John P. Hegarty II

All Publications

• A Twin Study of Altered White Matter Heritability in Youth With Autism Spectrum Disorder. Journal of the American Academy of Child and Adolescent Psychiatry Hegarty, J. P., Monterrey, J. C., Tian, Q., Cleveland, S. C., Gong, X., Phillips, J. M., Wolke, O., McNab, J. A., Hallmayer, J., Reiss, A. L., Hardan, A. Y., Lazzeroni, L. C. 2023

  Abstract

  OBJECTIVE: White matter alterations are frequently reported in autism spectrum disorder (ASD), yet the etiology is currently unknown. The objective of this investigation was to examine, for the first time, the impact of genetic and environmental factors on white matter microstructure in twins with ASD compared to control twins without ASD.METHOD: Diffusion-weighted MRIs were obtained from same-sex twin pairs (aged 6-15 years) in which at least one twin was diagnosed with ASD or neither twin exhibited a history of neurological or psychiatric disorders. Fractional anisotropy (FA) and mean diffusivity (MD) were examined across different white matter tracts in the brain and statistical and twin modeling were completed to assess the proportion of variation associated with additive genetic (A) and common/shared (C) or unique (E) environmental factors. We also developed a new version of the twin-pair difference score analysis method that estimates the contribution of genetic and environmental factors to shared covariance between different brain and behavioral traits.RESULTS: Good quality data were available from 84 twin pairs, 50 ASD pairs [32 concordant for ASD (16 monozygotic; 16 dizygotic), 16 discordant for ASD (3 monozygotic; 13 dizygotic), and 2 pairs in which one twin had ASD and the other exhibited some subthreshold symptoms (1 monozygotic; 1 dizygotic)] and 34 control pairs (20 monozygotic; 14 dizygotic). Average FA and MD across the brain, respectively, were primarily genetically mediated in both control twins (A=0.80 [0.57,1.02]; A=0.80 [0.55,1.04]) and twins concordant for having ASD (A=0.71 [0.33,1.09]; A= 0.84 [0.32,1.36]). However, there were also significant tract-specific differences between groups. For instance, genetic effects on commissural fibers were primarily associated with differences in general cognitive abilities and perhaps some diagnostic differences for ASD, e.g., our new twin-pair difference-scores analysis indicated that genetic factors may have contributed to 40-50% of the covariation between IQ scores and FA of the corpus callosum. Conversely, the increased impact of environmental factors on some projection and association fibers were primarily associated with differences in symptom severity in twins with ASD, e.g., twin-pair difference-scores suggested that unique environmental factors may have contributed to 10-20% of the covariation between autism-related symptom severity and FA of the cerebellar peduncles and external capsule.CONCLUSION: White matter alterations in youth with ASD are associated with both genetic contributions and potentially increased vulnerability or responsivity to environmental influences.DIVERSITY & INCLUSION STATEMENT: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. One or more of the authors of this paper self-identifies as living with a disability. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.

  View details for DOI 10.1016/j.jaac.2023.05.030

  View details for PubMedID 37406770

• FAR: End-to-End Vibrotactile Distributed System Designed to Facilitate Affect Regulation in Children Diagnosed with Autism Spectrum Disorder Through Slow Breathing Miri, P., Arora, M., Malhotra, A., Flory, R., Hu, S., Lowber, A., Goyal, I., Nguyen, J., Hegarty, J., Kohn, M., Schneider, D., Culbertson, H., Yamins, D. K., Fung, L., Hardan, A., Gross, J. J., Marzullo, K., ACM ASSOC COMPUTING MACHINERY. 2022

  View details for DOI 10.1145/3491102.3517619

  View details for Web of Science ID 000922929503024

• Relationship Between MR Spectroscopy-Detected Glutamatergic Neurometabolites and Changes in Social Behaviors in a Pilot Open-Label Trial of Memantine for Adults With Autism Spectrum Disorder. Frontiers in psychiatry Nair, N., Hegarty, J. P., Cirstea, C. M., Gu, M., Appling, C. B., Beversdorf, D. Q. 2022; 13: 898006

  Abstract

  Background: The neurobiology underlying ASD is largely unknown but altered neural excitability/inhibitory ratios have been reported. Memantine is an N-methyl-D-aspartate (NMDA) glutamatergic antagonist studied for the treatment of core ASD symptoms, with mixed results. We examined whether glutamatergic levels were associated with and predicted response to memantine in an exploratory pilot study.Methods: Ten adult participants with ASD underwent proton magnetic resonance spectroscopy (1H-MRS) imaging at baseline and behavioral assessments before and after 12-weeks of open-label memantine. Post-treatment scores on Clinical Global Impressions-Improvement (CGI-I) for social interaction were the primary outcome measure, and scores on the Social Responsiveness Scale (SRS) were included as a secondary outcome. LCModel was used to quantify the concentrations of Point RESolved Spectroscopy-detected glutamate+glutamine (Glx) (and other neurometabolites, i.e., N-acetylaspartate, NAA; creatine+phosphocreatine, Cr+PCr, and myo-inositol, Ins), within the left dorsolateral prefrontal cortex (LDLPFC) and right (R) posterolateral cerebellum. SPM was used to perform brain tissue segmentation within the spectroscopic voxels. CGI-I scores post-treatment were used to classify the participants into two groups, responders (scores 1-3; n = 5) and non-responders (scores 4-7, or withdrew due to increase behaviors; n = 5). Independent samples t-tests, partial correlations and linear hierarchical regression models (SPSS) were used to determine between-group differences in neurometabolite concentrations and associations between neurometabolites and behavioral scores.Results: Responders and non-responders did not significantly differ in Glx levels in any region of interest, but differed in NAA levels in LDLPFC (higher in responders vs. non-responders). Although changes in CGI-I social scores were not correlated with Glx in any region of interest, the linear hierarchical regression did reveal that Glx and Ins levels in LDLPFC were predictors of post-treatment CGI-I social scores. Changes in SRS scores were correlated with baseline Cr+PCr levels in the LDLPFC.Discussion: Our pilot data suggest that baseline Glx, a marker of glutamatergic neurotransmission, did not directly predict response to memantine for social outcomes in adults with ASD. However, interactions between Glx and the neurometabolite associated with glial integrity (Ins) may help predict treatment response. Further, those with highest baseline NAA, a putative neuronal marker, and Cr+pCr, a brain energy metabolism marker, were the best responders. These preliminary results may explain some of the mixed results reported in previous memantine trials in ASD. Future studies will need to examine these results in a larger sample.

  View details for DOI 10.3389/fpsyt.2022.898006

  View details for PubMedID 35935413

• Assessing Glutamate Concentration as a Predictor for Social Behavioral Changes in Asd Due to Memantine Beversdorf, D., Riecken, C., Nair, N., Hegarty, J. P., Cirstea, C. WILEY. 2021: S36

  View details for Web of Science ID 000704705300049

• Frequency Drift in MR Spectroscopy at 3T. NeuroImage Hui, S. C., Mikkelsen, M., Zollner, H. J., Ahluwalia, V., Alcauter, S., Baltusis, L., Barany, D. A., Barlow, L. R., Becker, R., Berman, J. I., Berrington, A., Bhattacharyya, P. K., Blicher, J. U., Bogner, W., Brown, M. S., Calhoun, V. D., Castillo, R., Cecil, K. M., Choi, Y. B., Chu, W. C., Clarke, W. T., Craven, A. R., Cuypers, K., Dacko, M., de la Fuente-Sandoval, C., Desmond, P., Domagalik, A., Dumont, J., Duncan, N. W., Dydak, U., Dyke, K., Edmondson, D. A., Ende, G., Ersland, L., Evans, C. J., Fermin, A. S., Ferretti, A., Fillmer, A., Gong, T., Greenhouse, I., Grist, J. T., Gu, M., Harris, A. D., Hat, K., Heba, S., Heckova, E., Hegarty, J. P., Heise, K., Jacobson, A., Jansen, J. F., Jenkins, C. W., Johnston, S. J., Juchem, C., Kangarlu, A., Kerr, A. B., Landheer, K., Lange, T., Lee, P., Levendovszky, S. R., Limperopoulos, C., Liu, F., Lloyd, W., Lythgoe, D. J., Machizawa, M. G., MacMillan, E. L., Maddock, R. J., Manzhurtsev, A. V., Martinez-Gudino, M. L., Miller, J. J., Mirzakhanian, H., Moreno-Ortega, M., Mullins, P. G., Near, J., Noeske, R., Nordhoy, W., Oeltzschner, G., Osorio-Duran, R., Otaduy, M. C., Pasaye, E. H., Peeters, R., Peltier, S. J., Pilatus, U., Polomac, N., Porges, E. C., Pradhan, S., Prisciandaro, J. J., Puts, N. A., Rae, C. D., Reyes-Madrigal, F., Roberts, T. P., Robertson, C. E., Rosenberg, J. T., Rotaru, D., O'Gorman Tuura, R. L., Saleh, M. G., Sandberg, K., Sangill, R., Schembri, K., Schrantee, A., Semenova, N. A., Singel, D., Sitnikov, R., Smith, J., Song, Y., Stark, C., Stoffers, D., Swinnen, S. P., Tain, R., Tanase, C., Tapper, S., Tegenthoff, M., Thiel, T., Thioux, M., Truong, P., van Dijk, P., Vella, N., Vidyasagar, R., Vovk, A., Wang, G., Westlye, L. T., Wilbur, T. K., Willoughby, W. R., Wilson, M., Wittsack, H., Woods, A. J., Wu, Y., Xu, J., Lopez, M. Y., Yeung, D. K., Zhao, Q., Zhou, X., Zupan, G., Edden, R. A. 2021: 118430

  Abstract

  PURPOSE: Heating of gradient coils and passive shim components is a common cause of instability in the B0 field, especially when gradient intensive sequences are used. The aim of the study was to set a benchmark for typical drift encountered during MR spectroscopy (MRS) to assess the need for real-time field-frequency locking on MRI scanners by comparing field drift data from a large number of sites.METHOD: A standardized protocol was developed for 80 participating sites using 99 3T MR scanners from 3 major vendors. Phantom water signals were acquired before and after an EPI sequence. The protocol consisted of: minimal preparatory imaging; a short pre-fMRI PRESS; a ten-minute fMRI acquisition; and a long post-fMRI PRESS acquisition. Both pre- and post-fMRI PRESS were non-water suppressed. Real-time frequency stabilization/adjustment was switched off when appropriate. Sixty scanners repeated the protocol for a second dataset. In addition, a three-hour post-fMRI MRS acquisition was performed at one site to observe change of gradient temperature and drift rate. Spectral analysis was performed using MATLAB. Frequency drift in pre-fMRI PRESS data were compared with the first 5:20 minutes and the full 30:00 minutes of data after fMRI. Median (interquartile range) drifts were measured and showed in violin plot. Paired t-tests were performed to compare frequency drift pre- and post-fMRI. A simulated in vivo spectrum was generated using FID-A to visualize the effect of the observed frequency drifts. The simulated spectrum was convolved with the frequency trace for the most extreme cases. Impacts of frequency drifts on NAA and GABA were also simulated as a function of linear drift. Data from the repeated protocol were compared with the corresponding first dataset using Pearson's and intraclass correlation coefficients (ICC).RESULTS: Of the data collected from 99 scanners, 4 were excluded due to various reasons. Thus, data from 95 scanners were ultimately analyzed. For the first 5:20 min (64 transients), median (interquartile range) drift was 0.44 (1.29) Hz before fMRI and 0.83 (1.29) Hz after. This increased to 3.15 (4.02) Hz for the full 30 min (360 transients) run. Average drift rates were 0.29 Hz/min before fMRI and 0.43 Hz/min after. Paired t-tests indicated that drift increased after fMRI, as expected (p < 0.05). Simulated spectra convolved with the frequency drift showed that the intensity of the NAA singlet was reduced by up to 26%, 44 % and 18% for GE, Philips and Siemens scanners after fMRI, respectively. ICCs indicated good agreement between datasets acquired on separate days. The single site long acquisition showed drift rate was reduced to 0.03 Hz/min approximately three hours after fMRI.DISCUSSION: This study analyzed frequency drift data from 95 3T MRI scanners. Median levels of drift were relatively low (5-min average under 1 Hz), but the most extreme cases suffered from higher levels of drift. The extent of drift varied across scanners which both linear and nonlinear drifts were observed.

  View details for DOI 10.1016/j.neuroimage.2021.118430

  View details for PubMedID 34314848

• Genetic and environmental influences on structural brain measures in twins with autism spectrum disorder MOLECULAR PSYCHIATRY Hegarty, J. P., Pegoraro, L. L., Lazzeroni, L. C., Raman, M. M., Hallmayer, J. F., Monterrey, J. C., Cleveland, S. C., Wolke, O. N., Phillips, J. M., Reiss, A. L., Hardan, A. Y. 2020; 25 (10): 2556–66

  View details for DOI 10.1038/s41380-018-0330-z

  View details for Web of Science ID 000572540100029

• Effects of stress on functional connectivity during verbal processing. Brain imaging and behavior Nair, N., Hegarty, J. P., Ferguson, B. J., Hooshmand, S. J., Hecht, P. M., Tilley, M., Christ, S. E., Beversdorf, D. Q. 2019

  Abstract

  Effects of stress on functional connectivity (FC) in specific language processing regions of the brain during verbal fluency tasks were explored. Roles of gender and serotonin transporter gene polymorphisms (5-HTTLPR), associated with stress susceptibility, were also examined to understand their effect. Forty-five healthy volunteers (Mean age: 19.6±1.6years; 28 females) participated. Functional magnetic resonance imaging was carried out while participants performed letter and category fluency tasks. These tasks were interposed with the Montreal Imaging Stress Test to induce stress or a no-stress control task. Buccal swabs collected were used to genotype for the presence of polymorphisms on the SLC6A4 gene known to contribute to atypical stress responses. Significant variations in strength of FC were noted between several ROIs, including left inferior frontal gyrus and left middle temporal gyrus. Overall, males showed regional increases in FC strength over long and short distances during task under stress. Additionally, variability in effects of stress on task performance was associated with effects of stress on FC. Results suggest that long distance FC may be strengthened to compensate for additional cognitive load of the stressor but that specific short distance functional connections may be strengthened in a gender specific manner. Additionally, FC may serve as a marker for effects of stress on performance. This is the first study exploring stress effects on language tasks with imaging markers. Future studies will need to explore stress susceptible populations and establish the role of FC as a marker, with implications for targeted therapeutic interventions.

  View details for DOI 10.1007/s11682-019-00221-5

  View details for PubMedID 31833016

• Beta-adrenergic antagonism alters functional connectivity during associative processing in a preliminary study of individuals with and without autism. Autism : the international journal of research and practice Hegarty, J. P., Zamzow, R. M., Ferguson, B. J., Christ, S. E., Porges, E. C., Johnson, J. D., Beversdorf, D. Q. 2019: 1362361319868633

  Abstract

  Beta-adrenergic antagonism (e.g. propranolol) has been associated with cognitive/behavioral benefits following stress-induced impairments and for some cognitive/behavioral domains in individuals with autism spectrum disorder. In this preliminary investigation, we examined whether the benefits of propranolol are associated with functional properties in the brain. Adolescents/adults (mean age = 22.54 years) with (n = 13) and without autism spectrum disorder (n = 13) attended three sessions in which propranolol, nadolol (beta-adrenergic antagonist that does not cross the blood-brain barrier), or placebo was administered before a semantic fluency task during functional magnetic resonance imaging. Autonomic nervous system measures and functional connectivity between language/associative processing regions and within the fronto-parietal control, dorsal attention, and default mode networks were examined. Propranolol was associated with improved semantic fluency performance, which was correlated with the baseline resting heart rate. Propranolol also altered network efficiency of regions associated with semantic processing and in an exploratory analysis reduced functional differences in the fronto-parietal control network in individuals with autism spectrum disorder. Thus, the cognitive benefits from beta-adrenergic antagonism may be generally associated with improved information processing in the brain in domain-specific networks, but individuals with autism spectrum disorder may also benefit from additional improvements in domain-general networks. The benefits from propranolol may also be able to be predicted from baseline autonomic nervous system measures, which warrants further investigation.

  View details for DOI 10.1177/1362361319868633

  View details for PubMedID 31416333

• A pilot investigation of neuroimaging predictors for the benefits from pivotal response treatment for children with autism. Journal of psychiatric research Hegarty, J. P., Gengoux, G. W., Berquist, K. L., Millan, M. E., Tamura, S. M., Karve, S., Rosenthal, M. D., Phillips, J. M., Hardan, A. Y. 2019; 111: 140–44

  Abstract

  Children with autism spectrum disorder (ASD) frequently exhibit language delays and functional communication deficits. Pivotal response treatment (PRT) is an effective intervention for targeting these skills; however, similar to other behavioral interventions, response to PRT is variable across individuals. Thus, objective markers capable of predicting treatment response are critically-needed to identify which children are most likely to benefit from this intervention. In this pilot study, we investigated whether structural neuroimaging measures from language regions in the brain are associated with response to PRT. Children with ASD (n = 18) who were receiving PRT to target their language deficits were assessed with MRI at baseline. T1-weighted images were segmented with FreeSurfer and morphometric measures of the primary language regions (inferior frontal (IFG) and superior temporal (STG) gyri) were evaluated. Children with ASD and language deficits did not exhibit the anticipated relationships between baseline structural measures of language regions and baseline language abilities, as assessed by the number of utterances displayed during a structured laboratory observation (SLO). Interestingly, the level of improvement on the SLO was correlated with baseline asymmetry of the IFG, and the size of the left STG at baseline was correlated with the level of improvement on standardized parental questionnaires. Although very preliminary, the observed associations between baseline structural properties of language regions and improvement in language abilities following PRT suggest that neuroimaging measures may be able to help identify which children are most likely to benefit from specific language treatments, which could help improve precision medicine for children with ASD.

  View details for PubMedID 30771619

• Genetic and environmental influences on cortico-striatal circuits in twins with autism. Genetic and environmental influences on cortico-striatal circuits in twins with autism. Hegarty, J. P., Lazzeroni, L. C., Raman, M. M., Hallmayer, J. C., Cleveland, S. C., Phillips, J. M., Reiss, A. L., Hardan, A. Y. 2019

  View details for DOI 10.1503/jpn.190030

• Brain connectivity theories of autism Encyclopedia of Autism Spectrum Disorders Hegarty, J. P., Hardan, A. Y., Muller, R. Springer-Verlag. 2019; 2nd

  View details for DOI 10.1007/978-1-4614-6435-8_102064-1

• Effects of stress on functional connectivity during problem solving. NeuroImage Nair, N. n., Hegarty, J. P., Ferguson, B. J., Hecht, P. M., Tilley, M. n., Christ, S. E., Beversdorf, D. Q. 2019: 116407

  Abstract

  Our purpose was to examine how stress affects functional connectivity (FC) in language processing regions of the brain during a verbal problem solving task associated with creativity. We additionally explored how gender and the presence of the stress-susceptible short allele of the serotonin transporter gene polymorphism influenced this effect.Forty-five healthy participants (Mean age: 19.6 ± 1.6 years; 28 females) were recruited to be a part of this study and genotyped to determine the presence or absence of at least one copy of the short (S) allele of the serotonin transporter gene, which is associated with greater susceptibility to stress. The participants underwent functional magnetic resonance imaging in two separate sessions (stress and no stress control). One session utilized a modified version of the Montreal Imaging Stress Test (MIST) to induce stress while the other session consisted of a no stress control task. The MIST and control tasks were interleaved with task blocks during which the participants performed the compound remote associates task, a convergent task that engages divergent thinking, which is a critical component of creativity. We examined the relationship between stress effects on performance and effects on connectivity of language processing regions activated during this task.There was no main effect of stress on functional connectivity for individual ROI pairs. However, in the examination of whether stress effects on performance related to effects on connectivity, changes in middle temporal gyrus connectivity with stress correlated positively with changes in solution latency for individuals with the S allele, but anti-correlated for those with only the L allele. A trend towards a gene × stress interaction on solution latency was also observed.Results from the study suggest that genetic susceptibility to stress, such as the presence of the S allele, affects neural correlates of performance on tasks related to verbal problem solving, as indicated by connectivity of the middle temporal gyrus. Future work will need to determine whether connectivity of the middle temporal gyrus serves as a marker for the effect of stress susceptibility on cognition, extending into stress susceptible patient populations.

  View details for DOI 10.1016/j.neuroimage.2019.116407

  View details for PubMedID 31809888

• Genetic and Environmental Influences on Lobar Brain Structures in Twins With Autism. Cerebral cortex (New York, N.Y. : 1991) Hegarty, J. P., Lazzeroni, L. C., Raman, M. M., Pegoraro, L. F., Monterrey, J. C., Cleveland, S. C., Hallmayer, J. F., Wolke, O. N., Phillips, J. M., Reiss, A. L., Hardan, A. Y. 2019

  Abstract

  This investigation examined whether the variation of cerebral structure is associated with genetic or environmental factors in children with autism spectrum disorder (ASD) compared with typically developing (TD) controls. T1-weighted magnetic resonance imaging scans were obtained from twin pairs (aged 6-15 years) in which at least one twin was diagnosed with ASD or both were TD. Good quality data were available from 30 ASD, 18 discordant, and 34 TD pairs (n = 164). Structural measures (volume, cortical thickness, and surface area) were generated with FreeSurfer, and ACE modeling was completed. Lobar structures were primarily genetically mediated in TD twins (a2 = 0.60-0.89), except thickness of the temporal (a2 = 0.33 [0.04, 0.63]) and occipital lobes (c2 = 0.61 [0.45, 0.77]). Lobar structures were also predominantly genetically mediated in twins with ASD (a2 = 0.70-1.00); however, thickness of the frontal (c2 = 0.81 [0.71, 0.92]), temporal (c2 = 0.77 [0.60, 0.93]), and parietal lobes (c2 = 0.87 [0.77, 0.97]), and frontal gray matter (GM) volume (c2 = 0.79 [0.63, 0.95]), were associated with environmental factors. Conversely, occipital thickness (a2 = 0.93 [0.75, 1.11]) did not exhibit the environmental contributions that were found in controls. Differences in GM volume were associated with social communication impairments for the frontal (r = 0.52 [0.18, 0.75]), temporal (r = 0.61 [0.30, 0.80]), and parietal lobes (r = 0.53 [0.19, 0.76]). To our knowledge, this is the first investigation to suggest that environmental factors influence GM to a larger extent in children with ASD, especially in the frontal lobe.

  View details for DOI 10.1093/cercor/bhz215

  View details for PubMedID 31711118

• Cerebro-Cerebellar Functional Connectivity is Associated with Cerebellar Excitation-Inhibition Balance in Autism Spectrum Disorder JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS Hegarty, J. P., Weber, D. J., Cirstea, C. M., Beversdorf, D. Q. 2018; 48 (10): 3460–73

  View details for DOI 10.1007/s10803-018-3613-y

  View details for Web of Science ID 000445160900017

• Corpus callosum Encyclopedia of Autism Spectrum Disorders Hegarty, J. P., Hardan, A. Y., Frazier, T. W. Springer-Verlag. 2018; 2nd

  View details for DOI 10.1007/978-1-4614-6435-8_669-3

• Corpus callosum abnormalities in autism Encyclopedia of Autism Spectrum Disorders Hegarty, J. P., Hardan, A. Y., Frazier, T. W. Springer-Verlag. 2018; 2nd

  View details for DOI 10.1007/978-1-4614-6435-8_1913-3

• Agenesis of the corpus callosum Encyclopedia of Autism Spectrum Disorders Hegarty, J. P., Hardan, A. Y., Frazier, T. W. Springer-Verlag. 2018; 2nd

  View details for DOI 10.1007/978-1-4614-6435-8_657-3

• A proton MR spectroscopy study of the thalamus in twins with autism spectrum disorder. Progress in neuro-psychopharmacology & biological psychiatry Hegarty, J. P., Gu, M. n., Spielman, D. M., Cleveland, S. C., Hallmayer, J. F., Lazzeroni, L. C., Raman, M. M., Frazier, T. W., Phillips, J. M., Reiss, A. L., Hardan, A. Y. 2017

  Abstract

  Multiple lines of research have reported thalamic abnormalities in individuals with autism spectrum disorder (ASD) that are associated with social communication impairments (SCI), restricted and repetitive behaviors (RRB), or sensory processing abnormalities (SPA). Thus, the thalamus may represent a common neurobiological structure that is shared across symptom domains in ASD. Same-sex monozygotic (MZ) and dizygotic (DZ) twin pairs with and without ASD underwent cognitive/behavioral evaluation and magnetic resonance imaging to assess the thalamus. Neurometabolites were measured with (1)H magnetic resonance spectroscopy (MRS) utilizing a multi-voxel PRESS sequence and were referenced to creatine+phosphocreatine (tCr). N-acetyl aspartate (NAA), a marker of neuronal integrity, was reduced in twins with ASD (n=47) compared to typically-developing (TD) controls (n=33), and this finding was confirmed in a sub-sample of co-twins discordant for ASD (n=11). NAA in the thalamus was correlated to a similar extent with SCI, RRB, and SPA, such that reduced neuronal integrity was associated with greater symptom severity. Glutamate+glutamine (Glx) was also reduced in affected versus unaffected co-twins. Additionally, NAA and Glx appeared to be primarily genetically-mediated, based on comparisons between MZ and DZ twin pairs. Thus, thalamic abnormalities may be influenced by genetic susceptibility for ASD but are likely not domain-specific.

  View details for PubMedID 28941767

• Beta-adrenergic antagonism modulates functional connectivity in the default mode network of individuals with and without autism spectrum disorder. Brain imaging and behavior Hegarty, J. P., Ferguson, B. J., Zamzow, R. M., Rohowetz, L. J., Johnson, J. D., Christ, S. E., Beversdorf, D. Q. 2016: -?

  Abstract

  The beta-adrenergic antagonist propranolol benefits some social and communication domains affected in autism spectrum disorder (ASD), and these benefits appear to be associated with increased functional connectivity (FC) in the brain during task performance. FC is implicated in ASD, with the majority of studies suggesting long distance hypo-connectivity combined with regionally specific local hyper-connectivity. The objective in the current investigation was to examine the effect of propranolol on FC at rest and determine whether ASD-specific effects exist. Participants with and without ASD attended three sessions in which propranolol, nadolol (a beta-adrenergic antagonist that does not cross the blood-brain barrier), or placebo were administered. Resting-state fMRI data were acquired, and graph theory techniques were utilized to assess additional aspects of FC. Compared to placebo, propranolol administration was associated with decreased FC in the dorsal medial prefrontal cortex subnetwork of the default mode network and increased FC in the medial temporal lobe subnetwork, regardless of diagnosis. These effects were not seen with nadolol suggesting that the alterations in FC following propranolol administration were not exclusively due to peripheral cardiovascular effects. Thus, beta-adrenergic antagonism can up- or down- regulate FC, depending on the network, and alter coordinated functional activation in the brain. These changes in information processing, as demonstrated by FC, may mediate some of the clinical and behavioral effects of beta-adrenergic antagonism previously reported in patients with ASD.

  View details for PubMedID 27714553

• Morphological differences in the lateral geniculate nucleus associated with dyslexia NEUROIMAGE-CLINICAL Giraldo-Chica, M., Hegarty, J. P., Schneider, K. A. 2015; 7: 830-836

  Abstract

  Developmental dyslexia is a common learning disability characterized by normal intelligence but difficulty in skills associated with reading, writing and spelling. One of the most prominent, albeit controversial, theories of dyslexia is the magnocellular theory, which suggests that malfunction of the magnocellular system in the brain is responsible for the behavioral deficits. We sought to test the basis of this theory by directly measuring the lateral geniculate nucleus (LGN), the only location in the brain where the magnocellular and parvocellular streams are spatially disjoint. Using high-resolution proton-density weighted MRI scans, we precisely measured the anatomical boundaries of the LGN in 13 subjects with dyslexia (five female) and 13 controls (three female), all 22-26 years old. The left LGN was significantly smaller in volume in subjects with dyslexia and also differed in shape; no differences were observed in the right LGN. The functional significance of this asymmetry is unknown, but these results are consistent with the magnocellular theory and support theories of dyslexia that involve differences in the early visual system.

  View details for DOI 10.1016/j.nicl.2015.03.011

  View details for Web of Science ID 000373172600091

  View details for PubMedID 26082892

• Alexithymia and Impairment of Decoding Positive Affect: An fMRI Study JOURNAL OF COMMUNICATION Hesse, C., Floyd, K., Rauscher, E. A., Frye-Cox, N. E., Hegarty, J. P., Peng, H. 2013; 63 (4): 786-806

  View details for DOI 10.1111/jcom.12039

  View details for Web of Science ID 000322639400011