRI system is being developed that, if successful, can be inserted into any existing MRI system to enable simultaneous PET and MRI images of the brain to be acquired without mutual interference. The PET insert uses electro-optical coupling to relay all the signals from the PET detectors out of the MRI system using analog modulated lasers coupled to fiber optics. Because the fibers use light instead of electrical signals, the PET detector can be electrically decoupled from the MRI making it partially transmissive to the RF field of the MRI. The SiPM devices and low power lasers were powered using non-magnetic MRI compatible batteries. Also, the number of laser-fiber channels in the system was reduced using techniques adapted from the field of compressed sensing. Using the fact that incoming PET data is sparse in time and space, electronic circuits implementing constant weight codes uniquely encode the detector signals in order to reduce the number of electro-optical readout channels by 8-fold. Two out of a total of sixteen electro-optical detector modules have been built and tested with the entire RF-shielded detector gantry for the PET ring insert. The two detectors have been tested outside and inside of a 3T MRI system to study mutual interference effects and simultaneous performance with MRI. Preliminary results show that the PET insert is feasible for high resolution simultaneous PET/MRI imaging for applications in the brain.

    View details for DOI 10.1088/0031-9155/60/9/3459

    View details for Web of Science ID 000354104700007

    View details for PubMedID 25856511

  • Introducing co-activation pattern metrics to quantify spontaneous brain network dynamics NEUROIMAGE Chen, J. E., Chang, C., Greicius, M. D., Glover, G. H. 2015; 111: 476-488


    Recently, fMRI researchers have begun to realize that the brain's intrinsic network patterns may undergo substantial changes during a single resting state (RS) scan. However, despite the growing interest in brain dynamics, metrics that can quantify the variability of network patterns are still quite limited. Here, we first introduce various quantification metrics based on the extension of co-activation pattern (CAP) analysis, a recently proposed point-process analysis that tracks state alternations at each individual time frame and relies on very few assumptions; then apply these proposed metrics to quantify changes of brain dynamics during a sustained 2-back working memory (WM) task compared to rest. We focus on the functional connectivity of two prominent RS networks, the default-mode network (DMN) and executive control network (ECN). We first demonstrate less variability of global Pearson correlations with respect to the two chosen networks using a sliding-window approach during WM task compared to rest; then we show that the macroscopic decrease in variations in correlations during a WM task is also well characterized by the combined effect of a reduced number of dominant CAPs, increased spatial consistency across CAPs, and increased fractional contributions of a few dominant CAPs. These CAP metrics may provide alternative and more straightforward quantitative means of characterizing brain network dynamics than time-windowed correlation analyses.

    View details for DOI 10.1016/j.neuroimage.2015.01.057

    View details for PubMedID 25662866

  • Subcortical Volumes Differentiate Affective Disorders Sacchet, M. D., Livermore, E. E., Iglesias, J., Glover, G. H., Gotlib, I. H. ELSEVIER SCIENCE INC. 2015
  • BOLD fractional contribution to resting-state functional connectivity above 0.1Hz. NeuroImage Chen, J. E., Glover, G. H. 2015; 107: 207-218


    Blood oxygen level dependent (BOLD) spontaneous signals from resting-state (RS) brains have typically been characterized by low-pass filtered timeseries at frequencies ≤0.1Hz, and studies of these low-frequency fluctuations have contributed exceptional understanding of the baseline functions of our brain. Very recently, emerging evidence has demonstrated that spontaneous activities may persist in higher frequency bands (even up to 0.8Hz), while presenting less variable network patterns across the scan duration. However, as an indirect measure of neuronal activity, BOLD signal results from an inherently slow hemodynamic process, which in fact might be too slow to accommodate the observed high-frequency functional connectivity (FC). To examine whether the observed high-frequency spontaneous FC originates from BOLD contrast, we collected RS data as a function of echo time (TE). Here we focus on two specific resting state networks - the default-mode network (DMN) and executive control network (ECN), and the major findings are fourfold: (1) we observed BOLD-like linear TE-dependence in the spontaneous activity at frequency bands up to 0.5Hz (the maximum frequency that can be resolved with TR=1s), supporting neural relevance of the RSFC at a higher frequency range; (2) conventional models of hemodynamic response functions must be modified to support resting state BOLD contrast, especially at higher frequencies; (3) there are increased fractions of non-BOLD-like contributions to the RSFC above the conventional 0.1Hz (non-BOLD/BOLD contrast at 0.4-0.5Hz is ~4 times that at <0.1Hz); and (4) the spatial patterns of RSFC are frequency-dependent. Possible mechanisms underlying the present findings and technical concerns regarding RSFC above 0.1Hz are discussed.

    View details for DOI 10.1016/j.neuroimage.2014.12.012

    View details for PubMedID 25497686

  • Changes in brain activation following psychotherapy for youth with mood dysregulation at familial risk for bipolar disorder PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY Garrett, A. S., Miklowitz, D. J., Howe, M. E., Singh, M. K., Acquaye, T. K., Hawkey, C. G., Glover, G. H., Reiss, A. L., Chang, K. D. 2015; 56: 215-220


    Psychotherapy for youth with mood dysregulation can help stabilize mood and improve functioning, but the neural mechanisms of this improvement are not known. In this study we investigated the changes in brain activation underlying improvement in mood symptoms.Twenty-four subjects (ages 13-17) participated: 12 patients with clinically significant symptoms of depression and/or mania, and 12 healthy comparison subjects (HC) matched for age and sex. All subjects completed functional magnetic resonance imaging while viewing facial expressions. The patients then received up to 4 months of psychotherapy and were rescanned at end of treatment. Whole brain differences between patient and control groups were assessed with a voxel-wise analysis. Changes in activation from pre- to post-treatment within the patient group were tested for correlation with changes in mood symptoms.At baseline the patient group had hypoactivation in the dorsolateral prefrontal cortex (DLPFC) and hyperactivation in the posterior cingulate cortex compared to the HC group. Between pre- and post-treatment activation increased in the DLPFC and decreased in the amygdala. Increases in DLPFC activation were significantly correlated with improvement in mania symptoms.Enhancement of frontal executive control brain regions may underlie improvement in mood dysregulation in pediatric patients at familial risk for bipolar disorder.

    View details for DOI 10.1016/j.pnpbp.2014.09.007

    View details for Web of Science ID 000345526400030

    View details for PubMedCentralID PMC4258439

  • Changes in brain activation following psychotherapy for youth with mood dysregulation at familial risk for bipolar disorder. Progress in neuro-psychopharmacology & biological psychiatry Garrett, A. S., Miklowitz, D. J., Howe, M. E., Singh, M. K., Acquaye, T. K., Hawkey, C. G., Glover, G. H., Reiss, A. L., Chang, K. D. 2015; 56: 215-220


    Psychotherapy for youth with mood dysregulation can help stabilize mood and improve functioning, but the neural mechanisms of this improvement are not known. In this study we investigated the changes in brain activation underlying improvement in mood symptoms.Twenty-four subjects (ages 13-17) participated: 12 patients with clinically significant symptoms of depression and/or mania, and 12 healthy comparison subjects (HC) matched for age and sex. All subjects completed functional magnetic resonance imaging while viewing facial expressions. The patients then received up to 4 months of psychotherapy and were rescanned at end of treatment. Whole brain differences between patient and control groups were assessed with a voxel-wise analysis. Changes in activation from pre- to post-treatment within the patient group were tested for correlation with changes in mood symptoms.At baseline the patient group had hypoactivation in the dorsolateral prefrontal cortex (DLPFC) and hyperactivation in the posterior cingulate cortex compared to the HC group. Between pre- and post-treatment activation increased in the DLPFC and decreased in the amygdala. Increases in DLPFC activation were significantly correlated with improvement in mania symptoms.Enhancement of frontal executive control brain regions may underlie improvement in mood dysregulation in pediatric patients at familial risk for bipolar disorder.

    View details for DOI 10.1016/j.pnpbp.2014.09.007

    View details for PubMedID 25283342

  • Inferring deep-brain activity from cortical activity using functional near-infrared spectroscopy BIOMEDICAL OPTICS EXPRESS Liu, N., Cui, X., Bryant, D. M., Glover, G. H., Reiss, A. L. 2015; 6 (3): 1074-1089


    Functional near-infrared spectroscopy (fNIRS) is an increasingly popular technology for studying brain function because it is non-invasive, non-irradiating and relatively inexpensive. Further, fNIRS potentially allows measurement of hemodynamic activity with high temporal resolution (milliseconds) and in naturalistic settings. However, in comparison with other imaging modalities, namely fMRI, fNIRS has a significant drawback: limited sensitivity to hemodynamic changes in deep-brain regions. To overcome this limitation, we developed a computational method to infer deep-brain activity using fNIRS measurements of cortical activity. Using simultaneous fNIRS and fMRI, we measured brain activity in 17 participants as they completed three cognitive tasks. A support vector regression (SVR) learning algorithm was used to predict activity in twelve deep-brain regions using information from surface fNIRS measurements. We compared these predictions against actual fMRI-measured activity using Pearson's correlation to quantify prediction performance. To provide a benchmark for comparison, we also used fMRI measurements of cortical activity to infer deep-brain activity. When using fMRI-measured activity from the entire cortex, we were able to predict deep-brain activity in the fusiform cortex with an average correlation coefficient of 0.80 and in all deep-brain regions with an average correlation coefficient of 0.67. The top 15% of predictions using fNIRS signal achieved an accuracy of 0.7. To our knowledge, this study is the first to investigate the feasibility of using cortical activity to infer deep-brain activity. This new method has the potential to extend fNIRS applications in cognitive and clinical neuroscience research.

    View details for DOI 10.1364/BOE.6.001074

    View details for Web of Science ID 000350802000035

    View details for PubMedID 25798327

    View details for PubMedCentralID PMC4361422

  • Quality Assurance in Functional MRI FMRI: FROM NUCLEAR SPINS TO BRAIN FUNCTIONS Liu, T. T., Glover, G. H., Mueller, B. A., Greve, D. N., Rasmussen, J., Voyvodic, J. T., Turner, J. A., Erp, T. M., Mathalon, D. H., Andersen, K., Lu, K., Brown, G. G., Keator, D. B., Calhoun, V. D., Lee, H., Ford, J. M., Diaz, M., O'Leary, D. S., Gadde, S., Preda, A., Lim, K. O., Wible, C. G., Stern, H. S., Belger, A., McCarthy, G., Ozyurt, B., Potkin, S. G., FBIRN, Uludag, K., Ugurbil, K., Berliner, L. 2015; 30: 245–70
  • Ballistocardiogram artifact removal with a reference layer and standard EEG cap. Journal of neuroscience methods Luo, Q., Huang, X., Glover, G. H. 2014; 233: 137-149


    In simultaneous EEG-fMRI, the EEG recordings are severely contaminated by ballistocardiogram (BCG) artifacts, which are caused by cardiac pulsations. To reconstruct and remove the BCG artifacts, one promising method is to measure the artifacts in the absence of EEG signal by placing a group of electrodes (BCG electrodes) on a conductive layer (reference layer) insulated from the scalp. However, current BCG reference layer (BRL) methods either use a customized EEG cap composed of electrode pairs, or need to construct the custom reference layer through additional model-building experiments for each EEG-fMRI experiment. These requirements have limited the versatility and efficiency of BRL. The aim of this study is to propose a more practical and efficient BRL method and compare its performance with the most popular BCG removal method, the optimal basis sets (OBS) algorithm.By designing the reference layer as a permanent and reusable cap, the new BRL method is able to be used with a standard EEG cap, and no extra experiments and preparations are needed to use the BRL in an EEG-fMRI experiment.The BRL method effectively removed the BCG artifacts from both oscillatory and evoked potential scalp recordings and recovered the EEG signal.Compared to the OBS, this new BRL method improved the contrast-to-noise ratios of the alpha-wave, visual, and auditory evoked potential signals by 101%, 76%, and 75%, respectively, employing 160 BCG electrodes. Using only 20 BCG electrodes, the BRL improved the EEG signal by 74%/26%/41%, respectively.The proposed method can substantially improve the EEG signal quality compared with traditional methods.

    View details for DOI 10.1016/j.jneumeth.2014.06.021

    View details for PubMedID 24960423

    View details for PubMedCentralID PMC4126606

  • Control of nucleus accumbens activity with neurofeedback NEUROIMAGE Greer, S. M., Trujillo, A. J., Glover, G. H., Knutson, B. 2014; 96: 237-244


    The nucleus accumbens (NAcc) plays critical roles in healthy motivation and learning, as well as in psychiatric disorders (including schizophrenia and attention deficit hyperactivity disorder). Thus, techniques that confer control of NAcc activity might inspire new therapeutic interventions. By providing second-to-second temporal resolution of activity in small subcortical regions, functional magnetic resonance imaging (fMRI) can resolve online changes in NAcc activity, which can then be presented as "neurofeedback." In an fMRI-based neurofeedback experiment designed to elicit NAcc activity, we found that subjects could increase their own NAcc activity, and that display of neurofeedback significantly enhanced their ability to do so. Subjects were not as capable of decreasing their NAcc activity, however, and enhanced control did not persist after subsequent removal of neurofeedback. Further analyses suggested that individuals who recruited positive aroused affect were better able to increase NAcc activity in response to neurofeedback, and that NAcc neurofeedback also elicited functionally correlated activity in the medial prefrontal cortex. Together, these findings suggest that humans can modulate their own NAcc activity and that fMRI-based neurofeedback may augment their efforts. The observed association between positive arousal and effective NAcc control further supports an anticipatory affect account of NAcc function.

    View details for DOI 10.1016/j.neuroimage.2014.03.073

    View details for Web of Science ID 000338809200022

    View details for PubMedID 24705203

    View details for PubMedCentralID PMC4181613

  • A multi-scanner study of subcortical brain volume abnormalities in schizophrenia PSYCHIATRY RESEARCH-NEUROIMAGING van Erp, T. G., Greve, D. N., Rasmussen, J., Turner, J., Calhoun, V. D., Young, S., Mueller, B., Brown, G. G., McCarthy, G., Glover, G. H., Lim, K. O., Bustillo, J. R., Belger, A., McEwen, S., Voyvodic, J., Mathalon, D. H., Keator, D., Preda, A., Dana Nguyen, D., Ford, J. M., Potkin, S. G. 2014; 222 (1-2): 10-16


    Schizophrenia patients show significant subcortical brain abnormalities. We examined these abnormalities using automated image analysis software and provide effect size estimates for prospective multi-scanner schizophrenia studies. Subcortical and intracranial volumes were obtained using FreeSurfer 5.0.0 from high-resolution structural imaging scans from 186 schizophrenia patients (mean age±S.D.=38.9±11.6, 78% males) and 176 demographically similar controls (mean age±S.D.=37.5±11.2, 72% males). Scans were acquired from seven 3-Tesla scanners. Univariate mixed model regression analyses compared between-group volume differences. Weighted mean effect sizes (and number of subjects needed for 80% power at α=0.05) were computed based on the individual single site studies as well as on the overall multi-site study. Schizophrenia patients have significantly smaller intracranial, amygdala, and hippocampus volumes and larger lateral ventricle, putamen and pallidum volumes compared with healthy volunteers. Weighted mean effect sizes based on single site studies were generally larger than effect sizes computed based on analysis of the overall multi-site sample. Prospectively collected structural imaging data can be combined across sites to increase statistical power for meaningful group comparisons. Even when using similar scan protocols at each scanner, some between-site variance remains. The multi-scanner effect sizes provided by this study should help in the design of future multi-scanner schizophrenia imaging studies.

    View details for DOI 10.1016/j.pscychresns.2014.02.011

    View details for Web of Science ID 000334739500002

    View details for PubMedID 24650452

  • Schizophrenia miR-137 Locus Risk Genotype Is Associated with Dorsolateral Prefrontal Cortex Hyperactivation BIOLOGICAL PSYCHIATRY van Erp, T. G., Guella, I., Vawter, M. P., Turner, J., Brown, G. G., McCarthy, G., Greve, D. N., Glover, G. H., Calhoun, V. D., Lim, K. O., Bustillo, J. R., Belger, A., Ford, J. M., Mathalon, D. H., Diaz, M., Preda, A., Nguyen, D., Macciardi, F., Potkin, S. G. 2014; 75 (5): 398-405


    miR-137 dysregulation has been implicated in the etiology of schizophrenia, but its functional role remains to be determined.Functional magnetic resonance imaging scans were acquired on 48 schizophrenia patients and 63 healthy volunteers (total sample size N = 111 subjects), with similar mean age and sex distribution, while subjects performed a Sternberg Item Response Paradigm with memory loads of one, three, and five numbers. Dorsolateral prefrontal cortex (DLPFC) retrieval activation for the working memory load of three numbers, for which hyperactivation had been shown in schizophrenia patients compared with control subjects, was extracted. The genome-wide association study confirmed schizophrenia risk single nucleotide polymorphism rs1625579 (miR-137 locus) was genotyped (schizophrenia: GG n = 0, GT n = 9, TT n = 39; healthy volunteers: GG = 2, GT n = 15, and TT n = 46). Fisher's exact test examined the effect of diagnosis on rs1625579 allele frequency distribution (p = nonsignificant). Mixed model regression analyses examined the effects of diagnosis and genotype on working memory performance measures and DLPFC activation.Patients showed significantly higher left DLPFC retrieval activation on working memory load 3, lower working memory performance, and longer response times compared with controls. There was no effect of genotype on working memory performance or response times in either group. However, individuals with the rs1625579 TT genotype had significantly higher left DLPFC activation than those with the GG/GT genotypes.Our study suggests that the rs1625579 TT (miR-137 locus) schizophrenia risk genotype is associated with the schizophrenia risk phenotype DLPFC hyperactivation commonly considered a measure of brain inefficiency.

    View details for DOI 10.1016/j.biopsych.2013.06.016

    View details for Web of Science ID 000330724100011

    View details for PubMedID 23910899

  • Magnetic Resonance in Medicine at 30 MAGNETIC RESONANCE IN MEDICINE Glover, G. H., Jones, D. K., Frahm, J., Henkelman, R., Hennig, J., Maudsley, A. A., Riederer, S. J., Wehrli, F. W., Bernstein, M. A. 2014; 71 (3): 901–2

    View details for PubMedID 24478240

  • Increased insula coactivation with salience networks in insomnia. Biological psychology Chen, M. C., Chang, C., Glover, G. H., Gotlib, I. H. 2014; 97: 1-8


    Insomnia is among the most prevalent and costly of all sleep-related disorders. To characterize the neural mechanisms underlying subjective dysfunction in insomnia, we examined brain activity in 17 female insomniacs and 17 female healthy controls using simultaneous functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) while they were resting and while they were trying to fall asleep. In examining the dynamic regional activity within intrinsic brain networks, we found that, compared with controls, insomniacs had greater involvement of the anterior insula with salience networks, as well as insula BOLD correlation with EEG gamma frequency power during rest in insomniacs. This increased involvement of the anterior insula was associated with negative affect in insomniacs. Aberrant activation of the insula, which integrates temporal and bodily states, in arousal networks may underlie the misperception of sleep quality and subjective distress in insomnia.

    View details for DOI 10.1016/j.biopsycho.2013.12.016

    View details for PubMedID 24412227

  • Cultural influences on the neural correlate of moral decision making processes. Behavioural brain research Han, H., Glover, G. H., Jeong, C. 2014; 259: 215-228


    This study compares the neural substrate of moral decision making processes between Korean and American participants. By comparison with Americans, Korean participants showed increased activity in the right putamen associated with socio-intuitive processes and right superior frontal gyrus associated with cognitive control processes under a moral-personal condition, and in the right postcentral sulcus associated with mental calculation in familiar contexts under a moral-impersonal condition. On the other hand, American participants showed a significantly higher degree of activity in the bilateral anterior cingulate cortex (ACC) associated with conflict resolution under the moral-personal condition, and in the right medial frontal gyrus (MFG) associated with simple cognitive branching in non-familiar contexts under the moral-impersonal condition when a more lenient threshold was applied, than Korean participants. These findings support the ideas of the interactions between the cultural background, education, and brain development, proposed in the field of cultural psychology and educational psychology. The study introduces educational implications relevant to moral psychologists and educators.

    View details for DOI 10.1016/j.bbr.2013.11.012

    View details for PubMedID 24263193

  • Improved Slice-Selective Adiabatic Excitation MAGNETIC RESONANCE IN MEDICINE Balchandani, P., Glover, G., Pauly, J., Spielman, D. 2014; 71 (1): 75-82


    PURPOSE: The purpose of this work is to design an improved Slice-selective Tunable-flip AdiaBatic Low peak-power Excitation (STABLE) pulse with shorter duration and increased off-resonance immunity to make it suitable for use in a greater range of applications and at higher field strengths. An additional aim is to design a variant of this pulse to achieve B(1) -insensitive, fat-suppressed excitation. METHODS: The adiabatic SLR algorithm was used to generate a more uniform spectral pulse envelope for this improved radiofrequency pulse for adiabatic slice-selective excitation, called STABLE-2. Pulse parameters were adjusted to design a version of STABLE-2 with a spectral null centered on lipids. RESULTS: In vivo images obtained of the human brain at 3 and 7 T demonstrate that STABLE-2 provides robust, uniform, slice-selective excitation over a range of B(1) values. Phantom and in vivo knee images obtained at 3 T demonstrate the effectiveness of STABLE-2 for fat suppression. CONCLUSIONS: STABLE-2 achieves B(1) -insensitive slice-selective excitation while providing greater off-resonance immunity and a shorter pulse duration, when compared to the original STABLE pulse. In particular, the 9.8-ms STABLE-2 pulse provides slice selectivity over 120 Hz whereas the 21-ms STABLE pulse is limited to 80 Hz off-resonance. B(1) -Insensitive fat-suppressed excitation may also be achieved by using a variant of this pulse. Magn Reson Med, 2013. © 2013 Wiley Periodicals, Inc.

    View details for DOI 10.1002/mrm.24630

    View details for Web of Science ID 000328580300010

    View details for PubMedID 23401184

  • Sparsely Sampled functional Magnetic Resonance Imaging Using Low-rank and Sparsity Constraints Nguyen, H. M., Glover, G. H., IEEE IEEE. 2014: 454–57
  • RF-Transmissive PET Detector Insert for Simultaneous PET/MRI Lee, B. J., Grant, A. M., Chang, C., Glover, G. H., Levin, C. S., IEEE IEEE. 2014
  • Causal interactions between fronto-parietal central executive and default-mode networks in humans PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Chen, A. C., Oathes, D. J., Chang, C., Bradley, T., Zhou, Z., Williams, L. M., Glover, G. H., Deisseroth, K., Etkin, A. 2013; 110 (49): 19944-19949


    Information processing during human cognitive and emotional operations is thought to involve the dynamic interplay of several large-scale neural networks, including the fronto-parietal central executive network (CEN), cingulo-opercular salience network (SN), and the medial prefrontal-medial parietal default mode networks (DMN). It has been theorized that there is a causal neural mechanism by which the CEN/SN negatively regulate the DMN. Support for this idea has come from correlational neuroimaging studies; however, direct evidence for this neural mechanism is lacking. Here we undertook a direct test of this mechanism by combining transcranial magnetic stimulation (TMS) with functional MRI to causally excite or inhibit TMS-accessible prefrontal nodes within the CEN or SN and determine consequent effects on the DMN. Single-pulse excitatory stimulations delivered to only the CEN node induced negative DMN connectivity with the CEN and SN, consistent with the CEN/SN's hypothesized negative regulation of the DMN. Conversely, low-frequency inhibitory repetitive TMS to the CEN node resulted in a shift of DMN signal from its normally low-frequency range to a higher frequency, suggesting disinhibition of DMN activity. Moreover, the CEN node exhibited this causal regulatory relationship primarily with the medial prefrontal portion of the DMN. These findings significantly advance our understanding of the causal mechanisms by which major brain networks normally coordinate information processing. Given that poorly regulated information processing is a hallmark of most neuropsychiatric disorders, these findings provide a foundation for ways to study network dysregulation and develop brain stimulation treatments for these disorders.

    View details for DOI 10.1073/pnas.1311772110

    View details for Web of Science ID 000327744900066

    View details for PubMedID 24248372

    View details for PubMedCentralID PMC3856839

  • Efficient bloch-siegert B1 (+) mapping using spiral and echo-planar readouts. Magnetic resonance in medicine Saranathan, M., Khalighi, M. M., Glover, G. H., Pandit, P., Rutt, B. K. 2013; 70 (6): 1669-1673


    The Bloch-Siegert (B-S) B(1) (+) mapping technique is a fast, phase-based method that is highly SAR limited especially at 7T, necessitating the use of long repetition times. Spiral and echo-planar readouts were incorporated in a gradient-echo based B-S sequence to reduce specific absoprtion rate (SAR) and improve its scan efficiency. A novel, numerically optimized 4 ms B-S off-resonant pulse at + 1960 Hz was used to increase sensitivity and further reduce SAR compared with the conventional 6 ms Fermi B-S pulse. Using echo-planar and spiral readouts, scan time reductions of 8-16 were achieved. By reducing the B-S pulse width by a factor of 1.5, SAR was reduced by a factor of 1.5 and overall sensitivity was increased by a factor of 1.33 due to the nearly halved resonance offset of the new B-S pulse. This was validated on phantoms and volunteers at 7 T. Magn Reson Med, 2013. © 2013 Wiley Periodicals, Inc.

    View details for DOI 10.1002/mrm.24599

    View details for PubMedID 23401024

    View details for PubMedCentralID PMC3657582

  • Ferumoxytol enhanced resting state fMRI and relative cerebral blood volume mapping in normal human brain. NeuroImage D'Arceuil, H., Coimbra, A., Triano, P., Dougherty, M., Mello, J., Moseley, M., Glover, G., Lansberg, M., Blankenberg, F. 2013; 83: 200-209


    The brain demonstrates spontaneous low-frequency (<0.1Hz) cerebral blood flow (CBF) fluctuations, measurable by resting state functional MRI (rs-fMRI). Ultra small superparamagnetic iron oxide particles have been shown to enhance task-based fMRI signals (cerebral blood volume fMRI or CBV-fMRI), compared to the BOLD effect, by a factor of ≈2.5 at 3T in primates and humans. We evaluated the use of ferumoxytol for steady state, resting state FMRI (CBV-rs-fMRI) and relative cerebral blood volume (rCBV) mapping, at 3T, in healthy volunteers. All standard resting state networks (RSNs) were identified in all subjects. On average the RSN Z statistics (MELODIC independent components) and volumes of the visual and default mode (DMN) networks were comparable. rCBV values were averaged for the visual (Vis) and DMN networks and correlated with the corresponding DMN and visual network Z statistics. There was a negative correlation between the rCBV and the Z statistics for the DMN, for both BOLD and CBV-rs-fMRI contrast (R(2)=0.63, 0.76). A similar correlation was not found for the visual network. Short repetition time rs-fMRI data were Fourier transformed to evaluate the effect of ferumoxytol on cardiac and respiratory fluctuations in the brain rs-BOLD, CBV signals. Cardiac and respiratory fluctuations decreased to baseline within large vessels post ferumoxytol. Robust rs-fMRI and CBV mapping is possible in normal human brain.

    View details for DOI 10.1016/j.neuroimage.2013.06.066

    View details for PubMedID 23831413

  • Response to: Letter from Paul Eugene Summers, Federico Giove, and Carlo Adolfo Porro. Pain Nash, P., Glover, G., Mackey, S. 2013; 154 (11): 2574-2575

    View details for DOI 10.1016/j.pain.2013.08.014

    View details for PubMedID 23973361

  • Grand Challenges in Mapping the Human Brain: NSF Workshop Report IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING He, B., Coleman, T., Genin, G. M., Glover, G., Hu, X., Johnson, N., Liu, T., Makeig, S., Sajda, P., Ye, K. 2013; 60 (11): 2983-2992


    This report summarizes the outcomes of the NSF Workshop on Mapping and Engineering the Brain, held at Arlington, VA, during August 13-14, 2013. Three grand challenges were identified, including high spatiotemporal resolution neuroimaging, perturbation-based neuroimaging, and neuroimaging in naturalistic environments. It was highlighted that each grand challenge requires groundbreaking discoveries, enabling technologies, appropriate knowledge transfer, and multi- and transdisciplinary education and training for success.

    View details for DOI 10.1109/TBME.2013.2283970

    View details for Web of Science ID 000325974500001

    View details for PubMedID 24108705

  • Dynamic functional connectivity: Promise, issues, and interpretations NEUROIMAGE Hutchison, R. M., Womelsdorf, T., Allen, E. A., Bandettini, P. A., Calhoun, V. D., Corbetta, M., Della Penna, S., Duyn, J. H., Glover, G. H., Gonzalez-Castillo, J., Handwerker, D. A., Keilholz, S., Kiviniemi, V., Leopold, D. A., De Pasquale, F., Sporns, O., Walter, M., Chang, C. 2013; 80: 360-378


    The brain must dynamically integrate, coordinate, and respond to internal and external stimuli across multiple time scales. Non-invasive measurements of brain activity with fMRI have greatly advanced our understanding of the large-scale functional organization supporting these fundamental features of brain function. Conclusions from previous resting-state fMRI investigations were based upon static descriptions of functional connectivity (FC), and only recently studies have begun to capitalize on the wealth of information contained within the temporal features of spontaneous BOLD FC. Emerging evidence suggests that dynamic FC metrics may index changes in macroscopic neural activity patterns underlying critical aspects of cognition and behavior, though limitations with regard to analysis and interpretation remain. Here, we review recent findings, methodological considerations, neural and behavioral correlates, and future directions in the emerging field of dynamic FC investigations.

    View details for DOI 10.1016/j.neuroimage.2013.05.079

    View details for Web of Science ID 000322416000030

    View details for PubMedID 23707587

    View details for PubMedCentralID PMC3807588

  • Cross-Strip Multiplexed Electro-Optical Coupled Scintillation Detector for Integrated PET/MRI IEEE TRANSACTIONS ON NUCLEAR SCIENCE Olcott, P. D., Glover, G., Levin, C. S. 2013; 60 (5): 3198-3204
  • A Modified Generalized Series Approach: Application to Sparsely Sampled fMRI IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING Nguyen, H. M., Glover, G. H. 2013; 60 (10): 2867-2877


    In functional MRI, it is often desirable to reduce the readout duration to make the acquired data less prone to T₂* susceptibility artifacts. In addition, a shorter readout length allows for a shorter minimum TE, which is important for optimizing SNR. This can be achieved by undersampling the k-space. However, the conventional Fourier transform-based reconstruction method suffers from under-sampling artifacts such as high-frequency ringing and loss of resolution. To address this problem, we revisit the constrained-model approach using the generalized-series (GS) which has been proposed to address the undersampling problem for dynamic MRI. We propose a modification to the conventional use of the model in order to reflect small hemodynamic signal changes typical in fMRI. Specifically, while realizing that having high model order is necessary to capture missing information, we found that it is not necessary to span all frequencies of GS basis functions uniformly. Instead, having k -space and GS "sampling" trajectories covering low-frequencies uniformly while spanning high-frequencies sparsely, was observed to be an efficient strategy. The ability of the method over the conventional GS approach in improving resolution of functional images and activation maps while reducing undersampling ringing is demonstrated by simulations and experiments at 3T. Reduction in the readout time allowed an increase of statistical signal power as compared to the fully sampled acquisition. Unlike compressed sensing approaches, the proposed method is linear and hence has lower computational complexity. The method could prove useful for other imaging modalities where the signal change is smaller than the baseline component.

    View details for DOI 10.1109/TBME.2013.2265699

    View details for Web of Science ID 000324830800021

    View details for PubMedID 23744655

  • The Medial Prefrontal Cortex and the Emergence of Self-Conscious Emotion in Adolescence PSYCHOLOGICAL SCIENCE Somerville, L. H., Jones, R. M., Ruberry, E. J., Dyke, J. P., Glover, G., Casey, B. J. 2013; 24 (8): 1554-1562


    In the present study, we examined the relationship between developmental modulation of socioaffective brain systems and adolescents' preoccupation with social evaluation. Child, adolescent, and adult participants viewed cues indicating that a camera was alternately off, warming up, or projecting their image to a peer during the acquisition of behavioral-, autonomic-, and neural-response (functional MRI) data. Believing that a peer was actively watching them was sufficient to induce self-conscious emotion that rose in magnitude from childhood to adolescence and partially subsided into adulthood. Autonomic arousal was uniquely heightened in adolescents. These behavioral patterns were paralleled by emergent engagement of the medial prefrontal cortex (MPFC) and striatum-MPFC connectivity during adolescence, which are thought to promote motivated social behavior in adolescence. These findings demonstrate that adolescents' self-consciousness is related to age-dependent sensitivity of brain systems critical to socioaffective processes. Further, unique interactions between the MPFC and striatum may provide a mechanism by which social-evaluation contexts influence adolescent behavior.

    View details for DOI 10.1177/0956797613475633

    View details for Web of Science ID 000322904700019

    View details for PubMedID 23804962

    View details for PubMedCentralID PMC3742683

  • A SURVEY OF THE SOURCES OF NOISE IN FMRI PSYCHOMETRIKA Greve, D. N., Brown, G. G., Mueller, B. A., Glover, G., Liu, T. T. 2013; 78 (3): 396-416


    Functional magnetic resonance imaging (fMRI) is a noninvasive method for measuring brain function by correlating temporal changes in local cerebral blood oxygenation with behavioral measures. fMRI is used to study individuals at single time points, across multiple time points (with or without intervention), as well as to examine the variation of brain function across normal and ill populations. fMRI may be collected at multiple sites and then pooled into a single analysis. This paper describes how fMRI data is analyzed at each of these levels and describes the noise sources introduced at each level.

    View details for DOI 10.1007/S11336-012-9294-0

    View details for Web of Science ID 000320446500001

    View details for PubMedID 25106392

  • Functional magnetic resonance imaging identifies somatotopic organization of nociception in the human spinal cord. Pain Nash, P., Wiley, K., Brown, J., Shinaman, R., Ludlow, D., Sawyer, A., Glover, G., Mackey, S. 2013; 154 (6): 776-781


    Functional magnetic resonance imaging (fMRI) is a technique that uses blood oxygen-level-dependent (BOLD) signals to elucidate discrete areas of neuronal activity. Despite the significant number of fMRI human brain studies, few researchers have applied fMRI technology to investigating neuronal activity within the human spinal cord. Our study goals were to demonstrate that fMRI could reveal the following: (i) appropriate somatotopic activations in response to noxious stimuli in the deep and superficial dorsal horn of the human cervical spinal cord, and (ii) lateralization of fMRI activations in response to noxious stimulation in the right and left upper extremity. We subjected healthy participants to noxious stimulation during fMRI scans. Using a spiral in-out image sequence and retrospective correction for physiologic noise, we demonstrated that fMRI can create high-resolution, neuronal activation maps of the human cervical spinal cord. During nociceptive stimulation of all 4 sites (left deltoid, right deltoid, left thenar eminence and right thenar eminence), we found ipsilateral dorsal horn activation. Stimulation of the deltoid activated C5, whereas stimulation of the thenar eminence activated C6. Our study contributes to creating an objective analysis of pain transmission; other investigators can use these results to further study central nervous system changes that occur in patients with acute and chronic pain.

    View details for DOI 10.1016/j.pain.2012.11.008

    View details for PubMedID 23618495

  • An Introduction to Normalization and Calibration Methods in Functional MRI PSYCHOMETRIKA Liu, T. T., Glover, G. H., Mueller, B. A., Greve, D. N., Brown, G. G. 2013; 78 (2): 308-321


    In functional magnetic resonance imaging (fMRI), the blood oxygenation level dependent (BOLD) signal is often interpreted as a measure of neural activity. However, because the BOLD signal reflects the complex interplay of neural, vascular, and metabolic processes, such an interpretation is not always valid. There is growing evidence that changes in the baseline neurovascular state can result in significant modulations of the BOLD signal that are independent of changes in neural activity. This paper introduces some of the normalization and calibration methods that have been proposed for making the BOLD signal a more accurate reflection of underlying brain activity for human fMRI studies.

    View details for DOI 10.1007/s11336-012-9309-x

    View details for Web of Science ID 000316344000007

  • Association between heart rate variability and fluctuations in resting-state functional connectivity NEUROIMAGE Chang, C., Metzger, C. D., Glover, G. H., Duyn, J. H., Heinze, H., Walter, M. 2013; 68: 93-104


    Functional connectivity has been observed to fluctuate across the course of a resting state scan, though the origins and functional relevance of this phenomenon remain to be shown. The present study explores the link between endogenous dynamics of functional connectivity and autonomic state in an eyes-closed resting condition. Using a sliding window analysis on resting state fMRI data from 35 young, healthy male subjects, we examined how heart rate variability (HRV) covaries with temporal changes in whole-brain functional connectivity with seed regions previously described to mediate effects of vigilance and arousal (amygdala and dorsal anterior cingulate cortex; dACC). We identified a set of regions, including brainstem, thalamus, putamen, and dorsolateral prefrontal cortex, that became more strongly coupled with the dACC and amygdala seeds during states of elevated HRV. Effects differed between high and low frequency components of HRV, suggesting specific contributions of parasympathetic and sympathetic tone on individual connections. Furthermore, dynamics of functional connectivity could be separated from those primarily related to BOLD signal fluctuations. The present results contribute novel information about the neural basis of transient changes of autonomic nervous system states, and suggest physiological and psychological components of the recently observed non-stationarity in resting state functional connectivity.

    View details for DOI 10.1016/j.neuroimage.2012.11.038

    View details for Web of Science ID 000314492700011

    View details for PubMedID 23246859

  • Pneumatically driven finger movement: a novel passive functional MR imaging technique for presurgical motor and sensory mapping. AJNR. American journal of neuroradiology Shriver, S., Knierim, K. E., O'Shea, J. P., Glover, G. H., Golby, A. J. 2013; 34 (1): E5-7


    Two of the most common reasons for failure to obtain adequate preoperative functional data are inadequate task performance and excessive head motion. With an MR imaging-compatible pneumatically driven manipulandum, passive motor tasks elicited reproducible contralateral activation in the M1 and S1 in 10 healthy controls and 6 patients. The SMA was localized in all healthy controls and in 5 of 6 patients. Head motion was reduced in passive tasks compared with active tasks.

    View details for DOI 10.3174/ajnr.A2626

    View details for PubMedID 21778242

  • PUBERTAL STAGE AND BRAIN ANATOMY IN GIRLS (vol 217, pg 105, 2012) NEUROSCIENCE Blanton, R. E., Cooney, R. E., Joormann, J., Eugene, F., Glover, G. H., Gotlib, I. H. 2012; 227: 382-382
  • More Education, Less Administration: Reflections of Neuroimagers' Attitudes to Ethics Through the Qualitative Looking Glass SCIENCE AND ENGINEERING ETHICS Kehagia, A. A., Tairyan, K., Federico, C., Glover, G. H., Illes, J. 2012; 18 (4): 775-788


    In follow-up to a large-scale ethics survey of neuroscientists whose research involves neuroimaging, brain stimulation and imaging genetics, we conducted focus groups and interviews to explore their sense of responsibility about integrating ethics into neuroimaging and readiness to adopt new ethics strategies as part of their research. Safety, trust and virtue were key motivators for incorporating ethics into neuroimaging research. Managing incidental findings emerged as a predominant daily challenge for faculty, while student reports focused on the malleability of neuroimaging data and scientific integrity. The most frequently cited barrier was time and administrative burden associated with the ethics review process. Lack of scholarly training in ethics also emerged as a major barrier. Participants constructively offered remedies to these challenges: development and dissemination of best practices and standardized ethics review for minimally invasive neuroimaging protocols. Students in particular, urged changes to curricula to include early, focused training in ethics.

    View details for DOI 10.1007/s11948-011-9282-2

    View details for Web of Science ID 000312074200013

    View details for PubMedID 21626219

  • Influence of dense-array EEG cap on fMRI signal MAGNETIC RESONANCE IN MEDICINE Luo, Q., Glover, G. H. 2012; 68 (3): 807-815


    Dense-array (>64 channel) electroencephalography (EEG) systems are increasingly being used in simultaneous EEG-functional magnetic resonance imaging (fMRI) studies. However, with increasing channel count, dense-array EEG caps can induce more severe signal dropout in the MRI images than conventional systems due to the radiofrequency shielding effect of the denser wire bundle. This study investigates the influence of a 256-channel EEG cap on MRI image quality and detection sensitivity of blood oxygen level dependent fMRI signal. A theoretical model is first established to describe the impact of the EEG cap on anatomic signal, noise, signal-to-noise ratio, and contrast-to-noise ratio of blood oxygen level dependent signal. Seven subjects were scanned to measure and compare the T(2)-weighted image quality and fMRI detection sensitivity with and without the EEG cap using an auditory/visual/sensorimotor task. The results show that the dense-array EEG cap can substantially reduce the anatomic signal in the brain areas (visual cortex) near the conducting wires (average percent decrease ≈ 38%). However, the image signal-to-noise ratio with and without the EEG cap was comparable (percent decrease < 8%, not statistically significant), and there was no statistically significant difference in the extent of blood oxygen level dependent activation. This suggests that the ability to detect fMRI signal is nearly unaffected by dense-array EEG caps in simultaneous EEG-fMRI experiments.

    View details for DOI 10.1002/mrm.23299

    View details for Web of Science ID 000308098100016

    View details for PubMedID 22161695

    View details for PubMedCentralID PMC3309174

  • PUBERTAL STAGE AND BRAIN ANATOMY IN GIRLS NEUROSCIENCE Blanton, R. E., Cooney, R. E., Joormann, J., Eugene, F., Glover, G. H., Gotlib, I. H. 2012; 217: 105-112


    Studies of puberty have focused primarily on changes in hormones and on observable physical bodily characteristics. Little is known, however, about the nature of the relation between pubertal status and brain physiology. This is particularly important given findings that have linked the onset of puberty with both changes in cognitive functioning and increases in the incidence of depression and anxiety. The present study examined relations between pubertal stage, as assessed by Tanner staging, and brain anatomy in a sample of 54 girls aged 9-15 years. Brain morphometric analysis was conducted using high-resolution magnetic resonance imaging (MRI). The hippocampus and amygdala were manually traced on MRI scans in all participants. Stepwise regression analyses were conducted with total intracranial volume (ICV), age, and pubertal status as the predictor variables and hippocampus and amygdala volumes as outcome variables. Pubertal status was significantly associated with left amygdala volume, after controlling for both age and ICV. In addition, puberty was related to right hippocampus and amygdala volumes, after controlling for ICV. In contrast, no significant associations were found between age and hippocampal and amygdala volumes after controlling for pubertal status and ICV. These findings highlight the importance of the relation between pubertal status and morphometry of the hippocampus and amygdala, and of limbic and subcortical structures that have been implicated in emotional and social behaviors.

    View details for DOI 10.1016/j.neuroscience.2012.04.059

    View details for Web of Science ID 000306156000011

    View details for PubMedID 22569152

  • Spiral imaging in fMRI NEUROIMAGE Glover, G. H. 2012; 62 (2): 706-712


    T2*-weighted Blood Oxygen Level Dependent (BOLD) functional magnetic resonance imaging (fMRI) requires efficient acquisition methods in order to fully sample the brain in a several second time period. The most widely used approach is Echo Planar Imaging (EPI), which utilizes a Cartesian trajectory to cover k-space. This trajectory is subject to ghosts from off-resonance and gradient imperfections and is intrinsically sensitive to cardiac-induced pulsatile motion from substantial first- and higher order moments of the gradient waveform near the k-space origin. In addition, only the readout direction gradient contributes significant energy to the trajectory. By contrast, the spiral method samples k-space with an Archimedean or similar trajectory that begins at the k-space center and spirals to the edge (spiral-out), or its reverse, ending at the origin (spiral-in). Spiral methods have reduced sensitivity to motion, shorter readout times, improved signal recovery in most frontal and parietal brain regions, and exhibit blurring artifacts instead of ghosts or geometric distortion. Methods combining spiral-in and spiral-out trajectories have further advantages in terms of diminished susceptibility-induced signal dropout and increased BOLD signal. In measurements of temporal signal to noise ratio measured in 8 subjects, spiral-in/out exhibited significant increases over EPI in voxel volumes recovered in frontal and whole brain regions (18% and 10%, respectively).

    View details for DOI 10.1016/j.neuroimage.2011.10.039

    View details for Web of Science ID 000306390600021

    View details for PubMedID 22036995

    View details for PubMedCentralID PMC3279621

  • Function biomedical informatics research network recommendations for prospective multicenter functional MRI studies JOURNAL OF MAGNETIC RESONANCE IMAGING Glover, G. H., Mueller, B. A., Turner, J. A., van Erp, T. G., Liu, T. T., Greve, D. N., Voyvodic, J. T., Rasmussen, J., Brown, G. G., Keator, D. B., Calhoun, V. D., Lee, H. J., Ford, J. M., Mathalon, D. H., Diaz, M., O'Leary, D. S., Gadde, S., Preda, A., Lim, K. O., Wible, C. G., Stern, H. S., Belger, A., McCarthy, G., Ozyurt, B., Potkin, S. G. 2012; 36 (1): 39-54


    This report provides practical recommendations for the design and execution of multicenter functional MRI (MC-fMRI) studies based on the collective experience of the Function Biomedical Informatics Research Network (FBIRN). The study was inspired by many requests from the fMRI community to FBIRN group members for advice on how to conduct MC-fMRI studies. The introduction briefly discusses the advantages and complexities of MC-fMRI studies. Prerequisites for MC-fMRI studies are addressed before delving into the practical aspects of carefully and efficiently setting up a MC-fMRI study. Practical multisite aspects include: (i) establishing and verifying scan parameters including scanner types and magnetic fields, (ii) establishing and monitoring of a scanner quality program, (iii) developing task paradigms and scan session documentation, (iv) establishing clinical and scanner training to ensure consistency over time, (v) developing means for uploading, storing, and monitoring of imaging and other data, (vi) the use of a traveling fMRI expert, and (vii) collectively analyzing imaging data and disseminating results. We conclude that when MC-fMRI studies are organized well with careful attention to unification of hardware, software and procedural aspects, the process can be a highly effective means for accessing a desired participant demographics while accelerating scientific discovery.

    View details for DOI 10.1002/jmri.23572

    View details for PubMedID 22314879

  • Self-Refocused Adiabatic Pulse for Spin Echo Imaging at 7 T MAGNETIC RESONANCE IN MEDICINE Balchandani, P., Khalighi, M. M., Glover, G., Pauly, J., Spielman, D. 2012; 67 (4): 1077-1085


    Spin echo pulse sequences are used to produce clinically important T(2) contrast. However, conventional 180° radiofrequency pulses required to generate a spin echo are highly susceptible to the B(1) inhomogeneity at high magnetic fields such as 7 Tesla (7 T), resulting in varying signal and contrast over the region of interest. Adiabatic 180° pulses may be used to replace conventional 180° pulses in spin echo sequences to provide greater immunity to the inhomogeneous B(1) field at 7 T. However, because the spectral profile of an adiabatic 180° pulse has nonlinear phase, pairs of these pulses are needed for proper refocusing, resulting in increased radiofrequency power deposition and long minimum echo times. We used the adiabatic Shinnar Le-Roux method to generate a matched-phase adiabatic 90°-180° pulse pair to obviate the need for a second adiabatic 180° pulse for phase refocusing. The pulse pair was then reformulated into a single self-refocused pulse to minimize the echo time, and phantom and in vivo experiments were performed to validate pulse performance. The self-refocused adiabatic pulse produced transmit profiles that were substantially more uniform than those achieved using a conventional spin echo sequence.

    View details for DOI 10.1002/mrm.23089

    View details for Web of Science ID 000301533500021

    View details for PubMedID 21954048

    View details for PubMedCentralID PMC3548423

  • Analysis of the BOLD characteristics in pass-band bSSFP fMRI INTERNATIONAL JOURNAL OF IMAGING SYSTEMS AND TECHNOLOGY Kim, T. S., Lee, J., Lee, J. H., Glover, G. H., Pauly, J. M. 2012; 22 (1): 23-32


    Balanced steady-state free precession (bSSFP) has been proposed as an alternative method to acquire the blood oxygenation level dependent contrast. Particularly, pass-band bSSFP functional magnetic resonance imaging (fMRI) is believed to utilize the T2 sensitivity of bSSFP in a relatively wide and flat off-resonance frequency band of the bSSFP profile. The method has a potential to provide higher signal to noise ratio (SNR) efficiency with reduced imaging artifacts compared to conventional approaches. Previous experimental results suggested that the level of the functional contrast and its characteristics are significantly influenced by the sequence parameters. However, few of these contrast characteristics have been investigated systematically. In this study, a computer simulation was performed to investigate the sources of functional contrast and the influence of scan parameters on the functional contrast to elucidate the contrast characteristics of pass-band bSSFP fMRI. Experiments were performed to validate the simulation results.

    View details for DOI 10.1002/ima.21296

    View details for Web of Science ID 000300505200004

    View details for PubMedCentralID PMC3646401

  • Analysis of the BOLD Characteristics in Pass-Band bSSFP fMRI. International journal of imaging systems and technology Kim, T. S., Lee, J., Lee, J. H., Glover, G. H., Pauly, J. M. 2012; 22 (1): 23-32


    Balanced steady-state free precession (bSSFP) has been proposed as an alternative method to acquire the blood oxygenation level dependent contrast. Particularly, pass-band bSSFP functional magnetic resonance imaging (fMRI) is believed to utilize the T2 sensitivity of bSSFP in a relatively wide and flat off-resonance frequency band of the bSSFP profile. The method has a potential to provide higher signal to noise ratio (SNR) efficiency with reduced imaging artifacts compared to conventional approaches. Previous experimental results suggested that the level of the functional contrast and its characteristics are significantly influenced by the sequence parameters. However, few of these contrast characteristics have been investigated systematically. In this study, a computer simulation was performed to investigate the sources of functional contrast and the influence of scan parameters on the functional contrast to elucidate the contrast characteristics of pass-band bSSFP fMRI. Experiments were performed to validate the simulation results.

    View details for DOI 10.1002/ima.21296

    View details for PubMedID 23661904

    View details for PubMedCentralID PMC3646401

  • Differences in neural activation between preterm and full term born adolescents on a sentence comprehension task: Implications for educational accommodations DEVELOPMENTAL COGNITIVE NEUROSCIENCE Barde, L. H., Yeatman, J. D., Lee, E. S., Glover, G., Feldman, H. M. 2012; 2: S114-S128


    Adolescent survivors of preterm birth experience persistent functional problems that negatively impact academic outcomes, even when standardized measures of cognition and language suggest normal ability. In this fMRI study, we compared the neural activation supporting auditory sentence comprehension in two groups of adolescents (ages 9-16 years); sentences varied in length and syntactic difficulty. Preterms (n=18, mean gestational age 28.8 weeks) and full terms (n=14) had scores on verbal IQ, receptive vocabulary, and receptive language tests that were within or above normal limits and similar between groups. In early and late phases of the trial, we found interactions by group and length; in the late phase, we also found a group by syntactic difficulty interaction. Post hoc tests revealed that preterms demonstrated significant activation in the left and right middle frontal gyri as syntactic difficulty increased. ANCOVA showed that the interactions could not be attributed to differences in age, receptive language skill, or reaction time. Results are consistent with the hypothesis that preterm birth modulates brain-behavior relations in sentence comprehension as task demands increase. We suggest preterms' differences in neural processing may indicate a need for educational accommodations, even when formal test scores indicate normal academic achievement.

    View details for DOI 10.1016/j.dcn.2011.10.002

    View details for PubMedID 22682901

  • Maternal history of reading difficulty is associated with reduced language-related gray matter in beginning readers NEUROIMAGE Black, J. M., Tanaka, H., Stanley, L., Nagamine, M., Zakerani, N., Thurston, A., Kesler, S., Hulme, C., Lyytinen, H., Glover, G. H., Serrone, C., Raman, M. M., Reiss, A. L., Hoeft, F. 2012; 59 (3): 3021-3032


    Family history and poor preliteracy skills (referred to here as familial and behavioral risk, respectively) are critical predictors of developmental dyslexia. This study systematically investigated the independent contribution of familial and behavioral risks on brain structures, which had not been explored in past studies. We also examined the differential effects of maternal versus paternal history on brain morphometry, and familial risk dimensionally versus categorically, which were also novel aspects of the study. We assessed 51 children (5 to 6 years of age) with varying degrees of familial and behavioral risks for developmental dyslexia and examined associations with brain morphometry. We found that greater maternal history of reading disability was associated with smaller bilateral prefrontal and parieto-temporal gray, but not white matter volumes. Regressing out behavioral risk, socioeconomic status, and maternal education and other confounds did not change the results. No such relationship was observed for paternal reading history and behavioral risk. Results of cortical surface area and thickness further showed that there was a significant negative relationship between cortical surface area (but not thickness) and greater severity of maternal history, in particular within the left inferior parietal lobule, suggesting prenatal influence of maternal history on children's brain morphometry. The results suggested greater maternal, possibly prenatal, influence on language-related brain structures. These results help to guide future neuroimaging research focusing on environmental and genetic influences and provide new information that may help predict which child will develop dyslexia in the future.

    View details for DOI 10.1016/j.neuroimage.2011.10.024

    View details for Web of Science ID 000299494000100

    View details for PubMedID 22023744

    View details for PubMedCentralID PMC3628690

  • Temporal SNR characteristics in segmented 3D-EPI at 7T MAGNETIC RESONANCE IN MEDICINE van der Zwaag, W., Marques, J. P., Kober, T., Glover, G., Gruetter, R., Krueger, G. 2012; 67 (2): 344-352


    Three-dimensional segmented echo planar imaging (3D-EPI) is a promising approach for high-resolution functional magnetic resonance imaging, as it provides an increased signal-to-noise ratio (SNR) at similar temporal resolution to traditional multislice 2D-EPI readouts. Recently, the 3D-EPI technique has become more frequently used and it is important to better understand its implications for fMRI. In this study, the temporal SNR characteristics of 3D-EPI with varying numbers of segments are studied. It is shown that, in humans, the temporal variance increases with the number of segments used to form the EPI acquisition and that for segmented acquisitions, the maximum available temporal SNR is reduced compared to single shot acquisitions. This reduction with increased segmentation is not found in phantom data and thus likely due to physiological processes. When operating in the thermal noise dominated regime, fMRI experiments with a motor task revealed that the 3D variant outperforms the 2D-EPI in terms of temporal SNR and sensitivity to detect activated brain regions. Thus, the theoretical SNR advantage of a segmented 3D-EPI sequence for fMRI only exists in a low SNR situation. However, other advantages of 3D-EPI, such as the application of parallel imaging techniques in two dimensions and the low specific absorption rate requirements, may encourage the use of the 3D-EPI sequence for fMRI in situations with higher SNR.

    View details for DOI 10.1002/mrm.23007

    View details for Web of Science ID 000299376500009

    View details for PubMedID 21656557

    View details for PubMedCentralID PMC3627735

  • Hadamard-encoded sub-slice fMRI for reduced signal dropout MAGNETIC RESONANCE IMAGING Glover, G. H., Chang, C. 2012; 30 (1): 1-8


    T2*-weighted blood oxygen level-dependent functional magnetic resonance imaging is adversely affected by susceptibility-induced field gradients in brain regions adjoining air interfaces that cause image distortion and signal dropout. Reducing slice thickness diminishes signal dropout but is accompanied by reduced signal-to-noise ratio (SNR). This study proposes simultaneous excitation of subslices with total width equal to the desired slice thickness, employing alternating Hadamard-encoded radiofrequency pulses coupled with incoherent addition of the subslices to achieve reduction of through-plane dephasing with minimal SNR loss but at the expense of a reduction in temporal resolution. Using a sensory task and hypercapnic challenge with breathholding (BH), results with two subslices per slice and a twofold reduction in temporal resolution show improved activation relative to a conventional acquisition. Average (eight subjects) T-scores in the BH task increased by 16% (P<.0003), and activation extent increased by 12% (not significant). In frontal brain regions, significant improvements in BH activation extent (11.4%, P<.05) and T-scores (18%, P<.0002) were demonstrated. Higher temporal resolution can be achieved by tradeoff of SNR.

    View details for DOI 10.1016/j.mri.2011.07.019

    View details for Web of Science ID 000298212500001

    View details for PubMedID 21937181

  • Behavioral and neural correlates of delay of gratification 40 years later: Proc. Natl. Acad. Sci. U.S.A. 2011, Vol 108 No. 36:14998-5003. Annals of neurosciences Casey, B. J., Somerville, L. H., Gotlib, I. H., Ayduk, O., Franklin, N. T., Askrend, M. K., Jonides, J., Berman, M. G., Wilson, N. L., Teslovich, T., Glover, G., Zayas, V., Mischel, W., Shoda, Y. 2012; 19 (1): 27-28

    View details for DOI 10.5214/ans.0972.7531.180407

    View details for PubMedID 25205959

    View details for PubMedCentralID PMC4117069

  • Behavioral and Neural Properties of Social Reinforcement Learning JOURNAL OF NEUROSCIENCE Jones, R. M., Somerville, L. H., Li, J., Ruberry, E. J., Libby, V., Glover, G., Voss, H. U., Ballon, D. J., Casey, B. J. 2011; 31 (37): 13039-13045


    Social learning is critical for engaging in complex interactions with other individuals. Learning from positive social exchanges, such as acceptance from peers, may be similar to basic reinforcement learning. We formally test this hypothesis by developing a novel paradigm that is based on work in nonhuman primates and human imaging studies of reinforcement learning. The probability of receiving positive social reinforcement from three distinct peers was parametrically manipulated while brain activity was recorded in healthy adults using event-related functional magnetic resonance imaging. Over the course of the experiment, participants responded more quickly to faces of peers who provided more frequent positive social reinforcement, and rated them as more likeable. Modeling trial-by-trial learning showed ventral striatum and orbital frontal cortex activity correlated positively with forming expectations about receiving social reinforcement. Rostral anterior cingulate cortex activity tracked positively with modulations of expected value of the cues (peers). Together, the findings across three levels of analysis--social preferences, response latencies, and modeling neural responses--are consistent with reinforcement learning theory and nonhuman primate electrophysiological studies of reward. This work highlights the fundamental influence of acceptance by one's peers in altering subsequent behavior.

    View details for DOI 10.1523/JNEUROSCI.2972-11.2011

    View details for Web of Science ID 000294841900003

    View details for PubMedID 21917787

    View details for PubMedCentralID PMC3303166

  • Behavioral and neural correlates of delay of gratification 40 years later PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Casey, B. J., Somerville, L. H., Gotlib, I. H., Ayduk, O., Franklin, N. T., Askren, M. K., Jonides, J., Berman, M. G., Wilson, N. L., Teslovich, T., Glover, G., Zayas, V., Mischel, W., Shoda, Y. 2011; 108 (36): 14998-15003


    We examined the neural basis of self-regulation in individuals from a cohort of preschoolers who performed the delay-of-gratification task 4 decades ago. Nearly 60 individuals, now in their mid-forties, were tested on "hot" and "cool" versions of a go/nogo task to assess whether delay of gratification in childhood predicts impulse control abilities and sensitivity to alluring cues (happy faces). Individuals who were less able to delay gratification in preschool and consistently showed low self-control abilities in their twenties and thirties performed more poorly than did high delayers when having to suppress a response to a happy face but not to a neutral or fearful face. This finding suggests that sensitivity to environmental hot cues plays a significant role in individuals' ability to suppress actions toward such stimuli. A subset of these participants (n = 26) underwent functional imaging for the first time to test for biased recruitment of frontostriatal circuitry when required to suppress responses to alluring cues. Whereas the prefrontal cortex differentiated between nogo and go trials to a greater extent in high delayers, the ventral striatum showed exaggerated recruitment in low delayers. Thus, resistance to temptation as measured originally by the delay-of-gratification task is a relatively stable individual difference that predicts reliable biases in frontostriatal circuitries that integrate motivational and control processes.

    View details for DOI 10.1073/pnas.1108561108

    View details for Web of Science ID 000294543400057

    View details for PubMedID 21876169

    View details for PubMedCentralID PMC3169162

  • Associative retrieval processes in the human medial temporal lobe: Hippocampal retrieval success and CA1 mismatch detection LEARNING & MEMORY Chen, J., Olsen, R. K., Preston, A. R., Glover, G. H., Wagner, A. D. 2011; 18 (8): 523-528


    Hippocampal subfields CA(3) and CA(1) are hypothesized to differentially support the generation of associative predictions and the detection of associative mismatches, respectively. Using high-resolution functional MRI, we examined hippocampal subfield activation during associative retrieval and during subsequent comparisons of memory to matching or mismatching decision probes. Activity in the dentate gyrus/CA(2/3), CA(1), and other medial temporal lobe subregions tracked associative retrieval success, whereas activity in CA(1) and the perirhinal cortex tracked the presence of associative mismatches. These data support the hypothesis that CA(1) acts as a "comparator," detecting when memory for the past and sensory input in the present diverge.

    View details for DOI 10.1101/lm.2135211

    View details for Web of Science ID 000293858000004

    View details for PubMedID 21775513

    View details for PubMedCentralID PMC3256570

  • Variable-Density Spiral-In/Out Functional Magnetic Resonance Imaging MAGNETIC RESONANCE IN MEDICINE Chang, C., Glover, G. H. 2011; 65 (5): 1287-1296


    A variable-density spiral k-space trajectory is introduced for brain functional magnetic resonance imaging. The proposed spiral trajectory consists of an Archimedean spiral from the k-space origin to an arbitrary fraction r of the maximum k-space radius, extending beyond this point with a variable-density spiral in which the sampling density decreases as the k-space radius increases. It, therefore, permits a reduction in readout time at the expense of undersampling only the high spatial frequencies, in which the energy in T(2)*-weighted brain images is low. The trajectory was implemented in a two-dimensional spiral-in/out sequence, and single-shot high-resolution (1.72 × 1.72 mm(2) in-plane) functional magnetic resonance imaging data were acquired from human volunteers. Compared with a two-shot fully Archimedean spiral sequence with the same spatial coverage and total scan time, the variable-density sequence yielded greater activation magnitudes with improved temporal efficiency and minor artifacts.

    View details for DOI 10.1002/mrm.22722

    View details for Web of Science ID 000289760800011

    View details for PubMedID 21500257

    View details for PubMedCentralID PMC3126879

  • Characterization of RF-transparent electro-optically coupled PET block detectors for simultaneous PET/MR imaging Olcott, P., Levin, C., Glover, G. SOC NUCLEAR MEDICINE INC. 2011
  • Overview of Functional Magnetic Resonance Imaging NEUROSURGERY CLINICS OF NORTH AMERICA Glover, G. H. 2011; 22 (2): 133-?


    Blood Oxygen Level Dependent (BOLD) functional magnetic resonance imaging (fMRI) depicts changes in deoxyhemoglobin concentration consequent to task-induced or spontaneous modulation of neural metabolism. Since its inception in 1990, this method has been widely employed in thousands of studies of cognition for clinical applications such as surgical planning, for monitoring treatment outcomes, and as a biomarker in pharmacologic and training programs. More recently, attention is turning to the use of pattern classification and other statistical methods to draw increasingly complex inferences about cognitive brain states from fMRI data. This article reviews the methods, challenges, and future of fMRI.

    View details for DOI 10.1016/

    View details for Web of Science ID 000289654400003

    View details for PubMedID 21435566

    View details for PubMedCentralID PMC3073717

  • A Novel Method for Quantifying Scanner Instability in fMRI MAGNETIC RESONANCE IN MEDICINE Greve, D. N., Mueller, B. A., Liu, T., Turner, J. A., Voyvodic, J., Yetter, E., Diaz, M., McCarthy, G., Wallace, S., Roach, B. J., Ford, J. M., Mathalon, D. H., Calhoun, V. D., Wible, C. G., Brown, G. G., Potkin, S. G., Glover, G. 2011; 65 (4): 1053-1061


    A method was developed to quantify the effect of scanner instability on functional MRI data by comparing the instability noise to endogenous noise present when scanning a human. The instability noise was computed from agar phantom data collected with two flip angles, allowing for a separation of the instability from the background noise. This method was used on human data collected at four 3 T scanners, allowing the physiological noise level to be extracted from the data. In a "well-operating" scanner, the instability noise is generally less than 10% of physiological noise in white matter and only about 2% of physiological noise in cortex. This indicates that instability in a well-operating scanner adds very little noise to functional MRI results. This new method allows researchers to make informed decisions about the maximum instability level a scanner can have before it is taken off line for maintenance or rejected from a multisite consortium. This method also provides information about the background noise, which is generally larger in magnitude than the instability noise.

    View details for DOI 10.1002/mrm.22691

    View details for Web of Science ID 000288612000017

    View details for PubMedID 21413069

    View details for PubMedCentralID PMC3117086

  • High-resolution fMRI Reveals Match Enhancement and Attentional Modulation in the Human Medial Temporal Lobe JOURNAL OF COGNITIVE NEUROSCIENCE Dudukovic, N. M., Preston, A. R., Archie, J. J., Glover, G. H., Wagner, A. D. 2011; 23 (3): 670-682


    A primary function of the medial temporal lobe (MTL) is to signal prior encounter with behaviorally relevant stimuli. MTL match enhancement--increased activation when viewing previously encountered stimuli--has been observed for goal-relevant stimuli in nonhuman primates during delayed-match-to-sample tasks and in humans during more complex relational memory tasks. Match enhancement may alternatively reflect (a) an attentional response to familiar relative to novel stimuli or (b) the retrieval of contextual details surrounding the past encounter with familiar stimuli. To gain leverage on the functional significance of match enhancement in the hippocampus, high-resolution fMRI of human MTL was conducted while participants attended, ignored, or passively viewed face and scene stimuli in the context of a modified delayed-match-to-sample task. On each "attended" trial, two goal-relevant stimuli were encountered before a probe that either matched or mismatched one of the attended stimuli, enabling examination of the consequences of encountering one of the goal-relevant stimuli as a match probe on later memory for the other (nonprobed) goal-relevant stimulus. fMRI revealed that the hippocampus was insensitive to the attentional manipulation, whereas parahippocampal cortex was modulated by scene-directed attention, and perirhinal cortex showed more subtle and general effects of attention. By contrast, all hippocampal subfields demonstrated match enhancement to the probe, and a postscan test revealed more accurate recognition memory for the nonprobed goal-relevant stimulus on match relative to mismatch trials. These data suggest that match enhancement in human hippocampus reflects retrieval of other goal-relevant contextual details surrounding a stimulus's prior encounter.

    View details for Web of Science ID 000285160700014

    View details for PubMedID 20433244

  • Resting-state fMRI can reliably map neural networks in children NEUROIMAGE Thomason, M. E., Dennis, E. L., Joshi, A. A., Joshi, S. H., Dinov, I. D., Chang, C., Henry, M. L., Johnson, R. F., Thompson, P. M., Toga, A. W., Glover, G. H., Van Horn, J. D., Gotlib, I. H. 2011; 55 (1): 165-175


    Resting-state MRI (rs-fMRI) is a powerful procedure for studying whole-brain neural connectivity. In this study we provide the first empirical evidence of the longitudinal reliability of rs-fMRI in children. We compared rest-retest measurements across spatial, temporal and frequency domains for each of six cognitive and sensorimotor intrinsic connectivity networks (ICNs) both within and between scan sessions. Using Kendall'sW, concordance of spatial maps ranged from .60 to .86 across networks, for various derived measures. The Pearson correlation coefficient for temporal coherence between networks across all Time 1-Time 2 (T1/T2) z-converted measures was .66 (p<.001). There were no differences between T1/T2 measurements in low-frequency power of the ICNs. For the visual network, within-session T1 correlated with the T2 low-frequency power, across participants. These measures from resting-state data in children were consistent across multiple domains (spatial, temporal, and frequency). Resting-state connectivity is therefore a reliable method for assessing large-scale brain networks in children.

    View details for DOI 10.1016/j.neuroimage.2010.11.080

    View details for Web of Science ID 000287008900014

    View details for PubMedID 21134471

    View details for PubMedCentralID PMC3031732

  • A quantitative comparison of NIRS and fMRI across multiple cognitive tasks NEUROIMAGE Cui, X., Bray, S., Bryant, D. M., Glover, G. H., Reiss, A. L. 2011; 54 (4): 2808-2821


    Near infrared spectroscopy (NIRS) is an increasingly popular technology for studying brain function. NIRS presents several advantages relative to functional magnetic resonance imaging (fMRI), such as measurement of concentration changes in both oxygenated and deoxygenated hemoglobin, finer temporal resolution, and ease of administration, as well as disadvantages, most prominently inferior spatial resolution and decreased signal-to-noise ratio (SNR). While fMRI has become the gold standard for in vivo imaging of the human brain, in practice NIRS is a more convenient and less expensive technology than fMRI. It is therefore of interest to many researchers how NIRS compares to fMRI in studies of brain function. In the present study we scanned participants with simultaneous NIRS and fMRI on a battery of cognitive tasks, placing NIRS probes over both frontal and parietal brain regions. We performed detailed comparisons of the signals in both temporal and spatial domains. We found that NIRS signals have significantly weaker SNR, but are nonetheless often highly correlated with fMRI measurements. Both SNR and the distance between the scalp and the brain contributed to variability in the NIRS/fMRI correlations. In the spatial domain, we found that a photon path forming an ellipse between the NIRS emitter and detector correlated most strongly with the BOLD response. Taken together these findings suggest that, while NIRS can be an appropriate substitute for fMRI for studying brain activity related to cognitive tasks, care should be taken when designing studies with NIRS to ensure that: 1) the spatial resolution is adequate for answering the question of interest and 2) the design accounts for weaker SNR, especially in brain regions more distal from the scalp.

    View details for DOI 10.1016/j.neuroimage.2010.10.069

    View details for Web of Science ID 000286495800025

    View details for PubMedID 21047559

    View details for PubMedCentralID PMC3021967

  • Multisite reliability of cognitive BOLD data NEUROIMAGE Brown, G. G., Mathalon, D. H., Stern, H., Ford, J., Mueller, B., Greve, D. N., McCarthy, G., Voyvodic, J., Glover, G., Diaz, M., Yetter, E., Ozyurt, I. B., Jorgensen, K. W., Wible, C. G., Turner, J. A., Thompson, W. K., Potkin, S. G. 2011; 54 (3): 2163-2175


    Investigators perform multi-site functional magnetic resonance imaging studies to increase statistical power, to enhance generalizability, and to improve the likelihood of sampling relevant subgroups. Yet undesired site variation in imaging methods could off-set these potential advantages. We used variance components analysis to investigate sources of variation in the blood oxygen level-dependent (BOLD) signal across four 3-T magnets in voxelwise and region-of-interest (ROI) analyses. Eighteen participants traveled to four magnet sites to complete eight runs of a working memory task involving emotional or neutral distraction. Person variance was more than 10 times larger than site variance for five of six ROIs studied. Person-by-site interactions, however, contributed sizable unwanted variance to the total. Averaging over runs increased between-site reliability, with many voxels showing good to excellent between-site reliability when eight runs were averaged and regions of interest showing fair to good reliability. Between-site reliability depended on the specific functional contrast analyzed in addition to the number of runs averaged. Although median effect size was correlated with between-site reliability, dissociations were observed for many voxels. Brain regions where the pooled effect size was large but between-site reliability was poor were associated with reduced individual differences. Brain regions where the pooled effect size was small but between-site reliability was excellent were associated with a balance of participants who displayed consistently positive or consistently negative BOLD responses. Although between-site reliability of BOLD data can be good to excellent, acquiring highly reliable data requires robust activation paradigms, ongoing quality assurance, and careful experimental control.

    View details for DOI 10.1016/j.neuroimage.2010.09.076

    View details for Web of Science ID 000286302000040

    View details for PubMedID 20932915

    View details for PubMedCentralID PMC3009557

  • Neural systems predicting long-term outcome in dyslexia PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Hoeft, F., McCandliss, B. D., Black, J. M., Gantman, A., Zakerani, N., Hulme, C., Lyytinen, H., Whitfield-Gabrieli, S., Glover, G. H., Reiss, A. L., Gabrieli, J. D. 2011; 108 (1): 361-366


    Individuals with developmental dyslexia vary in their ability to improve reading skills, but the brain basis for improvement remains largely unknown. We performed a prospective, longitudinal study over 2.5 y in children with dyslexia (n = 25) or without dyslexia (n = 20) to discover whether initial behavioral or brain measures, including functional MRI (fMRI) and diffusion tensor imaging (DTI), can predict future long-term reading gains in dyslexia. No behavioral measure, including widely used and standardized reading and language tests, reliably predicted future reading gains in dyslexia. Greater right prefrontal activation during a reading task that demanded phonological awareness and right superior longitudinal fasciculus (including arcuate fasciculus) white-matter organization significantly predicted future reading gains in dyslexia. Multivariate pattern analysis (MVPA) of these two brain measures, using linear support vector machine (SVM) and cross-validation, predicted significantly above chance (72% accuracy) which particular child would or would not improve reading skills (behavioral measures were at chance). MVPA of whole-brain activation pattern during phonological processing predicted which children with dyslexia would improve reading skills 2.5 y later with >90% accuracy. These findings identify right prefrontal brain mechanisms that may be critical for reading improvement in dyslexia and that may differ from typical reading development. Brain measures that predict future behavioral outcomes (neuroprognosis) may be more accurate, in some cases, than available behavioral measures.

    View details for DOI 10.1073/pnas.1008950108

    View details for Web of Science ID 000285915000067

    View details for PubMedID 21173250

    View details for PubMedCentralID PMC3017159

  • Modulation of Subgenual Anterior Cingulate Cortex Activity With Real-Time Neurofeedback HUMAN BRAIN MAPPING Hamilton, J. P., Glover, G. H., Hsu, J., Johnson, R. F., Gotlib, I. H. 2011; 32 (1): 22-31


    The advent of real-time neurofeedback techniques has allowed us to begin to map the controllability of sensory and cognitive and, more recently, affective centers in the brain. The subgenual anterior cingulate cortex (sACC) is thought to be involved in generation of affective states and has been implicated in psychopathology. In this study, we examined whether individuals could use real-time fMRI neurofeedback to modulate sACC activity. Following a localizer task used to identify an sACC region of interest, an experimental group of eight women participated in four scans: (1) a pretraining scan in which they were asked to decrease activity in the sACC without neurofeedback; (2) two training scans in which sACC neurofeedback was presented along with instructions to decrease sACC activity; and (3) a neurofeedback-free post-training scan. An additional nine women in a yoked feedback control group saw sACC activity from the participants in the experimental group. Activity in the sACC was significantly reduced during neurofeedback training in the experimental group, but not in the control group. This training effect in the experimental group, however, did not generalize to the neurofeedback-free post-training scan. A psychophysiological interaction analysis showed decreased correlation in the experimental group relative to the sham control group between activity in the sACC and the posterior cingulate cortex during neurofeedback training relative to neurofeedback-free scans. The finding that individuals can down-modulate the sACC shows that a primary emotion center in which functional abnormality has been strongly implicated in affective disorders can be controlled with the aid of neurofeedback.

    View details for DOI 10.1002/hbm.20997

    View details for Web of Science ID 000285398000003

    View details for PubMedID 21157877

    View details for PubMedCentralID PMC3049174

  • Automated real-time behavioral and physiological data acquisition and display integrated with stimulus presentation for FMRI. Frontiers in neuroinformatics Voyvodic, J. T., Glover, G. H., Greve, D., Gadde, S. 2011; 5: 27-?


    Functional magnetic resonance imaging (fMRI) is based on correlating blood oxygen-level dependent (BOLD) signal fluctuations in the brain with other time-varying signals. Although the most common reference for correlation is the timing of a behavioral task performed during the scan, many other behavioral and physiological variables can also influence fMRI signals. Variations in cardiac and respiratory functions in particular are known to contribute significant BOLD signal fluctuations. Variables such as skin conduction, eye movements, and other measures that may be relevant to task performance can also be correlated with BOLD signals and can therefore be used in image analysis to differentiate multiple components in complex brain activity signals. Combining real-time recording and data management of multiple behavioral and physiological signals in a way that can be routinely used with any task stimulus paradigm is a non-trivial software design problem. Here we discuss software methods that allow users control of paradigm-specific audio-visual or other task stimuli combined with automated simultaneous recording of multi-channel behavioral and physiological response variables, all synchronized with sub-millisecond temporal accuracy. We also discuss the implementation and importance of real-time display feedback to ensure data quality of all recorded variables. Finally, we discuss standards and formats for storage of temporal covariate data and its integration into fMRI image analysis. These neuroinformatics methods have been adopted for behavioral task control at all sites in the Functional Biomedical Informatics Research Network (FBIRN) multi-center fMRI study.

    View details for DOI 10.3389/fninf.2011.00027

    View details for PubMedID 22232596

    View details for PubMedCentralID PMC3247706

  • COMT genotype affects prefrontal white matter pathways in children and adolescents NEUROIMAGE Thomason, M. E., Dougherty, R. F., Colich, N. L., Perry, L. M., Rykhlevskaia, E. I., Louro, H. M., Hallmayer, J. F., Waugh, C. E., Bammer, R., Glover, G. H., Gotlib, I. H. 2010; 53 (3): 926-934


    Diffusion tensor imaging is widely used to evaluate the development of white matter. Information about how alterations in major neurotransmitter systems, such as the dopamine (DA) system, influence this development in healthy children, however, is lacking. Catechol-O-metyltransferase (COMT) is the major enzyme responsible for DA degradation in prefrontal brain structures, for which there is a corresponding genetic polymorphism (val158met) that confers either a more or less efficient version of this enzyme. The result of this common genetic variation is that children may have more or less available synaptic DA in prefrontal brain regions. In the present study we examined the relation between diffusion properties of frontal white matter structures and the COMT val158met polymorphism in 40 children ages 9-15. We found that the val allele was associated with significantly elevated fractional anisotropy values and reduced axial and radial diffusivities. These results indicate that the development of white matter in healthy children is related to COMT genotype and that alterations in white matter may be related to the differential availability of prefrontal DA. This investigation paves the way for further studies of how common functional variants in the genome might influence the development of brain white matter.

    View details for DOI 10.1016/j.neuroimage.2010.01.033

    View details for Web of Science ID 000282039300015

    View details for PubMedID 20083203

    View details for PubMedCentralID PMC2902616

  • Reducing barriers to ethics in neuroscience FRONTIERS IN HUMAN NEUROSCIENCE Illes, J., Tairyan, K., Federico, C. A., Tabet, A., Glover, G. H. 2010; 4


    Ethics is a growing interest for neuroscientists, but rather than signifying a commitment to the protection of human subjects, care of animals, and public understanding to which the professional community is engaged in a fundamental way, interest has been consumed by administrative overhead and the mission creep of institutional ethics reviews. Faculty, trainees, and staff (n = 605) in North America whose work involves brain imaging and brain stimulation completed an online survey about ethics in their research. Using factor analysis and linear regression, we found significant effects for invasiveness of imaging technique, professional position, gender, and local presence of bioethics centers. We propose strategies for improving communication between the neuroscience community and ethics review boards, collaborations between neuroscientists and biomedical ethicists, and ethics training in graduate neuroscience programs to revitalize mutual goals and interests.

    View details for DOI 10.3389/fnhum.2010.00167

    View details for Web of Science ID 000289308000001

    View details for PubMedID 20953291

    View details for PubMedCentralID PMC2955400

  • Individual differences in auditory sentence comprehension in children: An exploratory event-related functional magnetic resonance imaging investigation BRAIN AND LANGUAGE Yeatman, J. D., Ben-Shachar, M., Glover, G. H., Feldman, H. M. 2010; 114 (2): 72-79


    The purpose of this study was to explore changes in activation of the cortical network that serves auditory sentence comprehension in children in response to increasing demands of complex sentences. A further goal is to study how individual differences in children's receptive language abilities are associated with such changes in cortical responses. Fourteen children, 10-16 years old, participated in an event-related functional magnetic resonance imaging experiment using a cross modal sentence-picture verification paradigm. We manipulated sentence difficulty and length in a 2x2 factorial design. Task-related activation covered large regions of the left and right superior temporal cortex, inferior parietal lobe, precuneous, cingulate, middle frontal gyrus and precentral gyrus. Sentence difficulty, independent of length, led to increased activation in the left temporal-parietal junction and right superior temporal gyrus. Changes in activation in frontal regions positively correlated with age-standardized receptive vocabulary scores and negatively correlated with reaction time on a receptive grammar test outside the scanner. Thus, individual differences in language skills were associated with changes in the network in response to changing task demands. These preliminary findings in a small sample of typically developing children suggest that the investigation of individual differences may prove useful in elucidating the underlying neural mechanisms of language disorders in children.

    View details for DOI 10.1016/j.bandl.2009.11.006

    View details for PubMedID 20053431

  • Detecting Blood Oxygen Level-Dependent (BOLD) Contrast in the Breast JOURNAL OF MAGNETIC RESONANCE IMAGING Rakow-Penner, R., Daniel, B., Glover, G. H. 2010; 32 (1): 120-129


    To develop a robust technique for detecting blood oxygenation level-dependent (BOLD) contrast in the human breast and to evaluate the signal in healthy and malignant breast.The design of this study focused on determining the optimal pulse sequence and stimulus for detecting BOLD contrast in the breast. For this study a single-shot fast spin echo (SSFSE) sequence was compared to a gradient echo (GRE) pulse sequence. Also, several hyperoxic stimuli were tested on 15 healthy volunteers to determine the best stimulus for inducing BOLD contrast in the breast: air interleaved with carbogen (95% O(2), 5% CO(2)), air interleaved with oxygen, and oxygen interleaved with carbogen. The stimulus with the most consistent results among the healthy population was tested on three breast cancer patients.An SSFSE pulse sequence produced improved BOLD contrast results in the breast compared to a GRE pulse sequence. Oxygen interleaved with carbogen yielded the most consistent results in the healthy population. BOLD contrast in healthy glandular breast tissue positively correlates with carbogen and malignant tissue mostly negatively correlates to carbogen.BOLD contrast can consistently be detected in the breast using a robust protocol. This methodology may be used in the future as a noninvasive method for evaluating tumor oxygenation.

    View details for DOI 10.1002/jmri.22227

    View details for Web of Science ID 000279439600015

    View details for PubMedID 20578018

  • Inspired gas-induced vascular change in tumors with magnetic-resonance-guided near-infrared imaging: human breast pilot study JOURNAL OF BIOMEDICAL OPTICS Carpenter, C. M., Rakow-Penner, R., Jiang, S., Daniel, B. L., Pogue, B. W., Glover, G. H., Paulsen, K. D. 2010; 15 (3)


    This study investigates differences in the response of breast tumor tissue versus healthy fibroglandular tissue to inspired gases. Cycles of carbogen and oxygen gas are administered while measuring the changes with magnetic-resonance-guided near-infrared imaging in a pilot study of breast cancers. For two patients, analyses are performed with cross-correlation techniques, which measure the strength of hemodynamic modulation. The results show that the overall vasoresponse, indicated by total hemoglobin, of healthy tissue has approximately a 72% and 41% greater correlation to the gas stimulus than the tumor region, in two patients respectively, when background physiological changes are controlled. These data support the hypothesis that tumor vasculature has a poorly functioning vasodilatory mechanism, most likely caused by dysfunctional smooth muscle cells lining the vasculature. This study presents a methodology to quantitatively analyze inspired gas changes in human breast tumors, and demonstrates this technique in a pilot patient population.

    View details for DOI 10.1117/1.3430729

    View details for Web of Science ID 000280642900041

    View details for PubMedID 20615028

    View details for PubMedCentralID PMC2887914

  • Improvements in Parallel Imaging Accelerated Functional MRI Using Multiecho Echo-Planar Imaging MAGNETIC RESONANCE IN MEDICINE Schmiedeskamp, H., Newbould, R. D., Pisani, L. J., Skare, S., Glover, G. H., Pruessmann, K. P., Bammer, R. 2010; 63 (4): 959-969


    Multiecho echo-planar imaging (EPI) was implemented for blood-oxygenation-level-dependent functional MRI at 1.5 T and compared to single-echo EPI with and without parallel imaging acceleration. A time-normalized breath-hold task using a block design functional MRI protocol was carried out in combination with up to four echo trains per excitation and parallel imaging acceleration factors R = 1-3. Experiments were conducted in five human subjects, each scanned in three sessions. Across all reduction factors, both signal-to-fluctuation-noise ratio and the total number of activated voxels were significantly lower using a single-echo EPI pulse sequence compared with the multiecho approach. Signal-to-fluctuation-noise ratio and total number of activated voxels were also considerably reduced for nonaccelerated conventional single-echo EPI when compared to three-echo measurements with R = 2. Parallel imaging accelerated multiecho EPI reduced geometric distortions and signal dropout, while it increased blood-oxygenation-level-dependent signal sensitivity all over the brain, particularly in regions with short underlying T*(2). Thus, the presented method showed multiple advantages over conventional single-echo EPI for standard blood-oxygenation-level-dependent functional MRI experiments.

    View details for DOI 10.1002/mrm.22222

    View details for Web of Science ID 000276064300013

    View details for PubMedID 20373397

    View details for PubMedCentralID PMC2906757

  • Monitoring of hemodynamic changes induced in the healthy breast through inspired gas stimuli with MR-guided diffuse optical imaging MEDICAL PHYSICS Carpenter, C. M., Rakow-Penner, R., Jiang, S., Pogue, B. W., Glover, G. H., Paulsen, K. D. 2010; 37 (4): 1638-1646


    The modulation of tissue hemodynamics has important clinical value in medicine for both tumor diagnosis and therapy. As an oncological tool, increasing tissue oxygenation via modulation of inspired gas has been proposed as a method to improve cancer therapy and determine radiation sensitivity. As a radiological tool, inducing changes in tissue total hemoglobin may provide a means to detect and characterize malignant tumors by providing information about tissue vascular function. The ability to change and measure tissue hemoglobin and oxygenation concentrations in the healthy breast during administration of three different types of modulated gas stimuli (oxygen/ carbogen, air/carbogen, and air/oxygen) was investigated.Subjects breathed combinations of gases which were modulated in time. MR-guided diffuse optical tomography measured total hemoglobin and oxygen saturation in the breast every 30 s during the 16 min breathing stimulus. Metrics of maximum correlation and phase lag were calculated by cross correlating the measured hemodynamics with the stimulus. These results were compared to an air/air control to determine the hemodynamic changes compared to the baseline physiology.This study demonstrated that a gas stimulus consisting of alternating oxygen/carbogen induced the largest and most robust hemodynamic response in healthy breast parenchyma relative to the changes that occurred during the breathing of room air. This stimulus caused increases in total hemoglobin and oxygen saturation during the carbogen phase of gas inhalation, and decreases during the oxygen phase. These findings are consistent with the theory that oxygen acts as a vasoconstrictor, while carbogen acts as a vasodilator. However, difficulties in inducing a consistent change in tissue hemoglobin and oxygenation were observed because of variability in intersubject physiology, especially during the air/oxygen or air/carbogen modulated breathing protocols.MR-guided diffuse optical imaging is a unique tool that can measure tissue hemodynamics in the breast during modulated breathing. This technique may have utility in determining the therapeutic potential of pretreatment tissue oxygenation or in investigating vascular function. Future gas modulation studies in the breast should use a combination of oxygen and carbogen as the functional stimulus. Additionally, control measures of subject physiology during air breathing are critical for robust measurements.

    View details for DOI 10.1118/1.3358123

    View details for Web of Science ID 000276211200028

    View details for PubMedID 20443485

  • Time-frequency dynamics of resting-state brain connectivity measured with fMRI NEUROIMAGE Chang, C., Glover, G. H. 2010; 50 (1): 81-98


    Most studies of resting-state functional connectivity using fMRI employ methods that assume temporal stationarity, such as correlation and data-driven decompositions computed across the duration of the scan. However, evidence from both task-based fMRI studies and animal electrophysiology suggests that functional connectivity may exhibit dynamic changes within time scales of seconds to minutes. In the present study, we investigated the dynamic behavior of resting-state connectivity across the course of a single scan, performing a time-frequency coherence analysis based on the wavelet transform. We focused on the connectivity of the posterior cingulate cortex (PCC), a primary node of the default-mode network, examining its relationship with both the "anticorrelated" ("task-positive") network as well as other nodes of the default-mode network. It was observed that coherence and phase between the PCC and the anticorrelated network was variable in time and frequency, and statistical testing based on Monte Carlo simulations revealed the presence of significant scale-dependent temporal variability. In addition, a sliding-window correlation procedure identified other regions across the brain that exhibited variable connectivity with the PCC across the scan, which included areas previously implicated in attention and salience processing. Although it is unclear whether the observed coherence and phase variability can be attributed to residual noise or modulation of cognitive state, the present results illustrate that resting-state functional connectivity is not static, and it may therefore prove valuable to consider measures of variability, in addition to average quantities, when characterizing resting-state networks.

    View details for DOI 10.1016/j.neuroimage.2009.12.011

    View details for Web of Science ID 000274810100009

    View details for PubMedID 20006716

    View details for PubMedCentralID PMC2827259

  • A Genetic Variant BDNF Polymorphism Alters Extinction Learning in Both Mouse and Human SCIENCE Soliman, F., Glatt, C. E., Bath, K. G., Levita, L., Jones, R. M., Pattwell, S. S., Jing, D., Tottenham, N., Amso, D., Somerville, L. H., Voss, H. U., Glover, G., Ballon, D. J., Liston, C., Teslovich, T., Van Kempen, T., Lee, F. S., Casey, B. J. 2010; 327 (5967): 863-866


    Mouse models are useful for studying genes involved in behavior, but whether they are relevant to human behavior is unclear. Here, we identified parallel phenotypes in mice and humans resulting from a common single-nucleotide polymorphism in the brain-derived neurotrophic factor (BDNF) gene, which is involved in anxiety-related behavior. An inbred genetic knock-in mouse strain expressing the variant BDNF recapitulated the phenotypic effects of the human polymorphism. Both were impaired in extinguishing a conditioned fear response, which was paralleled by atypical frontoamygdala activity in humans. Thus, this variant BDNF allele may play a role in anxiety disorders showing impaired learning of cues that signal safety versus threat and in the efficacy of treatments that rely on extinction mechanisms, such as exposure therapy.

    View details for DOI 10.1126/science.1181886

    View details for Web of Science ID 000274408300061

    View details for PubMedID 20075215

    View details for PubMedCentralID PMC2829261

  • High-resolution fMRI of Content-sensitive Subsequent Memory Responses in Human Medial Temporal Lobe JOURNAL OF COGNITIVE NEUROSCIENCE Preston, A. R., Bornstein, A. M., Hutchinson, J. B., Gaare, M. E., Glover, G. H., Wagner, A. D. 2010; 22 (1): 156-173


    The essential role of the medial temporal lobe (MTL) in long-term memory for individual events is well established, yet important questions remain regarding the mnemonic functions of the component structures that constitute the region. Within the hippocampus, recent functional neuroimaging findings suggest that formation of new memories depends on the dentate gyrus and the CA(3) field, whereas the contribution of the subiculum may be limited to retrieval. During encoding, it has been further hypothesized that structures within MTL cortex contribute to encoding in a content-sensitive manner, whereas hippocampal structures may contribute to encoding in a more domain-general manner. In the current experiment, high-resolution fMRI techniques were utilized to assess novelty and subsequent memory effects in MTL subregions for two classes of stimuli--faces and scenes. During scanning, participants performed an incidental encoding (target detection) task with novel and repeated faces and scenes. Subsequent recognition memory was indexed for the novel stimuli encountered during scanning. Analyses revealed voxels sensitive to both novel faces and novel scenes in all MTL regions. However, similar percentages of voxels were sensitive to novel faces and scenes in perirhinal cortex, entorhinal cortex, and a combined region comprising the dentate gyrus, CA(2), and CA(3), whereas parahippocampal cortex, CA(1), and subiculum demonstrated greater sensitivity to novel scene stimuli. Paralleling these findings, subsequent memory effects in perirhinal cortex were observed for both faces and scenes, with the magnitude of encoding activation being related to later memory strength, as indexed by a graded response tracking recognition confidence, whereas subsequent memory effects were scene-selective in parahippocampal cortex. Within the hippocampus, encoding activation in the subiculum correlated with subsequent memory for both stimulus classes, with the magnitude of encoding activation varying in a graded manner with later memory strength. Collectively, these findings suggest a gradient of content sensitivity from posterior (parahippocampal) to anterior (perirhinal) MTL cortex, with MTL cortical regions differentially contributing to successful encoding based on event content. In contrast to recent suggestions, the present data further indicate that the subiculum may contribute to successful encoding irrespective of event content.

    View details for Web of Science ID 000272352100012

    View details for PubMedID 19199423

  • Development, validation, and comparison of ICA-based gradient artifact reduction algorithms for simultaneous EEG-spiral in/out and echo-planar fMRI recordings NEUROIMAGE Ryali, S., Glover, G. H., Chang, C., Menon, V. 2009; 48 (2): 348-361


    EEG data acquired in an MRI scanner are heavily contaminated by gradient artifacts that can significantly compromise signal quality. We developed two new methods based on independent component analysis (ICA) for reducing gradient artifacts from spiral in-out and echo-planar pulse sequences at 3 T, and compared our algorithms with four other commonly used methods: average artifact subtraction (Allen, P., Josephs, O., Turner, R., 2000. A method for removing imaging artifact from continuous EEG recorded during functional MRI. NeuroImage 12, 230-239.), principal component analysis (Niazy, R., Beckmann, C., Iannetti, G., Brady, J., Smith, S., 2005. Removal of FMRI environment artifacts from EEG data using optimal basis sets. NeuroImage 28, 720-737.), Taylor series ( Wan, X., Iwata, K., Riera, J., Kitamura, M., Kawashima, R., 2006. Artifact reduction for simultaneous EEG/fMRI recording: adaptive FIR reduction of imaging artifacts. Clin. Neurophysiol. 117, 681-692.) and a conventional temporal ICA algorithm. Models of gradient artifacts were derived from simulations as well as a water phantom and performance of each method was evaluated on datasets constructed using visual event-related potentials (ERPs) as well as resting EEG. Our new methods recovered ERPs and resting EEG below the beta band (<12.5 Hz) with high signal-to-noise ratio (SNR>4). Our algorithms outperformed all of these methods on resting EEG in the theta and alpha bands (SNR>4); however, for all methods, signal recovery was modest (SNR approximately 1) in the beta band and poor (SNR<0.3) in the gamma band and above. We found that the conventional ICA algorithm performed poorly with uniformly low SNR (<0.1). Taken together, our new ICA-based methods offer a more robust technique for gradient artifact reduction when scanning at 3 T using spiral in-out and echo-planar pulse sequences. We provide new insights into the strengths and weaknesses of each method using a unified subspace framework.

    View details for DOI 10.1016/j.neuroimage.2009.06.072

    View details for Web of Science ID 000274723900005

    View details for PubMedID 19580873

  • BDNF genotype modulates resting functional connectivity in children FRONTIERS IN HUMAN NEUROSCIENCE Thomason, M. E., Yoo, D. J., Glover, G. H., Gotlib, I. H. 2009; 3


    A specific polymorphism of the brain-derived neurotrophic factor (BDNF) gene is associated with alterations in brain anatomy and memory; its relevance to the functional connectivity of brain networks, however, is unclear. Given that altered hippocampal function and structure has been found in adults who carry the methionine (met) allele of the BDNF gene and the molecular studies elucidating the role of BDNF in neurogenesis and synapse formation, we examined the association between BDNF gene variants and neural resting connectivity in children and adolescents. We observed a reduction in hippocampal and parahippocampal to cortical connectivity in met-allele carriers within both default-mode and executive networks. In contrast, we observed increased connectivity to amygdala, insula and striatal regions in met-carriers, within the paralimbic network. Because of the known association between the BDNF gene and neuropsychiatric disorder, this latter finding of greater connectivity in circuits important for emotion processing may indicate a new neural mechanism through which these gene-related psychiatric differences are manifest. Here we show that the BDNF gene, known to regulate synaptic plasticity and connectivity in the brain, affects functional connectivity at the neural systems level. In addition, we demonstrate that the spatial topography of multiple high-level resting state networks in healthy children and adolescents is similar to that observed in adults.

    View details for DOI 10.3389/neuro.09.055.2009

    View details for Web of Science ID 000274619300004

    View details for PubMedID 19956404

    View details for PubMedCentralID PMC2786303

  • Optimizing Saturation-Recovery Measurements of the Longitudinal Relaxation Rate Under Time Constraints MAGNETIC RESONANCE IN MEDICINE Hsu, J., Glover, G. H., Zaharchuk, G. 2009; 62 (5): 1202-1210


    The saturation-recovery method using two and three recovery times is studied for conditions in which the sum of recovery times is 1.5T(1) to 3T(1), where T(1) is the longitudinal relaxation time. These conditions can reduce scan time considerably for long T(1) species and make longitudinal relaxation rate R(1) (R(1) = 1/T(1)) mapping for body fluids clinically feasible. Monte Carlo computer simulation is carried out to determine the ideal set of recovery times under various constraints of the sum of recovery times. The ideal set is found to be approximately invariant to the signal-to-noise ratio. For the three-point method, two of the recovery times should be set the same or approximately the same and should be shorter than the third one. Only marginal improvements in accuracy and precision can be achieved by the three-point method over the two-point method under a common constraint of the sum of recovery times. Three-dimensional, high resolution, whole-brain saturation-recovery scans on volunteers with a fast-spin-echo technique (XETA) and completed in a scan time of 10 min generated R(1) measurements of cerebrospinal fluid (T(1) approximately 4 s) in agreement with the computer simulation and literature results, which demonstrates the clinical feasibility of applying the two-point saturation-recovery method for R(1) mapping for long relaxation components.

    View details for DOI 10.1002/mrm.22111

    View details for PubMedID 19780164

  • COMT genotype and resting brain perfusion in children NEUROIMAGE Thomason, M. E., Waugh, C. E., Glover, G. H., Gotlib, I. H. 2009; 48 (1): 217-222


    Levels of extra-synaptic dopamine in the brain vary as a function of polymorphisms at the val158met locus of the catechol-O-methyltransferase (COMT) gene. In vivo studies of this polymorphism in the human brain have typically measured patterns of neural activation during dopamine-mediated tasks in adults. This study is the first to investigate the effects of COMT on brain physiology during rest and in children. We used flow-sensitive arterial spin-labeling (ASL) magnetic resonance imaging to examine brain blood flow (CBF) in 42 children. Compared with val-allele carriers, met-allele homozygotes exhibited greater CBF in mesolimbic, mesocortical, and nigrostriatal dopamine (DA) pathways. Higher CBF in DA-rich brain structures reflects COMT-related baseline differences that (1) underlie the selective behavioral advantages associated with each genotype; (2) affect interpretations of previously reported genotype differences in BOLD signal changes; and (3) serve as a foundation for future studies on the effects of COMT on brain development.

    View details for DOI 10.1016/j.neuroimage.2009.05.076

    View details for Web of Science ID 000269321100025

    View details for PubMedID 19500679

    View details for PubMedCentralID PMC2735191

  • Effects of model-based physiological noise correction on default mode network anti-correlations and correlations NEUROIMAGE Chang, C., Glover, G. H. 2009; 47 (4): 1448-1459


    Previous studies have reported that the spontaneous, resting-state time course of the default-mode network is negatively correlated with that of the "task-positive network", a collection of regions commonly recruited in demanding cognitive tasks. However, all studies of negative correlations between the default-mode and task-positive networks have employed some form of normalization or regression of the whole-brain average signal ("global signal"); these processing steps alter the time series of voxels in an uninterpretable manner as well as introduce spurious negative correlations. Thus, the extent of negative correlations with the default mode network without global signal removal has not been well characterized, and it is has recently been hypothesized that the apparent negative correlations in many of the task-positive regions could be artifactually induced by global signal pre-processing. The present study aimed to examine negative and positive correlations with the default-mode network when model-based corrections for respiratory and cardiac noise are applied in lieu of global signal removal. Physiological noise correction consisted of (1) removal of time-locked cardiac and respiratory artifacts using RETROICOR (Glover, G.H., Li, T.Q., Ress, D., 2000. Image-based method for retrospective correction of physiological motion effects in fMRI: RETROICOR. Magn. Reson. Med. 44, 162-167), and (2) removal of low-frequency respiratory and heart rate variations by convolving these waveforms with pre-determined transfer functions (Birn et al., 2008; Chang et al., 2009) and projecting the resulting two signals out of the data. It is demonstrated that negative correlations between the default-mode network and regions of the task-positive network are present in the majority of individual subjects both with and without physiological noise correction. Physiological noise correction increased the spatial extent and magnitude of negative correlations, yielding negative correlations within task-positive regions at the group-level (p<0.05, uncorrected; no regions at the group level were significant at FDR=0.05). Furthermore, physiological noise correction caused region-specific decreases in positive correlations within the default-mode network, reducing apparent false positives. It was observed that the low-frequency respiratory volume and cardiac rate regressors used within the physiological noise correction algorithm displayed significant (but not total) shared variance with the global signal, and constitute a model-based alternative to correcting for non-neural global noise.

    View details for DOI 10.1016/j.neuroimage.2009.05.012

    View details for Web of Science ID 000269035100034

    View details for PubMedID 19446646

    View details for PubMedCentralID PMC2995588

  • Relationship between respiration, end-tidal CO2, and BOLD signals in resting-state fMRI NEUROIMAGE Chang, C., Glover, G. H. 2009; 47 (4): 1381-1393


    A significant component of BOLD fMRI physiological noise is caused by variations in the depth and rate of respiration. It has previously been demonstrated that a breath-to-breath metric of respiratory variation (respiratory volume per time; RVT), computed from pneumatic belt measurements of chest expansion, has a strong linear relationship with resting-state BOLD signals across the brain. RVT is believed to capture breathing-induced changes in arterial CO(2), which is a cerebral vasodilator; indeed, separate studies have found that spontaneous fluctuations in end-tidal CO(2) (PETCO(2)) are correlated with BOLD signal time series. The present study quantifies the degree to which RVT and PETCO(2) measurements relate to one another and explain common aspects of the resting-state BOLD signal. It is found that RVT (particularly when convolved with a particular impulse response, the "respiration response function") is highly correlated with PETCO(2), and that both explain remarkably similar spatial and temporal BOLD signal variance across the brain. In addition, end-tidal O(2) is shown to be largely redundant with PETCO(2). Finally, the latency at which PETCO(2) and respiration belt measures are correlated with the time series of individual voxels is found to vary across the brain and may reveal properties of intrinsic vascular response delays.

    View details for DOI 10.1016/j.neuroimage.2009.04.048

    View details for Web of Science ID 000269035100028

    View details for PubMedID 19393322

    View details for PubMedCentralID PMC2721281

  • Performance-Related Sustained and Anticipatory Activity in Human Medial Temporal Lobe during Delayed Match-to-Sample JOURNAL OF NEUROSCIENCE Olsen, R. K., Nichols, E. A., Chen, J., Hunt, J. F., Glover, G. H., Gabrieli, J. D., Wagner, A. D. 2009; 29 (38): 11880-11890


    The medial temporal lobe (MTL)-hippocampus and surrounding perirhinal, parahippocampal, and entorhinal cortical areas-has long been known to be critical for long-term memory for events. Recent functional neuroimaging and neuropsychological data in humans performing short-delay tasks suggest that the MTL also contributes to performance even when retention intervals are brief, and single-unit data in rodents reveal sustained, performance-related delay activity in the MTL during delayed-non-match-to-sample tasks. The current study used functional magnetic resonance imaging to examine the relationship between activation in human MTL subregions and performance during a delayed-match-to-sample task with repeated (non-trial-unique) stimuli. On critical trials, the presentation of two faces was followed by a 30 s delay period, after which participants performed two-alternative forced-choice recognition. Functional magnetic resonance imaging revealed significant delay period activity in anterior hippocampus, entorhinal cortex, and perirhinal cortex over the 30 s retention interval, with the magnitude of activity being significantly higher on subsequently correct compared with subsequently incorrect trials. In contrast, posterior hippocampus, parahippocampal cortex, and fusiform gyrus activity linearly increased across the 30 s delay, suggesting an anticipatory response, and activity in parahippocampal cortex and hippocampus was greater during the probe period on correct compared with incorrect trials. These results indicate that at least two patterns of MTL delay period activation-sustained and anticipatory-are present during performance of short-delay recognition memory tasks, providing novel evidence that multiple processes govern task performance. Implications for understanding the role of the hippocampus and surrounding MTL cortical areas in recognition memory after short delays are discussed.

    View details for DOI 10.1523/JNEUROSCI.2245-09.2009

    View details for Web of Science ID 000270102000018

    View details for PubMedID 19776274

    View details for PubMedCentralID PMC2775810

  • Interleaved Spiral-In/Out With Application to Functional MRI (fMRI) MAGNETIC RESONANCE IN MEDICINE Law, C. S., Glover, G. H. 2009; 62 (3): 829-834


    The conventional spiral-in/out trajectory samples k-space sufficiently in the spiral-in path and sufficiently in the spiral-out path to enable creation of separate images. We propose an "interleaved spiral-in/out" trajectory comprising a spiral-in path that gathers one half of the k-space data, and a complimentary spiral-out path that gathers the other half. The readout duration is thereby reduced by approximately half, offering two distinct advantages: reduction of signal dropout due to susceptibility-induced field gradients (at the expense of signal-to-noise ratio [SNR]), and the ability to achieve higher spatial resolution when the readout duration is identical to the conventional method. Two reconstruction methods are described; both involve temporal filtering to remove aliasing artifacts. Empirically, interleaved spiral-in/out images are free from false activation resulting from signal pileup around the air/tissue interface, which is common in the conventional spiral-out method. Comparisons with conventional methods using a hyperoxia stimulus reveal greater frontal-orbital activation volumes but a slight reduction of overall activation in other brain regions.

    View details for DOI 10.1002/mrm.22056

    View details for Web of Science ID 000269404900033

    View details for PubMedID 19449373

    View details for PubMedCentralID PMC2763441

  • Rapid Methods for Concurrent Measurement of the RF-Pulse Flip Angle and the Longitudinal Relaxation Time MAGNETIC RESONANCE IN MEDICINE Hsu, J., Zaharchuk, G., Glover, G. H. 2009; 61 (6): 1319-1325


    Measuring both the flip angle (FA) and the longitudinal relaxation time T(1) is essential in quantitative and longitudinal studies because the signal amplitude is dependent on these quantities. Conventional methods can only measure one of them at a time and require long scan times. In this work, two mutually consistent methods are developed; each can acquire multislice data for determining both the FA and T(1) in a scan time about half the time needed for a conventional FA measurement. On the basis of a recent development of longitudinal-relaxation measurement (Hsu and Lowe, J Magn Reson 2004;169:270-278; Hsu and Glover, J Magn Reson 2006;181:98-106), one of the methods uses RF pulse trains of two FAs whereas the other uses pulse trains of different pulse spacing. When only the FA or T(1) is needed, the present methods can still be faster than conventional methods for the needed quantity. In benchmarking with a uniform-density sample, both methods generate precise T(1) values independent of the FA chosen (except at and near 90 degrees ). In the demonstration with three normal volunteers at 3 T, the T(1) values of frontal and occipital white matter, putamen, and caudate are compared; the T(1) values are in agreement with literature values and the intrasubject deviation is 0.2%-2.8%.

    View details for DOI 10.1002/mrm.21900

    View details for Web of Science ID 000266429900007

    View details for PubMedID 19267342

  • Increasing Spatial Coverage for High-Resolution Functional MRI MAGNETIC RESONANCE IN MEDICINE Hu, Y., Glover, G. H. 2009; 61 (3): 716-722


    For high-resolution functional MRI (fMRI) studies, one of the major challenges is limited spatial coverage, which results because of the tradeoffs between temporal resolution and covering more k-space. Given the same temporal resolution, fewer slices can be collected for high-resolution fMRI. If the number of slices is not large enough to cover all regions of interest, additional scans may become necessary, which increases both the total scan time and the complexity of interpreting data. In this work, we propose a method that combines the undersampled 3D stack-of-spirals acquisition method with the UNFOLD technique to significantly increase the spatial coverage for high-resolution fMRI. Undersampling allows more slices to be fit into a given temporal resolution. The signal-to-noise ratio (SNR) drop associated with undersampling can be compensated by the increase in the excited volume in 3D acquisitions. Theoretical analysis shows that although there is a negligible increase in temporal coherence due to spectral filtering in the UNFOLD technique, twice the spatial coverage can be achieved given the same total scan time and similar quality of activation maps, which was confirmed by experiments on normal subjects.

    View details for DOI 10.1002/mrm.21898

    View details for Web of Science ID 000263608300025

    View details for PubMedID 19097247

  • Development of Spatial and Verbal Working Memory Capacity in the Human Brain JOURNAL OF COGNITIVE NEUROSCIENCE Thomason, M. E., Race, E., Burrows, B., Whitfield-Gabrieli, S., Glover, G. H., Gabrieli, J. D. 2009; 21 (2): 316-332


    A core aspect of working memory (WM) is the capacity to maintain goal-relevant information in mind, but little is known about how this capacity develops in the human brain. We compared brain activation, via fMRI, between children (ages 7-12 years) and adults (ages 20-29 years) performing tests of verbal and spatial WM with varying amounts (loads) of information to be maintained in WM. Children made disproportionately more errors than adults as WM load increased. Children and adults exhibited similar hemispheric asymmetry in activation, greater on the right for spatial WM and on the left for verbal WM. Children, however, failed to exhibit the same degree of increasing activation across WM loads as was exhibited by adults in multiple frontal and parietal cortical regions. Thus, children exhibited adult-like hemispheric specialization, but appeared immature in their ability to marshal the neural resources necessary to maintain large amounts of verbal or spatial information in WM.

    View details for Web of Science ID 000262909700009

    View details for PubMedID 18510448

  • The bivalent side of the nucleus accumbens NEUROIMAGE Levita, L., Hare, T. A., Voss, H. U., Glover, G., Ballon, D. J., Casey, B. J. 2009; 44 (3): 1178-1187


    An increasing body of evidence suggests that the nucleus accumbens (NAcc) is engaged in both incentive reward processes and in adaptive responses to conditioned and unconditioned aversive stimuli. Yet, it has been argued that NAcc activation to aversive stimuli may be a consequence of the rewarding effects of their termination, i.e., relief. To address this question we used fMRI to delineate brain response to the onset and offset of unpleasant and pleasant auditory stimuli in the absence of learning or motor response. Increased NAcc activity was seen for the onset of both pleasant and unpleasant stimuli. Our results support the expanded bivalent view of NAcc function and call for expansion of current models of NAcc function that are solely focused on reward.

    View details for DOI 10.1016/j.neuroimage.2008.09.039

    View details for Web of Science ID 000262301500057

    View details for PubMedID 18976715

    View details for PubMedCentralID PMC2659952

  • Influence of heart rate on the BOLD signal: The cardiac response function NEUROIMAGE Chang, C., Cunningham, J. P., Glover, G. H. 2009; 44 (3): 857-869


    It has previously been shown that low-frequency fluctuations in both respiratory volume and cardiac rate can induce changes in the blood-oxygen level dependent (BOLD) signal. Such physiological noise can obscure the detection of neural activation using fMRI, and it is therefore important to model and remove the effects of this noise. While a hemodynamic response function relating respiratory variation (RV) and the BOLD signal has been described [Birn, R.M., Smith, M.A., Jones, T.B., Bandettini, P.A., 2008b. The respiration response function: The temporal dynamics of fMRI signal fluctuations related to changes in respiration. Neuroimage 40, 644-654.], no such mapping for heart rate (HR) has been proposed. In the current study, the effects of RV and HR are simultaneously deconvolved from resting state fMRI. It is demonstrated that a convolution model including RV and HR can explain significantly more variance in gray matter BOLD signal than a model that includes RV alone, and an average HR response function is proposed that well characterizes our subject population. It is observed that the voxel-wise morphology of the deconvolved RV responses is preserved when HR is included in the model, and that its form is adequately modeled by Birn et al.'s previously-described respiration response function. Furthermore, it is shown that modeling out RV and HR can significantly alter functional connectivity maps of the default-mode network.

    View details for DOI 10.1016/j.neuroimage.2008.09.029

    View details for Web of Science ID 000262301500026

    View details for PubMedID 18951982

    View details for PubMedCentralID PMC2677820

  • WOMEN WITH HYPOACTIVE SEXUAL DESIRE DISORDER COMPARED TO NORMAL FEMALES: A FUNCTIONAL MAGNETIC RESONANCE IMAGING STUDY NEUROSCIENCE Arnow, B. A., Millheiser, L., Garrett, A., Polan, M. L., Glover, G. H., Hill, K. R., Lightbody, A., Watson, C., Banner, L., Smart, T., Buchanan, T., Desmond, J. E. 2009; 158 (2): 484-502


    Lack of sexual interest is the most common sexual complaint among women. However, factors affecting sexual desire in women have rarely been studied. While the role of the brain in integrating the sensory, attentional, motivational, and motor aspects of sexual response is commonly acknowledged as important, little is known about specific patterns of brain activation and sexual interest or response, particularly among women. We compared 20 females with no history of sexual dysfunction (NHSD) to 16 women with hypoactive sexual desire disorder (HSDD) in a functional magnetic resonance imaging (fMRI) study that included assessment of subjective sexual arousal, peripheral sexual response using a vaginal photoplethysmograph (VPP), as well as brain activation across three time points. Video stimuli included erotic, sports, and relaxing segments. Subjective arousal to erotic stimuli was significantly greater in NHSD participants compared with HSDD. In the erotic-sports contrast, NHSD women showed significantly greater activation in the bilateral entorhinal cortex than HSDD women. In the same contrast, HSDD females demonstrated higher activation than NHSD females in the medial frontal gyrus (Brodmann area (BA) 10), right inferior frontal gyrus (BA 47) and bilateral putamen. There were no between group differences in VPP-correlated brain activation and peripheral sexual response was not significantly associated with either subjective sexual response or brain activation patterns. Findings were consistent across the three experimental sessions. The results suggest differences between women with NHSD and HSDD in encoding arousing stimuli, retrieval of past erotic experiences, or both. The findings of greater activation in BA 10 and BA 47 among women with HSDD suggest that this group allocated significantly more attention to monitoring and/or evaluating their responses than NHSD participants, which may interfere with normal sexual response.

    View details for DOI 10.1016/j.neuroscience.2008.09.044

    View details for Web of Science ID 000262959900012

    View details for PubMedID 18976696

  • Tuning in to the Voices: A Multisite fMRI Study of Auditory Hallucinations SCHIZOPHRENIA BULLETIN Ford, J. M., Roach, B. J., Jorgensen, K. W., Turner, J. A., Brown, G. G., Notestine, R., Bischoff-Grethe, A., Greve, D., Wible, C., Lauriello, J., Belger, A., Mueller, B. A., Calhoun, V., Preda, A., Keator, D., O'Leary, D. S., Lim, K. O., Glover, G., Potkin, S. G., Mathalon, D. H. 2009; 35 (1): 58-66


    Auditory hallucinations or voices are experienced by 75% of people diagnosed with schizophrenia. We presumed that auditory cortex of schizophrenia patients who experience hallucinations is tonically "tuned" to internal auditory channels, at the cost of processing external sounds, both speech and nonspeech. Accordingly, we predicted that patients who hallucinate would show less auditory cortical activation to external acoustic stimuli than patients who did not.At 9 Functional Imaging Biomedical Informatics Research Network (FBIRN) sites, whole-brain images from 106 patients and 111 healthy comparison subjects were collected while subjects performed an auditory target detection task. Data were processed with the FBIRN processing stream. A region of interest analysis extracted activation values from primary (BA41) and secondary auditory cortex (BA42), auditory association cortex (BA22), and middle temporal gyrus (BA21). Patients were sorted into hallucinators (n = 66) and nonhallucinators (n = 40) based on symptom ratings done during the previous week.Hallucinators had less activation to probe tones in left primary auditory cortex (BA41) than nonhallucinators. This effect was not seen on the right.Although "voices" are the anticipated sensory experience, it appears that even primary auditory cortex is "turned on" and "tuned in" to process internal acoustic information at the cost of processing external sounds. Although this study was not designed to probe cortical competition for auditory resources, we were able to take advantage of the data and find significant effects, perhaps because of the power afforded by such a large sample.

    View details for DOI 10.1093/schbul/sbn140

    View details for Web of Science ID 000261682700010

    View details for PubMedID 18987102

    View details for PubMedCentralID PMC2643968

  • Working memory and DLPFC inefficiency in schizophrenia: The FBIRN study SCHIZOPHRENIA BULLETIN Potkin, S. G., Turner, J. A., Brown, G. G., McCarthy, G., Greve, D. N., Glover, G. H., Manoach, D. S., Belger, A., Diaz, M., Wible, C. G., Ford, J. M., Mathalon, D. H., Gollub, R., Lauriello, J., O'Leary, D., van Erp, T. G., Toga, A. W., Preda, A., Lim, K. O. 2009; 35 (1): 19-31


    The Functional Imaging Biomedical Informatics Network is a consortium developing methods for multisite functional imaging studies. Both prefrontal hyper- or hypoactivity in chronic schizophrenia have been found in previous studies of working memory.In this functional magnetic resonance imaging (fMRI) study of working memory, 128 subjects with chronic schizophrenia and 128 age- and gender-matched controls were recruited from 10 universities around the United States. Subjects performed the Sternberg Item Recognition Paradigm1,2 with memory loads of 1, 3, or 5 items. A region of interest analysis examined the mean BOLD signal change in an atlas-based demarcation of the dorsolateral prefrontal cortex (DLPFC), in both groups, during both the encoding and retrieval phases of the experiment over the various memory loads.Subjects with schizophrenia performed slightly but significantly worse than the healthy volunteers and showed a greater decrease in accuracy and increase in reaction time with increasing memory load. The mean BOLD signal in the DLPFC was significantly greater in the schizophrenic group than the healthy group, particularly in the intermediate load condition. A secondary analysis matched subjects for mean accuracy and found the same BOLD signal hyperresponse in schizophrenics.The increase in BOLD signal change from minimal to moderate memory loads was greater in the schizophrenic subjects than in controls. This effect remained when age, gender, run, hemisphere, and performance were considered, consistent with inefficient DLPFC function during working memory. These findings from a large multisite sample support the concept not of hyper- or hypofrontality in schizophrenia, but rather DLPFC inefficiency that may be manifested in either direction depending on task demands. This redirects the focus of research from direction of difference to neural mechanisms of inefficiency.

    View details for DOI 10.1093/schbul/sbn162

    View details for Web of Science ID 000261682700007

    View details for PubMedID 19042912

    View details for PubMedCentralID PMC2643959

  • Brain-Performance Correlates of Working Memory Retrieval in Schizophrenia: A Cognitive Modeling Approach SCHIZOPHRENIA BULLETIN Brown, G. G., McCarthy, G., Bischoff-Grethe, A., Ozyurt, B., Greve, D., Potkin, S. G., Turner, J. A., Notestine, R., Calhoun, V. D., Ford, J. M., Mathalon, D., Manoach, D. S., Gadde, S., Glover, G. H., Wible, C. G., Belger, A., Gollub, R. L., Lauriello, J., O'Leary, D., Lim, K. O. 2009; 35 (1): 32-46


    Correlations of cognitive functioning with brain activation during a sternberg item recognition paradigm (SIRP) were investigated in patients with schizophrenia and in healthy controls studied at 8 sites. To measure memory scanning times, 4 response time models were fit to SIRP data. The best fitting model assumed exhaustive serial memory scanning followed by self-terminating memory search and involved one intercept parameter to represent SIRP processes not contributing directly to memory scanning. Patients displayed significantly longer response times with increasing memory load and differed on the memory scanning, memory search, and intercept parameters of the best fitting probability model. Groups differed in the correlation between the memory scanning parameter and linear brain response to increasing memory load within left inferior and left middle frontal gyrus, bilateral caudate, and right precuneus. The pattern of findings in these regions indicated that high scanning capacity was associated with high neural capacity among healthy subjects but that scanning speed was uncoupled from brain response to increasing memory load among schizophrenia patients. Group differences in correlation of the best fitting model's scanning parameter with a quadratic trend in brain response to increasing memory load suggested inefficient or disordered patterns of neural inhibition among individuals with schizophrenia, especially in the left perirhinal and entorhinal cortices. The results show at both cognitive and neural levels that disordered memory scanning contributes to deficient SIRP performance among schizophrenia patients.

    View details for DOI 10.1093/schbul/sbn149

    View details for Web of Science ID 000261682700008

    View details for PubMedID 19023127

    View details for PubMedCentralID PMC2643949

  • Sliding-Window Sensitivity Encoding (SENSE) Calibration for Reducing Noise in Functional MRI (fMRI) MAGNETIC RESONANCE IN MEDICINE Law, C. S., Liu, C., Glover, G. H. 2008; 60 (5): 1090-1103


    Functional magnetic resonance imaging (fMRI) at high magnetic field with parallel imaging (PI) has become increasingly popular for high-resolution imaging. We present a method of self-calibrated PI-fMRI in which sensitivity profiles are calculated using a sliding window of fully sampled multishot imaging data. We show that by updating these sensitivity profiles in a sliding fashion, thermal noise is reduced in the reconstructed image time series. This is accomplished by retaining thermal noise in the sensitivity profiles; no spatial smoothing is performed. These noisy profiles actually provide a closer match to those required for thermal noise-free reconstruction than conventional sensitivity map generation. Our proposed technique is especially applicable for acquiring high-spatial-resolution images, where thermal noise exceeds physiological noise. With conventional sensitivity calculation, PI-fMRI sensitivity is preserved only when using a voxel size large enough such that physiological noise predominates. With small voxel size, our technique reveals activation from visual stimulation where conventional sensitivity calculation techniques falter. Our technique enhances fMRI detection, especially when higher spatial resolution is desired.

    View details for DOI 10.1002/mrm.21701

    View details for PubMedID 18956461

  • Neuroanatomical Abnormalities in Adolescents With Attention-Deficit/Hyperactivity Disorder JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY Garrett, A., Penniman, L., Epstein, J. N., Casey, B. J., Hinshaw, S. P., Glover, G., Tonev, S., Vitolo, A., Davidson, M., Spicer, J., Greenhill, L. L., Reiss, A. L. 2008; 47 (11): 1321-1328


    Several neuroanatomic abnormalities have been reported in patients with attention-deficit/hyperactivity disorder (ADHD). However, findings are not always consistent, perhaps because of heterogeneous subject samples. Studying youths with documented familial ADHD provides an opportunity to examine a more homogeneous population.Twenty-four youths with a confirmed history of familial ADHD and 10 control youths underwent high-resolution structural magnetic resonance imaging examinations. Archived magnetic resonance imaging scan data from 12 control youths were included in the analysis to increase statistical power. Individually drawn region-of-interest methods were used to examine the frontal lobe gyri and caudate.Cerebral total tissue was similar between groups. The volumes of the right caudate and right inferior frontal lobe were larger in the ADHD youths compared with the control youths. Data from a subgroup of the ADHD youths suggest that increasing left caudate volume is associated with decreasing functional activation of this region.Because previous studies have focused primarily on younger subjects or used an extended age range, the present results may reflect neurodevelopmental changes specific to late adolescence in familial ADHD.

    View details for DOI 10.1097/CHI.0b013e318185d285

    View details for Web of Science ID 000260444800012

    View details for PubMedID 18827721

    View details for PubMedCentralID PMC2644065

  • Mapping and correction of vascular hemodynamic latency in the BOLD signal NEUROIMAGE Chang, C., Thomason, M. E., Glover, G. H. 2008; 43 (1): 90-102


    Correlation and causality metrics can be applied to blood-oxygen level-dependent (BOLD) signal time series in order to infer neural synchrony and directions of information flow from fMRI data. However, the BOLD signal reflects both the underlying neural activity and the vascular response, the latter of which is governed by local vasomotor physiology. The presence of potential vascular latency differences thus poses a confound in the detection of neural synchrony as well as inferences about the causality of neural processes. In the present study, we investigate the use of a breath holding (BH) task for characterizing and correcting for voxel-wise neurovascular latency differences across the whole brain. We demonstrate that BH yields reliable measurements of relative timing differences between voxels, and further show that a BH-derived latency correction can impact both functional connectivity maps of the resting-state default-mode network and activation maps of an event-related working memory (WM) task.

    View details for DOI 10.1016/j.neuroimage.2008.06.030

    View details for Web of Science ID 000259927400010

    View details for PubMedID 18656545

    View details for PubMedCentralID PMC2587338

  • THE ACQUISITION AND STATISTICAL ANALYSIS OF RAPID 3D FMRI DATA STATISTICA SINICA Lindquist, M. A., Zhang, C., Glover, G., Shepp, L. 2008; 18 (4): 1395-1419
  • Test-retest and between-site reliability in a multicenter fMRI study HUMAN BRAIN MAPPING Friedman, L., Stern, H., Brown, G. G., Mathalon, D. H., Turner, J., Glover, G. H., Gollub, R. L., Lauriello, J., Lim, K. O., Cannon, T., Greve, D. N., Bockholt, H. J., Belger, A., Mueller, B., Doty, M. J., He, J., Wells, W., Smyth, P., Pieper, S., Kim, S., Kubicki, M., Vangel, M., Potkin, S. G. 2008; 29 (8): 958-972


    In the present report, estimates of test-retest and between-site reliability of fMRI assessments were produced in the context of a multicenter fMRI reliability study (FBIRN Phase 1, Five subjects were scanned on 10 MRI scanners on two occasions. The fMRI task was a simple block design sensorimotor task. The impulse response functions to the stimulation block were derived using an FIR-deconvolution analysis with FMRISTAT. Six functionally-derived ROIs covering the visual, auditory and motor cortices, created from a prior analysis, were used. Two dependent variables were compared: percent signal change and contrast-to-noise-ratio. Reliability was assessed with intraclass correlation coefficients derived from a variance components analysis. Test-retest reliability was high, but initially, between-site reliability was low, indicating a strong contribution from site and site-by-subject variance. However, a number of factors that can markedly improve between-site reliability were uncovered, including increasing the size of the ROIs, adjusting for smoothness differences, and inclusion of additional runs. By employing multiple steps, between-site reliability for 3T scanners was increased by 123%. Dropping one site at a time and assessing reliability can be a useful method of assessing the sensitivity of the results to particular sites. These findings should provide guidance toothers on the best practices for future multicenter studies.

    View details for DOI 10.1002/hbm.20440

    View details for Web of Science ID 000258226900007

    View details for PubMedID 17636563

    View details for PubMedCentralID PMC3670112

  • Default-mode function and task-induced deactivation have overlapping brain substrates in children NEUROIMAGE Thomason, M. E., Chang, C. E., Glover, G. H., Gabrieli, J. D., Greicius, M. D., Gotlib, I. H. 2008; 41 (4): 1493-1503


    The regions that comprise the functionally connected resting-state default-mode network (DMN) in adults appear to be the same as those that are characterized by task-induced decreases in blood-oxygen-level-dependent (BOLD) signal. Independent component analysis can be used to produce a picture of the DMN as an individual rests quietly in the scanner. Contrasts across conditions in which cognitive load is parametrically modulated can delineate neural structures that have decreases in activation in response to high-demand task conditions. Examination of the degree to which these networks subsume dissociable brain substrates, and of the degree to which they overlap, provides insight concerning their purpose, function, and the nature of their associations. Few studies have examined the DMN in children, and none have tested whether the neural regions that comprise the DMN during a resting condition are the same regions that show reduced activity when children engage in cognitive tasks. In this paper we describe regions that show both task-related decreases and spontaneous intrinsic activity at rest in children, and we examine the co-localization of these networks. We describe ways in which the DMN in 7-12-year-old children is both similar to and different from the DMN in adults; moreover, we document that task-induced deactivations and default-mode resting-state activity in children share common neural substrates. It appears, therefore, that even before adolescence a core aspect of task-induced deactivation involves reallocating processing resources that are active at rest. We describe how future studies assessing the development of these systems would benefit from examining these constructs as part of one continuous system.

    View details for DOI 10.1016/j.neuroimage.2008.03.029

    View details for Web of Science ID 000256620400029

    View details for PubMedID 18482851

    View details for PubMedCentralID PMC2735193

  • Resting in peace or noise: Scanner background noise suppresses default-mode network HUMAN BRAIN MAPPING Gaab, N., Gabrieli, J. D., Glover, G. H. 2008; 29 (7): 858-867


    Studies have identified specific brain regions that increase activation during rest relative to attention-demanding tasks; these regions subserve the "default mode of brain function". Most of these studies have been conducted in the presence of scanner background noise (SBN). This noise has been shown to lead to altered attentional demands, and thus may modulate the default-mode network. Twelve subjects were examined during a rest condition that was contrasted with an auditory task. Words were presented either with SBN employing a conventional acquisition or without SBN using a sparse sampling approach. The number of experimental and resting trials was equated between the designs. Selecting the images in the condition with SBN that corresponded in time with the images in the condition without SBN made a direct comparison of the default-mode network (rest contrasted with active task) possible. There was typical activation of the default-mode network during rest versus task for both designs. However, SBN suppressed major components of the default-mode network, including medial prefrontal cortex, posterior cingulate, and precuneus. Our results suggest that the default mode of brain function differs when assessed in the presence compared to the absence of scanner noise, with the presence of scanner noise perhaps adding attentional demands that diminish activation changes between rest and task in a nonlinear way within the default network. Further studies are needed to clarify whether the use of a sparse sampling technique might enhance clinical utilities that have been proposed for analysis of the default-mode network.

    View details for DOI 10.1002/hbm.20578

    View details for Web of Science ID 000256674400014

    View details for PubMedID 18454447

  • Your pain or mine? Common and distinct neural systems supporting the perception of pain in self and other SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE Ochsner, K. N., Zaki, J., Hanelin, J., Ludlow, D. H., Knierim, K., Ramachandran, T., Glover, G. H., Mackey, S. C. 2008; 3 (2): 144-160


    Humans possess a remarkable capacity to understand the suffering of others. Cognitive neuroscience theories of empathy suggest that this capacity is supported by 'shared representations' of self and other. Consistent with this notion, a number of studies have found that perceiving others in pain and experiencing pain oneself recruit overlapping neural systems. Perception of pain in each of these conditions, however, may also cause unique patterns of activation, that may reveal more about the processing steps involved in each type of pain. To address this issue, we examined neural activity while participants experienced heat pain and watched videos of other individuals experiencing injuries. Results demonstrated (i) that both tasks activated anterior cingulate cortex and anterior insula, consistent with prior work; (ii) whereas self-pain activated anterior and mid insula regions implicated in interoception and nociception, other pain activated frontal, premotor, parietal and amygdala regions implicated in emotional learning and processing social cues; and (iii) that levels of trait anxiety correlated with activity in rostral lateral prefrontal cortex during perception of other pain but not during self-pain. Taken together, these data support the hypothesis that perception of pain in self and other, while sharing some neural commonalities, differ in their recruitment of systems specifically associated with decoding and learning about internal or external cues.

    View details for DOI 10.1093/scan/nsn006

    View details for Web of Science ID 000256525000008

    View details for PubMedID 19015105

    View details for PubMedCentralID PMC2555461

  • Biological substrates of emotional reactivity and regulation in adolescence during an emotional go-nogo task BIOLOGICAL PSYCHIATRY Hare, T. A., Tottenham, N., Galvan, A., Voss, H. U., Glover, G. H., Casey, B. J. 2008; 63 (10): 927-934


    Adolescence is a transition period from childhood to adulthood that is often characterized by emotional instability. This period is also a time of increased incidence of anxiety and depression, underscoring the importance of understanding biological substrates of behavioral and emotion regulation during adolescence. Developmental changes in the brain in concert with individual predispositions for anxiety might underlie the increased risk for poor outcomes reported during adolescence. We tested the hypothesis that difficulties in regulating behavior in emotional contexts in adolescents might be due to competition between heightened activity in subcortical emotional processing systems and immature top-down prefrontal systems. Individual differences in emotional reactivity might put some teens at greater risk during this sensitive transition in development.We examined the association between emotion regulation and frontoamygdala circuitry in 60 children, adolescents, and adults with an emotional go-nogo paradigm. We went beyond examining the magnitude of neural activity and focused on neural adaptation within this circuitry across time with functional magnetic resonance imaging.Adolescents showed exaggerated amygdala activity relative to children and adults. This age-related difference decreased with repeated exposures to the stimuli, and individual differences in self-ratings of anxiety predicted the extent of adaptation or habituation in amygdala. Individuals with higher trait anxiety showed less habituation over repeated exposures. This failure to habituate was associated with less functional connectivity between ventral prefrontal cortex and amygdala.These findings suggest that exaggerated emotional reactivity during adolescence might increase the need for top-down control and put individuals with less control at greater risk for poor outcomes.

    View details for DOI 10.1016/j.biopsych.2008.03.015

    View details for Web of Science ID 000255604000004

    View details for PubMedID 18452757

    View details for PubMedCentralID PMC2664095

  • Full-brain coverage and high-resolution Imaging capabilities of passband b-SSFP fMRI at 3T MAGNETIC RESONANCE IN MEDICINE Lee, J. H., Dumoulin, S. O., Saritas, E. U., Glover, G. H., Wandell, B. A., Nishimura, D. G., Pauly, J. M. 2008; 59 (5): 1099-1110


    Passband balanced-steady-state free precession (b-SSFP) fMRI is a recently developed method that utilizes the passband (flat portion) of the b-SSFP off-resonance response to measure MR signal changes elicited by changes in tissue oxygenation following increases in neuronal activity. Rapid refocusing and short readout durations of b-SSFP, combined with the relatively large flat portion of the b-SSFP off-resonance spectrum allows distortion-free full-brain coverage with only two acquisitions. This allows for high-resolution functional imaging, without the spatial distortion frequently encountered in conventional high-resolution functional images. Finally, the 3D imaging compatibility of the b-SSFP acquisitions permits isotropic-voxel-size high-resolution acquisitions. In this study we address some of the major technical issues involved in obtaining passband b-SSFP-based functional brain images with practical imaging parameters and demonstrate the advantages through breath-holding and visual field mapping experiments.

    View details for DOI 10.1002/mrm.21576

    View details for Web of Science ID 000255230700020

    View details for PubMedID 18421687

    View details for PubMedCentralID PMC2694041

  • Electronically Switchable Sham Transcranial Magnetic Stimulation (TMS) System PLOS ONE Hoeft, F., Wu, D., Hernandez, A., Glover, G. H., Shimojo, S. 2008; 3 (4)


    Transcranial magnetic stimulation (TMS) is increasingly being used to demonstrate the causal links between brain and behavior in humans. Further, extensive clinical trials are being conducted to investigate the therapeutic role of TMS in disorders such as depression. Because TMS causes strong peripheral effects such as auditory clicks and muscle twitches, experimental artifacts such as subject bias and placebo effect are clear concerns. Several sham TMS methods have been developed, but none of the techniques allows one to intermix real and sham TMS on a trial-by-trial basis in a double-blind manner. We have developed an attachment that allows fast, automated switching between Standard TMS and two types of control TMS (Sham and Reverse) without movement of the coil or reconfiguration of the setup. We validate the setup by performing mathematical modeling, search-coil and physiological measurements. To see if the stimulus conditions can be blinded, we conduct perceptual discrimination and sensory perception studies. We verify that the physical properties of the stimulus are appropriate, and that successive stimuli do not contaminate each other. We find that the threshold for motor activation is significantly higher for Reversed than for Standard stimulation, and that Sham stimulation entirely fails to activate muscle potentials. Subjects and experimenters perform poorly at discriminating between Sham and Standard TMS with a figure-of-eight coil, and between Reverse and Standard TMS with a circular coil. Our results raise the possibility of utilizing this technique for a wide range of applications.

    View details for DOI 10.1371/journal.pone.0001923

    View details for Web of Science ID 000260795500007

    View details for PubMedID 18398456

    View details for PubMedCentralID PMC2271126

  • Reduction of truncation artifacts in rapid 3D articular cartilage imaging JOURNAL OF MAGNETIC RESONANCE IMAGING Rakow-Penner, R., Gold, G., Daniel, B., Stevens, K., Rosenberg, J., Mazin, S. 2008; 27 (4): 860-865


    To reduce Gibbs ringing artifact in three-dimensional (3D) articular knee cartilage imaging with linear prediction (LP).A reconstruction method using LP in 3D was applied to truncated data sets of six healthy knees. The technique first linearizes the data before applying the prediction algorithm. Three radiologists blindly reviewed and ranked images of the full, truncated, and predicted data sets. Statistical analysis of the radiologists' reviews was performed for image quality, clinical acceptability of the images, and equivalence with the gold standard.LP applied to 3D knee cartilage imaging allows for 40% decreased scan time while providing image quality with statistical equivalence to a full data set.3D spoiled gradient echo imaging (SPGR) knee cartilage imaging requires significant scan time. This 40% reduction in scan time will allow such scans to be more feasible without sacrificing clinical acceptability.

    View details for DOI 10.1002/jmri.21312

    View details for PubMedID 18383247

  • Resilience after 9/11: Multimodal neuroimaging evidence for stress-related change in the healthy adult brain NEUROIMAGE Ganzel, B. L., Kim, P., Glover, G. H., Temple, E. 2008; 40 (2): 788-795


    Exposure to psychological trauma is common and predicts long-term physical and mental health problems, even in those who initially appear resilient. Here, we used multimodal neuroimaging in healthy adults who were at different distances from the World Trade Center on 9/11/01 to examine the neural mechanisms that may underlie this association. More than 3 years after 9/11/01, adults with closer proximity to the disaster had lower gray matter volume in amygdala, hippocampus, insula, anterior cingulate, and medial prefrontal cortex, with control for age, gender, and total gray matter volume. Further analysis showed a nonlinear (first-order quadratic) association between total number of traumas in lifetime and amygdala gray matter volume and function in the whole group. Post hoc analysis of subgroups with higher versus lower levels of lifetime trauma exposure revealed systematic associations between amygdala gray matter volume, amygdala functional reactivity, and anxiety that suggest a nonlinear trajectory in the neural response to accumulated trauma in healthy adults.

    View details for DOI 10.1016/j.neuroimage.2007.12.010

    View details for Web of Science ID 000254627700039

    View details for PubMedID 18234524

    View details for PubMedCentralID PMC2405811

  • The Alzheimer's Disease Neuroimaging Initiative (ADNI): MRI methods JOURNAL OF MAGNETIC RESONANCE IMAGING Jack, C. R., Bernstein, M. A., Fox, N. C., Thompson, P., Alexander, G., Harvey, D., Borowski, B., Britson, P. J., Whitwell, J. L., Ward, C., Dale, A. M., Felmlee, J. P., Gunter, J. L., Hill, D. L., Killiany, R., Schuff, N., Fox-Bosetti, S., Lin, C., Studholme, C., DeCarli, C. S., Krueger, G., Ward, H. A., Metzger, G. J., Scott, K. T., Mallozzi, R., Blezek, D., Levy, J., Debbins, J. P., Fleisher, A. S., Albert, M., Green, R., Bartzokis, G., Glover, G., Mugler, J., Weiner, M. W. 2008; 27 (4): 685-691


    The Alzheimer's Disease Neuroimaging Initiative (ADNI) is a longitudinal multisite observational study of healthy elders, mild cognitive impairment (MCI), and Alzheimer's disease. Magnetic resonance imaging (MRI), (18F)-fluorodeoxyglucose positron emission tomography (FDG PET), urine serum, and cerebrospinal fluid (CSF) biomarkers, as well as clinical/psychometric assessments are acquired at multiple time points. All data will be cross-linked and made available to the general scientific community. The purpose of this report is to describe the MRI methods employed in ADNI. The ADNI MRI core established specifications that guided protocol development. A major effort was devoted to evaluating 3D T(1)-weighted sequences for morphometric analyses. Several options for this sequence were optimized for the relevant manufacturer platforms and then compared in a reduced-scale clinical trial. The protocol selected for the ADNI study includes: back-to-back 3D magnetization prepared rapid gradient echo (MP-RAGE) scans; B(1)-calibration scans when applicable; and an axial proton density-T(2) dual contrast (i.e., echo) fast spin echo/turbo spin echo (FSE/TSE) for pathology detection. ADNI MRI methods seek to maximize scientific utility while minimizing the burden placed on participants. The approach taken in ADNI to standardization across sites and platforms of the MRI protocol, postacquisition corrections, and phantom-based monitoring of all scanners could be used as a model for other multisite trials.

    View details for DOI 10.1002/jmri.21049

    View details for Web of Science ID 000254709500001

    View details for PubMedID 18302232

    View details for PubMedCentralID PMC2544629

  • Rapid three-dimensional functional magnetic resonance imaging of the initial negative BOLD response JOURNAL OF MAGNETIC RESONANCE Lindquist, M. A., Zhang, C., Glover, G., Shepp, L. 2008; 191 (1): 100-111


    Functional MRI is most commonly used to study the local changes in blood flow that accompanies neuronal activity. In this work we introduce a new approach towards acquiring and analyzing fMRI data that instead provides the potential to study the initial oxygen consumption in the brain that accompanies activation. As the oxygen consumption is closer in timing to the underlying neuronal activity than the subsequent blood flow, this approach promises to provide more precise information about the location and timing of activity. Our approach is based on using a new single shot 3D echo-volumar imaging sequence which samples a small central region of 3D k-space every 100ms, thereby giving a low spatial resolution snapshot of the brain with extremely high temporal resolution. Explicit and simple rules for implementing the trajectory are provided, together with a straightforward reconstruction algorithm. Using our approach allows us to effectively study the behavior of the brain in the time immediately following activation through the initial negative BOLD response, and we discuss new techniques for detecting the presence of the negative response across the brain. The feasibility and efficiency of the approach is confirmed using data from a visual-motor task and an auditory-motor-visual task. The results of these experiments provide a proof of concept of our methodology, and indicate that rapid imaging of the initial negative BOLD response can serve an important role in studying cognition tasks involving rapid mental processing in more than one region.

    View details for DOI 10.1016/j.jmr.2007.12.016

    View details for Web of Science ID 000253500700011

    View details for PubMedID 18207441

  • Switching language switches mind: linguistic effects on developmental neural bases of 'Theory of Mind' SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE Kobayashi, C., Glover, G. H., Temple, E. 2008; 3 (1): 62-70


    Theory of mind (ToM)--our ability to predict behaviors of others in terms of their underlying intentions--has been examined through false-belief (FB) tasks. We studied 12 Japanese early bilingual children (8-12 years of age) and 16 late bilingual adults (18-40 years of age) with FB tasks in Japanese [first language (L1)] and English [second language (L2)], using fMRI. Children recruited more brain regions than adults for processing ToM tasks in both languages. Moreover, children showed an overlap in brain activity between the L1 and L2 ToM conditions in the medial prefrontal cortex (mPFC). Adults did not show such a convergent activity in the mPFC region, but instead, showed brain activity that varied depending on the language used in the ToM task. The developmental shift from more to less ToM specific brain activity may reflect increasing automatization of ToM processing as people age. These results also suggest that bilinguals recruit different resources to understand ToM depending on the language used in the task, and this difference is greater later in life.

    View details for DOI 10.1093/scan/nsm039

    View details for Web of Science ID 000256174000008

    View details for PubMedID 19015096

    View details for PubMedCentralID PMC2569814

  • Practical approaches to incidental findings in brain imaging research NEUROLOGY Illes, J., Kirschen, M. P., Edwards, E., Bandettini, P., Cho, M. K., Ford, P. J., Glover, G. H., Kulynych, J., Macklin, R., Michael, D. B., Wolf, S. M., Grabowski, T., Seto, B. 2008; 70 (5): 384-390


    A decade of empirical work in brain imaging, genomics, and other areas of research has yielded new knowledge about the frequency of incidental findings, investigator responsibility, and risks and benefits of disclosure. Straightforward guidance for handling such findings of possible clinical significance, however, has been elusive. In early work focusing on imaging studies of the brain, we suggested that investigators and institutional review boards must anticipate and articulate plans for handling incidental findings. Here we provide a detailed analysis of different approaches to the problem and evaluate their merits in the context of the goals and setting of the research and the involvement of neurologists, radiologists, and other physicians. Protecting subject welfare and privacy, as well as ensuring scientific integrity, are the highest priorities in making choices about how to handle incidental findings. Forethought and clarity will enable these goals without overburdening research conducted within or outside the medical setting.

    View details for PubMedID 18227420

  • Controlled inspiration depth reduces variance in breath-holding-induced BOLD signal NEUROIMAGE Thomason, M. E., Glover, G. H. 2008; 39 (1): 206-214


    Recent studies have shown that blood oxygen level dependent (BOLD) response amplitude during short periods of breath holding (BH) measured by functional magnetic resonance imaging (fMRI) can be an effective metric for intersubject calibration procedures. However, inconsistency in the depth of inspiration during the BH scan may account for a portion of BOLD variation observed in such scans, and it is likely to reduce the effectiveness of the calibration measurement. While modulation of BOLD signal has been correlated with end-tidal CO2 and other measures of breathing, fluctuations in performance of BH have not been studied in the context of their impact on BOLD signal. Here, we studied the degree to which inspiration depth corresponds to BOLD signal change and tested the effectiveness of a method designed to control inspiration level through visual cues during the BH task paradigm. We observed reliable differences in BOLD signal amplitude corresponding to the depth of inspiration. It was determined that variance in BOLD signal response to BH could be significantly reduced when subjects were given visual feedback during task inspiration periods. The implications of these findings for routine BH studies of BOLD-derived neurovascular response are discussed.

    View details for DOI 10.1016/j.neuroimage.2007.08.014

    View details for Web of Science ID 000251406000018

    View details for PubMedID 17905599

    View details for PubMedCentralID PMC2151095

  • Fast functional magnetic resonance imaging-a new approach towards neuroimaging STATISTICS AND ITS INTERFACE Zhang, C., Lindquist, M. A., Cho, Z., Glover, G., Shepp, L. 2008; 1 (1): 13-21
  • Three-dimensional spiral technique for high-resolution functional MRI MAGNETIC RESONANCE IN MEDICINE Hu, Y., Glover, G. H. 2007; 58 (5): 947-951


    For high-resolution functional MRI (fMRI) studies, signal-to-noise ratio (SNR) plays an important role. Any method that results in an improvement in SNR will be able to improve the quality of activation maps. Three-dimensional (3D) acquisition methods in general can provide higher SNR than that of 2D methods due to volume excitation. To demonstrate the superiority of 3D methods for high-resolution fMRI scans, a comparison study between 3D and 2D spiral methods was performed using a contrast-reversing checkerboard visual stimulus. A 3-inch surface coil was used to limit the in-plane FOV to 14 cm x 14 cm so that 32 1-mm slices with an in-plane voxel size of 1.1 mm x 1.1 mm could be acquired within 5.76 seconds. Results showed that average numbers of activated voxels were 407 and 841 for 2D and 3D methods, respectively (P < 0.01). Therefore, the 3D technique may be a useful alternative to the conventional 2D method for high resolution fMRI studies.

    View details for DOI 10.1002/mrm.21328

    View details for Web of Science ID 000250560000012

    View details for PubMedID 17969117

  • Frontostriatal connectivity and its role in cognitive control in parent-child dyads with ADHD AMERICAN JOURNAL OF PSYCHIATRY Casey, B. J., Epstein, J. N., Buhle, J., Liston, C., Davidson, M. C., Tonev, S. T., Spicer, J., Niogi, S., Millner, A. J., Reiss, A., Garrett, A., Hinshaw, S. P., Greenhill, L. L., Shafritz, K. M., Vitolo, A., Kotler, L. A., Jarrett, M. A., Glover, G. 2007; 164 (11): 1729-1736


    Many studies have linked the structure and function of frontostriatal circuitry to cognitive control deficits in attention deficit hyperactivity disorder (ADHD). Few studies have examined the role of white matter tracts between these structures or the extent to which white matter tract myelination and regularity correlate in family members with the disorder.Functional imaging maps from a go/nogo task were used to identify portions of the ventral prefrontal cortex and striatum involved in suppressing an inappropriate action (i.e., cognitive control) in 30 parent-child dyads (N=60), including 20 dyads (N=40) with ADHD and 10 dyads (N=20) without ADHD. An automated fiber-tracking algorithm was used to delineate white matter fibers adjacent to these functionally defined regions based on diffusion tensor images. Fractional anisotropy, an index of white matter tract myelination and regularity derived from diffusion tensor images, was calculated to characterize the associations between white matter tracts and function.Fractional anisotropy in right prefrontal fiber tracts correlated with both functional activity in the inferior frontal gyrus and caudate nucleus and performance of a go/nogo task in parent-child dyads with ADHD, even after controlling for age. Prefrontal fiber tract measures were tightly associated between ADHD parents and their children.Collectively, these findings support previous studies suggesting heritability of frontostriatal structures among individuals with ADHD and suggest disruption in frontostriatal white matter tracts as one possible pathway to the disorder.

    View details for DOI 10.1176/appi.ajp.2007.06101754

    View details for Web of Science ID 000250811200020

    View details for PubMedID 17974939

  • Resting-state functional connectivity in major depression: Abnormally increased contributions from subgenual cingulate cortex and thalamus BIOLOGICAL PSYCHIATRY Greicius, M. D., Flores, B. H., Menon, V., Glover, G. H., Solvason, H. B., Kenna, H., Reiss, A. L., Schatzberg, A. F. 2007; 62 (5): 429-437


    Positron emission tomography (PET) studies of major depression have revealed resting-state abnormalities in the prefrontal and cingulate cortices. Recently, fMRI has been adapted to examine connectivity within a specific resting-state neural network--the default-mode network--that includes medial prefrontal and anterior cingulate cortices. The goal of this study was to examine resting-state, default-mode network functional connectivity in subjects with major depression and in healthy controls.Twenty-eight subjects with major depression and 20 healthy controls underwent 5-min fMRI scans while resting quietly. Independent component analysis was used to isolate the default-mode network in each subject. Group maps of the default-mode network were compared. A within-group analysis was performed in the depressed group to explore effects of depression refractoriness on functional connectivity.Resting-state subgenual cingulate and thalamic functional connectivity with the default-mode network were significantly greater in the depressed subjects. Within the depressed group, the length of the current depressive episode correlated positively with functional connectivity in the subgenual cingulate.This is the first study to explore default-mode functional connectivity in major depression. The findings provide cross-modality confirmation of PET studies demonstrating increased thalamic and subgenual cingulate activity in major depression. Further, the within-subject connectivity analysis employed here brings these previously isolated regions of hypermetabolism into the context of a disordered neural network. The correlation between refractoriness and subgenual cingulate functional connectivity within the network suggests that a quantitative, resting-state fMRI measure could be used to guide therapy in individual subjects.

    View details for DOI 10.1016/j.biopsych.2006.09.020

    View details for Web of Science ID 000249042800009

    View details for PubMedID 17210143

    View details for PubMedCentralID PMC2001244

  • ADHD- and medication-related brain activation effects in concordantly affected parent-child dyads with ADHD JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY Epstein, J. N., Casey, B. J., Tonev, S. T., Davidson, M. C., Reiss, A. L., Garrett, A., Hinshaw, S. P., Greenhill, L. L., Glover, G., Shafritz, K. M., Vitolo, A., Kotler, L. A., Jarrett, M. A., Spicer, J. 2007; 48 (9): 899-913


    Several studies have documented fronto-striatal dysfunction in children and adolescents with attention deficit/hyperactivity disorder (ADHD) using response inhibition tasks. Our objective was to examine functional brain abnormalities among youths and adults with ADHD and to examine the relations between these neurobiological abnormalities and response to stimulant medication.A group of concordantly diagnosed ADHD parent-child dyads was compared to a matched sample of normal parent-child dyads. In addition, ADHD dyads were administered double-blind methylphenidate and placebo in a counterbalanced fashion over two consecutive days of testing. Frontostriatal function was measured using functional magnetic resonance imaging (fMRI) during performance of a go/no-go task.Youths and adults with ADHD showed attenuated activity in fronto-striatal regions. In addition, adults with ADHD appeared to activate non-fronto-striatal regions more than normals. A stimulant medication trial showed that among youths, stimulant medication increased activation in fronto-striatal and cerebellar regions. In adults with ADHD, increases in activation were observed in the striatum and cerebellum, but not in prefrontal regions.This study extends findings of fronto-striatal dysfunction to adults with ADHD and highlights the importance of frontostriatal and frontocerebellar circuitry in this disorder, providing evidence of an endophenotype for examining the genetics of ADHD.

    View details for DOI 10.1111/j.1469-7610.2007.01761.x

    View details for Web of Science ID 000249130800007

    View details for PubMedID 17714375

  • Cultural and linguistic effects on neural bases of 'Theory of Mind' in American and Japanese children BRAIN RESEARCH Kobayashi, C., Glover, G. H., Temple, E. 2007; 1164: 95-107


    Theory of Mind (ToM) has been defined as our ability to predict behaviors of others in terms of their underlying intentions. While the developmental trajectory of ToM had been thought to be invariant across cultures, several ToM studies conducted outside the Anglo-American cultural or linguistic milieus have obtained mixed results. To examine effects of culture/language on the development of neural bases of ToM, we studied 12 American monolingual children and 12 Japanese bilingual children with second-order false-belief story and cartoon tasks, using functional magnetic resonance imaging (fMRI). While a few brain regions such as ventro-medial prefrontal cortex (vmPFC) and precuneus were recruited by both cultural/linguistic groups, several brain areas including inferior frontal gyrus (IFG) and temporo-parietal junction (TPJ) were employed in a culture/language-dependent manner during the ToM tasks. These results suggest that the neural correlates of ToM may begin to vary depending upon cultural/linguistic background from early in life.

    View details for DOI 10.1016/j.brainres.2007.06.022

    View details for Web of Science ID 000249321900010

    View details for PubMedID 17643400

    View details for PubMedCentralID PMC2964053

  • Assessing the influence of scanner background noise on auditory processing. I. An fMRI study comparing three experimental designs with varying degrees of scanner noise HUMAN BRAIN MAPPING Gaab, N., Gabrieli, J. D., Glover, G. H. 2007; 28 (8): 703-720


    We compared two experimental designs aimed at minimizing the influence of scanner background noise (SBN) on functional MRI (fMRI) of auditory processes with one conventional fMRI design. Ten subjects listened to a series of four one-syllable words and had to decide whether two of the words were identical. This was contrasted with a no-stimulus control condition. All three experimental designs had a duration of approximately 17 min: 1) a behavior interleaved gradients (BIG; Eden et al. [1999] J Magn Reson Imaging 41:13-20) design (repetition time, TR, = 6 s), where stimuli were presented during the SBN-free periods between clustered volume acquisitions (CVA); 2) a sparse temporal sampling technique (STsamp; e.g., Gaab et al., [2003] Neuroimage 19:1417-1426) acquiring only one set of slices following each of the stimulations with a 16-s TR and jittered delay times between stimulus offset and image acquisition; and 3) an event-related design with continuous scanning (ERcont) using the stimulation design of STsamp but with a 2-s TR. The results demonstrated increased signal within Heschl's gyrus for the STsamp and BIG-CVA design in comparison to ERcont as well as differences in the overall functional anatomy among the designs. The possibility to obtain a time course of activation as well as the full recovery of the stimulus- and SBN-induced hemodynamic response function signal and lack of signal suppression from SBN during the STsamp design makes this technique a powerful approach for conducting auditory experiments using fMRI. Practical strengths and limitations of the three auditory acquisition paradigms are discussed.

    View details for DOI 10.1002/hbm.20298

    View details for Web of Science ID 000248613100002

    View details for PubMedID 17080440

  • Assessing the influence of scanner background noise on auditory processing. II. An fMRI study comparing auditory processing in the absence and presence of recorded scanner noise using a sparse design HUMAN BRAIN MAPPING Gaab, N., Gabrieli, J. D., Glover, G. H. 2007; 28 (8): 721-732


    Several studies reported decreased signal intensities within auditory areas for experimental designs employing continuous scanner background noise (SBN) in comparison to designs with less or no SBN. This study examined the source for this SBN-induced masking effect of the blood oxygenation level-dependent (BOLD) response by directly comparing two experimental sessions with the same auditory stimulation, which was presented either with or without recorded scanner background noise (RecSBN). Ten subjects listened to a series of four one-syllable words and had to decide whether two of the words were identical. The words were either presented with a silent background or with added RecSBN. This was then contrasted with either silence or RecSBN. A sparse temporal sampling method was used in both sessions, which enabled us to directly assess the influence of RecSBN without varying scanning parameters, acquisition quantities, or auditory stimulations. Our results suggest that previously reported SBN-induced masking of the BOLD response in experimental designs with SBN might be caused by an interaction between increased baseline levels and nonlinearity effects within auditory cortices. Adding SBN to an experimental condition does not enhance signal intensities to the same degree that SBN does when presented with a silent background, and therefore contrasting an experimental and baseline condition that both have SBN may lead to signal decreases. In addition, our study shows this effect is greatest in Heschl's gyrus, but can also be observed in higher-order auditory areas.

    View details for DOI 10.1002/hbm.20299

    View details for Web of Science ID 000248613100003

    View details for PubMedID 17089376

  • Neuroimaging for the diagnosis and study of psychiatric disorders IEEE SIGNAL PROCESSING MAGAZINE Turner, J. A., Potkin, S. G., Brown, G. G., Keator, D. B., McCarthy, G., Glover, G. H. 2007; 24 (4): 112-117
  • Prediction of children's reading skills using behavioral, functional, and structural neuroimaging measures BEHAVIORAL NEUROSCIENCE Hoeft, F., Ueno, T., Reiss, A. L., Meyler, A., Whitfield-Gabrieli, S., Glover, G. H., Keller, T. A., Kobayashi, N., Mazaika, P., Jo, B., Just, M. A., Gabrieli, J. D. 2007; 121 (3): 602-613


    The ability to decode letters into language sounds is essential for reading success, and accurate identification of children at high risk for decoding impairment is critical for reducing the frequency and severity of reading impairment. We examined the utility of behavioral (standardized tests), and functional and structural neuroimaging measures taken with children at the beginning of a school year for predicting their decoding ability at the end of that school year. Specific patterns of brain activation during phonological processing and morphology, as revealed by voxel-based morphometry (VBM) of gray and white matter densities, predicted later decoding ability. Further, a model combining behavioral and neuroimaging measures predicted decoding outcome significantly better than either behavioral or neuroimaging models alone. Results were validated using cross-validation methods. These findings suggest that neuroimaging methods may be useful in enhancing the early identification of children at risk for poor decoding and reading skills.

    View details for DOI 10.1037/0735-7044.121.3.602

    View details for Web of Science ID 000247359300017

    View details for PubMedID 17592952

  • The aftermath of 9/11: Effect of intensity and recency of trauma on outcome EMOTION Ganzel, B., Casey, B. J., Glover, G., Voss, H. U., Temple, E. 2007; 7 (2): 227-238


    Does trauma exposure have a long-term impact on the brain and behavior of healthy individuals? The authors used functional magnetic resonance imaging to assess the impact of proximity to the disaster of September 11, 2001, on amygdala function in 22 healthy adults. More than three years after the terrorist attacks, bilateral amygdala activity in response to viewing fearful faces compared to calm ones was higher in people who were within 1.5 miles of the World Trade Center on 9/11, relative to those who were living more than 200 miles away (all were living in the New York metropolitan area at time of scan). This activity mediated the relationship between group status and current symptoms of posttraumatic stress disorder. In turn, the effect of group status on both amygdala activation (fearful vs. calm faces) and current symptoms was statistically explained by time since worst trauma in lifetime and intensity of worst trauma, as indicated by reported symptoms at time of the trauma. These data are consistent with a model of heightened amygdala reactivity following high-intensity trauma exposure, with relatively slow recovery.

    View details for DOI 10.1037/1528-3542.7.2.227

    View details for Web of Science ID 000246412200001

    View details for PubMedID 17516802

    View details for PubMedCentralID PMC2759706

  • Risk-taking and the adolescent brain: who is at risk? DEVELOPMENTAL SCIENCE Galvan, A., Hare, T., Voss, H., Glover, G., Casey, B. J. 2007; 10 (2): F8-F14


    Relative to other ages, adolescence is described as a period of increased impulsive and risk-taking behavior that can lead to fatal outcomes (suicide, substance abuse, HIV, accidents, etc.). This study was designed to examine neural correlates of risk-taking behavior in adolescents, relative to children and adults, in order to predict who may be at greatest risk. Activity in reward-related neural circuitry in anticipation of a large monetary reward was measured with functional magnetic resonance imaging, and anonymous self-report ratings of risky behavior, anticipation of risk and impulsivity were acquired in individuals between the ages of 7 and 29 years. There was a positive association between accumbens activity and the likelihood of engaging in risky behavior across development. This activity also varied as a function of individuals' ratings of anticipated positive or negative consequences of such behavior. Impulsivity ratings were not associated with accumbens activity, but rather with age. These findings suggest that during adolescence, some individuals may be especially prone to engage in risky behaviors due to developmental changes in concert with variability in a given individual's predisposition to engage in risky behavior, rather than to simple changes in impulsivity.

    View details for DOI 10.1111/j.1467-7687.2006.00579.x

    View details for Web of Science ID 000243910100002

    View details for PubMedID 17286837

  • Dissociable intrinsic connectivity networks for salience processing and executive control JOURNAL OF NEUROSCIENCE Seeley, W. W., Menon, V., Schatzberg, A. F., Keller, J., Glover, G. H., Kenna, H., Reiss, A. L., Greicius, M. D. 2007; 27 (9): 2349-2356


    Variations in neural circuitry, inherited or acquired, may underlie important individual differences in thought, feeling, and action patterns. Here, we used task-free connectivity analyses to isolate and characterize two distinct networks typically coactivated during functional MRI tasks. We identified a "salience network," anchored by dorsal anterior cingulate (dACC) and orbital frontoinsular cortices with robust connectivity to subcortical and limbic structures, and an "executive-control network" that links dorsolateral frontal and parietal neocortices. These intrinsic connectivity networks showed dissociable correlations with functions measured outside the scanner. Prescan anxiety ratings correlated with intrinsic functional connectivity of the dACC node of the salience network, but with no region in the executive-control network, whereas executive task performance correlated with lateral parietal nodes of the executive-control network, but with no region in the salience network. Our findings suggest that task-free analysis of intrinsic connectivity networks may help elucidate the neural architectures that support fundamental aspects of human behavior.

    View details for DOI 10.1523/JNEUROSCI.5587-06.2007

    View details for Web of Science ID 000244758500023

    View details for PubMedID 17329432

    View details for PubMedCentralID PMC2680293

  • Restricted field of view magnetic resonance imaging of a dynamic time series MAGNETIC RESONANCE IN MEDICINE Pisani, L., Bammer, R., Glover, G. 2007; 57 (2): 297-307


    A restricted field of view (rFOV) approach for imaging a dynamic time series of volumes of limited spatial extent within a larger subject is described. The shorter readout with rFOV-MRI can be exploited to either limit image artifacts or increase spatial resolution. To accomplish rFOV imaging of a multislice volume for a dynamic series, an outer volume suppression (OVS) preparation that saturates signal external to a cylinder through the subject is followed by slice-selective excitation and a spiral readout. The pass- and stopband efficiencies of the OVS in an agar gel phantom were 97% (+/-1.5%) and 3% (+/-1%), respectively. Profiles of the temporal signal-to-noise ratio (SNR) were measured in a phantom and an adult brain. The rFOV sequence reduced distortions from off-resonance signal and T2*-induced blurring compared to a conventional sequence. Sequence utility is demonstrated for high-resolution rFOV functional MRI (fMRI) in the visual cortex. The rFOV sequence may prove to be useful for other multislice dynamic and high-resolution imaging applications.

    View details for DOI 10.1002/mrm.21115

    View details for Web of Science ID 000243946300009

    View details for PubMedID 17260360

  • Calibration of BOLD fMRI using breath holding reduces group variance during a cognitive task HUMAN BRAIN MAPPING Thomason, M. E., Foland, L. C., Glover, G. H. 2007; 28 (1): 59-68


    The proportionality of blood oxygen level-dependent (BOLD) response during a cognitive task and that from a hypercapnic challenge was investigated in cortical structures involved in working memory (WM). Breath holding (BH) following inspiration was used to induce a BOLD response characteristic of regional vasomotor reactivity but devoid of metabolic changes. BOLD effects measured during BH were used to normalize individual subject activations during WM, which effectively reduced the confounding influence of individual- and region-specific differences in hemodynamic responsivity common to both tasks. In a study of seven subjects, the BH calibration reduced intersubject variability in WM effect amplitude by 24.8% (P < 0.03). Reduced intersubject variability resulted in a 23.7% increase in group WM activation voxel extent significant at P < 0.001, with further increases at more stringent thresholds. Because the BH task does not require CO(2) inhalation or other invasive manipulations and is broadly applicable across cortical regions, the proposed approach is simple to implement and may be beneficial for use not only in quantitative group fMRI analyses, but also for multicenter and longitudinal studies.

    View details for DOI 10.1002/hbm.20241

    View details for Web of Science ID 000242944100006

    View details for PubMedID 16671081

  • Sensitivity of the nucleus accumbens to violations in expectation of reward NEUROIMAGE Spicer, J., Galvan, A., Hare, T. A., Voss, H., Glover, G., Casey, B. J. 2007; 34 (1): 455-461


    This study examined whether ventral frontostriatal regions differentially code expected and unexpected reward outcomes. We parametrically manipulated the probability of reward and examined the neural response to reward and nonreward for each probability condition in the ventral striatum and the orbitofrontal cortex (OFC). By late trials of the experiment, subjects showed slower behavioral responses for the condition with the lowest probability of reward, relative to the condition with the highest probability of reward. At the neural level, both the nucleus accumbens (NAcc) and OFC showed greater activation to rewarded relative to nonrewarded trials, but the accumbens appeared to be most sensitive to violations in expected reward outcomes. These data suggest distinct roles for frontostriatal circuitry in reward prediction and in responding to violations in expectations.

    View details for DOI 10.1016/j.neuroimage.2006.09.012

    View details for Web of Science ID 000242735300045

    View details for PubMedID 17049884

    View details for PubMedCentralID PMC1796943

  • Children's and adults' neural bases of verbal and nonverbal 'theory of mind' NEUROPSYCHOLOGIA Kobayashi, C., Glover, G. H., Temple, E. 2007; 45 (7): 1522-1532


    Theory of mind (ToM) - our ability to predict behaviors of others in terms of their underlying intentions - has been examined through verbal and nonverbal false-belief (FB) tasks. Previous brain imaging studies of ToM in adults have implicated medial prefrontal cortex (mPFC) and temporo-parietal junction (TPJ) for adults' ToM ability. To examine age and modality related differences and similarities in neural correlates of ToM, we tested 16 adults (18-40 years old) and 12 children (8-12 years old) with verbal (story) and nonverbal (cartoon) FB tasks, using functional magnetic resonance imaging (fMRI). Both age groups showed significant activity in the TPJ bilaterally and right inferior parietal lobule (IPL) in a modality-independent manner, indicating that these areas are important for ToM during both adulthood and childhood, regardless of modality. We also found significant age-related differences in the ToM condition-specific activity for the story and cartoon tasks in the left inferior frontal gyrus (IFG) and left TPJ. These results suggest that depending on the modality adults may utilize different brain regions from children in understanding ToM.

    View details for DOI 10.1016/j.neuropsychologia.2006.11.017

    View details for Web of Science ID 000245477100016

    View details for PubMedID 17208260

    View details for PubMedCentralID PMC1868677

  • Laminar profiles of functional activity in the human brain NEUROIMAGE Ress, D., Glover, G. H., Liu, J., Wandell, B. 2007; 34 (1): 74-84


    Functional magnetic resonance imaging (fMRI) data were obtained in human visual cortex using sub-millimeter voxels at a field strength of 3 T. Reliable functional signals were largely confined to the gray matter and these responses measure the retinotopic organization of visual cortex. Functional signals were further characterized with respect to their laminar position within the cortical gray matter. The laminar response profiles during our visuospatial attention task, normalized for cortical thickness, had a stereotypical shape, with a peak in the superficial gray matter and declining in the deeper layers. The thickness of the sheet producing functional signals was in excellent agreement with the estimated structural thickness of the gray matter throughout early visual cortex (error < 0.5 mm). Thickness measurements were highly repeatable from session-to-session (error < 0.4 mm). Hence, it is feasible and useful to use high-resolution fMRI to measure laminar activity profiles. The ability to distinguish signals arising in different lamina has significant potential scientific and clinical applications.

    View details for DOI 10.1016/j.neuroimage.2006.08.020

    View details for Web of Science ID 000242735300008

    View details for PubMedID 17011213

  • An adaptive filter for suppression of cardiac and respiratory noise in MRI time series data NEUROIMAGE Deckers, R. H., van Gelderen, P., Ries, M., Barret, O., Duyn, J. H., Ikonomidou, V. N., Fukunaga, M., Glover, G. H., de Zwart, J. A. 2006; 33 (4): 1072-1081


    The quality of MRI time series data, which allows the study of dynamic processes, is often affected by confounding sources of signal fluctuation, including the cardiac and respiratory cycle. An adaptive filter is described, reducing these signal fluctuations as long as they are repetitive and their timing is known. The filter, applied in image domain, does not require temporal oversampling of the artifact-related fluctuations. Performance is demonstrated for suppression of cardiac and respiratory artifacts in 10-minute brain scans on 6 normal volunteers. Experimental parameters resemble a typical fMRI experiment (17 slices; 1700 ms TR). A second dataset was acquired at a rate well above the Nyquist frequency for both cardiac and respiratory cycle (single slice; 100 ms TR), allowing identification of artifacts specific to the cardiac and respiratory cycles, aiding assessment of filtering performance. Results show significant reduction in temporal standard deviation (SD(t)) in all subjects. For all 6 datasets with 1700 ms TR combined, the filtering method resulted in an average reduction in SD(t) of 9.2% in 2046 voxels substantially affected by respiratory artifacts, and 12.5% for the 864 voxels containing substantial cardiac artifacts. The maximal SD(t) reduction achieved was 52.7% for respiratory and 55.3% for cardiac filtering. Performance was found to be at least equivalent to the previously published RETROICOR method. Furthermore, the interaction between the filter and fMRI activity detection was investigated using Monte Carlo simulations, demonstrating that filtering algorithms introduce a systematic error in the detected BOLD-related signal change if applied sequentially. It is demonstrated that this can be overcome by combining physiological artifact filtering and detection of BOLD-related signal changes simultaneously. Visual fMRI data from 6 volunteers were analyzed with and without the filter proposed here. Inclusion of the cardio-respiratory regressors in the design matrix yielded a 4.6% t-score increase and 4.0% increase in the number of significantly activated voxels.

    View details for DOI 10.1016/j.neuroimage.2006.08.006

    View details for Web of Science ID 000242262900006

    View details for PubMedID 17011214

    View details for PubMedCentralID PMC1716734

  • Reducing interscanner variability of activation in a multicenter fMRI study: Controlling for signal-to-fluctuation-noise-ratio (SFNR) differences NEUROIMAGE Friedman, L., Glover, G. H. 2006; 33 (2): 471-481


    Variation in scanner performance will lead to variation in activation patterns in multicenter fMRI studies. The purpose of this investigation was to evaluate the effect of statistically covarying for scanner differences in signal-to-fluctuation-noise-ratio (SFNR) on reducing scanner differences in activation effect size as part of a multicenter fMRI project (FIRST BIRN). For SFNR, "signal" is typically the mean intensity over time and "fluctuation noise" is the temporal standard deviation. Five subjects were sent to 9 centers (10 scanners) and scanned on two consecutive days using a sensorimotor fMRI protocol. High-field (4 T and 3 T) and low-field (1.5 T) scanners from three vendors (GE, Siemens and Picker) were included. The effect size for the detection of neural activation during a sensorimotor task was evaluated as the percent of temporal variance accounted for by our model (percent of variance accounted for, or PVAF). Marked scanner effects were noted for both PVAF as well as SFNR. After covariate adjustment with one of several measures of SFNR, there were dramatic reductions in scanner-to-scanner variations in activation effect size. Variance components analyses revealed 75%-81% reductions in variance due to scanner with this method. Thus, controlling for scanner variation in SFNR may be an effective method to homogenize activation effect sizes in multicenter studies.

    View details for DOI 10.1016/j.neuroimage.2006.07.012

    View details for Web of Science ID 000241406800005

    View details for PubMedID 16952468

  • Fast metabolic imaging of systems with sparse spectra: Application for hyperpolarized C-13 imaging MAGNETIC RESONANCE IN MEDICINE Mayer, D., Levin, Y. S., Hurd, R. E., Glover, G. H., Spielman, D. M. 2006; 56 (4): 932-937


    A fast spiral chemical shift imaging (spCSI) sequence was developed for application to hyperpolarized (13)C imaging. The sequence exploits sparse spectra, which can occur in such applications, and prior knowledge of resonance frequencies to reduce the measurement time by undersampling the data in the spectral domain. As a consequence, multiple reconstructions of a given data set have to be computed in which only components with frequencies within a certain bandwidth are reconstructed "in focus" while others are severely blurred ("spectral tomosynthesis"). The sequence was tested at 3 T on a phantom containing approximately 1.5-M solutions of alanine (Ala), lactate (Lac), and pyruvate-pyruvate hydrate C1-C2 ester (with two resonances, PPE1 and PPE2) at thermal equilibrium polarization, all enriched to 99% (13)C in the C1 carbonyl positions. Results from spCSI with a single spatial interleaf (single-shot spCSI) and three interleaves (three-shot spCSI) were compared with those obtained by phase-encoded free induction decay CSI (FIDCSI). The metabolic maps of all four resonances for three-shot spCSI, and of PPE1 and PPE2 for single-shot spCSI demonstrate resolution and localization properties similar to those of the FIDCSI images. The metabolic maps of Ala and Lac for single-shot spCSI contain minor artifacts due to signal overlap of aliased resonances.

    View details for DOI 10.1002/mrm.21025

    View details for Web of Science ID 000240897000028

    View details for PubMedID 16941617

  • Reducing inter-scanner variability of activation in a multicenter fMRI study: Role of smoothness equalization NEUROIMAGE Friedman, L., Glover, G. H., Krenz, D., Magnotta, V. 2006; 32 (4): 1656-1668


    Scanner-to-scanner variability of activation in multicenter fMRI studies is often considered undesirable. The purpose of this investigation was to evaluate the effect of a new procedure, "smoothness equalization", on reducing scanner differences in activation effect size as part of a multicenter fMRI project (FIRST BIRN). Five subjects were sent to 9 centers (10 scanners) and scanned on 2 consecutive days using a sensorimotor fMRI protocol. High-field (4 T and 3 T) and low-field (1.5 T) scanners from three vendors (GE, Siemens, and Picker) were included. The activation effect size of the scanners for the detection of neural activation during a sensorimotor task was evaluated as the percent of temporal variance accounted for by our model (percent of variance accounted for or PVAF). Marked scanner effects were noted for both PVAF as well as the degree of smoothness of the raw and processed images. After smoothness equalization, there was a dramatic (low field) or consistent (high-field) reduction in scanner-to-scanner variation of activation. It was shown that the likely basis of the scanner differences in smoothness was differences in k-space filtering algorithms. This work highlights the need to account for differences in smoothness when comparing scanners on activation effect size in multicenter fMRI studies.

    View details for DOI 10.1016/j.neuroimage.2006.03.062

    View details for Web of Science ID 000240969200014

    View details for PubMedID 16875843

  • A generalization of the two-dimensional prolate spheroidal wave function method for nonrectilinear MRI data acquisition methods IEEE TRANSACTIONS ON IMAGE PROCESSING Lindquist, M. A., Zhang, C., Glover, G., Shepp, L., Yang, Q. X. 2006; 15 (9): 2792-2804


    The two-dimensional (2-D) prolate spheroidal wave function (2-D PSWF) method was previously introduced as an efficient method for trading off between spatial and temporal resolution in magnetic resonance imaging (MRI), with minimal penalty due to truncation and partial volume effects. In the 2-D PSWF method, the k-space sampling area and a matching 2-D PSWF filter, with optimal signal concentration and minimal truncation artifacts, are determined by the shape and size of a given convex region of interest (ROI). The spatial information in the reduced k-space data is used to calculate the total image intensity over a nonsquare ROI instead of producing a low-resolution image. This method can be used for tracking dynamic signals from non-square ROIs using a reduced k-space sampling area, while achieving minimal signal leakage. However, the previous theory is limited to the case of rectilinear sampling. In order to make the 2-D PSWF method more suitable for dynamic studies, this paper presents a generalized version of the 2-D PSWF theory that can be applied to nonrectilinear data acquisition methods. The method is applied to an fMRI study using a spiral trajectory, which illustrates the methods efficiency at tracking hemodynamic signals with high temporal resolution.

    View details for DOI 10.1109/TIP.2006.877314

    View details for Web of Science ID 000239774800030

    View details for PubMedID 16948323

  • Cultural and linguistic influence on neural bases of 'theory of mind': An fMRI study with Japanese bilinguals BRAIN AND LANGUAGE Kobayashi, C., Glover, G. H., Temple, E. 2006; 98 (2): 210-220


    Theory of mind (ToM)-our ability to predict behaviors of others in terms of their underlying intentions-has been thought to be universal and invariant across different cultures. However, several ToM studies conducted outside the Anglo-American cultural or linguistic boundaries have obtained mixed results. To examine the influence of culture/language on neural bases of ToM, we studied 16 American English-speaking monolinguals and 16 Japanese-English bilinguals with second-order false-belief story tasks, using functional magnetic resonance imaging (fMRI). Several neural correlates of ToM including medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC) were recruited by both cultural/linguistic groups. However, some other brain areas including inferior frontal gyrus (IFG) were employed in a culture/language-specific manner, during the ToM tasks. These results suggest that the ways in which adults understand ToM are not entirely universal.

    View details for DOI 10.1016/j.bandl.2006.04.013

    View details for Web of Science ID 000240168700008

    View details for PubMedID 16753205

  • Rapid MRI method for mapping the longitudinal relaxation time JOURNAL OF MAGNETIC RESONANCE Hsu, J., Glover, G. H. 2006; 181 (1): 98-106


    A novel method for mapping the longitudinal relaxation time in a clinically acceptable time is developed based on a recent proposal [J.-J. Hsu, I.J. Lowe, Spin-lattice relaxation and a fast T1-map acquisition method in MRI with transient-state magnetization, J. Magn. Reson. 169 (2004) 270-278] and the speed of the spiral pulse sequence. The method acquires multiple curve-fitting samples with one RF pulse train. It does not require RF pulses of specific flip angles (e.g., 90 degrees or 180 degrees ), nor are the long recovery waiting time and the measurement of the magnetization at thermal equilibrium needed. Given the value of the flip angle, the curve fitting is semi-logarithmic and not computationally intensive. On a heterogeneous phantom, the average percentage difference between measurements of the present method and those of an inversion-recovery method is below 2.7%. In mapping the human brain, the present method, for example, can obtain four curve-fitting samples for five 128 x 128 slices in less than 3.2s and the results are in agreement with other studies in the literature.

    View details for DOI 10.1016/j.jmr.2006.03.014

    View details for Web of Science ID 000238548000010

    View details for PubMedID 16621631

  • Earlier development of the accumbens relative to orbitofrontal cortex might underlie risk-taking behavior in adolescents JOURNAL OF NEUROSCIENCE Galvan, A., Hare, T. A., Parra, C. E., Penn, J., Voss, H., Glover, G., Casey, B. J. 2006; 26 (25): 6885-6892


    Adolescence has been characterized by risk-taking behaviors that can lead to fatal outcomes. This study examined the neurobiological development of neural systems implicated in reward-seeking behaviors. Thirty-seven participants (7-29 years of age) were scanned using event-related functional magnetic resonance imaging and a paradigm that parametrically manipulated reward values. The results show exaggerated accumbens activity, relative to prefrontal activity in adolescents, compared with children and adults, which appeared to be driven by different time courses of development for these regions. Accumbens activity in adolescents looked like that of adults in both extent of activity and sensitivity to reward values, although the magnitude of activity was exaggerated. In contrast, the extent of orbital frontal cortex activity in adolescents looked more like that of children than adults, with less focal patterns of activity. These findings suggest that maturing subcortical systems become disproportionately activated relative to later maturing top-down control systems, biasing the adolescent's action toward immediate over long-term gains.

    View details for DOI 10.1523/JNEUROSCI.1062-06.2006

    View details for Web of Science ID 000238473600025

    View details for PubMedID 16793895

  • Report on a multicenter fMRI quality assurance protocol JOURNAL OF MAGNETIC RESONANCE IMAGING Friedman, L., Glover, G. H. 2006; 23 (6): 827-839


    Temporal stability during an fMRI acquisition is very important because the blood oxygen level-dependent (BOLD) effects of interest are only a few percent in magnitude. Also, studies involving the collection of groups of subjects over time require stable scanner performance over days, weeks, months, and even years. We describe a protocol designed by one of the authors that has been tested for several years within the context of a large, multicenter collaborative fMRI research project (FIRST-BIRN). A full description of the phantom, the quality assurance (QA) protocol, and the several calculations used to measure performance is provided. The results obtained with this protocol at multiple sites over time are presented. These data can be used as benchmarks for other centers involved in fMRI research. Some issues with the various protocol measures are highlighted and discussed, and possible protocol improvements are also suggested. Overall, we expect that other fMRI centers will find this approach to QA useful and this report may facilitate developing a similar QA protocol locally. Based on the findings reported herein, the authors are convinced that monitoring QA in this way will improve the quality of fMRI data.

    View details for DOI 10.1002/jmri.20583

    View details for Web of Science ID 000238070400006

    View details for PubMedID 16649196

  • Partial-k-space acquisition method for improved SNR efficiency and temporal resolution in 3D fMRI MAGNETIC RESONANCE IN MEDICINE Hu, Y., Glover, G. H. 2006; 55 (5): 1106-1113


    Previous studies have shown the relative importance of physiological noise and thermal noise in 2D MR images. Since physiological noise is proportional to the signal, it can be the dominant component at the center of k-space. In this study we demonstrate that the signal-to-noise ratio (SNR) efficiency and temporal resolution for 3D functional MRI (fMRI) are increased by the use of a partial-k-space acquisition method. In partial-k-space methods, the high-spatial-frequency components are doubled in amplitude during reconstruction, resulting in twice as much noise from those components. However, in sum these contributions are relatively small compared to those at the low spatial frequencies, where physiological noise is dominant. Therefore, the effect on the final MR images is almost negligible due to the square summation rule. Thus, the partial-k-space 3D method sacrifices much less SNR than is expected from the thermal noise model, and the SNR efficiency is increased compared to a full-k-space acquisition since more time frames can be collected for the same scan time. Accordingly, the temporal resolution can be increased in 3D acquisitions because only partial coverage of k-space is necessary. Experimental results confirm that more activation with a higher average t-score is detected by this method.

    View details for DOI 10.1002/mrm.20877

    View details for Web of Science ID 000237151600017

    View details for PubMedID 16598724

  • Ethics - Incidental findings in brain imaging research SCIENCE Illes, J., Kirschen, M. P., Edwards, E., Stanford, L. R., Bandettini, P., Cho, M. K., Ford, P. J., Glover, G. H., Kulynych, J., Macklin, R., Michael, D. B., Wolf, S. M. 2006; 311 (5762): 783-784

    View details for DOI 10.1126/science.1115429

    View details for PubMedID 16469905

  • Dual-echo spiral in/in acquisition method for reducing magnetic susceptibility artifacts in blood-oxygen-level-dependent functional magnetic resonance imaging 11th Annual Meeting of the International-Society-for-Magnetic-Resonance-in-Medicine Li, T. Q., Takahashi, A., Wang, Y., Mathews, V., Glover, G. H. JOHN WILEY & SONS INC. 2006: 325–34


    MRI signal dropout in gradient recalled echo acquisitions limits the capability of blood-oxygen-level-dependent functional magnetic resonance imaging (fMRI) to study activation tasks that involve the orbitofrontal, temporal, and basal areas of the brain where significant macroscopic magnetic susceptibility differences exist. Among the various approaches aimed to address this issue, the acquisition method based on spiral in/out trajectories is one of the most time-efficient and effective techniques. In this study, we extended further the spiral in/out approach into 3D acquisition and compared the effectiveness of the different spiral in/out trajectory combinations in reducing signal dropout. The activation results from whole brain fMRI studies using complex finger tapping and breath-holding tasks demonstrate that the acquisition method based on dual-echo spiral in/in (DSPIN) trajectories is the most favorable. The DSPIN acquisition method has the following advantages: (1) It reduces most effectively signal dropout in the brain where magnetic susceptibility inhomogeneity is problematic and significantly improves the sensitivity to detect functional activations in those regions. (2) It significantly improves SNR in the whole brain by dual echo averaging without compromising functional contrast. (3) There is no reduction in time-efficiency and spatial resolution.

    View details for DOI 10.1002/mrm.20783

    View details for Web of Science ID 000235326500014

    View details for PubMedID 16408267

  • Relaxation times of breast tissue at 1.5T and 3T measured using IDEAL JOURNAL OF MAGNETIC RESONANCE IMAGING Rakow-Penner, R., Daniel, B., Yu, H. Z., Sawyer-Glover, A., Glover, G. H. 2006; 23 (1): 87-91


    To accurately measure T1 and T2 of breast fibroglandular tissue and fat at 1.5T and 3T, and note the partial volume effects of the admixture of fibroglandular tissue and fat on the relaxation rates using an approach termed iterative decomposition of water and fat with echo asymmetry and least squares estimation (IDEAL) imaging.T1 and T2 values were measured on the right breasts of five healthy women at 1.5T and 3T. T1 data were collected using two sequences: inversion recovery without IDEAL, and inversion recovery with IDEAL. T2 data were collected using Hahn Echo scans. SNR and CNR analyses were conducted on collected data.T1 increased for both fat (21%) and glandular tissue (17%) from 1.5T to 3T. Thus, the TR and TI of breast protocols at 3T should be lengthened accordingly. SNR more than doubled for both tissue types from 1.5T to 3T. IDEAL imaging demonstrated the partial volume effects of fat and glandular tissue on measuring relaxation rates of independent tissue types.With separated fat and water images, more precise measurements can be made for the lipid component in fat, and the water component in fibroglandular tissue.

    View details for DOI 10.1002/jmri.20469

    View details for Web of Science ID 000234488500013

    View details for PubMedID 16315211

  • Neural correlates of individual differences in pain-related fear and anxiety PAIN Ochsner, K. N., Ludlow, D. H., Knierim, K., Hanelin, J., Ramachandran, T., Glover, G. C., Mackey, S. C. 2006; 120 (1-2): 69-77


    Although individual differences in fear and anxiety modulate the pain response and may even cause more suffering than the initiating physical stimulus, little is known about the neural systems mediating this relationship. The present study provided the first examination of the neural correlates of individual differences in the tendency to (1) feel anxious about the potentially negative implications of physical sensations, as measured by the anxiety sensitivity index (ASI), and (2) fear various types of physical pain, as indexed by the fear of pain questionnaire (FPQ). In separate sessions, participants completed these questionnaires and experienced alternating blocks of noxious thermal stimulation (45-50 degrees C) and neutral thermal stimulation (38 degrees C) during the collection of whole-brain fMRI data. Regression analyses demonstrated that during the experience of pain, ASI scores predicted activation of a medial prefrontal region associated with self-focused attention, whereas FPQ scores predicted activation of a ventral lateral frontal region associated with response regulation and anterior and posterior cingulate regions associated with monitoring and evaluation of affective responses. These functional relationships cannot be wholly explained by generalized anxiety (indexed by STAI-T scores), which did not significantly correlate with activation of any regions. The present findings may help clarify both the impact of individual differences in emotion on the neural correlates of pain, and the roles in anxiety, fear, and pain processing played by medial and orbitofrontal systems.

    View details for DOI 10.1016/j.pain.2005.10.014

    View details for Web of Science ID 000235111100009

    View details for PubMedID 16364548

    View details for PubMedCentralID PMC2914607

  • Control over brain activation and pain learned by using real-time functional MRI PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA deCharms, R. C., Maeda, F., Glover, G. H., Ludlow, D., Pauly, J. M., Soneji, D., Gabrieli, J. D., Mackey, S. C. 2005; 102 (51): 18626-18631


    If an individual can learn to directly control activation of localized regions within the brain, this approach might provide control over the neurophysiological mechanisms that mediate behavior and cognition and could potentially provide a different route for treating disease. Control over the endogenous pain modulatory system is a particularly important target because it could enable a unique mechanism for clinical control over pain. Here, we found that by using real-time functional MRI (rtfMRI) to guide training, subjects were able to learn to control activation in the rostral anterior cingulate cortex (rACC), a region putatively involved in pain perception and regulation. When subjects deliberately induced increases or decreases in rACC fMRI activation, there was a corresponding change in the perception of pain caused by an applied noxious thermal stimulus. Control experiments demonstrated that this effect was not observed after similar training conducted without rtfMRI information, or using rtfMRI information derived from a different brain region, or sham rtfMRI information derived previously from a different subject. Chronic pain patients were also trained to control activation in rACC and reported decreases in the ongoing level of chronic pain after training. These findings show that individuals can gain voluntary control over activation in a specific brain region given appropriate training, that voluntary control over activation in rACC leads to control over pain perception, and that these effects were powerful enough to impact severe, chronic clinical pain.

    View details for DOI 10.1073/pnas.0505210102

    View details for Web of Science ID 000234174300068

    View details for PubMedID 16352728

    View details for PubMedCentralID PMC1311906

  • The role of ventral frontostriatal circuitry in reward-based learning in humans JOURNAL OF NEUROSCIENCE Galvan, A., Hare, T. A., Davidson, M., Spicer, J., Glover, G., Casey, B. J. 2005; 25 (38): 8650-8656


    This study examined changes in behavior and neural activity with reward learning. Using an event-related functional magnetic resonance imaging paradigm, we show that the nucleus accumbens, thalamus, and orbital frontal cortex are each sensitive to reward magnitude, with the accumbens showing the greatest discrimination between reward values. Mean reaction times were significantly faster to cues predicting the greatest reward and slower to cues predicting the smallest reward. This behavioral change over the course of the experiment was paralleled by a shift in peak in accumbens activity from anticipation of the reward (immediately after the response), to the cue predicting the reward. The orbitofrontal and thalamic regions peaked in anticipation of the reward throughout the experiment. Our findings suggest discrete functions of regions within basal ganglia thalamocortical circuitry in adjusting behavior to maximize reward.

    View details for DOI 10.1523/JNEUROSCI.2431-05-2005

    View details for Web of Science ID 000232028500007

    View details for PubMedID 16177032

  • Contributions of the hippocampus and the striatum to simple association and frequency-based learning NEUROIMAGE Amso, D., Davidson, M. C., Johnson, S. P., Glover, G., Casey, B. J. 2005; 27 (2): 291-298


    Using fMRI and a learning paradigm, this study examined the independent contributions of the hippocampus and striatum to simple association and frequency-based learning. We scanned 10 right-handed young adult subjects using a spiral in/out sequence on a GE 3.0 T scanner during performance of the learning paradigm. The paradigm consisted of 2 cues that predicted each of 3 targets with varying probabilities. Simultaneously, we varied the frequency with which each target was presented throughout the task, independent of cue associations. Subjects had shorter response latencies to frequently occurring and highly associated target stimuli and longer response latencies to infrequent target stimuli, indicating learning. Imaging results showed increased caudate activity to infrequent relative to frequent targets and increased hippocampal activity to infrequent relative to frequent cue-target associations. This work provides evidence of different neural mechanisms underlying learning based on simple frequencies versus associations within a single paradigm.

    View details for DOI 10.1016/j.neuroimage.2005.02.035

    View details for Web of Science ID 000231154900004

    View details for PubMedID 16061152

    View details for PubMedCentralID PMC2517901

  • The neural bases of amusement and sadness: A comparison of block contrast and subject-specific emotion intensity regression approaches NEUROIMAGE Goldin, P. R., Hutcherson, C. A., Ochsner, K. N., Glover, G. H., Gabrieli, J. D., Gross, J. J. 2005; 27 (1): 26-36


    Neuroimaging studies have made substantial progress in elucidating the neural bases of emotion. However, few studies to date have directly addressed the subject-specific, time-varying nature of emotional responding. In the present study, we employed functional magnetic resonance imaging to examine the neural bases of two common emotions--amusement and sadness--using both (a) a stimulus-based block contrast approach and (b) a subject-specific regression analysis using continuous ratings of emotional intensity. Thirteen women viewed a set of nine 2-min amusing, sad, or neutral film clips two times. During the first viewing, participants watched the film stimuli. During the second viewing, they made continuous ratings of the intensity of their own amusement and sadness during the first film viewing. For sad films, both block contrast and subject-specific regression approaches resulted in activations in medial prefrontal cortex, inferior frontal gyrus, superior temporal gyrus, precuneus, lingual gyrus, amygdala, and thalamus. For amusing films, the subject-specific regression analysis demonstrated significant activations not detected by the block contrast in medial, inferior frontal gyrus, dorsolateral prefrontal cortex, posterior cingulate, temporal lobes, hippocampus, thalamus, and caudate. These results suggest a relationship between emotion-specific temporal dynamics and the sensitivity of different data analytic methods for identifying emotion-related neural responses. These findings shed light on the neural bases of amusement and sadness, and highlight the value of using emotional film stimuli and subject-specific continuous emotion ratings to characterize the dynamic, time-varying components of emotional responses.

    View details for DOI 10.1016/j.neuroimage.2005.03.018

    View details for Web of Science ID 000230701200003

    View details for PubMedID 15890534

  • Effects of spatial and temporal resolution for MR image-guided thermal ablation of prostate with transurethral ultrasound JOURNAL OF MAGNETIC RESONANCE IMAGING Pisani, L. J., Ross, A. B., Diederich, C. J., Nau, W. H., Sommer, F. G., Glover, G. H., Butts, K. 2005; 22 (1): 109-118


    To describe approaches for determining optimal spatial and temporal resolutions for the proton resonance frequency shift method of quantitative magnetic resonance temperature imaging (MRTI) guidance of transurethral ultrasonic prostate ablation.Temperature distributions of two transurethral ultrasound applicators (90 degrees sectored tubular and planar arrays) for canine prostate ablation were measured via MRTI during in vivo sonication, and agree well with two-dimensional finite difference model simulations at various spatial resolutions. Measured temperature distributions establish the relevant signal-to-noise ratio (SNR) range for thermometry in an interventional MR scanner, and are reconstructed at different resolutions to compare resultant temperature measurements. Various temporal resolutions are calculated by averaging MRTI frames.When noise is added to simulated temperature distributions for tubular and planar applicators, the minimum root mean squared (RMS) error is achieved by reconstructing to pixel sizes of 1.9 and 1.7 mm, respectively. In in vivo measurements, low spatial resolution MRTI data are shown to reduce the noise without significantly affecting thermal dose calculations. Temporal resolution of 0.66 frames/minute leads to measurement errors of more than 12 degrees C during rapid heating.Optimizing MRTI pixel size entails balancing large pixel SNR gain with accuracy in representing underlying temperature distributions.

    View details for DOI 10.1002/jmri.20339

    View details for PubMedID 15971190

  • Distributed neural representation of expected value JOURNAL OF NEUROSCIENCE Knutson, B., Taylor, J., Kaufman, M., Peterson, R., Glover, G. 2005; 25 (19): 4806-4812


    Anticipated reward magnitude and probability comprise dual components of expected value (EV), a cornerstone of economic and psychological theory. However, the neural mechanisms that compute EV have not been characterized. Using event-related functional magnetic resonance imaging, we examined neural activation as subjects anticipated monetary gains and losses that varied in magnitude and probability. Group analyses indicated that, although the subcortical nucleus accumbens (NAcc) activated proportional to anticipated gain magnitude, the cortical mesial prefrontal cortex (MPFC) additionally activated according to anticipated gain probability. Individual difference analyses indicated that, although NAcc activation correlated with self-reported positive arousal, MPFC activation correlated with probability estimates. These findings suggest that mesolimbic brain regions support the computation of EV in an ascending and distributed manner: whereas subcortical regions represent an affective component, cortical regions also represent a probabilistic component, and, furthermore, may integrate the two.

    View details for DOI 10.1523/JNEUROSCI.0642-05.2005

    View details for Web of Science ID 000229038300014

    View details for PubMedID 15888656

  • Breath holding reveals differences in fMRI BOLD signal in children and adults NEUROIMAGE Thomason, M. E., Burrows, B. E., Gabrieli, J. D., Glover, G. H. 2005; 25 (3): 824-837


    Application of fMRI to studies of cognitive development is of growing interest because of its sensitivity and non-invasive nature. However, interpretation of fMRI results in children is presently based on vascular dynamics that have been studied primarily in healthy adults. Comparison of the neurological basis of cognitive development is valid to the extent that the neurovascular responsiveness between children and adults is equal. The present study was designed to detect age-related vascular differences that may contribute to altered BOLD fMRI signal responsiveness. We examined BOLD signal changes in response to breath holding, a global, systemic state change in brain oxygenation. Children exhibited greater percent signal changes than adults in grey and white matter, and this was accompanied by an increase in noise. Consequently, the volume of activation exceeding statistical threshold was reduced in children. The reduced activation in children was well modeled by adding noise to adult data. These findings raise the possibility that developmental differences in fMRI findings between children and adults could, under some circumstances, reflect greater noise in the BOLD response in the brains of children than adults. BOLD responses varied across brain regions, but showed similar regional variation in children and adults.

    View details for DOI 10.1016/j.neuroimage.2004.12.026

    View details for Web of Science ID 000228383500018

    View details for PubMedID 15808983

  • Foundations of advanced magnetic resonance imaging. NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics Bammer, R., Skare, S., Newbould, R., Liu, C., Thijs, V., Ropele, S., Clayton, D. B., Krueger, G., Moseley, M. E., Glover, G. H. 2005; 2 (2): 167-196


    During the past decade, major breakthroughs in magnetic resonance imaging (MRI) quality were made by means of quantum leaps in scanner hardware and pulse sequences. Some advanced MRI techniques have truly revolutionized the detection of disease states and MRI can now-within a few minutes-acquire important quantitative information noninvasively from an individual in any plane or volume at comparatively high resolution. This article provides an overview of the most common advanced MRI methods including diffusion MRI, perfusion MRI, functional MRI, and the strengths and weaknesses of MRI at high magnetic field strengths.

    View details for PubMedID 15897944

  • Contributions of amygdala and striatal activity in emotion regulation BIOLOGICAL PSYCHIATRY Hare, T. A., Tottenham, N., Davidson, M. C., Glover, G. H., Casey, B. J. 2005; 57 (6): 624-632


    Emotional information can facilitate or interfere with cognitive processes. In this study, we examined the influence of emotional information in biasing performance and the biological basis underlying this influence.Ten human subjects (five female) were scanned with functional magnetic resonance imaging while performing an emotional go/nogo task.Subjects were slower to approach fearful target expressions and had more difficulty avoiding happy nontarget expressions. The amygdala was recruited most for negative emotional context, and activity in this region was positively correlated with response time when detecting negative expressions. Increased signal in the right caudate nucleus was observed when avoiding nontargets and was negatively correlated with the number of false alarms subjects made.Emotional context can alter behavioral and biological responses when approaching or avoiding a stimulus. We showed that recruitment of the amygdala, a region implicated in evaluating emotional significance, was associated with longer response latencies when approaching negative information, whereas recruitment of the caudate nucleus, a structure previously implicated in reward and impulse control, was most active when avoiding positive information. Our findings have significant implications for exaggerated and inhibited emotional responses that are characteristic of a number of psychiatric disorders.

    View details for DOI 10.1016/j.biopsych.2004.12.038

    View details for Web of Science ID 000227626200007

    View details for PubMedID 15780849

  • Mitigation of susceptibility-induced signal loss in neuroimaging using localized shim coils MAGNETIC RESONANCE IN MEDICINE Hsu, J. J., Glover, G. H. 2005; 53 (2): 243-248


    Correction of magnetic field distortions is essential for obtaining accurate brain blood-oxygen-level-dependent functional magnetic resonance imaging (fMRI) activation maps. The present work introduces an active shimming method that utilizes the magnetic field generated by resistive shim coils placed in the mouth to locally homogenize the magnetic field in the inferior portion of the frontal lobe, where the field is most seriously distorted. The shimming field can be optimized in situ patient by patient for the region of interest of the scanner operator's choice. The method at 1.5 T is shown to be effective in reducing field inhomogeneity and in recovery of fMRI signal. For example, in a region of interest approximately of 149 cm3, a coil of simple geometry can reduce the root mean square of the magnetic field by more than 50% and the recovered signal increases the extent of activation detected in a breath-holding fMRI experiment.

    View details for DOI 10.1002/mrm.20365

    View details for Web of Science ID 000226651100001

    View details for PubMedID 15678531

  • Hippocampal involvement in detection of deviant auditory and visual stimuli HIPPOCAMPUS Crottaz-Herbette, S., Lau, K. M., Glover, G. H., Menon, V. 2005; 15 (1): 132-139


    Recent models of hippocampal function have emphasized its role in processing sequences of events. In this study, we used an oddball task to investigate hippocampal responses to the detection of deviant "target" stimuli that were embedded in a sequence of repetitive "standard" stimuli. Evidence from intracranial event-related potential studies has suggested a critical role for the hippocampus in oddball tasks. However, functional neuroimaging experiments have failed to detect activation in the hippocampus in response to deviant stimuli. Our study aimed to resolve this discrepancy by using a novel functional magnetic resonance imaging (fMRI) technique that drastically improves signal detection in the hippocampus. Significant hippocampal activation was observed during both auditory and visual oddball tasks. Although there was no difference in the overall level of hippocampal activation in the two modalities, significant modality differences in the profile of activation along the long axis of the hippocampus were observed. In both left and right hippocampi, an anterior-to-posterior gradient in the activation (anterior to posterior) was observed during the auditory oddball task, whereas a posterior-to-anterior gradient (posterior to anterior) was observed during the visual oddball task. These results indicate that the hippocampus is involved in the detection of deviant stimuli regardless of stimulus modality, and that there are prominent modality differences along the long axis of the hippocampus. The implications of our findings for understanding hippocampal involvement in processing sequences of events are discussed.

    View details for DOI 10.1002/hipo.20039

    View details for Web of Science ID 000226952900014

    View details for PubMedID 15390157

  • Neural correlates of rapid spectrotemporal processing in musicians and nonmusicians Conference of the Neurosciences and Music II Gaab, N., Tallal, P., Kim, H., Lakshminarayanan, K., Archie, J. J., Glover, G. H., Gabrieli, J. D. NEW YORK ACAD SCIENCES. 2005: 82–88


    Our results suggest that musical training alters the functional anatomy of rapid spectrotemporal processing, resulting in improved behavioral performance along with a more efficient functional network primarily involving traditional language regions. This finding may have important implications for improving language/reading skills, especially in children struggling with dyslexia.

    View details for Web of Science ID 000236996500010

    View details for PubMedID 16597753

  • The contribution of novel brain imaging techniques to understanding the neurobiology of mental retardation and developmental disabilities MENTAL RETARDATION AND DEVELOPMENTAL DISABILITIES RESEARCH REVIEWS Gothelf, D., Furfaro, J. A., Penniman, L. C., Glover, G. H., Reiss, A. L. 2005; 11 (4): 331-339


    Studying the biological mechanisms underlying mental retardation and developmental disabilities (MR/DD) is a very complex task. This is due to the wide heterogeneity of etiologies and pathways that lead to MR/DD. Breakthroughs in genetics and molecular biology and the development of sophisticated brain imaging techniques during the last decades have facilitated the emergence of a field called Behavioral Neurogenetics. Behavioral Neurogenetics focuses on studying genetic diseases with known etiologies that are manifested by unique cognitive and behavioral phenotypes. In this review, we describe the principles of magnetic resonance imaging (MRI) techniques, including structural MRI, functional MRI, and diffusion tensor imaging (DTI), and how they are implemented in the study of Williams (WS), velocardiofacial (VCFS), and fragile X (FXS) syndromes. From WS we learn that dorsal stream abnormalities can be associated with visuospatial deficits; VCFS is a model for exploring the molecular and brain pathways that lead to psychiatric disorders for which subjects with MR/DD are at increased risk; and finally, findings from multimodal imaging techniques show that aberrant frontal-striatal connections are implicated in the executive function and attentional deficits of subjects with FXS. By deciphering the molecular pathways and brain structure and function associated with cognitive deficits, we will gain a better understanding of the pathophysiology of MR/DD, which will eventually make possible more specific treatments for this population.

    View details for DOI 10.1002/mrdd.20089

    View details for Web of Science ID 000232943600008

    View details for PubMedID 16240408

  • ICA-based procedures for removing ballistocardiogram artifacts from EEG data acquired in the MRI scanner NEUROIMAGE Srivastava, G., Crottaz-Herbette, S., Lau, K. M., Glover, G. H., Menon, V. 2005; 24 (1): 50-60


    Electroencephalogram (EEG) data acquired in the MRI scanner contains significant artifacts, one of the most prominent of which is ballistocardiogram (BCG) artifact. BCG artifacts are generated by movement of EEG electrodes inside the magnetic field due to pulsatile changes in blood flow tied to the cardiac cycle. Independent Component Analysis (ICA) is a statistical algorithm that is useful for removing artifacts that are linearly and independently mixed with signals of interest. Here, we demonstrate and validate the usefulness of ICA in removing BCG artifacts from EEG data acquired in the MRI scanner. In accordance with our hypothesis that BCG artifacts are physiologically independent from EEG, it was found that ICA consistently resulted in five to six independent components representing the BCG artifact. Following removal of these components, a significant reduction in spectral power at frequencies associated with the BCG artifact was observed. We also show that our ICA-based procedures perform significantly better than noise-cancellation methods that rely on estimation and subtraction of averaged artifact waveforms from the recorded EEG. Additionally, the proposed ICA-based method has the advantage that it is useful in situations where ECG reference signals are corrupted or not available.

    View details for DOI 10.1016/j.neuroimage.2004.09.041

    View details for Web of Science ID 000225811800006

    View details for PubMedID 15588596

  • Reflecting upon feelings: an fMRI study of neural systems supporting the attribution of emotion to self and other JOURNAL OF COGNITIVE NEUROSCIENCE Ochsner, K. N., Knierim, K., Ludlow, D. H., Hanelin, J., Ramachandran, T., Glover, G., Mackey, S. C. 2004; 16 (10): 1746-1772


    Understanding one's own and other individual's emotional states is essential for maintaining emotional equilibrium and strong social bonds. Although the neural substrates supporting ref lection upon one's own feelings have been investigated, no studies have directly examined attributions about the internal emotional states of others to determine whether common or distinct neural systems support these abilities. The present study sought to directly compare brain regions involved in judging one's own, as compared to another individual's, emotional state. Thirteen participants viewed mixed valence blocks of photos drawn from the International Affective Picture System while whole-brain fMRI data were collected. Preblock cues instructed participants to evaluate either their emotional response to each photo, the emotional state of the central figure in each photo, or (in a baseline condition) whether the photo was taken indoors or outdoors. Contrasts indicated (1) that both self and other judgments activated the medial prefrontal cortex (MPFC), the superior temporal gyrus, and the posterior cingulate/precuneus, (2) that self judgments selectively activated subregions of the MPFC and the left temporal cortex, whereas (3) other judgments selectively activated the left lateral prefrontal cortex (including Broca's area) and the medial occipital cortex. These results suggest (1) that self and other evaluation of emotion rely on a network of common mechanisms centered on the MPFC, which has been hypothesized to support mental state attributions in general, and (2) that medial and lateral PFC regions selectively recruited by self or other judgments may be involved in attention to, and elaboration of, internally as opposed to externally generated information.

    View details for Web of Science ID 000226002800007

    View details for PubMedID 15701226

  • Discovery and disclosure of incidental findings in neuroimaging research 33rd Annual Meeting of the Society-for-Neuroscience Illes, J., Kirschen, M. P., Karetsky, K., Kelly, M., Saha, A., Desmond, J. E., Raffin, T. A., Glover, G. H., Atlas, S. W. JOHN WILEY & SONS INC. 2004: 743–47


    To examine different protocols for handling incidental findings on brain research MRIs, and provide a platform for establishing formal discussions of related ethical and policy issues.Corresponding authors identified from a database of peer-reviewed publications in 1991-2002 involving functional MRI (fMRI), alone or in combination with other imaging modalities, were invited to participate in this web-based survey. The survey asked questions regarding knowledge and handling of incidental findings, as well as characteristics of the scanning environment, training required, IRB protocol requirements, and neuroradiologist involvement.Seventy-four investigators who conduct MRI studies in the United States and abroad responded. Eighty-two percent (54/66) reported discovering incidental findings in their studies, such as arteriovenous malformations, brain tumors, and developmental abnormalities. Substantial variability was found in the procedures for handling and communicating findings to subjects, neuroradiologist involvement, personnel permitted to operate equipment, and training.Guidelines for minimum and optimum standards for detecting and communicating incidental findings on brain MRI research are needed.

    View details for DOI 10.1002/jmri.20180

    View details for Web of Science ID 000224762700001

    View details for PubMedID 15503329

    View details for PubMedCentralID PMC1506385

  • Altered cortical visual processing in PD with hallucinations - An fMRI study NEUROLOGY Stebbins, G. T., Goetz, C. G., Carrillo, M. C., Bangen, K. J., TURNER, D. A., Glover, G. H., Gabrieli, J. D. 2004; 63 (8): 1409-1416


    To compare fMRI activation during two visual stimulation paradigms in Parkinson disease (PD) subjects with chronic visual hallucinations vs PD patients who had never hallucinated.Twelve pairs of PD subjects, matched for age, PD duration, and dopaminergic drug exposure duration, participated in this study. The authors examined group differences in activation during stroboscopic (flashing) vs no visual stimulation and kinematic (apparent motion) vs stationary visual stimulation.During stroboscopic stimulation, non-hallucinating PD subjects showed significantly greater activation in the parietal lobe and cingulate gyrus compared to hallucinating PD subjects. In contrast, the hallucinating subjects showed significantly greater activation in the inferior frontal gyrus and the caudate nucleus. During kinematic stimulation, non-hallucinating PD subjects showed significantly greater activation in area V5/MT, parietal lobe, and cingulate gyrus compared to hallucinating PD subjects. Hallucinating PD subjects showed significantly greater activation in the superior frontal gyrus.PD patients with chronic visual hallucinations respond to visual stimuli with greater frontal and subcortical activation and less visual cortical activation than non-hallucinating PD subjects. Shifting visual circuitry from posterior to anterior regions associated primarily with attention processes suggests altered network organization may play a role in the pathophysiology of visual hallucinations in PD.

    View details for Web of Science ID 000224732400014

    View details for PubMedID 15505157

  • Improved combination of spiral-in/out images for BOLD fMRI MAGNETIC RESONANCE IN MEDICINE Glover, G. H., Thomason, M. E. 2004; 51 (4): 863-868


    Acquisitions with the spiral-in/out technique result in two separate image timeseries obtained during the spiral-in and spiral-out trajectory. In uniform brain regions the two components have comparable signal and BOLD contrast and can be averaged, but in regions compromised by susceptibility effects where both signal and noise can differ in the two images other combination methods may be more effective. Here, several weighting schemes are compared for signal and activation contrast recovery in whole brain and prefrontal cortex using verbal working memory (seven subjects) and breathholding tasks (six subjects) scanned at 3 T. It was found that a statistically weighted combination based on activation maps derived separately from the spiral-in and spiral-out images provides activation volumes with increases of 33-59% over second-choice signal-weighted combination and 100-200% increases over spiral-out acquisition alone, and that simple averaging is inferior to signal-weighted combination.

    View details for DOI 10.1002/mrm.20016

    View details for Web of Science ID 000220557200029

    View details for PubMedID 15065263

  • Acquiring and inhibiting prepotent responses in schizophrenia - Event-related brain potentials and functional magnetic resonance imaging ARCHIVES OF GENERAL PSYCHIATRY Ford, J. M., Gray, M., Whitfield, S. L., Turken, A. U., Glover, G., Faustman, W. O., Mathalon, D. H. 2004; 61 (2): 119-129


    Schizophrenia is associated with deficits in using context to establish prepotent responses in complex paradigms and failures to inhibit prepotent responses once established.To assess prepotent response establishment and inhibition in patients with schizophrenia using event-related brain potential (ERP) and functional magnetic resonance imaging (fMRI) in a simple NoGo task. To combine fMRI and ERP data to focus on fMRI activations associated with the brief (approximately 200 ms) moment of context updating reflected in the NoGo P300 ERP component.We collected ERP and fMRI data while subjects performed a NoGo task requiring a speedy button press to X stimuli (P=.88) but not to K stimuli (P=.12). The ERPs were collected at the Veterans Affairs Palo Alto Health Care System, Palo Alto, Calif; fMRIs were collected at Stanford University, Stanford, Calif.We recruited patients with DSM-IV schizophrenia (n=11) from the community and the VA hospital and sex- and age-matched healthy control subjects (n=11) from the community.Behavioral accuracy, P300 amplitudes and latencies, and fMRI activations suggested that patients with schizophrenia did not establish as strong a prepotent tendency to respond to the Go stimulus as healthy subjects. In healthy subjects, NoGo P300 was related to activations in the anterior cingulate cortex, dorsal lateral prefrontal cortex, and right inferior parietal lobule and caudate nucleus, perhaps reflecting conflict experienced when withholding a response, control needed to inhibit a response, and stopping a response in action, respectively. In patients with schizophrenia, NoGo P300 was modestly related to activations in the anterior cingulate cortex, which is consistent with experiencing conflict.The difference in ERP and fMRI responses to Go and NoGo stimuli suggested that inhibiting a response was easier for patients with schizophrenia than for healthy subjects. Correlations of P300 and fMRI data suggested that patients with schizophrenia and healthy subjects used different neural structures to inhibit responses, with healthy subjects using a more complex system.

    View details for Web of Science ID 000188652800002

    View details for PubMedID 14757588

  • Neural systems underlying the suppression of unwanted memories SCIENCE Anderson, M. C., Ochsner, K. N., Kuhl, B., Cooper, J., Robertson, E., Gabrieli, S. W., Glover, G. H., Gabrieli, J. D. 2004; 303 (5655): 232-235


    Over a century ago, Freud proposed that unwanted memories can be excluded from awareness, a process called repression. It is unknown, however, how repression occurs in the brain. We used functional magnetic resonance imaging to identify the neural systems involved in keeping unwanted memories out of awareness. Controlling unwanted memories was associated with increased dorsolateral prefrontal activation, reduced hippocampal activation, and impaired retention of those memories. Both prefrontal cortical and right hippocampal activations predicted the magnitude of forgetting. These results confirm the existence of an active forgetting process and establish a neurobiological model for guiding inquiry into motivated forgetting.

    View details for Web of Science ID 000187908500049

    View details for PubMedID 14716015

  • Learned regulation of spatially localized brain activation using real-time fMRI NEUROIMAGE DeCharms, R. C., Christoff, K., Glover, G. H., Pauly, J. M., Whitfield, S., Gabrieli, J. D. 2004; 21 (1): 436-443


    It is not currently known whether subjects can learn to voluntarily control activation in localized regions of their own brain using neuroimaging. Here, we show that subjects were able to learn enhanced voluntary control over task-specific activation in a chosen target region, the somatomotor cortex. During an imagined manual action task, subjects were provided with continuous direction regarding their cognitive processes. Subjects received feedback information about their current level of activation in a target region of interest (ROI) derived using real-time functional magnetic resonance imaging (rtfMRI), and they received automatically-adjusted instructions for the level of activation to achieve. Information was provided both as continously upated graphs and using a simple virtual reality interface that provided an image analog of the level of activation. Through training, subjects achieved an enhancement in their control over brain activation that was anatomically specific to the target ROI, the somatomotor cortex. The enhancement took place when rtfMRI-based training was provided, but not in a control group that received similar training without rtfMRI information, showing that the effect was not due to conventional, practice-based neural plasticity alone. Following training, using cognitive processes alone subjects could volitionally induce fMRI activation in the somatomotor cortex that was comparable in magnitude to the activation observed during actual movement. The trained subjects increased fMRI activation without muscle tensing, and were able to continue to control brain activation even when real-time fMRI information was no longer provided. These results show that rtfMRI information can be used to direct cognitive processes, and that subjects are able to learn volitionally regulate activation in an anatomically-targeted brain region, surpassing the task-driven activation present before training.

    View details for DOI 10.1016/j.neuroimage.2003.08.041

    View details for Web of Science ID 000188597500044

    View details for PubMedID 14741680

  • Comparison of spiral-in/out and spiral-out BOLD fMRI at 1.5 and 3T NEUROIMAGE Preston, A. R., Thomason, M. E., Ochsner, K. N., Cooper, J. C., Glover, G. H. 2004; 21 (1): 291-301


    Spiral-in/out functional magnetic resonance imaging (fMRI) methods acquire one image before the echo time (TE) and a second image after TE during each scan. Weighted combination of the two images provides a time series with reduced susceptibility dropout in frontal and medial temporal regions as well as increased signal-to-noise ratio (SNR) in regions of uniform cortex. In this study, task activation with the spiral-in/out method was compared to that with conventional spiral-out acquisitions at two field strengths (1.5 and 3.0 T) using episodic memory encoding, verbal working memory, and affective processing tasks in eight human volunteers. With the conventional spiral-out sequence, greater signal dropout is observed in lateral and medial prefrontal, amygdalar, and medial temporal regions at 3 T relative to 1.5 T, whereas such dropout at 3 T is reduced or mitigated with the spiral-in/out method. Similarly, activation volumes for frontal, amygdalar, and medial temporal regions are reduced for spiral-out acquisitions relative to spiral-in/out, and this difference is more apparent at 3 T than at 1.5 T. In addition, significant regionally specific increases in Z scores are obtained with the spiral-in/out sequence relative to spiral-out acquisitions at both field strengths. It is concluded the spiral-in/out sequence may provide significant advantages over conventional spiral methods, especially at 3 T.

    View details for DOI 10.1016/j.neuroimage.2003.09.017

    View details for Web of Science ID 000188597500031

    View details for PubMedID 14741667

  • Female sexual arousal: a behavioral analysis FERTILITY AND STERILITY Polan, M. L., Desmond, J. E., Banner, L. L., Pryor, M. R., McCallum, S. W., Atlas, S. W., Glover, G. H., Arnow, B. A. 2003; 80 (6): 1480-1487


    This study was designed to assess female sexual arousal by using a combination of physiologic measures and self-reported level of arousal.Twenty subjects viewed a 23-minute sequence of randomly ordered relaxation and erotic tapes, both with and without auditory stimulus. The physiologic parameters of vaginal blood flow, galvanic skin resistance, respiration, pulse, and blood pressure, as well as self-reported level of arousal, were simultaneously recorded and correlated with video segments.An academic teaching hospital.The 20 subjects (mean age +/- SD: 24.9 +/- 3.0 years) included Caucasian (10), Hispanic (2), Asian-American (4), and African-American (4) women. All women were screened for normal sexual function with the Female Sexual Function Index (FSFI) and with the Beck Anxiety Inventory and Beck Depression Inventory.Randomly ordered sequences of erotic and relaxation tapes with and without sound.Physiologic and behavioral data, as well as subjective arousal rating, were acquired. The resulting set of multichannel data was correlated with erotic segments and analyzed for sound vs. no sound and time to maximal physiologic arousal.Four independent variables were found to have beta values that were significantly different from 0: respiration (mean = -0.239, SD = 0.177, range = -0.55-0.09, t = -6.04), VPP (mean = 0.158, SD = 0.37, range = -0.48-0.80, t = 1.91), rVPP (mean = 0.161, SD = 0.35, range = -0.537-0.686, t = 2.075), and erotic marker (mean = 0.582, SD = 0.191, range = 0.16-0.85, t = 13.6). Neither heart rate nor galvanic skin resistance beta values approached significance. Respiration period was correlated negatively with arousal rating, indicating that subjects breathed faster when aroused. Auditory stimuli during erotic segments did not increase subjective arousal, and for both subjective arousal rating as well as VPP measurement, maximal response occurred within 2 minutes.Simultaneous measurement of vaginal blood flow, respiration, pulse, and a variable accounting for the onset and offset of erotic video segments accounts for approximately 50% of the variance in predicting subjective female arousal. Regardless of the presence or absence of audio input, 2 minutes was the average minimum time required to reach maximal arousal in young, sexually functional women.

    View details for DOI 10.1016/S0015-0282(03)02210-6

    View details for Web of Science ID 000187284200029

    View details for PubMedID 14667887

  • The effect of task block arrangement on the detectability of activation in fMRI MAGNETIC RESONANCE IMAGING Nakai, T., Matsumura, A., Nose, T., Kato, C., Glover, G. H., Matsuo, K. 2003; 21 (9): 941-947


    The effect of task block arrangements on the detection of brain activation was investigated. Sessions of functional magnetic resonance imaging (fMRI) including the same number of two different task conditions but with different arrangements were compared. The two task conditions were, A) Ellipse-shaped black and white checkerboard flicker stimulation at 4.2 Hz covering the bilateral visual field, and B) the same flicker stimuli covering only the left visual field. In the rest blocks (0), the subjects looked at a fixation point. Four different task block arrangements were compared, 1) A0 (0A0A0A0) and B0 (0B0B0B0), 2) A0B0 (0A0B0A0B0A0B0), 3) AB0 (0AB0AB0AB0) and 4) AB (0ABABAB). Bilateral V1, V2, V3 and the left V5 were activated by condition A, and the right V1 and V2 by B. The activation in the left visual field by A0 was larger than in the other three conditions. In a differential analysis between conditions A and B, activation in the left V3 and V5 was declined by AB0 or AB. When rest blocks were located in the post-stimulus undershoot phase, the % signal change of the BOLD signal was emphasized, which caused augmented significance in the detection of the activity. It was indicated that the outcome of the activation map was influenced by the arrangement of task blocks, even though the same number of task blocks were repeated within the sessions. In fMRI studies, task conditions should be carefully compared within or across sessions considering the characteristics of hemodynamic response functions.

    View details for DOI 10.1016/S0730-725X(03)00196-6

    View details for Web of Science ID 000187457100001

    View details for PubMedID 14684194

  • Generalized reconstruction of phase contrast MRI: Analysis and correction of the effect of gradient field distortions MAGNETIC RESONANCE IN MEDICINE Markl, M., Bammer, R., Alley, M. T., Elkins, C. J., Draney, M. T., Barnett, A., Moseley, M. E., Glover, G. H., Pelc, N. J. 2003; 50 (4): 791-801


    To characterize gradient field nonuniformity and its effect on velocity encoding in phase contrast (PC) MRI, a generalized model that describes this phenomenon and enables the accurate reconstruction of velocities is presented. In addition to considerable geometric distortions, inhomogeneous gradient fields can introduce deviations from the nominal gradient strength and orientation, and therefore spatially-dependent first gradient moments. Resulting errors in the measured phase shifts used for velocity encoding can therefore cause significant deviations in velocity quantification. The true magnitude and direction of the underlying velocities can be recovered from the phase difference images by a generalized PC velocity reconstruction, which requires the acquisition of full three-directional velocity information. The generalized reconstruction of velocities is applied using a matrix formalism that includes relative gradient field deviations derived from a theoretical model of local gradient field nonuniformity. In addition, an approximate solution for the correction of one-directional velocity encoding is given. Depending on the spatial location of the velocity measurements, errors in velocity magnitude can be as high as 60%, while errors in the velocity encoding direction can be up to 45 degrees. Results of phantom measurements demonstrate that effects of gradient field nonuniformity on PC-MRI can be corrected with the proposed method.

    View details for DOI 10.1002/mrm.10582

    View details for Web of Science ID 000185698000019

    View details for PubMedID 14523966

  • Analysis and generalized correction of the effect of spatial gradient field distortions in diffusion-weighted imaging MAGNETIC RESONANCE IN MEDICINE Bammer, R., Markl, M., Barnett, A., Acar, B., Alley, M. T., Pelc, N. J., Glover, G. H., Moseley, M. E. 2003; 50 (3): 560-569


    Nonuniformities of magnetic field gradients can cause serious artifacts in diffusion imaging. While it is well known that nonlinearities of the imaging gradients lead to image warping, those imperfections can also cause spatially dependent errors in the direction and magnitude of the diffusion encoding. This study shows that the potential errors in diffusion imaging are considerable. Further, we show that retrospective corrections can be applied to reduce these errors. A general mathematical framework was formulated to characterize the contribution of gradient nonuniformities to diffusion experiments. The gradient field was approximated using spherical harmonic expansion, and this approximation was employed (after geometric distortions were eliminated) to predict and correct the errors in diffusion encoding. Before the corrections were made, the experiments clearly revealed marked deviations of the calculated diffusivity for fields of view (FOVs) generally used in diffusion experiments. These deviations were most significant farther away from the magnet's isocenter. For an FOV of 25 cm, the resultant errors in absolute diffusivity ranged from approximately -10% to +20%. Within the same FOV, the diffusion-encoding direction and the orientation of the calculated eigenvectors can be significantly altered if the perturbations by the gradient nonuniformities are not considered. With the proposed correction scheme, most of the errors introduced by gradient nonuniformities can be removed.

    View details for DOI 10.1002/mrm.10545

    View details for Web of Science ID 000185174500015

    View details for PubMedID 12939764

  • Fast algorithms for GS-model-based image reconstruction in data-sharing Fourier imaging IEEE TRANSACTIONS ON MEDICAL IMAGING Liang, Z. P., Madore, B., Glover, G. H., Pelc, N. J. 2003; 22 (8): 1026-1030


    Many imaging experiments involve acquiring a time series of images. To improve imaging speed, several "data-sharing" methods have been proposed, which collect one (or a few) high-resolution reference(s) and a sequence of reduced data sets. In image reconstruction, two methods, known as "Keyhole" and reduced-encoding imaging by generalized-series reconstruction (RIGR), have been used. Keyhole fills in the unmeasured high-frequency data simply with those from the reference data set(s), whereas RIGR recovers the unmeasured data using a generalized series (GS) model, of which the basis functions are constructed based on the reference image(s). This correspondence presents a fast algorithm (and two extensions) for GS-based image reconstruction. The proposed algorithms have the same computational complexity as the Keyhole algorithm, but are more capable of capturing high-resolution dynamic signal changes.

    View details for DOI 10.1109/TMI.2003.815896

    View details for Web of Science ID 000184567100011

    View details for PubMedID 12906256

  • Finger movements lighten neural loads in the recognition of ideographic characters COGNITIVE BRAIN RESEARCH Matsuo, K., Kato, C., Okada, T., Moriya, T., Glover, G. H., Nakai, T. 2003; 17 (2): 263-272


    The role of finger writing movements in recognizing Japanese ideographic characters (Kanji) was investigated using functional magnetic resonance imaging at 3 T. A total of 12 healthy native Japanese-speaking volunteers were studied while counting the number of strokes in ideographic characters. In experiment 1, a representation of the pronunciation of an ideographic character was displayed using Japanese syllabic characters. Volunteers were required to count the strokes of the ideographic character corresponding to the displayed phonogram. This procedure included retrieval and generation of ideographic characters. In experiment 2, the ideographic character itself was displayed and the volunteers counted its strokes. This procedure focused on visuospatial imagery processes. Each experiment was conducted under two different motor conditions. One condition allowed the subject to use finger movements to count the strokes, while the other disallowed any finger movements. In both experiments, movement-allowed conditions duly activated the primary motor area. The phonogram-displayed and movement-disallowed condition induced an augmented activation in a part of the left premotor area, which was assumed to be Exner's area. This area might have been activated by a demand for sequential generation of character graphemes that corresponded to the phonogram displayed. The ideographic-character-displayed and movement-disallowed condition activated the dorsal occipitoparietal areas and the primary visual area, which might be involved in the visuospatial mental imagery processes. These results suggest that execution of finger movements during stroke counting of ideographic characters lightens the neural loads for grapheme generation on Exner's area and for the visuospatial imagery processes on the dorsal pathway.

    View details for DOI 10.1016/S0926-6410(03)00114-9

    View details for Web of Science ID 000186120200008

    View details for PubMedID 12880898

  • A functional magnetic resonance imaging study of internal modulation of an external visual cue for motor execution BRAIN RESEARCH Nakai, T., Kato, C., Glover, G. H., Toma, K., Moriya, T., Matsuo, K. 2003; 968 (2): 238-247


    The strategy to perform a task differs according to how a cue is interpreted. In order to investigate the basic mechanisms of temporal regulation in the higher motor areas, the interaction between two different types of internal modulations of an external visual cue was evaluated using functional magnetic resonance imaging (fMRI). An opposing finger movement task guided by dot prompting was employed. In the intermittent tapping experiment, two taps per second and a rest for one second were alternatively repeated in the task blocks. In the constant tapping experiments, the volunteers performed finger movements at 0.5, 1 or 2 Hz. The activation in the primary sensory motor area correlated with the amount of movement. Activities in the supplementary motor area, left dorsal pre-motor area, left superior parietal lobule and right cerebellum depended on the demand for internal modulation. Activation in these areas was maximum for the intermittent task which was a combination of two different internal modulations, and minimum for the 1 Hz movement that did not require internal modulation. It was suggested that these four areas are directly involved in the generation of a complex movement sequence driven by a visual cue, and they are organized for performance. The translation of external pacing and initiation for self-pacing may share the same neuronal basis. Activation in the left supramarginal gyrus, bilateral frontal operticula and basal ganglia did not depend on the combination of the two internal modulations.

    View details for DOI 10.1016/S0006-8993(03)02249-2

    View details for Web of Science ID 000182141000008

    View details for PubMedID 12663093

  • Comparison of fMRI activation at 3 and 1.5 T during perceptual, cognitive, and affective processing NEUROIMAGE Krasnow, B., Tamm, L., Greicius, M. D., Yang, T. T., Glover, G. H., Reiss, A. L., Menon, V. 2003; 18 (4): 813-826


    Previous studies comparing fMRI data acquired at 1.5 T and higher field strengths have focused on examining signal increases in the visual and motor cortices. No information is, however, available on the relative gain, or the comparability of data, obtained at higher field strengths for other brain regions such as the prefrontal and other association cortices. In the present study, we investigated fMRI activation at 1.5 and 3 T during visual perception, visuospatial working memory, and affect-processing tasks. A 23% increase in striate and extrastriate activation volume was observed at 3 T compared with that for 1.5 T during the visual perception task. During the working memory task significant increases in activation volume were observed in frontal and parietal association cortices as well as subcortical structures, including the caudate, globus pallidus, putamen, and thalamus. Increases in working memory-related activation volume of 82, 73, 83, and 36% were observed in the left frontal, right frontal, left parietal, and right parietal lobes, respectively, for 3 T compared with 1.5 T. These increases were characterized by increased activation at 3 T in several prefrontal and parietal cortex regions that showed activation at 1.5 T. More importantly, at 3 T, activation was detected in several regions, such as the ventral aspects of the inferior frontal gyrus, orbitofrontal gyrus, and lingual gyrus, which did not show significant activation at 1.5 T. No difference in height or extent of activation was detected between the two scanners in the amygdala during affect processing. Signal dropout in the amygdala from susceptibility artifact was greater at 3 T, with a 12% dropout at 3 T compared with a 9% dropout at 1.5 T. The spatial smoothness of T2* images was greater at 3 T by less than 1 mm, suggesting that the greater extent of activation at 3 T beyond these spatial scales was not due primarily to increased intrinsic spatial correlations at 3 T. Rather, the increase in percentage of voxels activated reflects increased sensitivity for detection of brain activation at higher field strength. In summary, our findings suggest that functional imaging of prefrontal and other association cortices can benefit significantly from higher magnetic field strength.

    View details for DOI 10.1016/S1053-8119(03)00002-8

    View details for Web of Science ID 000182606000001

    View details for PubMedID 12725758

  • Dissociated neural representations of intensity and valence in human olfaction NATURE NEUROSCIENCE Anderson, A. K., Christoff, K., Stappen, I., Panitz, D., Ghahremani, D. G., Glover, G., Gabrieli, J. D., Sobel, N. 2003; 6 (2): 196-202


    Affective experience has been described in terms of two primary dimensions: intensity and valence. In the human brain, it is intrinsically difficult to dissociate the neural coding of these affective dimensions for visual and auditory stimuli, but such dissociation is more readily achieved in olfaction, where intensity and valence can be manipulated independently. Using event-related functional magnetic resonance imaging (fMRI), we found amygdala activation to be associated with intensity, and not valence, of odors. Activity in regions of orbitofrontal cortex, in contrast, were associated with valence independent of intensity. These findings show that distinct olfactory regions subserve the analysis of the degree and quality of olfactory stimulation, suggesting that the affective representations of intensity and valence draw upon dissociable neural substrates.

    View details for DOI 10.1038/nn1001

    View details for Web of Science ID 000180669100021

    View details for PubMedID 12536208

  • Neural correlates of auditory perception in Williams syndrome: An fMRI study NEUROIMAGE Levitin, D. J., Menon, V., Schmitt, J. E., Eliez, S., White, C. D., Glover, G. H., Kadis, J., Korenberg, J. R., Bellugi, U., Reiss, A. L. 2003; 18 (1): 74-82


    Williams syndrome (WS), a neurogenetic developmental disorder, is characterized by a rare fractionation of higher cortical functioning: selective preservation of certain complex faculties (language, music, face processing, and sociability) in contrast to marked and severe deficits in nearly every other cognitive domain (reasoning, spatial ability, motor coordination, arithmetic, problem solving). WS people are also known to suffer from hyperacusis and to experience heightened emotional reactions to music and certain classes of noise. We used functional magnetic resonance imaging to examine the neural basis of auditory processing of music and noise in WS patients and age-matched controls and found strikingly different patterns of neural organization between the groups. Those regions supporting music and noise processing in normal subjects were found not to be consistently activated in the WS participants (e.g., superior temporal and middle temporal gyri). Instead, the WS participants showed significantly reduced activation in the temporal lobes coupled with significantly greater activation in the right amygdala. In addition, WS participants (but not controls) showed a widely distributed network of activation in cortical and subcortical structures, including the brain stem, during music processing. Taken together with previous ERP and cytoarchitectonic studies, this first published report of WS using fMRI provides additional evidence of a different neurofunctional organization in WS people than normal people, which may help to explain their atypical reactions to sound. These results constitute an important first step in drawing out the links between genes, brain, cognition, and behavior in Williams syndrome.

    View details for DOI 10.1006/nimg.2002.1297

    View details for Web of Science ID 000180015200007

    View details for PubMedID 12507445

  • Variable effects of aging on frontal lobe contributions to memory NEUROREPORT Rosen, A. C., Prull, M. W., O'Hara, R., Race, E. A., Desmond, J. E., Glover, G. H., Yesavage, J. A., Gabrieli, J. D. 2002; 13 (18): 2425-2428


    Declarative memory declines with age, but there is profound variation in the severity of this decline. Healthy elderly adults with high or low memory scores and young adults viewed words under semantic or non-semantic encoding conditions while undergoing fMRI. Young adults had superior memory for the words, and elderly adults with high memory scores had better memory for the words than those with low memory scores. The elderly with high scores had left lateral and medial prefrontal activations for semantic encoding equal to the young, and greater right prefrontal activation than the young. The elderly with low scores had reduced activations in all three regions relative to the elderly with high memory scores. Thus, successful aging was characterized by preserved left prefrontal and enhanced right prefrontal activation that may have provided compensatory encoding resources.

    View details for DOI 10.1097/01.wnr.0000048001.96487.05

    View details for Web of Science ID 000180673200010

    View details for PubMedID 12499842

  • Neural correlates of timbre change in harmonic sounds NEUROIMAGE Menon, V., Levitin, D. J., Smith, B. K., Lembke, A., Krasnow, B. D., Glazer, D., Glover, G. H., McAdams, S. 2002; 17 (4): 1742-1754


    Timbre is a major structuring force in music and one of the most important and ecologically relevant features of auditory events. We used sound stimuli selected on the basis of previous psychophysiological studies to investigate the neural correlates of timbre perception. Our results indicate that both the left and right hemispheres are involved in timbre processing, challenging the conventional notion that the elementary attributes of musical perception are predominantly lateralized to the right hemisphere. Significant timbre-related brain activation was found in well-defined regions of posterior Heschl's gyrus and superior temporal sulcus, extending into the circular insular sulcus. Although the extent of activation was not significantly different between left and right hemispheres, temporal lobe activations were significantly posterior in the left, compared to the right, hemisphere, suggesting a functional asymmetry in their respective contributions to timbre processing. The implications of our findings for music processing in particular and auditory processing in general are discussed.

    View details for DOI 10.1006/nimg.2002.1295

    View details for Web of Science ID 000179969800008

    View details for PubMedID 12498748

  • Regularized higher-order in vivo shimming MAGNETIC RESONANCE IN MEDICINE Kim, D. H., Adalsteinsson, E., Glover, G. H., Spielman, D. M. 2002; 48 (4): 715-722


    A regularized algorithm is presented for localized in vivo shimming. The technique uses first- (X,Y,Z), second- (Z(2), ZX, ZY, X(2)-Y(2), XY), and third-order (Z(3)) shim coils, and is robust when applied to arbitrarily-shaped, as well as off-center, regions of interest (ROIs). A single-shot spiral pulse sequence is used for rapid field map acquisition, and a least-squares calculation of the shim currents is performed to minimize the root-mean-square (RMS) value of the B(0) inhomogeneity over a user-selected ROI. The use of a singular value decomposition (SVD) in combination with a regularization algorithm significantly improves the numerical stability of the least-squares fitting procedure. The fully automated shimming package is implemented on a 3 T GE Signa system and its robust performance is demonstrated in phantom and in vivo studies.

    View details for DOI 10.1002/mrm.10267

    View details for Web of Science ID 000178361000019

    View details for PubMedID 12353290

  • Estimating sample size in functional MRI (fMRI) neuroimaging studies: Statistical power analyses JOURNAL OF NEUROSCIENCE METHODS Desmond, J. E., Glover, G. H. 2002; 118 (2): 115-128


    Estimation of statistical power in functional MRI (fMRI) requires knowledge of the expected percent signal change between two conditions as well as estimates of the variability in percent signal change. Variability can be divided into intra-subject variability, reflecting noise within the time series, and inter-subject variability, reflecting subject-to-subject differences in activation. The purpose of this study was to obtain estimates of percent signal change and the two sources of variability from fMRI data, and then use these parameter estimates in simulation experiments in order to generate power curves. Of interest from these simulations were conclusions concerning how many subjects are needed and how many time points within a scan are optimal in an fMRI study of cognitive function. Intra-subject variability was estimated from resting conditions, and inter-subject variability and percent signal change were estimated from verbal working memory data. Simulations derived from these parameters illustrate how percent signal change, intra- and inter-subject variability, and number of time points affect power. An empirical test experiment, using fMRI data acquired during somatosensory stimulation, showed good correspondence between the simulation-based power predictions and the power observed within somatosensory regions of interest. Our analyses suggested that for a liberal threshold of 0.05, about 12 subjects were required to achieve 80% power at the single voxel level for typical activations. At more realistic thresholds, that approach those used after correcting for multiple comparisons, the number of subjects doubled to maintain this level of power.

    View details for Web of Science ID 000177967100003

    View details for PubMedID 12204303

  • Brain activation and sexual arousal in healthy, heterosexual males BRAIN Arnow, B. A., Desmond, J. E., Banner, L. L., Glover, G. H., Solomon, A., Polan, M. L., Lue, T. F., Atlas, S. W. 2002; 125: 1014-1023


    Despite the brain's central role in sexual function, little is known about relationships between brain activation and sexual response. In this study, we employed functional MRI (fMRI) to examine relationships between brain activation and sexual arousal in a group of young, healthy, heterosexual males. Each subject was exposed to two sequences of video material consisting of explicitly erotic (E), relaxing (R) and sports (S) segments in an unpredictable order. Data on penile turgidity was collected using a custom-built pneumatic pressure cuff. Both traditional block analyses using contrasts between sexually arousing and non-arousing video clips and a regression using penile turgidity as the covariate of interest were performed. In both types of analyses, contrast images were computed for each subject and these images were subsequently used in a random effects analysis. Strong activations specifically associated with penile turgidity were observed in the right subinsular region including the claustrum, left caudate and putamen, right middle occipital/ middle temporal gyri, bilateral cingulate gyrus and right sensorimotor and pre-motor regions. Smaller, but significant activation was observed in the right hypothalamus. Few significant activations were found in the block analyses. Implications of the findings are discussed. Our study demonstrates the feasibility of examining brain activation/sexual response relationships in an fMRI environment and reveals a number of brain structures whose activation is time-locked to sexual arousal.

    View details for Web of Science ID 000175626900010

    View details for PubMedID 11960892

  • Respiration-induced B-0 fluctuations and their spatial distribution in the human brain at 7 tesla MAGNETIC RESONANCE IN MEDICINE Van De Moortele, P. F., Pfeuffer, J., Glover, G. H., Ugurbil, K., Hu, X. P. 2002; 47 (5): 888-895


    In functional magnetic resonance imaging (fMRI), it is known that physiological influences such as cardiac pulsation, respiration, and brain motion can induce fluctuations in signal intensity and phase. Some of the mechanisms potentially involved in those phenomena are expected to be amplified at higher magnetic fields. This study addresses the issue of B(0) fluctuations induced by susceptibility changes during respiration attributed to movements of chest and diaphragm, and variations in the oxygen concentration. It is demonstrated that respiration-induced resonance offsets (RIROs) are significant at 7T. Data were acquired with an RF pulse (no gradients), multislice echo-planar imaging (EPI), and dynamic 3D fast low-angle shot (3D- FLASH) imaging. Three main observations summarize the experimental findings. First, in FIDs measured after a single RF pulse, a RIRO with a large amplitude was consistently detected, although the average amplitude varied between subjects from 1.45 Hz to 4 Hz. Second, in transverse EPI images obtained in the occipital lobe, the RIRO amplitude showed a monotonic increase along the z axis toward the lungs. Third, a more detailed spatial analysis with 3D-FLASH phase maps revealed that a previously published analytical model can accurately describe the spatial distribution of RIRO. Consequential apparent motions in the EPI series, as well as the implications of slice orientation for correction strategies are discussed.

    View details for DOI 10.1002/mrm.10145

    View details for Web of Science ID 000175346100008

    View details for PubMedID 11979567

  • A developmental fMRI study of the stroop color-word task NEUROIMAGE Adleman, N. E., Menon, V., Blasey, C. M., White, C. D., Warsofsky, I. S., Glover, G. H., Reiss, A. L. 2002; 16 (1): 61-75


    We used fMRI to investigate developmental changes in brain activation during a Stroop color-word interference task. A positive correlation was observed between age and Stroop-related activation (n = 30) in the left lateral prefrontal cortex, the left anterior cingulate, and the left parietal and parieto-occipital cortices. No regions showed a negative correlation between activation and age. We further investigated age-related differences by stratifying the sample into three age groups: children (ages 7-11), adolescents (ages 12-16), and young adults (ages 18-22). Young adult subjects (n = 11) displayed significant activation in the inferior and middle frontal gyri bilaterally, the left anterior cingulate, and bilateral inferior and superior parietal lobules. Between-group comparisons revealed that young adults had significantly greater activation than adolescent subjects (n = 11) in the left middle frontal gyrus and that young adults showed significantly greater activation than children (n = 8) in the anterior cingulate and left parietal and parieto-occipital regions, as well as in the left middle frontal gyrus. Compared to children, both adult and adolescent subjects exhibited significantly greater activation in the parietal cortex. Adult and adolescent groups, however, did not differ in activation for this region. Together, these data suggest that Stroop task-related functional development of the parietal lobe occurs by adolescence. In contrast, prefrontal cortex function contributing to the Stroop interference task continues to develop into adulthood. This neuromaturational process may depend on increased ability to recruit focal neural resources with age. Findings from this study, the first developmental fMRI investigation of the Stroop interference task, provide a template with which normal development and neurodevelopmental disorders of prefrontal cortex function can be assessed.

    View details for DOI 10.1006/nimg.2001.1046

    View details for Web of Science ID 000176624700007

    View details for PubMedID 11969318

  • Aging effects on memory encoding in the frontal lobes PSYCHOLOGY AND AGING Stebbins, G. T., Carrillo, M. C., Dorfman, J., Dirksen, C., Desmond, J. E., TURNER, D. A., Bennett, D. A., Wilson, R. S., Glover, G., Gabrieli, J. D. 2002; 17 (1): 44-55


    Functional magnetic resonance imaging (fMRI) was used to compare frontal-lobe activation in younger and older adults during encoding of words into memory. Participants made semantic or nonsemantic judgments about words. Younger adults exhibited greater activation for semantic relative to nonsemantic judgments in several regions, with the largest activation in the left inferior frontal gyrus. Older adults exhibited greater activation for semantic judgments in the same regions. but the extent of activation was reduced in left prefrontal regions. In older adults, there was a significant association between behavioral tests of declarative and working memory and extent of frontal activation. These results suggest that age-associated decreases in memory ability may be due to decreased frontal-lobe contributions to the initial encoding of experience.

    View details for DOI 10.1037//0882-7974.17.1.44

    View details for Web of Science ID 000174439300004

    View details for PubMedID 11933895

  • Correction of physiologically induced global off resonance effects in dynamic echo-planar and spiral functional imaging MAGNETIC RESONANCE IN MEDICINE Pfeuffer, J., Van de Moortele, P. F., Ugurbil, K., Hu, X. P., Glover, G. H. 2002; 47 (2): 344-353


    In functional magnetic resonance imaging, a rapid method such as echo-planar (EPI) or spiral is used to collect a dynamic series of images. These techniques are sensitive to changes in resonance frequency which can arise from respiration and are more significant at high magnetic fields. To decrease the noise from respiration-induced phase and frequency fluctuations, a simple correction of the "dynamic off-resonance in k-space" (DORK) was developed. The correction uses phase information from the center of k-space and a navigator echo and is illustrated with dynamic scans of single-shot and segmented EPI and, for the first time, spiral imaging of the human brain at 7 T. Image noise in the respiratory spectrum was measured with an edge operator. The DORK correction significantly reduced respiration-induced noise (image shift for EPI, blurring for spiral, ghosting for segmented acquisition). While spiral imaging was found to exhibit less noise than EPI before correction, the residual noise after the DORK correction was comparable. The correction is simple to apply and can correct for other sources of frequency drift and fluctuations in dynamic imaging.

    View details for Web of Science ID 000173578700017

    View details for PubMedID 11810679

  • Changes of cerebral blood flow, oxygenation, and oxidative metabolism during graded motor activation NEUROIMAGE Kastrup, A., Kruger, G., Neumann-Haefelin, T., Glover, G. H., Moseley, M. E. 2002; 15 (1): 74-82


    In the present studies fMRI and a hypercapnic calibration procedure were used to monitor simultaneous changes in cerebral blood flow (CBF), cerebral blood oxygenation, and cerebral metabolic rate of oxygen (CMRO(2)) during activation in the sensorimotor cortex. In the first set of experiments seven volunteers performed bilateral, self-paced finger tapping and in the second set of experiments six volunteers performed bilateral finger tapping with six different frequencies (0.5-3 Hz). During the latter task relative CBF and BOLD signal intensity changes varied linearly as a function of stimulus frequency. In good agreement with recent PET and fMRI data increases in CMRO(2) were smaller than the corresponding changes in CBF during self-paced finger tapping and at all levels of graded motor activation. At a single level of activation and during graded activation there was a positive linear relationship between CBF and CMRO(2) with ratios of approximately 3:1. Comparable proportionality constants have been found in the visual cortex and primary sensory cortex, indicating similarities between the relationship of CBF and CMRO(2) in various cortical regions.

    View details for DOI 10.1006/nimg.2001.0916

    View details for Web of Science ID 000173174900007

    View details for PubMedID 11771975

  • Activation during endogenous orienting of visual attention using symbolic pointers in the human parietal and frontal cortices: a functional magnetic resonance imaging study NEUROSCIENCE LETTERS Kato, C., Matsuo, K., Matsuzawa, M., Moriya, T., Glover, G. H., Nakai, T. 2001; 314 (1-2): 5-8


    Brain activation induced by endogenous orienting with a motor response was investigated by functional magnetic resonance imaging. We conducted four cued-attention experiments in which peripheral attention was caused by one of three symbolic pointers (eyes, squares as artificial eyes, or an arrow) that was predictive or not predictive of the target location. Attentional shift caused by the predictive and non-predictive cues induced right and left parietal activation across cue modalities, respectively. Regardless of the predictability of the target location, the eyes and arrow induced left parietal and frontal activation, and the arrow induced left parietal activation more than the squares. These results suggested that the left parieto-frontal network was involved in motor attention caused by natural or familiar pointers, whereas the right parietal cortex was involved in endogenous orienting.

    View details for Web of Science ID 000172473500002

    View details for PubMedID 11698133

  • Prefrontal regions involved in keeping information in and out of mind BRAIN Bunge, S. A., Ochsner, K. N., Desmond, J. E., Glover, G. H., Gabrieli, J. D. 2001; 124: 2074-2086


    Goal-directed behaviour depends on keeping relevant information in mind (working memory) and irrelevant information out of mind (behavioural inhibition or interference resolution). Prefrontal cortex is essential for working memory and for interference resolution, but it is unknown whether these two mental abilities are mediated by common or distinct prefrontal regions. To address this question, functional MRI was used to identify brain regions activated by separate manipulations of working memory load and interference within a single task (the Sternberg item recognition paradigm). Both load and interference manipulations were associated with performance decrements. Subjects were unaware of the interference manipulation. There was a high degree of overlap between the regions activated by load and interference, which included bilateral ventrolateral and dorsolateral prefrontal cortex, anterior insula, anterior cingulate and parietal cortex. Critically, no region was activated exclusively by interference. Several regions within this common network exhibited a brain-behaviour correlation across subjects for the load or interference manipulation. Activation within the right middle frontal gyrus and left inferior frontal gyrus was correlated with the ability to resolve interference efficiently, but not the ability to manage an increased working memory load efficiently. Conversely, activation of the anterior cingulate was correlated with load susceptibility, but was not correlated with interference susceptibility. These findings suggest that, within the circuitry engaged by this task, some regions are more critically involved in the resolution of interference whereas others are more involved in the resolution of an increase in load. The anterior cingulate was engaged to a greater extent by the load than interference manipulation, suggesting that this region, which is thought to be involved in detecting the need for greater allocation of attentional resources, may be particularly implicated during awareness of the need for cognitive control. In the present study, interference resolution did not involve recruitment of additional inhibitory circuitry, but was instead mediated by a subset of the neural system supporting working memory.

    View details for Web of Science ID 000171501000015

    View details for PubMedID 11571223

  • Physiological noise in oxygenation-sensitive magnetic resonance imaging MAGNETIC RESONANCE IN MEDICINE Kruger, G., Glover, G. H. 2001; 46 (4): 631-637


    The physiological noise in the resting brain, which arises from fluctuations in metabolic-linked brain physiology and subtle brain pulsations, was investigated in six healthy volunteers using oxygenation-sensitive dual-echo spiral MRI at 3.0 T. In contrast to the system and thermal noise, the physiological noise demonstrates a signal strength dependency and, unique to the metabolic-linked noise, an echo-time dependency. Variations of the MR signal strength by changing the flip angle and echo time allowed separation of the different noise components and revealed that the physiological noise at 3.0 T (1) exceeds other noise sources and (2) is significantly greater in cortical gray matter than in white matter regions. The SNR in oxygenation-sensitive MRI is predicted to saturate at higher fields, suggesting that noise measurements of the resting brain at 3.0 T and higher may provide a sensitive probe of functional information.

    View details for Web of Science ID 000171217600001

    View details for PubMedID 11590638

  • Functional neuroanatomy of visuo-spatial working memory in Turner syndrome HUMAN BRAIN MAPPING Haberecht, M. F., Menon, V., Warsofsky, I. S., White, C. D., Dyer-Friedman, J., Glover, G. H., Neely, E. K., Reiss, A. L. 2001; 14 (2): 96-107


    Turner syndrome (TS), a genetic disorder characterized by the absence of an X chromosome in females, has been associated with cognitive and visuo-spatial processing impairments. We utilized functional MRI (fMRI) to investigate the neural substrates that underlie observed deficits in executive functioning and visuo-spatial processing. Eleven females with TS and 14 typically developing females (ages 7-20) underwent fMRI scanning while performing 1-back and 2-back versions of a standard visuo-spatial working memory (WM) task. On both tasks, TS subjects performed worse than control subjects. Compared with controls, TS subjects showed increased activation in the left and right supramarginal gyrus (SMG) during the 1-back task and decreased activation in these regions during the 2-back task. In addition, decreased activation in the left and right dorsolateral prefrontal cortex (DLPFC) and caudate nucleus was observed during the 2-back task in TS subjects. Activation differences localized to the SMG, in the inferior parietal lobe, may reflect deficits in visuo-spatial encoding and WM storage mechanisms in TS. In addition, deficits in the DLPFC and caudate may be related to deficits in executive function during WM performance. Together these findings point to deficits in frontal-striatal and frontal-parietal circuits subserving multiple WM functions in TS.

    View details for PubMedID 11500993

  • Spiral-in/out BOLD fMRI for increased SNR and reduced susceptibility artifacts MAGNETIC RESONANCE IN MEDICINE Glover, G. H., Law, C. S. 2001; 46 (3): 515-522


    BOLD fMRI is hampered by dropout of signal in the orbitofrontal and parietal brain regions due to magnetic field gradients near air-tissue interfaces. This work reports the use of spiral-in trajectories that begin at the edge of k-space and end at the origin, and spiral in/out trajectories in which a spiral-in readout is followed by a conventional spiral-out trajectory. The spiral-in trajectory reduces the dropout and increases the BOLD contrast. The spiral-in and spiral-out images can be combined in several ways to simultaneously achieve increased signal-to-noise ratio (SNR) and reduced dropout artifacts. Activation experiments employing an olfaction task demonstrate significantly increased activation volumes due to reduced dropout, and overall increased SNR in all regions.

    View details for Web of Science ID 000170740300016

    View details for PubMedID 11550244

  • Functional neuroanatomy of visuospatial working memory in fragile X syndrome: Relation to behavioral and molecular measures AMERICAN JOURNAL OF PSYCHIATRY Kwon, H., Menon, V., Eliez, S., Warsofsky, I. S., White, C. D., Dyer-Friedman, J., Taylor, A. K., Glover, G. H., Reiss, A. L. 2001; 158 (7): 1040-1051


    Fragile X syndrome is a neurogenetic disorder that is the most common known heritable cause of neurodevelopmental disability. This study examined the neural substrates of working memory in female subjects with fragile X syndrome. Possible correlations among behavioral measures, brain activation, and the FMR1 gene product (FMRP expression), as well as between IQ and behavioral measures, were investigated.Functional magnetic resonance imaging was used to examine visuospatial working memory in 10 female subjects with fragile X syndrome and 15 typically developing female subjects (ages 10-23 years). Subjects performed standard 1-back and 2-back visuospatial working memory tasks. Brain activation was examined in four regions of the cortex known to play a critical role in visuospatial working memory. Correlations between behavioral, neuroimaging, and molecular measures were examined.Relative to the comparison group, subjects with fragile X syndrome performed significantly worse on the 2-back task but not on the 1-back task. In a region-of-interest analysis focused on the inferior frontal gyrus, middle frontal gyrus, superior parietal lobule, and supramarginal gyrus, comparison subjects showed significantly increased brain activation between the 1-back and 2-back tasks, but subjects with fragile X syndrome showed no change in activation between the two tasks. Significant correlations were found in comparison subjects between activation in the frontal and parietal regions and the rate of correct responses on the 2-back task, but not on the 1-back task. In subjects with fragile X syndrome, significant correlations were found during the 2-back task between FMRP expression and activation in the right inferior and bilateral middle frontal gyri and the bilateral supramarginal gyri.Subjects with fragile X syndrome are unable to modulate activation in the prefrontal and parietal cortex in response to an increasing working memory load, and these deficits are related to a lower level of FMRP expression in fragile X syndrome subjects than in normal comparison subjects. The observed correlations between biological markers and brain activation provide new evidence for links between gene expression and cognition.

    View details for Web of Science ID 000169773000009

    View details for PubMedID 11431225

  • Visual language and handwriting movement: Functional magnetic resonance imaging at 3 tesla during generation of ideographic characters BRAIN RESEARCH BULLETIN Matsuo, K., Kato, C., Tanaka, S., Sugio, T., Matsuzawa, M., Inui, T., Moriya, T., Glover, G. H., Nakai, T. 2001; 55 (4): 549-554


    A functional magnetic resonance imaging experiment at 3 tesla was performed to investigate the collaborative mechanism between visuospatial processing and motor execution in performing visual language generation tasks. Japanese Kanji, ideographic characters, were utilized to design tasks. The bilateral border portions between the inferior parietal lobule and the occipital lobe were involved during a Kanji puzzle task, which required subjects to combine several parts into a Kanji. The higher motor areas, such as the premotor areas and the pre-supplementary motor areas, were also activated bilaterally during the puzzle task. The parieto-occipital activation may be related to analysis of configuration or segmentation/integration of Kanji figures. Activation in the higher motor areas may be induced by cognitive components related to motor function to perform the visuospatial language task, such as intense reference for displayed characters and finding a proper character for puzzle solution. A collaborative mechanism in these areas may explain the effectiveness of tactile reading in letter recognition by patients with pure alexia or kinesthetic facilitation by Kanji users when recalling difficult Kanji.

    View details for Web of Science ID 000170900300014

    View details for PubMedID 11543956

  • Reorganization of frontal systems used by alcoholics for spatial working memory: An fMRI study NEUROIMAGE Pfefferbaum, A., Desmond, J. E., Galloway, C., Menon, V., Glover, G. H., SULLIVAN, E. V. 2001; 14 (1): 7-20


    Chronic alcoholism is associated with impairment in sustained attention and visual working memory. Thus, alcoholics have reduced ability, but not necessarily inability, to perform these executive tasks, assumed to be subserved by regions of prefrontal cortex. To identify neural substrates associated with this impairment, we used functional MRI (fMRI) to determine whether alcoholics invoke the same or different brain systems as controls when engaged in working memory tasks that the two groups were able to perform at equivalent levels. The fMRI spatial working memory paradigm instructed subjects to respond with a button press when a target position was either in the center of the field (match to center) or matched the spatial position of one presented two items previously (match 2-back) or to rest. Using whole-brain fMRI, alcoholics showed diminished activation frontal cortical systems compared to controls (bilateral dorsolateral prefrontal cortex) when responding 2-back vs rest. In the center vs rest contrast, the control group compared with the alcoholic group activated a large expanse of prefrontal cortex (including Brodmann areas 9, 10, and 45), whereas there was significantly greater activation by the alcoholic group relative to the control group localized more posteriorly and inferiorly in the frontal cortex (area 47). Examination of within group activation patterns revealed two different patterns of activation: the control group exhibited activation of the dorsal ("Where?") stream for visual spatial working memory processing, whereas the alcoholic group exhibited activation of the ventral ("What?") stream and declarative memory systems to accomplish the spatial working memory task. The differences in the pattern of brain activations exhibited by the alcoholic and control groups, despite equivalence in behavioral performance, is consistent with a functional reorganization of the brain systems invoked by alcoholic individuals or invocation of an inappropriate brain system when engaged in a visual spatial task requiring working memory.

    View details for Web of Science ID 000169498000002

    View details for PubMedID 11525339

  • Effects of image orientation on the comparability of pediatric brain volumes using three-dimensional MR data JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY Patwardhan, A. J., Eliez, S., Warsofsky, I. S., Glover, G. H., White, C. D., Giedd, J. N., Peterson, B. S., Rojas, D. C., Reiss, A. L. 2001; 25 (3): 452-457


    The purpose of this study was to examine the comparability of morphometric measurements made on pediatric data sets collected at five scanner locations, each using variations on a 3D spoiled gradient-recalled echo (SPGR) pulse sequence.Archived MR data from 60 typically developing children were collected and separated into seven groups based on the pulse sequence used. A highly automated image-processing procedure was used to segment the brain data into white tissue, gray tissue, and CSF compartments and into various neuroanatomic regions of interest.Volumetric comparisons between groups revealed differences in areas of the temporal and occipital lobes. These differences were observed when comparing data sets with different image orientations and appeared to be due to partial volume averaging (PVA) and susceptibility-induced geometric distortions.Our results indicate that slice selection and image resolution should be controlled in volumetric studies using aggregated data from multiple centers to minimize the effects of PVA and susceptibility-induced geometric distortions.

    View details for Web of Science ID 000168573200020

    View details for PubMedID 11351198

  • Neuroimaging at 1.5 T and 3.0 T: Comparison of oxygenation-sensitive magnetic resonance imaging MAGNETIC RESONANCE IN MEDICINE Kruger, G., Kastrup, A., Glover, G. H. 2001; 45 (4): 595-604


    Noise properties, the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and signal responses were compared during functional activation of the human brain at 1.5 and 3.0 T. At the higher field spiral gradient-echo (GRE) brain images revealed an average gain in SNR of 1.7 in fully relaxed and 2.2 in images with a repetition time (TR) of 1.5 sec. The tempered gain at longer TRs reflects the fact that the physiological noise depends on the signal strength and becomes a larger fraction of the total noise at 3.0 T. Activation of the primary motor and visual cortex resulted in a 36% and 44% increase of "activated pixels" at 3.0 T, which reflects a greater sensitivity for the detection of activated gray matter at the higher field. The gain in the CNR exhibited a dependency on the underlying tissue, i.e., an increase of 1.8x in regions of particular high activation-induced signal changes (presumably venous vessels) and of 2.2x in the average activated areas. These results demonstrate that 3.0 T provides a clear advantage over 1.5 T for neuroimaging of homogeneous brain tissue, although stronger physiological noise contributions, more complicated signal features in the proximity of strong susceptibility gradients, and changes in the intrinsic relaxation times may mediate the enhancement. Magn Reson Med 45:595-604, 2001.

    View details for Web of Science ID 000167819100010

    View details for PubMedID 11283987

  • Functional magnetic resonance imaging evidence for disrupted basal ganglia function in schizophrenia AMERICAN JOURNAL OF PSYCHIATRY Menon, V., Anagnoson, R. T., Glover, G. H., Pfefferbaum, A. 2001; 158 (4): 646-649


    This study was an examination of basal ganglia dysfunction in schizophrenia using functional magnetic resonance imaging (fMRI).The authors used a motor sequencing task to investigate activation of the caudate, anterior putamen plus globus pallidus, and posterior putamen plus globus pallidus in eight subjects with schizophrenia and 12 group-matched comparison subjects. Differences in activation of the thalamus, the target of direct output from the globus pallidus, were also examined.The schizophrenia subjects showed significant bilateral deficits in the posterior putamen, globus pallidus, and thalamus but not the anterior putamen plus globus pallidus or caudate. Functional connectivity analysis revealed that the deficits in thalamic activation were related to deficits in posterior putamen and globus pallidus activation.These results provide fMRI evidence for basal ganglia dysfunction in subjects with schizophrenia and suggest that this deficit results in disrupted outflow to the thalamus. These deficits may underlie the behavioral impairments in goal-directed action observed in schizophrenia.

    View details for Web of Science ID 000167931900023

    View details for PubMedID 11282705

  • Error-related brain activation during a Go/NoGo response inhibition task HUMAN BRAIN MAPPING Menon, V., Adleman, N. E., White, C. D., Glover, G. H., Reiss, A. L. 2001; 12 (3): 131-143


    Inhibitory control and performance monitoring are critical executive functions of the human brain. Lesion and imaging studies have shown that the inferior frontal cortex plays an important role in inhibition of inappropriate response. In contrast, specific brain areas involved in error processing and their relation to those implicated in inhibitory control processes are unknown. In this study, we used a random effects model to investigate error-related brain activity associated with failure to inhibit response during a Go/NoGo task. Error-related brain activation was observed in the rostral aspect of the right anterior cingulate (BA 24/32) and adjoining medial prefrontal cortex, the left and right insular cortex and adjoining frontal operculum (BA 47) and left precuneus/posterior cingulate (BA 7/31/29). Brain activation related to response inhibition and competition was observed bilaterally in the dorsolateral prefrontal cortex (BA 9/46), pars triangularis region of the inferior frontal cortex (BA 45/47), premotor cortex (BA 6), inferior parietal lobule (BA 39), lingual gyrus and the caudate, as well as in the right dorsal anterior cingulate cortex (BA 24). These findings provide evidence for a distributed error processing system in the human brain that overlaps partially, but not completely, with brain regions involved in response inhibition and competition. In particular, the rostal anterior cingulate and posterior cingulate/precuneus as well as the left and right anterior insular cortex were activated only during error processing, but not during response competition, inhibition, selection, or execution. Our results also suggest that the brain regions involved in the error processing system overlap with brain areas implicated in the formulation and execution of articulatory plans.

    View details for Web of Science ID 000167259000001

    View details for PubMedID 11170305

  • Functional neuroanatomy of auditory working memory in schizophrenia: Relation to positive and negative symptoms NEUROIMAGE Menon, V., Anagnoson, R. T., Mathalon, D. H., Glover, G. H., Pfefferbaum, A. 2001; 13 (3): 433-446


    Functional brain imaging studies of working memory (WM) in schizophrenia have yielded inconsistent results regarding deficits in the dorsolateral prefrontal (DLPFC) and parietal cortices. In spite of its potential importance in schizophrenia, there have been few investigations of WM deficits using auditory stimuli and no functional imaging studies have attempted to relate brain activation during auditory WM to positive and negative symptoms of schizophrenia. We used a two-back auditory WM paradigm in a functional MRI study of men with schizophrenia (N = 11) and controls (N = 13). Region of interest analysis was used to investigate group differences in activation as well as correlations with symptom scores from the Brief Psychiatric Rating Scale. Patients with schizophrenia performed significantly worse and were slower than control subjects in the WM task. Patients also showed decreased lateralization of activation and significant WM related activation deficits in the left and right DLPFC, frontal operculum, inferior parietal, and superior parietal cortex but not in the anterior cingulate or superior temporal gyrus. These results indicate that in addition to the prefrontal cortex, parietal cortex function is also disrupted during WM in schizophrenia. Withdrawal-retardation symptom scores were inversely correlated with frontal operculum activation. Thinking disturbance symptom scores were inversely correlated with right DLPFC activation. Our findings suggest an association between thinking disturbance symptoms, particularly unusual thought content, and disrupted WM processing in schizophrenia.

    View details for DOI 10.1006/nimg.2000.0699

    View details for Web of Science ID 000167154300005

    View details for PubMedID 11170809

  • Basal ganglia involvement in memory-guided movement sequencing NEUROREPORT Menon, V., Anagnoson, R. T., Glover, G. H., Pfefferbaum, A. 2000; 11 (16): 3641-3645


    The basal ganglia (BG) are thought to play a critical role in motor planning and movement sequencing. While electrophysiological and imaging studies have shown that the dorso-lateral prefrontal cortex (DLPFC) is involved in working memory (WM), the involvement of the BG in this process is not well understood. We used a motor sequencing task to investigate the differential role of BG nuclei in memory-guided movement. Significant activation was observed in the DLPFC and posterior putamen and globus pallidus (GP), with a trend in the caudate and no differences in the anterior putamen. We then investigated the effect of BG outflow on thalamic activation using functional connectivity analysis. Activation in the posterior putamen + GP was found to be correlated with thalamic activation only in the hemisphere contralateral to movement. These results provide the first fMRI evidence that the BG may modulate activity in the thalamus during working memory-guided movement sequencing. Our findings suggest that the BG activation may reflect increased motor sequencing demands during the memory-guided movement condition and, specifically, that the posterior putamen and GP may play a role in maintenance of representations in WM in a manner that contributes to planning and temporal organization of motor sequencing.

    View details for Web of Science ID 000165301600048

    View details for PubMedID 11095535

  • Changes in baseline cerebral blood flow in humans do not influence regional cerebral blood flow response to photic stimulation JOURNAL OF MAGNETIC RESONANCE IMAGING Li, T. Q., Kastrup, A., Moseley, M. E., Glover, G. H. 2000; 12 (5): 757-762


    The effect of changes in baseline regional cerebral blood flow (rCBF) values on the cerebral blood flow response during neuronal activation was studied with functional magnetic resonance imaging (fMRI). Using a breath-holding challenge as a hypercapnic stimulus, rCBF alterations during photic stimulation under normo- and hypercapnia were determined in nine volunteers. With breath-holding, baseline rCBF in areas corresponding to the visual cortex significantly increased from 54 +/- 5 ml/100 g/min to 85 +/- 9 ml/100 g/min (P < 0.001). Despite this significant change in baseline flow values, the rCBF increase during visual stimulation was very similar under normo- and hypercapnic conditions (28 +/- 8 ml/100 g/min versus 26 +/- 8 ml/100 g/min, respectively). This study supports the notion that within wide physiologic variations, task-induced cerebral blood flow changes are independent of baseline rCBF values.

    View details for Web of Science ID 000171295400014

    View details for PubMedID 11050647

  • Dissociating prefrontal and parietal cortex activation during arithmetic processing NEUROIMAGE Menon, V., Rivera, S. M., White, C. D., Glover, G. H., Reiss, A. L. 2000; 12 (4): 357-365


    Lesion and brain-imaging studies have implicated the prefrontal and parietal cortices in arithmetic processing, but do not exclude the possibility that these brain areas are also involved in nonarithmetic operations. In the present study, we used functional magnetic resonance imaging to explore which brain areas contribute uniquely to numeric computation. Task difficulty was manipulated in a factorial design by varying the number of operands and the rate of stimulus presentation. Both manipulations increased the number of operations to be performed in unit time. Manipulating the number of operands allowed us to investigate the specific effect of calculation, while manipulating the rate of presentation allowed us to increase task difficulty independent of calculation. We found quantitative changes in activation patterns in the prefrontal and parietal cortices as well as the recruitment of additional brain regions, including the caudate and midcerebellar cortex, with increasing task difficulty. More importantly, the main effect of arithmetic complexity was observed in the left and right angular gyrus, while the main effect of rate of stimulus presentation was observed in the left insular/orbitofrontal cortex. Our findings indicate a dissociation in prefrontal and parietal cortex function during arithmetic processing and further provide the first evidence for a specific role for the angular gyrus in arithmetic computation independent of other processing demands.

    View details for Web of Science ID 000089737000001

    View details for PubMedID 10988030

  • Analysis of a distributed neural system involved in spatial information, novelty, and memory processing HUMAN BRAIN MAPPING Menon, V., White, C. D., Eliez, S., Glover, G. H., Reiss, A. L. 2000; 11 (2): 117-129


    Perceiving a complex visual scene and encoding it into memory involves a hierarchical distributed network of brain regions, most notably the hippocampus (HIPP), parahippocampal gyrus (PHG), lingual gyrus (LNG), and inferior frontal gyrus (IFG). Lesion and imaging studies in humans have suggested that these regions are involved in spatial information processing as well as novelty and memory encoding; however, the relative contributions of these regions of interest (ROIs) are poorly understood. This study investigated regional dissociations in spatial information and novelty processing in the context of memory encoding using a 2 x 2 factorial design with factors Novelty (novel vs. repeated) and Stimulus (viewing scenes with rich vs. poor spatial information). Greater activation was observed in the right than left hemisphere; however, hemispheric effects did not differ across regions, novelty, or stimulus type. Significant novelty effects were observed in all four regions. A significant ROI x Stimulus interaction was observed - spatial information processing effects were largest effects in the LNG, significant in the PHG and HIPP and nonsignificant in the IFG. Novelty processing was stimulus dependent in the LNG and stimulus independent in the PHG, HIPP, and IFG. Analysis of the profile of Novelty x Stimulus interaction across ROIs provided evidence for a hierarchical independence in novelty processing characterized by increased dissociation from spatial information processing. Despite these differences in spatial information processing, memory performance for novel scenes with rich and poor spatial information was not significantly different. Memory performance was inversely correlated with right IFG activation, suggesting the involvement of this region in strategically flawed encoding effort. Stepwise regression analysis revealed that memory encoding accounted for only a small fraction of the variance (< 16%) in medial temporal lobe activation. The implications of these results for spatial information, novelty, and memory processing in each stage of the distributed network are discussed.

    View details for Web of Science ID 000089712000005

    View details for PubMedID 11061338

  • Assessment of hemodynamic response during focal neural activity in human using bolus tracking, arterial spin labeling and BOLD techniques NEUROIMAGE Li, T. Q., Haefelin, T. N., Chan, B., Kastrup, A., Jonsson, T., Glover, G. H., Moseley, M. E. 2000; 12 (4): 442-451


    In this study, the hemodynamic response and changes in oxidative metabolism during functional activation were measured using three functional magnetic resonance imaging (fMRI) techniques: the blood oxygenation level-dependent (BOLD) technique, flow-sensitive alternating inversion recovery (FAIR), and bolus tracking (BT) of an MR contrast agent. With these three techniques we independently determined changes in BOLD signal, relative cerebral blood flow (rCBF), and cerebral blood volume (rCBV) associated with brain activation in eight healthy volunteers. In the motor cortex, the BOLD signal increased by 1.8 +/- 0.5%, rCBF by 36.3 +/- 8.2% (FAIR), and 35.1 +/- 8.6% (BT), and rCBV by 19.4 +/- 4.1% (BT) in response to simultaneous bilateral finger tapping. In the visual cortex, BOLD signal increased by 2.6 +/- 0.5%, rCBF by 38.5% +/- 7.6 (FAIR), and 36.9 +/- 8.8% (BT), and rCBV by 18.8 +/- 2.8% (BT) during flickering checkerboard stimulation. Comparing the experimentally measured rCBV with the calculated rCBV using Grubb's power-law relation, we conclude that the use of power-law relationship results in systematic underestimate of rCBV.

    View details for Web of Science ID 000089737000009

    View details for PubMedID 10988038

  • A model for faculty mentoring in academic radiology ACADEMIC RADIOLOGY Illes, J., Glover, G. H., Wexler, L., Leung, A. N., Glazer, G. M. 2000; 7 (9): 717-724


    The purpose of this report is to describe the development and implementation of a faculty mentoring program in radiology designed to promote the career development of junior faculty and enhance communication in the department.The mentoring program was implemented in five stages: organizational readiness, participant recruitment, mentor matching and orientation, implementation, and evaluation. Evaluations were based on Likert scale ratings and qualitative feedback. A retrospective analysis was also conducted of the annual performance reviews of junior faculty in the areas of research, teaching, patient care, and overall performance.An average of 83% (19 of 23) of the junior faculty participated in the pilot phase of the mentoring program. During five rounds of testing, the median rating (1 indicates not important; 10, extremely important) from responding junior faculty was 10 for overall value of individual mentoring meetings; the median rating for the mentors responding was 8.75. Research and academic development were identified as the areas of greatest importance to the faculty. Research and patient care were most improved as assessed by faculty peers during performance reviews. The schedule of semiannual formal mentoring meetings was reported to be optimal.The program was implemented to the satisfaction of junior faculty and mentors, and longitudinal performance suggests positive effects. Issues to be contended with include confidentiality and the time needed for mentoring beyond already saturated schedules. Overall, the authors propose that mentoring programs can be an asset to academic radiology departments and a key factor in maintaining their vitality.

    View details for Web of Science ID 000089143200007

    View details for PubMedID 10987334

  • Image-based method for retrospective correction of physiological motion effects in fMRI: RETROICOR MAGNETIC RESONANCE IN MEDICINE Glover, G. H., Li, T. Q., Ress, D. 2000; 44 (1): 162-167


    Respiration effects and cardiac pulsatility can induce signal modulations in functional MR image time series that increase noise and degrade the statistical significance of activation signals. A simple image-based correction method is described that does not have the limitations of k-space methods that preclude high spatial frequency correction. Low-order Fourier series are fit to the image data based on time of each image acquisition relative to the phase of the cardiac and respiratory cycles, monitored using a photoplethysmograph and pneumatic belt, respectively. The RETROICOR method is demonstrated using resting-state experiments on three subjects and compared with the k-space method. The method is found to perform well for both respiration- and cardiac-induced noise without imposing spatial filtering on the correction. Magn Reson Med 44:162-167, 2000.

    View details for Web of Science ID 000087917000023

    View details for PubMedID 10893535

  • Functional magnetic resonance imaging evidence for right-hemisphere involvement in processing unusual semantic relationships NEUROPSYCHOLOGY Seger, C. A., Desmond, J. E., Glover, G. H., Gabrieli, J. D. 2000; 14 (3): 361-369


    Brain areas active in generating usual (typical) or unusual (atypical) noun-verb relations were examined using functional magnetic resonance imaging. Seven adults generated the 1st verb to come to mind (usual verb) in response to novel and repeated nouns (priming test) and then generated either an unusual verb or the 1st verb to come to mind in response to novel nouns (unusual test). The left inferior prefrontal cortex (LIPC) and right cerebellum were more active when generating usual verbs to novel nouns than to repeated nouns. When participants generated unusual verbs, there was no increased activation in LIPC, but there was increased activity in the right middle and superior frontal gyri, left middle frontal gyrus, and bilateral cerebellum. Results support theories that the right hemisphere is involved in the processing of distant associations that may be useful in creative thought and problem solving.

    View details for DOI 10.1037//0894-4105.14.3.361

    View details for Web of Science ID 000088253400004

    View details for PubMedID 10928739

  • Abstract: MRI: basic principles and future potential Computer aided surgery : official journal of the International Society for Computer Aided Surgery Glover, G. H. 2000; 5 (2): 132

    View details for PubMedID 10862136

  • Functional optimization of arithmetic processing in perfect performers COGNITIVE BRAIN RESEARCH Menon, V., Rivera, S. M., White, C. D., Eliez, S., Glover, G. H., Reiss, A. L. 2000; 9 (3): 343-345


    Lesion and imaging studies to date have not clarified which sub-regions of the parietal lobe are specialized for arithmetic processing, and which perform supporting functions. We used functional magnetic resonance imaging to investigate parietal lobe function during arithmetic processing. Functional optimization was examined by analyzing regional differences in brain activation between perfect (100% accuracy) and imperfect performers. Perfect performers had significantly less activation only in the left angular gyrus, a finding that may be associated with skill mastery and long-term practice effects. The present results provide the first direct evidence of localized functional optimization for arithmetic processing in the human brain.

    View details for Web of Science ID 000087193400013

    View details for PubMedID 10808145

  • Monitoring of high-intensity focused ultrasound-induced temperature changes in vitro using an interleaved spiral acquisition MAGNETIC RESONANCE IN MEDICINE Stafford, R. J., Hazle, J. D., Glover, G. H. 2000; 43 (6): 909-912


    An interleaved, spoiled gradient-echo spiral acquisition technique was implemented to monitor high-intensity focused ultrasound heating of porcine kidney ex vivo by measuring temperature induced phase shifts in the detected MR signal. Echo time, flip angle, repetition time, number of interleaves, and readout time were varied to observes effects on temperature sensitivity and phase-difference noise. The temperature response of the interleaved spiral acquisition was found to be comparable to a spoiled fast gradient-echo sequence of comparable in-plane spatial resolution. However, when imaging with an optimal echo time, spiral acquisition offers dramatically increased temporal resolution for comparable spatial resolution. Magn Reson Med 43:909-912, 2000.

    View details for Web of Science ID 000087430000020

    View details for PubMedID 10861889

  • Dynamic breast MRI with spiral trajectories: 3D versus 2D JOURNAL OF MAGNETIC RESONANCE IMAGING Yen, Y. F., Han, K. F., Daniel, B. L., Heiss, S., Birdwell, R. L., Herfkens, R. J., Sawyer-Glover, A. M., Glover, G. H. 2000; 11 (4): 351-359


    A three-dimensional (3)D spiral sequence was developed for dynamic breast magnetic resonance (MR) imaging with much improved image quality. Partial Z phase encoding was applied to obtain thinner slices for a coverage of the whole breast. Comparison between the 3D and a previously developed multi-slice 2D spiral sequences was performed on ten healthy volunteers without contrast and five breast patients with gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA). The 3D spiral images had significantly less off-resonance blurring and spiral artifacts. With a small compromise on temporal resolution (7.7 seconds in 2D and 10.6 seconds in 3D), we obtained 32 interpolated 3-5 mm slices (with 20 Z phase encodes) for a full coverage of 10-16 cm breast with the same 1 x 1 mm2 in-plane resolution as the 2D sequence, which had 12 8-13 mm slices. Contrast between glandular and soft tissue in normal breasts was increased by about 25%. The reduced repetition time in the 3D spiral acquisition led to an increased Gd-enhanced signal. The difference between the enhancement of malignant and benign lesions increased by sevenfold. We expect that this new development could lead to improved specificity in characterizing breast lesions using MR imaging.

    View details for Web of Science ID 000087572700002

    View details for PubMedID 10767063

  • Characterization of breast lesion morphology with delayed 3DSSMT: An adjunct to dynamic breast MRI JOURNAL OF MAGNETIC RESONANCE IMAGING Leong, C. S., Daniel, B. L., Herfkens, R. J., Birdwell, R. L., Jeffrey, S. S., Ikeda, D. M., Sawyer-Glover, A. M., Glover, G. H. 2000; 11 (2): 87-96


    The purpose of the study was to determine the sensitivity and specificity of various morphologic criteria in distinguishing malignant from benign breast lesions using a new sequence (3DSSMT) performed immediately after dynamic breast MRI. 3DSSMT combines a water-selective spectral-spatial excitation and an on-resonance magnetization transfer pulse with three-dimensional spoiled gradient-echo imaging. Morphologic features of 87 pathologically confirmed lesions were analyzed. The presence of either skin thickening, or a combination of a spiculated or microlobulated border, with a rim, ductal, linear, or clumped enhancement pattern was 94% specific and 54% sensitive for malignancy. Conversely, the presence of either a perfectly smooth border, a well-defined margin, non-enhancing internal septations, or a macrolobulated border was 97% specific and 35% sensitive for a benign diagnosis. In conclusion, delayed 3DSSMT discriminates a significant number of benign and malignant breast lesions; it has the potential to improve the diagnostic accuracy of dynamic breast MRI.

    View details for Web of Science ID 000086078100003

    View details for PubMedID 10713939

  • Time course of odorant-induced activation in the human primary olfactory cortex JOURNAL OF NEUROPHYSIOLOGY Sobel, N., Prabhakaran, V., Zhao, Z., Desmond, J. E., Glover, G. H., SULLIVAN, E. V., Gabrieli, J. D. 2000; 83 (1): 537-551


    Paradoxically, attempts to visualize odorant-induced functional magnetic resonance imaging (fMRI) activation in the human have yielded activations in secondary olfactory regions but not in the primary olfactory cortex-piriform cortex. We show that odorant-induced activation in primary olfactory cortex was not previously made evident with fMRI because of the unique time course of activity in this region: in primary olfactory cortex, odorants induced a strong early transient increase in signal amplitude that then habituated within 30-40 s of odorant presence. This time course of activation seen here in the primary olfactory cortex of the human is almost identical to that recorded electrophysiologically in the piriform cortex of the rat. Mapping activation with analyses that are sensitive to both this transient increase in signal amplitude, and temporal-variance, enabled us to use fMRI to consistently visualize odorant-induced activation in the human primary olfactory cortex. The combination of continued accurate odorant detection at the behavioral level despite primary olfactory cortex habituation at the physiological level suggests that the functional neuroanatomy of the olfactory response may change throughout prolonged olfactory stimulation.

    View details for Web of Science ID 000084777800048

    View details for PubMedID 10634894

  • Hemispheric asymmetries and individual differences in visual concept learning as measured by functional MRI NEUROPSYCHOLOGIA Seger, C. A., Poldrack, R. A., Prabhakaran, V., Zhao, M., Glover, G. H., Gabrieli, J. D. 2000; 38 (9): 1316-1324


    Dynamic changes in brain regions active while learning novel visual concepts were examined in humans using functional magnetic resonance imaging. Participants learned to distinguish between exemplars of two categories, formed as distortions of different unseen prototype stimuli. Regions of the right hemisphere (dorsolateral prefrontal and inferior parietal areas) were active early in learning and throughout task performance, whereas homologous portions of the left hemisphere were active only in later stages of learning. Left dorsolateral prefrontal activation was found only in participants who showed superior conceptual learning. Such a progression from initial right-hemisphere processing of specific instances to bilateral activity as left-hemisphere conceptual processes are recruited may underlie the development of many forms of visual knowledge.

    View details for Web of Science ID 000088396500012

    View details for PubMedID 10865107

  • Convergent cortical representation of semantic processing in bilinguals BRAIN AND LANGUAGE Illes, J., Francis, W. S., Desmond, J. E., Gabrieli, J. D., Glover, G. H., Poldrack, R., Lee, C. J., Wagner, A. D. 1999; 70 (3): 347-363


    This study examined whether semantic processes in two languages (English and Spanish) are mediated by a common neural system in fluent bilinguals who acquired their second language years after acquiring their first language. Functional magnetic resonance imaging was performed while bilingual participants made semantic and nonsemantic decisions about words in Spanish and English. There was greater activation for semantic relative to nonsemantic decisions in left and right frontal regions, with greater left frontal activation. The locations of activations were similar for both languages, and no differences were found when semantic decisions for English and Spanish words were compared directly. These results demonstrate a shared frontal lobe system for semantic analysis of the languages and are consistent with cognitive research on bilingualism indicating that the two languages of a bilingual person access a common semantic system.

    View details for Web of Science ID 000084152700003

    View details for PubMedID 10600225

  • fMRI identifies a network of structures correlated with retention of positive and negative emotional memory PSYCHOBIOLOGY Canli, T., Zhao, Z., Desmond, J. E., Glover, G., Gabrieli, J. D. 1999; 27 (4): 441-452
  • Silicone breast implant rupture: Pitfalls of magnetic resonance imaging and relative efficacies of magnetic resonance, mammography, and ultrasound PLASTIC AND RECONSTRUCTIVE SURGERY Ikeda, D. M., Borofsky, H. B., Herfkens, R. J., Sawyer-Glover, A. M., Birdwell, R. L., Glover, G. H. 1999; 104 (7): 2054-2062


    The objective of this study was to evaluate the relative efficacies of magnetic resonance (MR) imaging, ultrasonography, and mammography in implant rupture detection and to illustrate pitfalls in MR image interpretation. Thirty patients referred by plastic surgeons with suspected breast implant rupture were prospectively evaluated using MR, ultrasonography, and mammography. Imaging examinations were interpreted independently and blindly for implant rupture and correlated to operative findings. Surgical correlation in 16 patients (53 percent) with 31 implants showed 13 (42 percent) were intact, 5 (16 percent) had severe gel bleed, and 13 (42 percent) were ruptured. MR sensitivity was 100 percent and specificity was 63 percent. Accuracy for rupture was 81 percent with MR, higher than with ultrasonography and mammography (77 and 59 percent, respectively). We describe a specific pitfall in MR interpretation, the "rat-tail" sign, composed of a medial linear extension of silicone along the chest wall. Seen in eight cases (four intact, three ruptures, one gel bleed), the rat-tail sign may lead to misdiagnosis of implant rupture if seen in isolation. Magnetic resonance imaging is more accurate and sensitive than ultrasonography and mammography in detecting breast implant rupture. We describe a new sign (rat-tail sign) composed of medial compression of the implant simulating silicone extrusion as a potential false-positive MR finding for rupture. This article presents clinical experience with magnetic resonance, mammography, and ultrasound in the diagnosis of implant rupture and defines and illustrates potential pitfalls of MR interpretation, including the new rat-tail sign.

    View details for Web of Science ID 000083854900017

    View details for PubMedID 11149768

  • Regional variability of cerebral blood oxygenation response to hypercapnia NEUROIMAGE Kastrup, A., Kruger, G., Glover, G. H., Neumann-Haefelin, T., Moseley, M. E. 1999; 10 (6): 675-681


    In functional magnetic resonance imaging studies changes in blood oxygenation level-dependent (BOLD) signal intensities during task activation are related to multiple physiological parameters such as cerebral blood flow, volume, and oxidative metabolism, as well as to the regional microvascular anatomy. Consequently, the magnitude of activation-induced BOLD signal changes may vary regionally and between subjects. The aim of this study was to use a uniform global stimulus such as hypercapnia to quantitatively investigate the regional BOLD response in the human brain. In 10 healthy volunteers, T2*-weighted gradient echo images were acquired for a total dynamic scanning time of 9 min during alternating periods of breath holding for 30 s after expiration and self-paced normal breathing for 60 s. Hypercapnia-induced BOLD signal changes in the sensorimotor cortex, frontal cortex, basal ganglia, visual cortex, and cerebellum were significantly different (P < 0.001) and varied from 1.8 to 5.1%. The highest BOLD signal changes were found in the cerebellum and visual cortex, whereas the lowest BOLD signal increase was observed in the frontal cortex. These results demonstrate a regional dependence of the BOLD signal changes during breath hold-induced hypercapnia, indirectly supporting the notion of regional different sensitivities of BOLD responses to task activation.

    View details for Web of Science ID 000084413100005

    View details for PubMedID 10600413

  • Unaliasing by Fourier-encoding the overlaps using the temporal dimension (UNFOLD), applied to cardiac imaging and fMRI MAGNETIC RESONANCE IN MEDICINE Madore, B., Glover, G. H., Pelc, N. J. 1999; 42 (5): 813-828


    In several applications, MRI is used to monitor the time behavior of the signal in an organ of interest; e.g., signal evolution because of physiological motion, activation, or contrast-agent accumulation. Dynamic applications involve acquiring data in a k-t space, which contains both temporal and spatial information. It is shown here that in some dynamic applications, the t axis of k-t space is not densely filled with information. A method is introduced that can transfer information from the k axes to the t axis, allowing a denser, smaller k-t space to be acquired, and leading to significant reductions in the acquisition time of the temporal frames. Results are presented for cardiac-triggered imaging and functional MRI (fMRI), and are compared with data obtained in a conventional way. The temporal resolution was increased by nearly a factor of two in the cardiac-triggered study, and by as much as a factor of eight in the fMRI study. This increase allowed the acquisition of fMRI activation maps, even when the acquisition time for a single full time frame was actually longer than the paradigm cycle period itself. The new method can be used to significantly reduce the acquisition time of the individual temporal frames in certain dynamic studies. This can be used, for example, to increase the temporal or spatial resolution, increase the spatial coverage, decrease the total imaging time, or alter sequence parameters e.g., repetition time (TR) and echo time (TE) and thereby alter contrast. Magn Reson Med 42:813-828, 1999.

    View details for Web of Science ID 000083447900001

    View details for PubMedID 10542340

  • A FAIR study of motor cortex activation under normo- and hypercapnia induced by breath challenge NEUROIMAGE Li, T. Q., Moseley, M. E., Glover, G. 1999; 10 (5): 562-569


    In this study an arterial spin-tagging technique based on flow-sensitive alternating inversion recovery (FAIR) with single-shot spiral data acquisition was used to study how the basal cerebral blood flow (CBF) elevated by breath holding affects the regional cerebral blood flow (rCBF) response to focal brain activation in the motor cortex. Six subjects were examined using three types of activation studies. These were (a) bilateral finger tapping paced at 4 Hz under normal breathing, (b) repeated expiration breath holding of 30 s, and (c) simultaneous breath holding and finger tapping. It was found that in five of six subjects the prevailing CBF level adjusted by breath challenge and the increase in rCBF in motor cortex associated with bilateral finger tapping were completely additive. This finding from FAIR-based functional magnetic resonance imaging is in accordance with that reported from published positron emission tomography studies. The results indicate that in the majority of the subjects examined the regulatory mechanisms for vasodilatory reaction to CO(2) and rCBF response to neural activation in motor cortex region are independent.

    View details for Web of Science ID 000083778900007

    View details for PubMedID 10547333

  • Gender differences in cerebral blood flow and oxygenation response during focal physiologic neural activity JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Kastrup, A., Li, T. Q., Glover, G. H., Kruger, G., Moseley, M. E. 1999; 19 (10): 1066-1071


    Using functional magnetic resonance imaging techniques CBF and oxygenation changes were measured during sustained checkerboard stimulation in 38 right-handed healthy volunteers (18 men and 20 women). The average blood oxygenation level dependent (BOLD) contrast technique signal intensity change was 1.67 +/- 0.6% in the group of male volunteers and 2.15 +/- 0.6% in the group of female volunteers (P < .05). Baseline regional CBF (rCBF) values in activated gray matter areas within the visual cortex were 57 +/- 10 mL x 100 g(-1) x min(-1) in women and 50 +/- 12 mL x 100 g(-1) x min(-1) in men, respectively (P = .09). Despite a broad overlap between both groups the rCBF increase was significantly higher in women compared to men (33 +/- 5 mL x 100 g(-1) x min(-1) versus 28 +/- 4 mL x 100 g(-1) x min(-1), P < .01). The increase of rCBF was not correlated with the baseline rCBF (mL x 100 g(-1) x min(-1)) (r(s) = 0.01, P = .9). Moreover, changes of rCBF were not correlated with changes in BOLD signal intensities (r(s) = 0.1, P = .7). Enhanced rCBF response in women during visual stimulation could be related to gender differences in visual physiology or may reflect gender differences in the vascular response to focal neuronal activation. Gender differences must be considered when interpreting the results of functional magnetic resonance imaging studies.

    View details for Web of Science ID 000084883900002

    View details for PubMedID 10532630

  • Simultaneous monitoring of dynamic changes in cerebral blood flow and oxygenation during sustained activation of the human visual cortex NEUROREPORT Kruger, G., Kastrup, A., Takahashi, A., Glover, G. H. 1999; 10 (14): 2939-2943


    Functional neuroimaging was used to investigate the effect of cerebral blood flow (CBF) adjustments on the blood oxygenation level dependent (BOLD) signal during visual stimulation. Temporal responses from both oxygenation- and perfusion-sensitized MRI revealed almost identical features during onset and ongoing activation, i.e. an activation-induced signal rise, and a gradual signal decrease during prolonged activation (overshoot). However, the post-stimulus responses exhibited a pronounced BOLD signal drop below prestimulus baseline (undershoot), but a rather rapid normalisation of the related CBF signal. Thus, an activation-induced initial BOLD signal rise and a gradual signal decrease reflect a coarse upregulation of CBF, which is followed by fine-tuning adjustments of flow. Regulations of other involved physiological parameters, including blood volume and oxidative metabolism give rise to a negative post-stimulus BOLD signal response.

    View details for Web of Science ID 000082865500015

    View details for PubMedID 10549801

  • Assessment of cerebral oxidative metabolism with breath holding and fMRI MAGNETIC RESONANCE IN MEDICINE Kastrup, A., Kruger, G., Glover, G. H., Moseley, M. E. 1999; 42 (3): 608-611


    Carbon dioxide inhalation can be used to map changes in cerebral metabolic rate of oxygen (CMRO(2)) during neuronal activation with functional MRI (fMRI). A hypercapnic stress also can be achieved with a simple breath-holding test. Using this test as means of manipulating cerebral blood flow (CBF) independent of CMRO(2), we assessed changes in CMRO(2) during visual stimulation. With this task, CBF increased by 61 +/- 7%, whereas CMRO(2) changed by 2.43 +/- 4.97%. These results are in good agreement with previous positron emission tomographic (PET) data, indicating that changes in oxidative metabolism during focal neuronal activity can potentially be determined with the breath-holding test. This test could easily be performed during a routine MRI examination. Magn Reson Med 42:608-611, 1999.

    View details for Web of Science ID 000082346300026

    View details for PubMedID 10467308

  • Simple analytic spiral K-space algorithm MAGNETIC RESONANCE IN MEDICINE Glover, G. H. 1999; 42 (2): 412-415


    The exact, hardware-constrained design of a spiral k-space trajectory requires the solution of a differential equation, thereby making real-time prescription difficult on scanners with limited computational power. This study describes a closed-form approximate solution for interleaved Archimedian spiral trajectories that closely matches the exact design. Both slew rate-limited and amplitude-limited regimes are incorporated. Magn Reson Med 42:412-415, 1999.

    View details for Web of Science ID 000081758100025

    View details for PubMedID 10440968

  • Cerebral blood flow-related signal changes during breath-holding AMERICAN JOURNAL OF NEURORADIOLOGY Kastrup, A., Li, T. Q., Glover, G. H., Moseley, M. E. 1999; 20 (7): 1233-1238


    In the past, functional MR imaging techniques have been used successfully to determine cerebrovascular reactivity (CVR) to various stimuli, complementing the arsenal of functional brain investigations feasible with MR imaging. While previous studies have focused on blood oxygenation changes under vasodilatory stress, the aim of this study was to assess regional cerebral blood flow (rCBF) changes during breath-holding by using a flow-sensitive alternating inversion recovery (FAIR) imaging technique.In six healthy volunteers, FAIR images were acquired during alternating periods of breath-holding and breathing at 40-second intervals after inspiration and at 30-second intervals after expiration, for a total dynamic scanning time of 10 minutes. To quantify the rCBF changes, we obtained 2.5-minute baseline samples during normal breathing.Repeated challenges of breath-holding induced an overall rise in rCBF. In general, rCBF changes were greatest in gray matter and were insignificant in white matter. Using the mean values of the baseline images collected before breath-holding to calculate the rCBF changes, we found that quantitative analysis yielded an rCBF increase of 47% to 87% after breath-holding. The rCBF changes clearly depended on the breath-holding duration and technique; however, for one given breath-holding paradigm the results showed relatively small interindividual variability.rCBF changes during a simple vascular challenge can be detected and quantified by means of functional MR imaging at 1.5 T. Noninvasive assessment of CVR could become a useful clinical tool to identify persons with impaired CVR.

    View details for Web of Science ID 000082349200010

    View details for PubMedID 10472977

  • Imagined transformations of bodies: an fMRI investigation NEUROPSYCHOLOGIA Zacks, J., Rypma, B., Gabrieli, J. D., Tversky, B., Glover, G. H. 1999; 37 (9): 1029-1040


    A number of spatial reasoning problems can be solved by performing an imagined transformation of one's egocentric perspective. A series of experiments were carried out to characterize this process behaviorally and in terms of its brain basis, using functional magnetic resonance imaging (tMRI). In a task contrast designed to isolate egocentric perspective transformations, participants were slower to make left-right judgments about a human figure from the figure's perspective than from their own. This transformation led to increased cortical activity around the left parietal-temporal-occipital junction, as well as in other areas including left frontal cortex. In a second task contrast comparing judgments about inverted figures to judgments about upright figures (always from the figure's perspective), participants were slower to make left-right judgments about inverted figures than upright ones. This transformation led to activation in posterior areas near those active in the first experiment, but weaker in the left hemisphere and stronger in the right, and also to substantial left frontal activation. Together, the data support the specialization of areas near the parietal-temporal-occipital junction for egocentric perspective transformations. These results are also suggestive of a dissociation between egocentric perspective transformations and object-based spatial transformations such as mental rotation.

    View details for Web of Science ID 000081926300004

    View details for PubMedID 10468366

  • 3D z-shim method for reduction of susceptibility effects in BOLD fMRI MAGNETIC RESONANCE IN MEDICINE Glover, G. H. 1999; 42 (2): 290-299


    Susceptibility-induced magnetic field gradients (SFGs) perpendicular to the slice plane often result in signal dropout in blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) experiments. Two-dimensional (2D) z-shim methods reduce these effects by acquiring multiple images with different slice refocusing gradient areas. In this work a 3D z-shim method is introduced as a more efficient alternative. The technique augments the k-space data for a conventional 3D phase encoding acquisition with N additional lines that extend the k(z) coverage sufficiently to sample k-space fully in regions with SFGs. Multiple subsets of these data are reconstructed using a sliding window that provides N +1 z-shim images. Fewer total acquisitions are required than with the 2D method for the same coverage, and finer z-shim steps are obtained. The technique is demonstrated with a motor task using intentionally introduced SFGs and compared with the 2D method. The results confirm increased BOLD SNR and activation with the new method in good agreement with theory. Magn Reson Med 42:290-299, 1999.

    View details for Web of Science ID 000081758100011

    View details for PubMedID 10440954

  • Functional specialization for semantic and phonological processing in the left inferior prefrontal cortex NEUROIMAGE Poldrack, R. A., Wagner, A. D., Prull, M. W., Desmond, J. E., Glover, G. H., Gabrieli, J. D. 1999; 10 (1): 15-35


    Neuroimaging and neuropsychological studies have implicated left inferior prefrontal cortex (LIPC) in both semantic and phonological processing. In this study, functional magnetic resonance imaging was used to examine whether separate LIPC regions participate in each of these types of processing. Performance of a semantic decision task resulted in extensive LIPC activation compared to a perceptual control task. Phonological processing of words and pseudowords in a syllable-counting task resulted in activation of the dorsal aspect of the left inferior frontal gyrus near the inferior frontal sulcus (BA 44/45) compared to a perceptual control task, with greater activation for nonwords compared to words. In a direct comparison of semantic and phonological tasks, semantic processing preferentially activated the ventral aspect of the left inferior frontal gyrus (BA 47/45). A review of the literature demonstrated a similar distinction between left prefrontal regions involved in semantic processing and phonological/lexical processing. The results suggest that a distinct region in the left inferior frontal cortex is involved in semantic processing, whereas other regions may subserve phonological processes engaged during both semantic and phonological tasks.

    View details for Web of Science ID 000081454800003

    View details for PubMedID 10385578

  • Relationship between cerebral blood flow changes during visual stimulation and baseline flow levels investigated with functional MRI NEUROREPORT Kastrup, A., Li, T. Q., Kruger, G., Glover, G. H., Moseley, M. E. 1999; 10 (8): 1751-1756


    Using fMRI, the relationship between regional cerebral blood flow (rCBF) changes during visual stimulation and the prevailing baseline global and regional flow levels was evaluated in 22 volunteers. The absolute increase in rCBF was not correlated with baseline rCBF values (r = 0.01, p = 0.8); however, the percentage change in rCBF showed a negative correlation (r=-0.78, p<0.001). Both absolute and relative changes in rCBF were independent of baseline global CBF values. These results indicate that caution should be exercised when comparing relative flow changes during focal brain activation, especially in functional neuroimaging studies dealing with altered baseline flow values.

    View details for Web of Science ID 000081225200025

    View details for PubMedID 10501569

  • Deconvolution of impulse response in event-related BOLD fMRI NEUROIMAGE Glover, G. H. 1999; 9 (4): 416-429


    The temporal characteristics of the BOLD response in sensorimotor and auditory cortices were measured in subjects performing finger tapping while listening to metronome pacing tones. A repeated trial paradigm was used with stimulus durations of 167 ms to 16 s and intertrial times of 30 s. Both cortical systems were found to be nonlinear in that the response to a long stimulus could not be predicted by convolving the 1-s response with a rectangular function. In the short-time regime, the amplitude of the response varied only slowly with stimulus duration. It was found that this character was predicted with a modification to Buxton's balloon model. Wiener deconvolution was used to deblur the response to concatenated short episodes of finger tapping at different temporal separations and at rates from 1 to 4 Hz. While the measured response curves were distorted by overlap between the individual episodes, the deconvolved response at each rate was found to agree well with separate scans at each of the individual rates. Thus, although the impulse response cannot predict the response to fully overlapping stimuli, linear deconvolution is effective when the stimuli are separated by at least 4 s. The deconvolution filter must be measured for each subject using a short-stimulus paradigm. It is concluded that deconvolution may be effective in diminishing the hemodynamically imposed temporal blurring and may have potential applications in quantitating responses in eventrelated fMRI.

    View details for Web of Science ID 000079863600006

    View details for PubMedID 10191170

  • A functional magnetic resonance imaging study of listening comprehension of languages in human at 3 tesla-comprehension Bevel and activation of the language areas NEUROSCIENCE LETTERS Nakai, T., Matsuo, K., Kato, C., Matsuzawa, M., Okada, T., Glover, G. H., Moriya, T., Inui, T. 1999; 263 (1): 33–36


    Passive listening comprehension of native and non-native language was investigated using high resolution functional magnetic resonance imaging (fMRI) at a static magnetic field strength of 3 tesla. Wernicke's area was activated by comprehensive and non-comprehensive languages indicating that this area is associated with common phonological processing of language. The task with comprehensive but non-native language activated Broca's area and angular gyrus most frequently. The activations in these areas may be related to demand in semantic and syntactic processing in listening comprehension. Supplementary motor area and pre-motor area were activated by comprehensive languages but not by non-comprehensive language. These motor controlling areas may be involved in semantic processing. Listening to comprehensive but non-native language seems to demand more networked co-processing.

    View details for DOI 10.1016/S0304-3940(99)00103-2

    View details for Web of Science ID 000079262100009

    View details for PubMedID 10218904

  • Blind smell: brain activation induced by an undetected air-borne chemical BRAIN Sobel, N., Prabhakaran, V., Hartley, C. A., Desmond, J. E., Glover, G. H., SULLIVAN, E. V., Gabrieli, J. D. 1999; 122: 209-217


    EEG and behavioural evidence suggests that air-borne chemicals can affect the nervous system without being consciously detected. EEG and behaviour, however, do not specify which brain structures are involved in chemical sensing that occurs below a threshold of conscious detection. Here we used functional MRI to localize brain activation induced by high and low concentrations of the air-borne compound oestra-1,3,5(10),16-tetraen-3yl acetate. Following presentations of both concentrations, eight of eight subjects reported verbally that they could not detect any odour (P = 0.004). Forced choice detection performed during the presentations revealed above-chance detection of the high concentration, but no better than chance detection of the low concentration compound. Both concentrations induced significant brain activation, primarily in the anterior medial thalamus and inferior frontal gyrus. Activation in the inferior frontal gyrus during the high concentration condition was significantly greater in the right than in the left hemisphere (P = 0.03). A trend towards greater thalamic activation was observed for the high concentration than the low concentration compound (P = 0.08). These findings localize human brain activation that was induced by an undetectable air-borne chemical (the low concentration compound).

    View details for Web of Science ID 000078756900005

    View details for PubMedID 10071050

  • Load-dependent roles of frontal brain regions in the maintenance of working memory NEUROIMAGE Rypma, B., Prabhakaran, V., Desmond, J. E., Glover, G. H., Gabrieli, J. D. 1999; 9 (2): 216-226


    Brain imaging studies have suggested a critical role for prefrontal cortex in working memory (WM) tasks that require both maintainenance and manipulation of information over time in delayed-response WM tasks. In the present study, functional magnetic resonance imaging (fMRI) was used to examine whether prefrontal areas are activated when only maintenance is required in a delayed-response WM task, without the overt requirement to manipulate the stored information. In two scans, six subjects performed WM tasks in which, on each trial, they (1) encoded 1, 3, or 6 to-be-remembered letters, (2) maintained these letters across a 5-second unfilled delay, and (3) determined whether a single probe letter was or was not part of the memory set. Activation of left caudal inferior frontal gyrus was observed, relative to the 1-letter task, when subjects were required to maintain 3 letters in WM. When subjects were required to maintain 6 letters in WM, additional prefrontal areas, most notably middle and superior frontal gyri, were activated bilaterally. Thus, increasing the amount of to-be-maintained information, without any overt manipulation requirement, resulted in the recruitment of wide-spread frontal-lobe regions. Inferior frontal gyrus activation was left-hemisphere dominant in both the 3- and 6-letter conditions, suggesting that such activation reflected material-specific verbal processes. Activation in middle and superior frontal gyri appeared only in the 6-letter condition and was right-hemisphere dominant, suggesting that such activation reflected material-independent executive processes.

    View details for Web of Science ID 000078608900004

    View details for PubMedID 9927550

  • Level of sustained entorhinal activity at study correlates with subsequent cued-recall performance: A functional magnetic resonance imaging study with high acquisition rate HIPPOCAMPUS Fernandez, G., Brewer, J. B., Zhao, Z., Glover, G. H., Gabrieli, J. D. 1999; 9 (1): 35-44


    Functional magnetic resonance imaging (fMRI) with high acquisition rate was performed during the intentional memorizing of words to specify which medial temporal lobe structure is important in determining what words are subsequently remembered in a cued-recall test and to characterize the time course of activation in that structure. Functional images of six healthy young subjects were analyzed by two subject- and voxel-wise statistics: First, to identify brain areas transiently engaged in encoding of words, brain activity during memorizing visually presented words and watching a fixation cross was compared by a Kolmogorov-Smirnov statistic (KS-test). Second, to identify brain areas whose activity correlates with memory encoding success, a Kendall's correlation was calculated between signal intensity at study and performance in a subsequent cued-recall test. Averaged signal intensities were plotted as a function of time to depict the time course of brain activity detected by both statistical tests. The level of slowly modulated, sustained activity in Brodmann area 28 (entorhinal cortex) did not respond transiently as study words appeared, but did correlate positively with subsequent test performance. More left than right activity in Brodmann area 45 (dorso-lateral prefrontal cortex) and bilateral activity in Brodmann area 44 (premotor cortex) exhibited transient hemodynamic responses that did not show any relation to subsequent memory performance. Thus, the study identified a novel pattern of slowly modulated brain activity in human entorhinal cortex that may represent a declarative memory encoding state whose level predicts whether experiences will be remembered or forgotten.

    View details for Web of Science ID 000079002000004

    View details for PubMedID 10088898

  • Relational processing during reasoning: An event-related fMRI study. Hadjiilieva, K., Prabhakaran, V., Dorfman, J., Dirksen, C., Zhao, Z., Desmond, J., Glover, G., Gabrieli, J. M I T PRESS. 1999: 60–60
  • Neuronal basis of contrast discrimination VISION RESEARCH Boynton, G. M., Demb, J. B., Glover, G. H., Heeger, D. J. 1999; 39 (2): 257-269


    Psychophysical contrast increment thresholds were compared with neuronal responses, inferred from functional magnetic resonance imaging (fMRI) to test the hypothesis that contrast discrimination judgements are limited by neuronal signals in early visual cortical areas. FMRI was used to measure human brain activity as a function of stimulus contrast, in each of several identifiable visual cortical areas. Contrast increment thresholds were measured for the same stimuli across a range of baseline contrasts using a temporal 2AFC paradigm. FMRI responses and psychophysical measurements were compared by assuming that: (1) fMRI responses are proportional to local average neuronal activity; (2) subjects choose the stimulus interval that evoked the greater average neuronal activity; and (3) variability in the observer's psychophysical judgements was due to additive (IID) noise. With these assumptions, FMRI responses in visual areas V1, V2d, V3d and V3A were found to be consistent with the psychophysical judgements, i.e. a contrast increment was detected when the fMRI responses in each of these brain areas increased by a criterion amount. Thus, the pooled activity of large numbers of neurons can reasonably well predict behavioral performance. The data also suggest that contrast gain in early visual cortex depends systematically on spatial frequency.

    View details for Web of Science ID 000078060400006

    View details for PubMedID 10326134

  • Functional magnetic resonance imaging of regional cerebral blood oxygenation changes during breath holding STROKE Kastrup, A., Li, T. Q., Takahashi, A., Glover, G. H., Moseley, M. E. 1998; 29 (12): 2641-2645


    BACKGROUND andRecently, noninvasive MRI methods have been developed that are now capable of detecting and mapping regional hemodynamic responses to various stress tests, which involve the use of vasoactive substances such as acetazolamide or inhalation of carbon dioxide. The aim of this study was to assess regional cerebral blood oxygenation changes during breath holding at 1.5 T.In 6 healthy volunteers, T2*-weighted gradient echo images were acquired for a total dynamic scanning time of 10 minutes during alternating periods of breath holding and normal breathing at 40-second intervals after inspiration, at 30-second intervals after expiration, and at 18 seconds after expiration. To quantify the relative signal changes, 2.5-minute baseline image sampling with normal breathing was carried out.Repeated challenges of breath holding of various durations induced an overall rise in blood oxygen level-dependent (BOLD) signal intensities. In general, BOLD signal intensity increases were greatest in gray matter and nonsignificant in white matter. Depending on the breath-holding duration and techniques, BOLD signal intensity increases of all activated pixels varied from 0.8% to 3.5%.The present study demonstrates that cerebral blood oxygenation changes during breath holding can be detected by means of fMRI at 1.5 T. The breath-holding test, a short and noninvasive method to study cerebral hemodynamics with fMRI, could become a useful alternative to the acetazolamide or CO2 test.

    View details for Web of Science ID 000077207900037

    View details for PubMedID 9836778

  • Selective effects of methylphenidate in attention deficit hyperactivity disorder: A functional magnetic resonance study PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Vaidya, C. J., Austin, G., Kirkorian, G., Ridlehuber, H. W., Desmond, J. E., Glover, G. H., Gabrieli, J. D. 1998; 95 (24): 14494-14499


    Functional MRI revealed differences between children with Attention Deficit Hyperactivity Disorder (ADHD) and healthy controls in their frontal-striatal function and its modulation by methylphenidate during response inhibition. Children performed two go/no-go tasks with and without drug. ADHD children had impaired inhibitory control on both tasks. Off-drug frontal-striatal activation during response inhibition differed between ADHD and healthy children: ADHD children had greater frontal activation on one task and reduced striatal activation on the other task. Drug effects differed between ADHD and healthy children: The drug improved response inhibition in both groups on one task and only in ADHD children on the other task. The drug modulated brain activation during response inhibition on only one task: It increased frontal activation to an equal extent in both groups. In contrast, it increased striatal activation in ADHD children but reduced it in healthy children. These results suggest that ADHD is characterized by atypical frontal-striatal function and that methylphenidate affects striatal activation differently in ADHD than in healthy children.

    View details for PubMedID 9826728

  • Material-specific lateralization of prefrontal activation during episodic encoding and retrieval NEUROREPORT Wagner, A. D., Poldrack, R. A., Eldridge, L. L., Desmond, J. E., Glover, G. H., Gabrieli, J. D. 1998; 9 (16): 3711-3717


    Although numerous neuroimaging studies have examined the functional neuroanatomy supporting episodic memory for verbal material, there have been few investigations of non-verbal episodic encoding and retrieval. We used fMRI to directly compare prefrontal activation elicited by verbal and non-verbal material during encoding and during retrieval. Regardless of the mnemonic operation (encoding/retrieval), inferior prefrontal activation lateralized based on material type. Verbal encoding and retrieval resulted in greater left inferior prefrontal activation, whereas non-verbal encoding and retrieval resulted in greater right inferior prefrontal activation. The similarity between inferior prefrontal activity during encoding and during retrieval indicates that these mnemonic operations depend on shared processes mediated by inferior prefrontal regions.

    View details for Web of Science ID 000077493400030

    View details for PubMedID 9858384

  • Breast disease: Dynamic spiral MR imaging 82nd Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America Daniel, B. L., Yen, Y. F., Glover, G. H., Ikeda, D. M., Birdwell, R. L., Sawyer-Glover, A. M., Black, J. W., Plevritis, S. K., Jeffrey, S. S., Herfkens, R. J. RADIOLOGICAL SOC NORTH AMERICA. 1998: 499–509


    To compare various subjective, empiric, and pharmacokinetic methods for interpreting findings at dynamic magnetic resonance (MR) imaging of the breast.Dynamic spiral breast MR imaging was performed in 52 women suspected of having or with known breast disease. Gadolinium-enhanced images were obtained at 12 locations through the whole breast every 7.8 seconds for 8.5 minutes after bolus injection of contrast material. Time-signal intensity curves from regions of interest corresponding to 57 pathologically proved lesions were analyzed by means of a two-compartment pharmacokinetic model, and the diagnostic performance of various parameters was analyzed.Findings included invasive carcinoma in 17 patients, isolated ductal carcinoma in situ (DCIS) in six, and benign lesions in 34. Although some overlap between carcinomas and benign diagnoses was noted for all parameters, receiver operating characteristic analysis indicated that the exchange rate constant had the greatest overall ability to discriminate benign and malignant disease. The elimination rate constant and washout were the most specific parameters. The exchange rate constant, wash-in, and extrapolation point were the most sensitive parameters. DCIS was not consistently distinguished from benign disease with any method.Dynamic spiral breast MR imaging proved an excellent method with which to collect contrast enhancement data rapidly enough that accurate comparisons can be made between many analytic methods.

    View details for PubMedID 9807580

  • Odorant-induced and sniff-induced activation in the cerebellum of the human JOURNAL OF NEUROSCIENCE Sobel, N., Prabhakaran, V., Hartley, C. A., Desmond, J. E., Zhao, Z., Glover, G. H., Gabrieli, J. D., SULLIVAN, E. V. 1998; 18 (21): 8990-9001


    Functional magnetic resonance imaging was used to test whether odorants induce activation in the cerebellum of the human. The odorants vanillin and propionic acid both induced significant activation, primarily in the posterior lateral hemispheres. Activation was concentration-dependent, greater after stimulation with higher concentration odorants. By contrast, the action of sniffing nonodorized air induced significant activation in the anterior cerebellum, primarily in the central lobule. These findings demonstrate that the cerebellum plays a role in human olfaction. A hypothesis is proposed whereby the cerebellum maintains a feedback mechanism that regulates sniff volume in relation to odor concentration.

    View details for Web of Science ID 000076616600042

    View details for PubMedID 9787004

  • Hemispheric asymmetry for emotional stimuli detected with fMRI NEUROREPORT Canli, T., Desmond, J. E., Zhao, Z., Glover, G., Gabrieli, J. D. 1998; 9 (14): 3233-3239


    Current brain models of emotion processing hypothesize that positive (or approach-related) emotions are lateralized towards the left hemisphere, whereas negative (or withdrawal-related) emotions are lateralized towards the right hemisphere. Brain imaging studies, however, have so far failed to document such hemispheric lateralization. In a functional magnetic resonance imaging (fMRI) study, 14 female subjects viewed alternating blocks of emotionally valenced positive and negative pictures. When the experience of valence was equated for arousal, overall brain reactivity was lateralized towards the left hemisphere for positive pictures and towards the right hemisphere for negative pictures. This study provides direct support for the valence hypothesis, under conditions of equivalent arousal, by means of functional brain imaging.

    View details for Web of Science ID 000076974600022

    View details for PubMedID 9831457

  • Prefrontal cortex and recognition memory - Functional-MRI evidence for context-dependent retrieval processes BRAIN Wagner, A. D., Desmond, J. E., Glover, G. H., Gabrieli, J. D. 1998; 121: 1985-2002


    Functional neuroimaging studies of episodic recognition memory consistently demonstrate retrieval-associated activation in right prefrontal regions, including the right anterior and right dorsolateral prefrontal cortices. In theory, these activations could reflect processes associated with retrieval success, retrieval effort or retrieval attempt; each of these hypotheses has some support from previous studies. In Experiment 1, we examined these functional interpretations using functional MRI to measure prefrontal activation across multiple levels of recognition performance. Results revealed similar patterns of right prefrontal activation across varying levels of retrieval success and retrieval effort, suggesting that these activations reflect retrieval attempt. Retrieval attempt may include initiation of retrieval search or evaluation of the products of retrieval, such as scrutiny of specific attributes of the test item in an effort to determine whether it was encountered previously. In Experiment 2, we examined whether engagement of retrieval attempt is context-dependent by varying the context in which retrieval was performed; this was done by changing test instructions. Importantly, study and test stimuli were held constant, with only the test instructions varying across conditions. Results revealed that the pattern of right prefrontal activation varied across retrieval contexts. Collectively, these experiments suggest that right prefrontal regions mediate processes associated with retrieval attempt, with the probability of engaging these regions depending upon the retrieval context. Conflicting results across previous studies may be reconciled if the influence of retrieval context on the adopted retrieval strategy is considered. Finally, these results suggest that right prefrontal regions activated during recognition are not critical for successful performance as similar magnitudes of activation were present across multiple levels of performance. These findings reconcile imaging results with the selective effects of prefrontal lesions on retrieval-intensive episodic memory tests.

    View details for Web of Science ID 000076550700013

    View details for PubMedID 9798751

  • Making memories: Brain activity that predicts how well visual experience will be remembered SCIENCE Brewer, J. B., Zhao, Z., Desmond, J. E., Glover, G. H., Gabrieli, J. D. 1998; 281 (5380): 1185-1187


    Experiences are remembered or forgotten, but the neural determinants for the mnemonic fate of experience are unknown. Event-related functional magnetic resonance imaging was used to identify specific brain activations that differentiated between visual experiences that were later remembered well, remembered less well, or forgotten. During scanning of medial temporal lobe and frontal lobe regions, subjects viewed complex, color photographs. Subjects later received a test of memory for the photographs. The magnitudes of focal activations in right prefrontal cortex and in bilateral parahippocampal cortex predicted which photographs were later remembered well, remembered less well, or forgotten.

    View details for Web of Science ID 000075531200051

    View details for PubMedID 9712581

  • Differential activation of dorsal basal ganglia during externally and self paced sequences of arm movements NEUROREPORT Menon, V., Glover, G. H., Pfefferbaum, A. 1998; 9 (7): 1567-1573


    The basal ganglia are thought to be critically involved in motor control. However, the relative contributions of the various sub-components are not known. Although, in principle, functional magnetic resonance imaging (fMRI) provides adequate resolution to image the basal ganglia at the spatial scale of the individual nuclei, activating these nuclei with fMRI has proven to be difficult. Here we report two tasks, involving externally and self paced sequences of arm movements, which resulted in significant activation of contralateral posterior (post-commissural) putamen and globus pallidus. This activation did not significantly differ between the tasks. In contrast, significant activation of the contralateral and ipsilateral anterior caudate and anterior putamen was observed only during externally paced arm movements. These results suggest a dissociation in the roles of the anterior and posterior dorsal basal ganglia: the anterior caudate and putamen may be involved in sensory to motor mapping and the posterior putamen and globus pallidus may be involved in the motor response itself. The findings support the hypothesis that the basal ganglia may be involved in gating sensory influences onto motor areas.

    View details for Web of Science ID 000074000000061

    View details for PubMedID 9631468

  • The International Society for Magnetic Resonance in Medicine. Research directions in MR imaging. Radiology Glover, G. H., Herfkens, R. J. 1998; 207 (2): 289-295

    View details for PubMedID 9577469

  • Dissociation of frontal and cerebellar activity in a cognitive task: Evidence for a distinction between selection and search NEUROIMAGE Desmond, J. E., Gabrieli, J. D., Glover, G. H. 1998; 7 (4): 368-376


    Human brain imaging studies have found that increases in functional activation in left-frontal cortex during cognitive tasks are often accompanied by similar increases in right-cerebellar regions. The present study used functional magnetic resonance imaging (fMRI) to investigate the distinctive contributions of these regions using a word stem completion task. Stems with many possible completions (MANY condition) were alternately presented with stems that had few possible completions (FEW condition), and subjects were asked to covertly complete each stem with a word and press a response switch for each successful completion. Prominent increases in activation in the MANY, relative to the FEW, condition were observed in the left middle frontal gyrus (Brodmann areas 9/10) and left caudate nucleus. In contrast, portions of the right-cerebellar hemisphere (posterior quadrangular lobule and superior semilunar lobule) and cerebellar vermis exhibited increases in the FEW, relative to the MANY, condition. This double dissociation suggests that the frontal and cerebellar regions make distinctive contributions to cognitive performance, with left-frontal (and striatal) activations reflecting response selection, which increases in difficulty when there are many appropriate responses, and right-cerebellar activation reflecting the search for responses, which increases in difficulty when even a single appropriate response is hard to retrieve.

    View details for Web of Science ID 000074048500009

    View details for PubMedID 9626676

  • Breast lesion localization: A freehand, interactive MR imaging-guided technique RADIOLOGY Daniel, B. L., Birdwell, R. L., Ikeda, D. M., Jeffrey, S. S., Black, J. W., Block, W. F., Sawyer-Glover, A. M., Glover, G. H., Herfkens, R. J. 1998; 207 (2): 455-463


    To evaluate interactive magnetic resonance (MR) imaging-guided preoperative needle localization and hookwire placement in the noncompressed breast in patients in the prone position.Nineteen MR imaging-guided breast lesion localization procedures were performed in 17 patients aged 38-70 years (mean age, 48 years) by using an open-platform breast coil in either a 1.5-T, closed-bore imager (n = 14) or a 0.5-T, open-bore imager (n = 5). Rapid imaging (fast spin-echo, water-selective fast spin-echo, or water-specific three-point Dixon gradient-echo) was alternated with freehand manipulation of an MR-compatible needle to achieve accurate needle placement.Up to three manipulations of the needle were required during an average of 9 minutes to reach the target lesion. MR imaging findings confirmed the final needle position within 9 mm of the target in all cases. The accuracy of 10 localizations was independently corroborated either at mammography or at ultrasonography. Nine lesions were visible on MR images only.Interactive MR imaging-guided, freehand needle localization is simple, accurate, and requires no special stereotactic equipment. Lesions throughout the breast, including those in the anterior part of the breast and those near the chest wall, which can be inaccessible with standard grid or compression-plate techniques, can be localized. A variety of needle trajectories in addition to the horizontal path are possible, including circumareolar approaches and tangential needle paths designed to avoid puncture of implants.

    View details for Web of Science ID 000073204300031

    View details for PubMedID 9577495

  • Breast cancer: Gadolinium-enhanced MR imaging with a 0.5-T open imager and three-point Dixon technique RADIOLOGY Daniel, B. L., Butts, K., Glover, G. H., Cooper, C., Herfkens, R. J. 1998; 207 (1): 183-190


    To investigate the three-point Dixon technique as a method for obtaining fat-nulled images of contrast material-enhancing breast lesions with a 0.5-T open magnetic resonance (MR) imager.Real and imaginary source images were obtained with an interleaved gradient-echo sequence with a repetition time of 550 msec and echo times of 12.8, 19.8, and 26.8 msec. Twenty-four to 28 sections were obtained in the sagittal plane with a 90 degrees flip angle, 256 x 192 matrix, 3-4.5-mm section thickness, and acquisition time of 10 minutes 54 seconds. A three-point Dixon reconstruction algorithm was used to generate water-specific, fat-specific, and combined images from the raw image data. Twelve breasts in 10 patients and one healthy volunteer were imaged.Three-point Dixon images were superior to extended two-point Dixon and fat-suppressed images and to images generated by means of subtraction of three-dimensional fast spoiled gradient-echo images obtained before contrast material injection from those obtained after.Three-point Dixon imaging provides a robust method for creating fat-nulled images of enhancing breast lesions in the 0.5-T open MR environment. Water-specific three-point Dixon images are successful in regions of B0 heterogeneity and are superior to fat-suppressed images. They are much less susceptible to motion artifact than are subtraction images.

    View details for PubMedID 9530315

  • Gradient characterization using a Fourier-transform technique MAGNETIC RESONANCE IN MEDICINE Alley, M. T., Glover, G. H., Pelc, N. J. 1998; 39 (4): 581-587


    This paper describes a technique for characterizing the gradient subsystem of a magnetic resonance (MR) system. The technique uses a Fourier-transform analysis to directly measure the k-space trajectory produced by an arbitrary gradient waveform. In addition, the method can be easily extended to multiple dimensions and can be adapted to measuring residual gradient effects such as eddy currents. Several examples of gradient waveform and eddy-current measurements are presented. Also, it is demonstrated how the eddy-current measurements can be parameterized with an impulse-response formalism for later use in system tuning. When compared to a peak-fitting analysis, this technique provides a more direct extraction of the k-space measurements, which reduces the possibility of analysis error. This approach also has several advantages as compared to the conventional eddy-current measurement technique, including the ability to measure very short time constant effects.

    View details for Web of Science ID 000072700900010

    View details for PubMedID 9543420

  • Sniffing and smelling: separate subsystems in the human olfactory cortex NATURE Sobel, N., Prabhakaran, V., Desmond, J. E., Glover, G. H., Goode, R. L., SULLIVAN, E. V., Gabrieli, J. D. 1998; 392 (6673): 282-286


    The sensation and perception of smell (olfaction) are largely dependent on sniffing, which is an active stage of stimulus transport and therefore an integral component of mammalian olfaction. Electrophysiological data obtained from study of the hedgehog, rat, rabbit, dog and monkey indicate that sniffing (whether or not an odorant is present) induces an oscillation of activity in the olfactory bulb, driving the piriform cortex in the temporal lobe, in other words, the piriform is driven by the olfactory bulb at the frequency of sniffing. Here we use functional magnetic resonance imaging (fMRI) that is dependent on the level of oxygen in the blood to determine whether sniffing can induce activation in the piriform of humans, and whether this activation can be differentiated from activation induced by an odorant. We find that sniffing, whether odorant is present or absent, induces activation primarily in the piriform cortex of the temporal lobe and in the medial and posterior orbito-frontal gyri of the frontal lobe. The source of the sniff-induced activation is the somatosensory stimulation that is induced by air flow through the nostrils. In contrast, a smell, regardless of sniffing, induces activation mainly in the lateral and anterior orbito-frontal gyri of the frontal lobe. The dissociation between regions activated by olfactory exploration (sniffing) and regions activated by olfactory content (smell) shows a distinction in brain organization in terms of human olfaction.

    View details for Web of Science ID 000072612300047

    View details for PubMedID 9521322

  • Event-related FMRI of medial lobe involvement in declarative memory formation. Brewer, J. B., Zhao, M., Marling, T. S., Desmond, J. E., Glover, G. H., Gabrieli, J. D. MIT PRESS. 1998: 121–121
  • Recognition memory in the inclusion-exclusion paradigm: An FMRI study. Dorfman, J., Wagner, A. D., Stebbins, G. T., Dirksen, C., Turner, D., Glover, G. H., Desmond, J. E., Gabrielli, D. E. MIT PRESS. 1998: 51–51
  • A fMRI study of the effect of aging on frontal activation during semantic encoding. Carrillo, M. C., Stebbins, G. T., Gabrieli, J. D., Desmond, J. E., Dirksen, C., Turner, D., Glover, G. H. MIT PRESS. 1998: 53–53
  • Influence of aging on semantic and episodic memory: A functional magnetic resonance imaging (fMRI) study. Stebbins, G. T., Gabrieli, J. D., Carrillo, M. C., Dorfman, J., Dirksen, C., Turner, D., Glover, G., Desmond, J. MIT PRESS. 1998: 52–52
  • Somatotopy of the human arm using fMRI NEUROREPORT Servos, P., Zacks, J., Rumelhart, D. E., Glover, G. H. 1998; 9 (4): 605-609


    We describe a technique for mapping out human somatosensory cortex using functional magnetic resonance imaging (fMRI). To produce cortical activation, a pneumatic apparatus presented subjects with a periodic series of air puffs in which a sliding window of five locations moved along the ventral surface of the left arm in a proximal-to-distal or distal-to-proximal direction. This approach, in which the phase-delay of the stimulus can be used to produce somatotopic maps of somatosensory cortex, is based on a method used to generate retinotopic maps of visual cortex. Functional images were acquired using an echoplanar 1.5T scanner and a T2*-weighted spiral acquisition pulse sequence. The periodic series of air puffs created phase-related activation in two cortical regions of the contralateral parietal lobe, the posterior bank of the central sulcus and a more posterior and lateral region.

    View details for Web of Science ID 000072541400009

    View details for PubMedID 9559924

  • Self-navigated spiral fMRI: Interleaved versus single-shot MAGNETIC RESONANCE IN MEDICINE Glover, G. H., Lai, S. 1998; 39 (3): 361-368


    This study compares the measured activation volumes in motor cortex as well as the fluctuation noise and off-resonance characteristics for 1-, 2-, and 4-shot spiral gradient-recalled echo blood oxygen level dependent contrast functional magnetic resonance imaging (fMRI) acquisitions, under conditions of constant resolution and scan time and with two readout durations. Reconstructions were made with and without self-navigator correction. It was found that the navigator correction provided a 50% reduction in image fluctuation noise with 4-shot acquisitions, and that multishot acquisitions perform as well as single-shot techniques when self-navigation is employed. An analysis of blurring showed that off-resonance delta f causes blurring when delta f > 1/(2*Tad), where Tad is the readout duration. Off-resonance effects were readily corrected during reconstruction with retrospective linear shim, even with the longer readout duration needed for single-shot methods. With navigator and shim correction, single-shot and multishot spiral methods are highly effective for fMRI acquisitions.

    View details for Web of Science ID 000072087900004

    View details for PubMedID 9498591

  • Concomitant gradient terms in phase contrast MR: Analysis and correction MAGNETIC RESONANCE IN MEDICINE Bernstein, M. A., Zhou, X. H., Polzin, J. A., King, K. F., Ganin, A., Pelc, N. J., Glover, G. H. 1998; 39 (2): 300-308


    Whenever a linear gradient is activated, concomitant magnetic fields with non-linear spatial dependence result. This is a consequence of Maxwell's equations, i.e., within the imaging volume the magnetic field must have zero divergence, and has negligible curl. The concomitant, or Maxwell field has been described in the MRI literature for over 10 years. In this paper, we theoretically and experimentally show the existence of two additional lowest-order terms in the concomitant field, which we call cross-terms. The concomitant gradient cross-terms only arise when the longitudinal gradient Gz is simultaneously active with a transverse gradient (Gx or Gy). The effect of all of the concomitant gradient terms on phase contrast imaging is examined in detail. Several methods for reducing or eliminating phase errors arising from the concomitant magnetic field are described. The feasibility of a joint pulse sequence-reconstruction method, which requires no increase in minimum TE, is demonstrated. Since the lowest-order terms of the concomitant field are proportional to G2/B0, the importance of concomitant gradient terms is expected to increase given the current interest in systems with stronger gradients and/or weaker main magnetic fields.

    View details for Web of Science ID 000071665800017

    View details for PubMedID 9469714

  • Three-dimensional spiral fMRI technique: A comparison with 2D spiral acquisition 4th Annual Meeting of ISMRM Lai, S., Glover, G. H. JOHN WILEY & SONS INC. 1998: 68–78


    A comparison study was performed of 3D and 2D spiral k-space fMRI techniques using BOLD contrast with a 4.25-min finger-tapping task paradigm. The 3D sequence uses the conventional 2D spiral technique in conjunction with Fourier phase encoding in the slice select direction. Characteristics that were compared included image appearances, signal-to-noise ratio (SNR), fluctuation noise, functional contrast-to-noise ratio (fCNR), detected activation areas, inflow effect, and large vessel involvement. The results showed that, with constant total scan time, the 3D spiral acquisition has higher SNR and fCNR despite its slightly higher fluctuation noise. The capability for thin-slice incoherent averaging is a further advantage of 3D over 2D. With these advantages as well as its intrinsic ability for contiguous slices and image reformatting, the 3D spiral fMRI technique may be superior to its 2D counterpart.

    View details for Web of Science ID 000071161400011

    View details for PubMedID 9438439

  • A comparison of fast MR scan techniques for cerebral activation studies at 1.5 Tesla MAGNETIC RESONANCE IN MEDICINE Yang, Y. H., Glover, G. H., van Gelderen, P., Patel, A. C., Mattay, V. S., Frank, J. A., Duyn, J. H. 1998; 39 (1): 61–67


    To evaluate the sensitivity of fast, gradient-echo MR scan techniques in their ability to detect blood oxygenation level dependent (BOLD) signal changes in task activation studies, three dedicated fast scan techniques, each with whole-brain coverage, were compared during a 3-min finger tapping paradigm on nine normal volunteers on a clinical 1.5 T scanner. Multislice (2D) single-shot spiral, 3D spiral, and multislice (2D) single-shot EPI scan techniques were done with similar temporal and spatial resolutions on each of the volunteers in random order. After image registration and statistical analysis, the sensitivity to detect activation was evaluated for the techniques by calculating t scores and number of activated voxels in predetermined regions of interest, including the contralateral primary sensorimotor cortex, the premotor region, the parietal region, the supplementary motor area, and the ipsilateral cerebellum. Baseline images acquired with the three techniques were qualitatively comparable and had a similar effective spatial resolution of around 5 x 5 x 5 mm3, as determined from autocorrelation analysis. The anatomical coverage was somewhat reduced (4 less slices per volume) with EPI at the identical temporal resolution of 1.76 s for all techniques. The use of multislice 2D spiral scan for motor cortex fMRI experiments provided for a superior overall temporal stability, and an increased sensitivity compared with multislice 2D EPI, and 3D spiral scan. The difference in sensitivity between multislice 2D spiral and EPI scans was small, in particular in the case of a ramp-sampled version of EPI. The difference in performance is attributed mainly to the difference in scan-to-scan stability.

    View details for DOI 10.1002/mrm.1910390111

    View details for Web of Science ID 000071161400010

    View details for PubMedID 9438438

  • The neural basis of visual skill learning: An fMRI study of mirror reading CEREBRAL CORTEX Poldrack, R. A., Desmond, J. E., Glover, G. H., Gabrieli, J. D. 1998; 8 (1): 1-10


    The learning of perceptual skills is thought to rely upon multiple regions in the cerebral cortex, but imaging studies have not yet provided evidence about the changes in neural activity that accompany visual skill learning. Functional magnetic resonance imaging (fMRI) was used to examine changes in activation of posterior brain regions associated with the acquisition of mirror-reading skill for novel and practiced stimuli. Multiple regions in the occipital lobe, inferior temporal cortex, superior parietal cortex and cerebellum were involved in the reading of mirror-reversed compared to normally oriented text. For novel stimuli, skilled mirror-reading was associated with decreased activation in the right superior parietal cortex and posterior occipital regions and increased activation in the left inferior temporal lobe. These results suggest that learning to read mirror-reversed text involves a progression from visuospatial transformation to direct recognition of transformed letters. Reading practiced, relative to unpracticed, stimuli was associated with decreased activation in occipital visual cortices, inferior temporal cortex and superior parietal cortex and increased activation in occipito-parietal and lateral temporal regions. By examining skill learning and item-specific repetition priming in the same task, this study demonstrates that both of these forms of learning exhibit shifts in the set of neural structures that contribute to performance.

    View details for Web of Science ID 000071691300001

    View details for PubMedID 9510380

  • A method for functional magnetic resonance imaging of olfaction JOURNAL OF NEUROSCIENCE METHODS Sobel, N., Prabhakaran, V., Desmond, J. E., Glover, G. H., SULLIVAN, E. V., Gabrieli, J. D. 1997; 78 (1-2): 115-123


    A method for generating olfactory stimuli for humans within a functional magnetic resonance imaging (fMRI) experimental design is described. The system incorporates a nasal-mask in which the change from odorant to no-odorant conditions occurs in less than 500 ms and is not accompanied by visual, auditory, tactile, or thermal cues. The mask provides an ordorant-free environment following prolonged ordorant presence. Specific imaging parameters that are conducive to the study of the human olfactory system are described. In a pilot study performed using these methods, the specific patterns of activation observed converged with published experimental and clinical findings.

    View details for Web of Science ID 000071852900012

    View details for PubMedID 9497007

  • Lobular patterns of cerebellar activation in verbal working-memory and finger-tapping tasks as revealed by functional MRI JOURNAL OF NEUROSCIENCE Desmond, J. E., Gabrieli, J. D., Wagner, A. D., GINIER, B. L., Glover, G. H. 1997; 17 (24): 9675-9685


    The lobular distributions of functional activation of the cerebellum during verbal working-memory and finger movement tasks were investigated using functional magnetic resonance imaging (fMRI). Relative to a rest control, finger tapping of the right hand produced ipsilateral-increased activation in HIV/HV [Roman numeral designations based on Larsell's () nomenclature] and HVI and weaker activation in HVIII that was stronger on the ipsilateral side. For a working-memory task, subjects were asked to remember six (high load) or one (low load) visually presented letters across a brief delay. To assess the motoric aspects of rehearsal in the absence of working memory, we asked the subjects to repeatedly read subvocally six or one letters at a rate that approximated the internally generated rehearsal of working memory (motoric rehearsal task). For both tasks, bilateral regions of the superior cerebellar hemispheres (left superior HVIIA and right HVI) and portions of posterior vermis (VI and superior VIIA) exhibited increased activation during high relative to low load conditions. In contrast, the right inferior cerebellar hemisphere (HVIIB) exhibited this load effect only during the working-memory task. We hypothesize that HVI and superior HVIIA activation represents input from the articulatory control system of working memory from the frontal lobes and that HVIIB activation is derived from the phonological store in temporal and parietal regions. From these inputs, the cerebellum could compute the discrepancy between actual and intended phonological rehearsal and use this information to update a feedforward command to the frontal lobes, thereby facilitating the phonological loop.

    View details for Web of Science ID A1997YK82200028

    View details for PubMedID 9391022

  • Semantic repetition priming for verbal and pictorial knowledge: A functional MRI study of left inferior prefrontal cortex JOURNAL OF COGNITIVE NEUROSCIENCE Wagner, A. D., Desmond, J. E., Demb, J. B., Glover, G. H., Gabrieli, J. D. 1997; 9 (6): 714-726


    Functional neuroimaging studies of single-word processing have demonstrated decreased activation in left inferior prefrontal cortex (LIPC) during repeated semantic processing relative to initial semantic processing. This item-specific memory effect occurs under implicit test instructions and represents word-toword semantic repetition priming. The present study examined the stimulus generality of LIPC function by measuring prefrontal cortical activation during repeated relative to initial semantic processing of words (word-to-word semantic repetition priming) and of pictures (picture-to-picture semantic repetition priming). For both words and pictures, LIPC activation decreased with repetition, suggesting that this area subserves semantic analysis of stimuli regardless of perceptual form. Decreased activation was greater in extent for words than for pictures. The LIPC area may act as a semantic executive system that mediates on-line retrieval of long-term conceptual knowledge necessary for guiding task performance.

    View details for Web of Science ID 000071078700002

    View details for PubMedID 23964594

  • Combined event-related fMRI and EEG evidence for temporal-parietal cortex activation during target detection NEUROREPORT Menon, V., Ford, J. M., Lim, K. O., Glover, G. H., Pfefferbaum, A. 1997; 8 (14): 3029-3037


    Target detection is the process of bringing a salient stimulus into conscious awareness. Target detection evokes a prominent event-related potential (ERP) component (P3) in the electroencephalogram (EEG). We combined the high spatial resolution of functional magnetic resonance imaging (fMRI) with the high temporal resolution of EEG to investigate the neural generators of the P3. Event-related brain activation (ERBA) and ERPs were computed by time-locked averaging of fMRI and EEG, respectively, recorded using the same paradigm in the same subjects. Target detection elicited significantly greater ERBAs bilaterally in the temporal-parietal cortex, thalamus and anterior cingulate. Spatio-temporal modelling of ERPs based on dipole locations derived from the ERBAs indicated that bilateral sources in the temporal-parietal cortex are the main generators of the P3. The findings provide convergent fMRI and EEG evidence for significant activation of the temporal-parietal cortex 285-610 ms after stimulus onset during target detection. The methods developed here provide a novel multimodal neuroimaging technique to investigate the spatio-temporal aspects of processes underlying brain function.

    View details for Web of Science ID A1997XX91000009

    View details for PubMedID 9331910

  • Interactive MR-guided, 14-gauge core-needle biopsy of enhancing lesions in a breast phantom model ACADEMIC RADIOLOGY Daniel, B. L., Birdwell, R. L., Black, J. W., Ikeda, D. M., Glover, G. H., Herfkens, R. J. 1997; 4 (7): 508-512


    The authors attempted to determine the accuracy of magnetic resonance (MR) imaging-guided core-needle biopsy performed with a titanium biopsy needle in a breast phantom.Eight 6-7-mm lesions were created at random positions in a lard breast phantom. Each 0.2-mL lesion contained 0.118 mg of gadopentetate dimeglumine, 0.0025 mL of methylene blue dye, and 23.8 mg of gelatin. Rapid fast spin-echo MR imaging was used to guide placement of a 14-gauge titanium core-biopsy needle. A 1.5-T MR imager was used with an open-platform phased-array breast coil.Visualization of blue dye in core specimens confirmed successful biopsy in 16 of 16 attempts. One (n = 13) or two (n = 3) passes through the "skin" of the phantom were necessary for biopsy. The needle trajectory was adjusted less than three times for each pass through the "skin" in 15 of 16 biopsies. Cores that contained lesion material were obtained in the first sample in 15 of 16 biopsies. On T1-weighted images, needles cast 7-mm-diameter artifacts.MR imaging can be used accurately to guide core-needle biopsy of 6-7-mm lesions in a breast phantom.

    View details for Web of Science ID A1997XG51800009

    View details for PubMedID 9232171

  • Neural substrates of fluid reasoning: An fMRI study of neocortical activation during performance of the Raven's Progressive Matrices Test COGNITIVE PSYCHOLOGY Prabhakaran, V., Smith, J. A., Desmond, J. E., Glover, G. H., Gabrieli, J. D. 1997; 33 (1): 43-63


    We examined brain activation, as measured by functional magnetic resonance imaging, during problem solving in seven young, healthy participants. Participants solved problems selected from the Raven's Progressive Matrices Test, a test known to predict performance on a wide range of reasoning tasks. In three conditions, participants solved problems requiring (1) analytic reasoning; (2) figural or visuospatial reasoning; or (3) simple pattern matching that served as a perceptual-motor control. Right frontal and bilateral parietal regions were activated more by figural than control problems. Bilateral frontal and left parietal, occipital, and temporal regions were activated more by analytic than figural problems. All of these regions were activated more by analytic than match problems. Many of these activations occurred in regions associated with working memory. Figural reasoning activated areas involved in spatial and object working memory. Analytic reasoning activated additional areas involved in verbal working memory and domain-independent associative and executive processes. These results suggest that fluid reasoning is mediated by a composite of working memory systems.

    View details for Web of Science ID A1997XG56600004

    View details for PubMedID 9212721

  • Separate neural bases of two fundamental memory processes in the human medial temporal lobe SCIENCE Gabrieli, J. D., Brewer, J. B., Desmond, J. E., Glover, G. H. 1997; 276 (5310): 264-266


    The participation of medial temporal-lobe structures in memory performance was examined by functional magnetic resonance imaging of local blood oxygenation level-dependent signals. Signals were measured during encoding into memory complex scenes or line drawings and during retrieval from memory of previously studied line drawings or words. Encoding tasks yielded increased signals for unfamiliar information in a posterior medial-temporal region that were focused in the parahippocampal cortex. Retrieval tasks yielded increased signals for successfully remembered information in an anterior medial-temporal region that were focused in the subiculum. These results indicate that separate components of the human medial temporal-lobe memory system are active during distinct memory processes.

    View details for Web of Science ID A1997WT92500048

    View details for PubMedID 9092477

  • Tissue ablation using an acoustic waveguide for high-intensity focused ultrasound MEDICAL PHYSICS Sommer, F. G., Sumanaweera, T. S., Glover, G. 1997; 24 (4): 537-538


    High-intensity focused ultrasound (HIFU) has been shown capable of selective tissue destruction in humans, with promise as a tool for ablation of tumors, although one practical problem is reflection of sound at gas or bony interfaces within the body. We evaluated a water-filled cylindrical metal tube as a waveguide for HIFU, since such a general technique might be useful for ablation of otherwise inaccessible tumors in the body. Our studies indicate that such a waveguide is capable of propagating HIFU from a piezoelectric source, with resultant heating of tissue specimens to greater than 80 degrees C, causing focal tissue destruction.

    View details for Web of Science ID A1997WU28400008

    View details for PubMedID 9127305

  • An extended two-point dixon algorithm for calculating separate water, fat, and B-0 images MAGNETIC RESONANCE IN MEDICINE Skinner, T. E., Glover, G. H. 1997; 37 (4): 628–30


    A new algorithm is presented that provides separate water, fat, and B0 images utilizing the in-phase and opposed-phase acquisitions of the two-point Dixon (2PD) method. The accuracy of the extended method (E2PD) compares favorably with the three-point Dixon (3PD) method, and the acquisition requires 2/3 the 3PD scan time. Slightly increased mismapping may occur in pixels containing an admixture of water and fat due to reduced SNR in the B0 field map compared with the 3PD method.

    View details for DOI 10.1002/mrm.1910370426

    View details for Web of Science ID A1997WQ66700022

    View details for PubMedID 9094088

  • Retinotopic organization in human visual cortex and the spatial precision of functional MRI CEREBRAL CORTEX Engel, S. A., Glover, G. H., Wandell, B. A. 1997; 7 (2): 181-192


    A method of using functional magnetic resonance imaging (fMRI) to measure retinotopic organization within human cortex is described. The method is based on a visual stimulus that creates a traveling wave of neural activity within retinotopically organized visual areas. We measured the fMRI signal caused by this stimulus in visual cortex and represented the results on images of the flattened cortical sheet. We used the method to locate visual areas and to evaluate the spatial precision of fMRI. Specifically, we: (i) identified the borders between several retinotopically organized visual areas in the posterior occipital lobe; (ii) measured the function relating cortical position to visual field eccentricity within area V1; (iii) localized activity to within 1.1 mm of visual cortex; and (iv) estimated the spatial resolution of the fMRI signal and found that signal amplitude falls to 60% at a spatial frequency of 1 cycle per 9 mm of visual cortex. This spatial resolution is consistent with a linespread whose full width at half maximum spreads across 3.5 mm of visual cortex.

    View details for Web of Science ID A1997WJ36100009

    View details for PubMedID 9087826

  • Neural correlates of mathematical reasoning: An fMRI study of word-problem solving 19th Annual Conference of the Cognitive-Science-Society Rypma, B., Prabhakaran, V., Smith, J. A., Desmond, J. E., Glover, G. H., Gabrieli, J. D. LAWRENCE ERLBAUM ASSOC PUBL. 1997: 662–667
  • Studying privileged access with functional MRI 19th Annual Conference of the Cognitive-Science-Society Stone, M., Prabakharan, V., Seger, C. A., Gabrieli, J. D., Glover, G. H. LAWRENCE ERLBAUM ASSOC PUBL. 1997: 1061–1061
  • Neural correlates of categorization: An fMRI study of probabilistic classification using the weather prediction task 19th Annual Conference of the Cognitive-Science-Society Prabhakaran, V., Seger, C. A., Poldrack, R. A., Desmond, J. E., Glover, G. H., Gabrieli, J. D. LAWRENCE ERLBAUM ASSOC PUBL. 1997: 1014–1014
  • Fast 3D functional magnetic resonance imaging at 1.5 T with spiral acquisition MAGNETIC RESONANCE IN MEDICINE Yang, Y. H., Glover, G. H., vanGelderen, P., Mattay, V. S., Santha, A. K., Sexton, R. H., Ramsey, N. F., Moonen, C. T., Weinberger, D. R., Frank, J. A., Duyn, J. H. 1996; 36 (4): 620–26


    A new method to perform rapid 3D fMRI in human brain is introduced and evaluated in normal subjects, on a standard clinical scanner at 1.5 Tesla. The method combines a highly stable gradient echo technique with a spiral scan method, to detect brain activation related changes in blood oxygenation with high sensitivity. A motor activation paradigm with a duration of less than 5 min, performed on 10 subjects, consistently showed significant changes in signal intensity in the area of the motor cortex. In all subjects, these changes survived high statistical thresholds.

    View details for DOI 10.1002/mrm.1910360418

    View details for Web of Science ID A1996VL63300017

    View details for PubMedID 8892216

  • Functional magnetic resonance imaging of semantic memory processes in the frontal lobes PSYCHOLOGICAL SCIENCE Gabrieli, J. D., Desmond, J. E., Demb, J. B., Wagner, A. D., Stone, M. V., Vaidya, C. J., Glover, G. H. 1996; 7 (5): 278-283
  • Linear systems analysis of functional magnetic resonance imaging in human V1 JOURNAL OF NEUROSCIENCE Boynton, G. M., Engel, S. A., Glover, G. H., Heeger, D. J. 1996; 16 (13): 4207-4221


    The linear transform model of functional magnetic resonance imaging (fMRI) hypothesizes that fMRI responses are proportional to local average neural activity averaged over a period of time. This work reports results from three empirical tests that support this hypothesis. First, fMRI responses in human primary visual cortex (V1) depend separably on stimulus timing and stimulus contrast. Second, responses to long-duration stimuli can be predicted from responses to shorter duration stimuli. Third, the noise in the fMRI data is independent of stimulus contrast and temporal period. Although these tests can not prove the correctness of the linear transform model, they might have been used to reject the model. Because the linear transform model is consistent with our data, we proceeded to estimate the temporal fMRI impulse-response function and the underlying (presumably neural) contrast-response function of human V1.

    View details for Web of Science ID A1996UT32300016

    View details for PubMedID 8753882

  • Decomposition of inflow and blood oxygen level-dependent (BOLD) effects with dual-echo spiral gradient-recalled echo (GRE) fMRI MAGNETIC RESONANCE IN MEDICINE Glover, G. H., Lemieux, S. K., Drangova, M., Pauly, J. M. 1996; 35 (3): 299-308


    Image contrast with gradient-recalled echo sequences (GRE) used for fMRI can have both blood oxygen level-dependent (BOLD) and inflow components, and the latter is often undesirable. A dual-echo technique can be used to differentiate these mechanisms, because modulation of signal from inflow is common to both echoes, whereas susceptibility and diffusion-related signal losses are larger in the second echo. An efficient dual-echo interleaved spiral sequence was developed for use with a conventional scanner. It uses a k-space trajectory that spirals out from the origin while the first echo is collected, then spirals back in while collecting the second echo. Decomposition of the data provides separate images of the inflow and T2-weighted components. Results demonstrate the decomposition with phantom experiments and with photic stimulation in normal volunteers.

    View details for Web of Science ID A1996TX77500003

    View details for PubMedID 8699940

  • Fast spill echo image distortion correction for MR-guided stereotactic pallidotomy 1996 Annual Meeting on the Physics of Medical Imaging Sumanaweera, T. S., Lim, K. O., Glover, G. H., Hemler, P. F., Heit, G., VANDENELSEN, P. A., Silverberg, G., Napel, S. SPIE - INT SOC OPTICAL ENGINEERING. 1996: 718–726
  • Functional MRI measurement of language lateralization in Wada-tested patients BRAIN Desmond, J. E., Sum, J. M., Wagner, A. D., Demb, J. B., Shear, P. K., Glover, G. H., Gabrieli, J. D., Morrell, M. J. 1995; 118: 1411-1419


    In this study the use of functional MRI (fMRI) for measuring language lateralization non-invasively was examined. The subjects were seven patients with histories of temporal lobe epilepsy who had undergone Wada testing for pre-surgical evaluation. Four patients were left-hemisphere-dominant and three were right-hemisphere-dominant for language. They received fMRI scans while they made semantic or perceptual judgments about visually presented words. Regions of the inferior frontal gyrus (pars triangularis and pars orbitalis) and neighbouring orbital cortex, corresponding to portions of Brodmann areas 45, 46 and 47, exhibited significant increases in activation during semantic relative to perceptual judgments. Lateralization of the increases in activation were consistent with the Wada test assessments of hemispheric language dominance in each of the seven patients. These results suggest that, in addition to providing a tool for investigating human cognitive processes, fMRI has significant clinical potential as a non-invasive measure of language lateralization.

    View details for Web of Science ID A1995TQ33300004

    View details for PubMedID 8595473



    Prefrontal cortical function was examined during semantic encoding and repetition priming using functional magnetic resonance imaging (fMRI), a noninvasive technique for localizing regional changes in blood oxygenation, a correlate of neural activity. Words studied in a semantic (deep) encoding condition were better remembered than words studied in both easier and more difficult nonsemantic (shallow) encoding conditions, with difficulty indexed by response time. The left inferior prefrontal cortex (LIPC) (Brodmann's areas 45, 46, 47) showed increased activation during semantic encoding relative to nonsemantic encoding regardless of the relative difficulty of the nonsemantic encoding task. Therefore, LIPC activation appears to be related to semantic encoding and not task difficulty. Semantic encoding decisions are performed faster the second time words are presented. This represents semantic repetition priming, a facilitation in semantic processing for previously encoded words that is not dependent on intentional recollection. The same LIPC area activated during semantic encoding showed decreased activation during repeated semantic encoding relative to initial semantic encoding of the same words. This decrease in activation during repeated encoding was process specific; it occurred when words were semantically reprocessed but not when words were nonsemantically reprocessed. The results were apparent in both individual and averaged functional maps. These findings suggest that the LIPC is part of a semantic executive system that contributes to the on-line retrieval of semantic information.

    View details for Web of Science ID A1995RU10800002

    View details for PubMedID 7666172



    We present a method to correct the geometric distortion caused by field inhomogeneity in MR images of patients wearing MR-compatible stereotaxic frames. Our previously published distortion correction method derives patient-dependent error maps by computing the phase-difference of 3D images acquired at different TEs. The time difference (delta TE = 4.9 ms at 1.5 T) is chosen such that the water and fat signals are in phase. However, delta TE is long enough to permit phase wraps in the difference images for frequency offsets greater than 205 Hz. Phase unwrapping techniques resolve these only for connected structures; therefore, the phase difference for fiducial rods may be off by multiples of 2 pi relative to the head. We remove this uncertainty by using an additional single 2D phase-different image with delta TE = 1 ms (during which time no phase-wraps are typically expected) to determine the correct multiple of 2 pi for each rod. We tested our method in a cadaver and in a patient using CT as the gold standard. Targets in the frame coordinates were chosen from CT and compared with their locations in MR. Localizing errors using MR compared with CT were as large as 3.7 mm before correction and were reduced to less than 1.11 mm after correction.

    View details for Web of Science ID A1995RF76800015

    View details for PubMedID 7674887



    A 3D projection reconstruction (3DPR) method was used to obtain in vivo 11B images in a large canine brain tumor model and in a human infused with borocaptate sodium (BSH). Studies were performed in dogs with and without gliosarcomas implanted and grown to a size of 2-3 cm. The 3DPR method demonstrates a signal-to-noise ratio (SNR) that allows qualitative kinetic studies of the boron compound in normal and tumor tissue of the head. The measurements indicate initial uptake of the BSH compound in tumor to be less than that in muscle with no uptake in normal brain tissue. Moreover, uptake of BSH in tissue was found to lag the boron concentration in blood with delays that depend on tissue type. In addition, the first human boron images were obtained on a patient who underwent surgical resection and volumetric debulking of a large (7 cm) glioblastoma multiforme. BSH was readily taken up in residual tumor tissue, while diffusion into the resection volume was slower.

    View details for DOI 10.1002/mrm.1910340109

    View details for Web of Science ID A1995RF76800008

    View details for PubMedID 7674898



    A technique is described for discriminating blood-oxygen-level-dependent (BOLD) signal changes originating from large venous vessels and those that arise from the cortical parenchyma based on examining the temporal delay of each pixel's response. Photic stimulation experiments were performed with a conventional 1.5 T scanner and correlated each pixel's time-course with sine and cosine functions at the frequency of the stimulus. It was found that the signal in pixels anatomically associated with gray matter was delayed between 4 and 8 s compared with the stimulus, whereas the signal in pixels correlated with visible vessels and sulci was generally delayed from 8 to 14 s. This larger delay is consistent with the longer time required for blood to reach the larger vessels. Finally, stimulus-induced NMR phase changes were observed for the largest vessels, which are attributed to bulk susceptibility shifts.

    View details for Web of Science ID A1995RA06400001

    View details for PubMedID 7651109



    The authors have developed a technique based on a solution of the Poisson equation to unwrap the phase in magnetic resonance (MR) phase images. The method is based on the assumption that the magnitude of the inter-pixel phase change is less than pi per pixel. Therefore, the authors obtain an estimate of the phase gradient by "wrapping" the gradient of the original phase image. The problem is then to obtain the absolute phase given the estimate of the phase gradient. The least-squares (LS) solution to this problem is shown to be a solution of the Poisson equation allowing the use of fast Poisson solvers. The absolute phase is then obtained by mapping the LS phase to the nearest multiple of 2 K from the measured phase. The proposed technique is evaluated using MR phase images and is proven to be robust in the presence of noise. An application of the proposed method to the 3-point Dixon technique for water and fat separation is demonstrated.

    View details for Web of Science ID A1995QV84500012

    View details for PubMedID 18290015

  • Functional MR imaging. Capabilities and limitations. Neuroimaging clinics of North America Moseley, M. E., Glover, G. H. 1995; 5 (2): 161-191


    Functional MR imaging techniques are showing promise in the detection and assessment of cerebral pathophysiology and, more recently, in the characterization and regional mapping of distinct human cognitive functions, such as vision, motor skills, language, and memory. This article discusses the mechanism of functional MR imaging, its capabilities, and its limitations.

    View details for PubMedID 7640883



    Activation signals based on BOLD contrast changes consequent to neuronal stimulation typically produce cortical intensity differences of < 10% at 1.5T. Hemodynamically driven pulsation of the brain can cause highly pulsatile phase shifts, which in turn result in motion artifacts whose intensity is larger than the activation signals in 2DFT scan methods. This paper presents a theoretical and experimental comparison of the magnitude of such artifacts for 2DFT and two other methods using non-Cartesian k-space trajectories. It is shown that artifacts increase with TR for 2DFT methods, and that projection reconstruction (PR) and spiral methods have significantly reduced artifact intensities, because these trajectories collect low spatial frequencies with every view. The spiral technique is found to be superior in terms of efficiency and motion insensitivity.

    View details for Web of Science ID A1995QV05800006

    View details for PubMedID 7596266



    A prospective study in 31 patients was designed to compare contrast quantitatively using axial conventional, gated spin-echo T2-weighted (T2W) (SE) (asymmetrical echo TE 30 and 80 ms) and axial dual-echo fast spin-echo (FSE) sequences (TEeff 20 and 120 ms) to image lumbar discs, nerve roots, and cerebrospinal fluid CSF. We used two quantitative measures, percent (%) contrast and contrast-to-noise ratio (CNR), to compare the sequences. The FSE sequence had greater % contrast and CNR on the first and second echo images for both disc and nerve root detection using these scan parameters. An axial FSE sequence, therefore, provided contrast characteristics similar to those of gated axial T2W SE sequence in the lumbar spine, with a 60% saving in acquisition time. The FSE sequence is now our standard axial T2W study for the lumbar spine.

    View details for Web of Science ID A1995QT61800002

    View details for PubMedID 7603591



    To compare the detectability of vertebral metastatic disease on T1-weighted, short-inversion-time inversion recovery (STIR), fast spin-echo (FSE), fat-saturated FSE, and inversion recovery FSE (IRFSE) MR sequences using percent contrast and contrast-to-noise ratios.Patients with proved metastatic disease underwent imaging on a 1.5-T MR system with sagittal T1-weighted (800/20/2 [repetition time/echo time/excitations]) (91 patients), STIR (1400/43/2; inversion time, 140) (91 patients), FSE (4000/180/2) (46 patients), fat-saturated FSE (4000/180/2) (16 patients), and IRFSE (29 patients) sequences. Percent contrast and contrast-to-noise ratio were calculated for the lesions. The number of metastatic lesions detected with each of the pulse sequences was also calculated.Mean percent contrast was, for T1-weighted sequence, -42.2 +/- 1%; STIR, 262 +/- 34%; FSE, 121 +/- 21%; fat-saturated FSE, 182 +/- 6%; and IRFSE, 272 +/- 47%. The mean contrast-to-noise ratio for T1-weighted was -4.63 +/- 1.7; STIR, 10.8 +/- .98; FSE, 4.16 +/- .76; fat-saturated FSE, 4.87 +/- .19; and IRFSE, 5.2 +/- .87. STIR and IRFSE showed the highest number of lesions, followed by T1-weighted, fat-saturated FSE, and FSE sequences. T1-weighted sequences showed 94%, FSE 55%, and fat-saturated FSE 78% of the lesions detected. Epidural metastatic lesions were better depicted on T1-weighted, FSE, and fat-saturated FSE sequences.STIR was superior to both T1-weighted and FSE (with and without fat saturation) for detection of metastatic lesions, in terms of both percent contrast and contrast-to-noise ratio and visibility. IRFSE was equal to STIR for the detection of metastasis by both subjective and objective criteria. T1-weighted, FSE, and fat-saturated FSE sequences were superior to STIR and IRFSE in the detection of epidural metastatic disease. IRFSE provided faster scanning time, which could be translated into greater resolution.

    View details for Web of Science ID A1995QG57400009

    View details for PubMedID 7726074

  • MAGNETIZATION-TRANSFER CONTRAST MRI OF MUSCULOSKELETAL NEOPLASMS SKELETAL RADIOLOGY Li, K. C., Hopkins, K. L., Moore, S. G., Loh, N. N., Bergman, G., Pike, G. B., Glover, G. H. 1995; 24 (1): 21-25


    Magnetic resonance imaging (MRI) examinations were performed in 15 patients with musculoskeletal neoplasms to assess the value of magnetization transfer contrast in tumor characterization. Multiplanar gradient-recalled echo sequences (TR 500-600/TE 15-20/flip angle 20-30 degrees) were performed first without and then with magnetization transfer contrast generated by a zero degree binomial pulse (MPGR and MTMPGR). Standard T1-weighted spin echo images (SE; TR 300-400/TE 12-20) and either T2-weighted SE (TR 2000-2900/TE 70-80) or T2-weighted fast spin echo (FSE; TR 4000-5000/TE 100-119 effective) images were also obtained. Signal intensities on MTMPGR scans were compared to those on MPGR scans for both tumors and normal tissues. Signal intensity ratios (SIR) and contrast-to-noise ratios (CNR) were also compared for all sequences. MTMPGR images provided better contrast between pathologic tissues and muscle than did standard MPGR images, increasing both conspicuity of lesions and definition of tumor/muscle interfaces. Benign and malignant tumors, with the exception of lipoma, underwent similar degrees of magnetization transfer and could not be distinguished by this technique.

    View details for Web of Science ID A1995QD35300005

    View details for PubMedID 7709247

  • Method for correcting magnetic resonance image distortion for frame-based stereotactic surgery, with preliminary results. Journal of image guided surgery Sumanaweera, T. S., Adler, J. R., Glover, G. H., Hemler, P. F., van den Elsen, P. A., Martin, D., Napel, S. 1995; 1 (3): 151-157


    We previously described a technique for correcting patient-specific magnetic field inhomogeneity spatial distortion in magnetic resonance images (MRI), which was not applicable to patients fitted with MRI-compatible stereotactic fiducial frames. Here we describe an improvement to the technique that permits application for these patients. Measurements with a cadaver head show that this method achieves MRI stereotactic localization accuracy of 1 mm.

    View details for PubMedID 9079440



    The different sources of spatial distortion in magnetic resonance images are reviewed from the point of view of stereotactic target localization. The extents of the two most complex sources of spatial distortion, gradient field nonlinearities and magnetic field inhomogeneities, are discussed both qualitatively and quantitatively. Several ways by which the spatial distortion resulting from these sources can be minimized are discussed. The clinical relevance of the spatial distortion along with some strategies to minimize the localization errors in magnetic resonance-guided stereotaxy are presented.

    View details for Web of Science ID A1994PH68700046

    View details for PubMedID 7808613



    Presently, the scores of three to four reviewers of each abstract are averaged and form a major component of the input for decisions made in choosing papers for oral and poster presentations, and in rejecting others. No normalization is made for differences in either mean or standard deviation between the reviewers of the same abstracts. In this paper, several techniques for normalizing the scores of reviewers are examined, and the consequences of applying such normalizations to several categories of the 1994 abstract submissions are examined. It was found that some alterations in the acceptance and assignments of papers as oral and posters resulted for one of the categories, and the normalized scores were used during the program assembly. It is recommended that future review procedures utilize reviewer normalization.

    View details for DOI 10.1002/mrm.1910320402

    View details for Web of Science ID A1994PJ32300001

    View details for PubMedID 7997106

  • FMRI OF HUMAN VISUAL-CORTEX NATURE Engel, S. A., Rumelhart, D. E., Wandell, B. A., Lee, A. T., Glover, G. H., Chichilnisky, E. J., Shadlen, M. N. 1994; 369 (6481): 525-525

    View details for Web of Science ID A1994NR29400030

    View details for PubMedID 8031403

  • QUANTIFYING MRI GEOMETRIC DISTORTION IN TISSUE MAGNETIC RESONANCE IN MEDICINE Sumanaweera, T., Glover, G., Song, S., Adler, T., Napel, S. 1994; 31 (1): 40-47


    We present a method to quantify the MR field inhomogeneity geometric distortion to subpixel accuracy without using objects of known dimensions and without using an external standard such as CT. Our method may be used to quantify the geometric accuracy of MR images of anatomical structures of unknown geometry and also to test any geometry correction scheme. We have quantified the distortion in a tissue phantom and found the largest error to be approximately 2.8 pixels (1.8 mm) for Bo = 1.5 T, G = 3.13 mT/m and FOV = 160 x 160 x 70.7 mm3. We also found that our previously published correction technique reduced the largest error to 0.3 pixels (mu = 0.02 and sigma = 0.07 pixels).

    View details for Web of Science ID A1994MP54200005

    View details for PubMedID 8121267



    To compare lesion enhancement after injection of gadopentetate dimeglumine on spin-echo and gradient-echo T1-weighted images.A total of 48 contrast-enhancing intracranial lesions were evaluated using a spin-echo and two gradient-echo T1-weighted pulse sequences. Percent contrast, contrast-to-noise, and signal-to-noise measurements were made on the spin-echo T1-weighted, three-dimensional gradient-echo, and multiplanar gradient-echo sequences.The measurements were somewhat different for the following categories of lesions: extraaxial, intraaxial with edema, and intraaxial without edema. The latter group provided the greatest diagnostic challenge: three of 19 such lesions 1 cm in size or smaller could not be identified on three-dimensional gradient-echo images, and one could not be identified on multi-planar gradient-echo images. The spin-echo T1-weighted sequence demonstrated significantly higher percent contrast (P < .05) and greater contrast to noise (P < .03) than either gradient-echo sequence for these small intraaxial lesions without edema. For extraaxial and intraaxial lesions with edema, percent C was similar for spin-echo T1-weighted and three-dimensional gradient-echo images, while contrast to noise was greater for spin-echo T1-weighted images. This reflected greater tissue noise with gradient-echo sequences.The T1-weighted spin-echo sequence was preferred for detecting the full spectrum of contrast-enhancing lesions of the central nervous system.

    View details for Web of Science ID A1994MT25700007

    View details for PubMedID 8141064



    The in vivo distribution of ethanol in normal human brain following the consumption of a moderate amount of alcohol was measured using magnetic resonance spectroscopic imaging. Three subjects were studied, and the spatial distribution of brain ethanol, 60-min postingestion and measured at a spatial resolution of 1.5 cm, was found to be highly nonuniform with the relative ethanol signal in cerebral spinal fluid, gray matter, and white matter determined to be 1.00, 0.72, and 0.37, respectively. These spectroscopic imaging results indicate that whereas in vivo magnetic resonance studies of ethanol are feasible, quantitative studies of alcohol need to account carefully for the various tissue types within the observed volume.

    View details for Web of Science ID A1993ME46800024

    View details for PubMedID 8279668



    We compared the effectiveness of pulsed magnetization transfer contrast (MTC) magnetic resonance imaging (MRI) and spin-echo MRI in detecting tumor necrosis.Adenocarcinoma cells were transplanted in the livers of 12 syngenic BDIX rats. To induce various degrees of tumor necrosis, the rats were randomly assigned to the following groups: 1) control; 2) localized hyperthermia; 3) intralesional cisplatin; and 4) hyperthermia plus intralesional cisplatin. At day 7 after treatment, the rats were imaged using a 1.5-T imager with 1) multiplanar gradient-recalled echo sequence (MPGR) 500/8/20 degrees with and without magnetization transfer contrast (MTC); 2) spin-echo 2500/20,80, and 3) spin-echo 300/20 pulse sequences. The rats were then sacrificed and pathologic specimens were prepared using MR images as guidance. T2 and ratios of signal intensity after saturation to signal intensity before saturation (Ms/Mo ratios) of the necrotic and granulation tissues and viable tumors were determined in 10 rats.Compared with standard MPGR images, MPGR images with MTC provided better contrast between the pathologic tissues and normal liver. However, T2 values were more useful than Ms/Mo ratios in distinguishing necrotic areas from viable tumor. The T2 values of coagulative necrosis and granulation tissue were significantly different from that of viable tumor. No significant difference between the Ms/Mo ratios of the different pathologic tissues and normal liver was found.Pulsed magnetization transfer contrast MRI was inferior to spin-echo MRI in distinguishing necrotic from viable tumors in rat livers using the pulse sequences described, and none of the sequences studied was thought to be reliable enough for this purpose.

    View details for Web of Science ID A1993MD17700004

    View details for PubMedID 8262743



    The authors have developed a method to reduce noise in three-dimensional (3D) phase-contrast magnetic resonance (MR) velocity measurements by exploiting the property that blood is incompressible and, therefore, the velocity field describing its flow must be divergence-free. The divergence-free condition is incorporated by a projection operation in Hilbert space. The velocity field obtained with 3D phase-contrast MR imaging is projected onto the space of divergence-free velocity fields. The reduction of noise is achieved because the projection operation eliminates the noise component that is not divergence-free. Signal-to-noise ratio (S/N) gains on the order of 15%-25% were observed. The immediate effect of this noise reduction manifests itself in higher-quality phase-contrast MR angiograms. Alternatively, the S/N gain can be traded for a reduction in imaging time and/or improved spatial resolution.

    View details for Web of Science ID A1993LM78100006

    View details for PubMedID 8347951

  • MR SUSCEPTIBILITY MISREGISTRATION CORRECTION IEEE TRANSACTIONS ON MEDICAL IMAGING Sumanaweera, T. S., Glover, G. H., Binford, T. O., Adler, J. R. 1993; 12 (2): 251-259


    The authors present a new in vivo method to correct the nonlinear, object-shape-dependent and material-dependent spatial distortion in magnetic resonance (MR) images caused by magnetic susceptibility variations. This distortion across the air/tissue interface before and after the correction is quantified using a phantom. The results are compared to the distortion-free computed tomography (CT) images of the same phantom by fusing CT and MR images using fiducials, with a registration accuracy of better than a millimeter. The distortion at the bone/tissue boundary is negligible compared to the typical MRI (MR imaging) resolution of 1 mm, while that at the air/tissue boundary creates displacements of about 2 mm (for G(x) 3.13 mT/m). This is a significant value if MRI is to provide highly accurate geometric measurements, as in the case of target localization for stereotaxic surgery. The correction scheme provides MR images with accuracy similar to that of CT: 1 mm. A new method to estimate the magnetic susceptibility of materials from MR images is presented. The magnetic susceptibility of cortical bone is measured using a SQUID magnetometer, and is found to be -8.86 ppm (with respect to air), which is quite similar to that of tissue (-9 ppm).

    View details for Web of Science ID A1993LV99000012

    View details for PubMedID 18218412



    Cross relaxation between macromolecular protons and water protons is known to be important in biologic tissue. In magnetic resonance (MR) imaging sequences, selective saturation of the characteristically short T2 macromolecular proton pool can produce contrast called magnetization transfer contrast, based on the cross-relaxation process. Selective saturation can be achieved with continuous wave irradiation several kilohertz off resonance or short, intense 0 degree pulses on resonance. The authors analyze 0 degree binomial pulses for T2 selective saturation, present design guidelines, and demonstrate the use of these pulses in spin-echo imaging sequences in healthy volunteers and patients. Using the phenomenologic Bloch equations modified for two-site exchange, the authors derive the analytic expressions for water proton relaxation under periodic pulsed saturation of the macromolecular protons. This relaxation is shown to be monoexponential, with a rate constant dependent on the saturation pulse repetition rate and the individual and cross-relaxation rates.

    View details for Web of Science ID A1993LC10000013

    View details for PubMedID 8324313

  • CHARACTERIZATION OF ATHEROSCLEROSIS WITH A 1.5-T IMAGING-SYSTEM JMRI-JOURNAL OF MAGNETIC RESONANCE IMAGING Gold, G. E., Pauly, J. M., Glover, G. H., Moretto, J. C., Macovski, A., Herfkens, R. J. 1993; 3 (2): 399-407


    It is shown that a conventional 1.5-T magnetic resonance (MR) imaging system can help characterize some of the key components of atherosclerotic plaque ex vivo. Fresh human aorta with atheromata was suspended in solutions of agarose and manganese chloride and heated to body temperature. The specimens were imaged with modified Dixon and projection-reconstruction imaging sequences. The specimens were then examined histologically to obtain direct correlation between images, spectra, and histologic characteristics. The results show that vessel wall and plaque components can be identified by means of their MR characteristics and correlated with their histologic appearance. The authors were able to identify normal vessel wall components, such as adventitial lipids and smooth muscle. They were also able to identify and localize plaque components such as fibrous tissue, calcification, lipids, and possible areas of hemorrhage and hemosiderin deposition.

    View details for Web of Science ID A1993KQ88100013

    View details for PubMedID 8448403



    Motion of the subject causes inconsistencies in MR scan data which in turn produce streaks in projection reconstruction (PR) scans or ghosts in 2DFT imaging. It is shown that a data manifold consistent with a static object may be extracted from input scan data by applying consistency criteria based on moment or Fourier expansions of the object's projections. The criteria limit the spectrum of azimuthal variation relative to the radial moments or radial spectral components, and their application diminishes k-space inconsistencies from motion or flow by discarding unallowed expansion terms. This consistent projection reconstruction (CPR) algorithm was applied to the reconstruction of projection data from a moving phantom and from human abdominal sections, and in each case provided reduced motion streaks relative to conventional reconstructions. In addition, CPR was found to be effective when used with 2DFT data by resampling the Cartesian data as radial projections, but to a lesser extent.

    View details for Web of Science ID A1993KQ35800009

    View details for PubMedID 8450743

  • QUANTIFICATION OF THE GEOMETRIC ACCURACY OF MRI IN TISSUE - A NEW APPROACH USING MRI ITSELF Nuclear Science Symposium and Medical Imaging Conference (NSS-MIC 93) Sumanaweera, T. S., Napel, S., Glover, G. H., Song, S. M. IEEE. 1993: 1789–1793
  • A LEAST-SQUARES BASED PHASE UNWRAPPING ALGORITHM FOR MRI Nuclear Science Symposium and Medical Imaging Conference (NSS-MIC 93) Song, S. M., Napel, S., Pelc, N. J., Glover, G. H. IEEE. 1993: 1784–1788


    Projection reconstruction (PR) techniques are shown to have intrinsic advantages over spin-warp (2DFT) methods with respect to diminished artifacts from respiratory motion. The benefits result from (1) portrayal of artifacts as radial streaks, with the amplitude smallest near the moving elements; (2) streak deployment perpendicular to the direction of motion of moving elements and often residing outside the anatomic boundaries of the subject; (3) inherent signal averaging of low spatial frequencies from oversampling of central k-space data. In addition, respiratory-ordered view angle (ROVA) acquisition is found to diminish residual streaking significantly by reducing interview inconsistencies. Comparisons of 2DFT and PR acquisitions are made with and without ROVA. Reconstructions from magnitude-only projections are found to have increased streaks from motion-induced phase shifts.

    View details for Web of Science ID A1992KB92200008

    View details for PubMedID 1461126

  • ARTERIAL AND VENOUS-BLOOD FLOW - NONINVASIVE QUANTITATION WITH MR IMAGING RADIOLOGY Pelc, L. R., Pelc, N. J., Rayhill, S. C., Castro, L. J., Glover, G. H., Herfkens, R. J., Miller, D. C., Jeffrey, R. B. 1992; 185 (3): 809-812


    Quantitative measurements of arterial and venous blood flow were obtained with phase-contrast cine magnetic resonance (MR) imaging and compared with such measurements obtained by means of implanted ultrasound (US) blood flow probes in anesthetized dogs. The US flowmeter was enabled during a portion of each MR imaging sequence to allow virtually simultaneous data acquisition with the two techniques. MR imaging data were gated by means of electrocardiography and divided into 16 phases per cardiac cycle. The rates of portal venous blood flow measured with MR imaging and averaged across the cardiac cycle (710 mL/min +/- 230 [standard deviation]) correlated well with those measured with the flowmeter and averaged in like fashion (751 mL/min +/- 238) (r = .995, slope = 1.053). The correspondence in arterial blood flow was almost as good. No statistically significant difference existed between the paired measurements of blood flow obtained with MR imaging and the implanted probe. It is concluded that, as a noninvasive means of accurate quantification of blood flow, phase-contrast MR imaging may be especially useful in deep blood vessels in humans.

    View details for PubMedID 1438767



    Fast spin-echo (FSE) magnetic resonance (MR) imaging was compared with conventional, peripherally gated T2-weighted spin-echo (SE) imaging in the detection of high- and low-signal-intensity lesions in the central nervous system. Lesion detectability was determined with percentage of contrast measurements and contrast-to-noise ratios with two different measurements for noise. All three measures of lesion detectability were similar. FSE and SE sequences were quantitatively equivalent in the detection of high-signal-intensity lesions. The SE sequence, however, was superior to the FSE sequence in the detection of small, low-signal-intensity lesions in the central nervous system caused by magnetic susceptibility effects.

    View details for Web of Science ID A1992JZ34700013

    View details for PubMedID 1438742

  • THE PELVIS - T2-WEIGHTED FAST SPIN-ECHO MR-IMAGING RADIOLOGY Nghiem, H. V., Herfkens, R. J., Francis, I. R., Sommer, F. G., Jeffrey, R. B., Li, K. C., Steiner, R. M., Glover, G. H. 1992; 185 (1): 213-217


    Fast spin-echo (SE) T2-weighted magnetic resonance (MR) imaging provides images with highly T2-weighted contrast in substantially reduced imaging times. In a prospective evaluation, fast SE T2-weighted imaging of the pelvis was compared with conventional SE T2-weighted imaging in 30 consecutive patients in whom pelvic pathologic conditions were suspected. Three reviewers independently analyzed the images for (a) overall image quality, (b) pelvic organ definition, (c) conspicuity of pelvic fluid, and (d) conspicuity of pelvic pathologic conditions. Fast SE images were rated superior to conventional SE T2-weighted images in 60% (54 of 90) of the case reviews for overall image quality, in 69% (62 of 90) for pelvic organ definition, in 63% (57 of 90) for conspicuity of pelvic fluid, and in 68% (43 of 63) for conspicuity of pelvic pathologic conditions. The fast SE examinations were typically three to four times faster than conventional SE T2-weighted examinations. No pathologic findings seen on conventional SE T2-weighted images were undetected on fast SE images. Fast SE images may replace conventional SE T2-weighted images in MR imaging of the pelvis.

    View details for Web of Science ID A1992JN60800039

    View details for PubMedID 1523311

  • MR IMAGING OF LUNG PARENCHYMA - A SOLUTION TO SUSCEPTIBILITY RADIOLOGY Bergin, C. J., Noll, D. C., Pauly, J. M., Glover, G. H., Macovski, A. 1992; 183 (3): 673-676


    The authors have developed a pulse sequence for imaging lung parenchyma with projection reconstruction magnetic resonance (MR) imaging that reduces the effects of motion and susceptibility. In this study, the projection reconstruction technique was further modified by optimizing MR signal frequencies for reconstructing the images. This was done by means of one of two methods. With the first method, a susceptibility map was derived from the raw image data and this map was used to indicate the optimal frequencies for reconstructing the images. The second method of susceptibility correction was a postprocessing technique in which the optimal reconstruction frequencies were selected with use of specific focusing criteria to generate the least blurred image. The effect of using susceptibility map correction on a phantom was demonstrated, and both of these methods were used to improve the visibility of pulmonary structures on images of subjects with normal and abnormal lungs.

    View details for Web of Science ID A1992HV57800017

    View details for PubMedID 1584917



    Time-of-flight (TOF) angiography based on inflow enhancement is limited by the steady-state signal differences between blood and the surrounding stationary tissues. We present a new TOF sequence in which magnetization transfer contrast is used to supplement wash-in effects. Angiograms demonstrating the superior performance of this technique are presented.

    View details for Web of Science ID A1992HX35600016

    View details for PubMedID 1614322



    Spectroscopic images of the brain have great potential in disease diagnosis and treatment monitoring. Unfortunately, interfering lipid signals from subcutaneous fat and poor water suppression due to magnetic field inhomogeneities can make such images difficult to obtain. A pulse sequence that uses inversion recovery for lipid suppression and a spectral-spatial refocusing pulse for water suppression is introduced. In contrast to methods that eliminate fat signal by restricting the excited volume to lie completely within the brain, inversion-recovery techniques allow imaging of an entire section without such restrictions. In addition, the spectral-spatial pulse was designed to provide water suppression insensitive to a reasonable range of B0 and B1 inhomogeneities. Several data processing algorithms have also been developed and used in conjunction with the new pulse sequence to produce metabolite maps covering large volumes of the human brain. Images from single- and multisection studies demonstrate the performance of these techniques.

    View details for Web of Science ID A1992HV08100001

    View details for PubMedID 1627859



    A three-dimensional projection reconstruction technique is described for imaging boron-11 distributions, with potential application to boron neutron capture therapy. The method samples a spherical volume of k space uniformly to obtain a 32 x 32 x 32 matrix with voxel size of 0.42 cm3. A signal-to-noise ratio (S/N) of 3 was obtained in 8.5 minutes in a phantom containing 75 micrograms/mL of boron in borocaptate sodium (BSH). Images were obtained in a dog after cessation of an intravenous infusion of BSH and again 30 minutes later, with a maximum boron S/N of about 12. Boron levels in the brain dropped about 6%-8% and were more diffusely distributed on the images obtained 30 minutes after BSH infusion.

    View details for Web of Science ID A1992HB35100007

    View details for PubMedID 1623280

  • LUNG PARENCHYMA - MAGNETIC-SUSCEPTIBILITY IN MR IMAGING RADIOLOGY Bergin, C. J., Glover, G. H., Pauly, J. M. 1991; 180 (3): 845-848


    Magnetic susceptibility effects in magnetic resonance (MR) imaging of normal lung parenchyma occur because of magnetic-field inhomogeneities induced by the microscopic heterogeneity of the lung. The effects on MR imaging of the lung are loss of signal from intravoxel phase dispersion (measured with T2') and a shift in the macroscopic resonant frequency from that of water toward that of air (delta v). These effects of MR imaging at 1.5 T were quantitated by measuring T2' decay and delta v at different locations in the lungs of two adult volunteers and one excised inflated human lung. The average T2' was 7 msec in the excised inflated specimen and 6.3 msec in normal in vivo lungs. There was a gravitational increase in T2' from nondependent to dependent lung. T2' increased to 35 msec in atelectatic lung tissue and to more than 140 msec in tumor. The macroscopic resonant lung frequency increased to 3.6 ppm more than that of mediastinal muscle. These values are important for developing MR pulse sequences appropriate for imaging lung parenchyma.

    View details for Web of Science ID A1991GB92600045

    View details for PubMedID 1871305



    Extensions to a previously described three-point Dixon magnetic resonance imaging technique are presented that use alternative water/fat phase-encoding strategies. The technique is generalized to phase encoding of (-theta, O, theta) or (O, theta, 2 theta) radians, and the signal-to-noise ratio (S/N) performance is evaluated. It was found that a theta of 2 pi/3 radians has optimal S/N but that a theta of pi radians is a good compromise and that phase encoding of (O, pi, 2 pi) radians offer an advantage over the previous method, which used (-pi, O, pi) increments, in that a T2' (intravoxel susceptibility dephasing) image may be obtained in addition to the usual water, fat, and Bo images. A new four-point method with phase encoding of (O, pi, 2 pi, 3 pi) radians that can also provide a measure of the spectral width of the fat resonance is suggested. The disadvantages of the method are the extra imaging time and low S/N efficiency.

    View details for Web of Science ID A1991HA76700003

    View details for PubMedID 1790376



    Three encoding strategies for the measurement of flow velocities in arbitrary directions with phase-contrast magnetic resonance imaging are presented; their noise and dynamic range performance are compared by means of theoretical analysis and computer simulation. A six-point measurement strategy is shown to be quite inefficient in terms of velocity variance per unit time. A simple four-point method exhibits equal dynamic range; its noise depends on flow direction but on average is equal to that of the six-point method. An alternate, balanced four-point method has noise that is direction independent and has, depending on implementation, possibly lower noise levels. Either four-point method is more efficient and is preferred over the six-point approach.

    View details for Web of Science ID A1991HA76600003

    View details for PubMedID 1790362



    Phase-offset multiplanar (POMP) imaging is a technique that excites several sections simultaneously for improved imaging efficiency. The centers of the reconstructed images from each of the POMP sections are offset from each other in the phase-encoding direction by means of view-dependent phase modulation of the radio-frequency (RF) excitation pulses and are placed adjacent to each other in the reconstruction. With a suitable reconstruction matrix size, the images can be made nonoverlapping and stored separately. At constant imaging time, signal-to-noise ratio (S/N), and resolution, POMP imaging produces a factor NP more sections than a conventional sequence but with a reduced field of view. Alternatively, imaging time may be increased by the factor NP to retain the same field of view but with the expected S/N advantage. The average RF power deposited by the 90 degrees composite RF pulse is greater by the factor Np, but the power for the 180 degrees pulse is unchanged. The POMP method is discussed and compared with three-dimensional and Hadamard techniques.

    View details for Web of Science ID A1991HA76600009

    View details for PubMedID 1790368



    We introduce a selective adiabatic pulse sequence suitable for generating selective spin-echoes for both MR imaging and spectroscopy. The technique is simple; one uses the echo generated by any pair of identical selective adiabatic inversion pulses. The nonlinear phase across the slice is compensated perfectly by the second pi pulse. This compensation is immune to RF inhomogeneity and nonlinearity. For imaging applications, we concentrate on a reduced-power version of the pulse sequence in which time is traded off variably for RF amplitude in the presence of a time-varying gradient. This technique, known as variable-rate excitation, mildly degrades the off-resonant slice profile when applied to amplitude-modulated pulses. We present theoretical explanations and experimental results that show that the variable-rate adiabatic pulses are immune to off-resonant degradation of the magnitude normally encountered in MR imaging.

    View details for Web of Science ID A1991EZ54700004

    View details for PubMedID 2062239

  • VARIABLE-RATE SELECTIVE EXCITATION JOURNAL OF MAGNETIC RESONANCE Conolly, S., Nishimura, D., Macovski, A., Glover, G. 1988; 78 (3): 440-458