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  • BOLD response delays represent local cortical processing CEREBRAL CORTEX Proulx, S., Farivar, R. 2026; 36 (4)

    Abstract

    A number of studies showed that stimulus or task conditions can alter the shape of the hemodynamic response (HR). Contrary to variations across brains and brain regions, vascular factors alone cannot account for within-voxel HR waveform variations. Instead, different neuron types may contribute differently to shaping the HR, suggesting that beyond detecting neural activations, measurements of stimulus- or task-specific HRs could inform on the nature of underlying neural processes. To assess this hypothesis, we measured HR apparent delays to oriented visual stimuli with 1 mm and 1-s resolution Blood Oxygenation Level Dependent (BOLD) functional MRI (fMRI) in healthy humans. As expected, decoding V1 patterns of HR amplitudes allowed robust cross-validated predictions of stimulus conditions, ie two orthogonal gratings and an overlay of the two. More interestingly, this was also true using patterns of HR delays alone, and predictions using both delay and amplitude information outperformed those using amplitude alone. Finally, while all stimuli evoked similar V1-averaged HR amplitudes, the overlay stimulus' HR waveform lagged ~180 ms behind that of grating stimuli. We interpret this increased HR delay as reflecting different neural computations, here more cross-orientation suppression with overlay stimuli, and conclude that neurally relevant information can be obtained from the HR waveform in addition to its commonly used amplitude.

    View details for DOI 10.1093/cercor/bhag040

    View details for Web of Science ID 001745484000001

    View details for PubMedID 42015405

    View details for PubMedCentralID PMC13099394

  • Visual stimulus-evoked blood velocity responses in individual human posterior cerebral arteries measured with dynamic phase-contrast functional MR angiography. Imaging neuroscience (Cambridge, Mass.) Hu, Z., Proulx, S., Hartung, G. A., Gomez, D. E., Chen, J. E., Varadarajan, D., Gökçal, E., Bollmann, S., Tan, C. O., Gurol, M. E., Polimeni, J. R. 2025; 3

    Abstract

    Functional MRI (fMRI) tracks brain activity through the associated hemodynamic changes via neurovascular coupling. Neurons communicate with the microvessels of the parenchyma to initiate a hemodynamic response, and these microvessels then communicate with upstream arterioles and arteries. The role of the larger feeding arteries-far upstream from the site of neuronal activity-in coordinating this response is incompletely understood, yet is important for the interpretation of fMRI. Functional transcranial Doppler (fTCD) can noninvasively measure blood velocity changes in a subset of the largest macrovessels, albeit with poor spatial resolution, whereas existing functional MR angiography (fMRA) methods can assess blood velocity in mid-sized macrovessels but still lack the temporal resolution required to capture dynamic responses. This study aims to propose a new, quantitative fMRA method for measuring blood velocity responses in individual vessels in humans at high spatiotemporal resolution. A dynamic functional phase-contrast MRA approach was developed to quantify responses evoked by visual stimuli in the "P2" segment of the posterior cerebral artery (PCA), located ~6 cm away from primary visual cortex. The achieved temporal resolution is comparable with that of conventional blood-oxygenation-level-dependent (BOLD) fMRI, enabling block-design stimulation paradigms similar to those used in conventional fMRI studies. The temporal and spatial properties of the blood velocity responses were evaluated using both long- and short-duration visual stimuli presented to either the full visual field or a single hemifield. Robust responses were measured on both 3T and 7T clinical MRI scanners, and an approximately 3.3 ± 1.2 cm/s increase in the blood velocity in the targeted segment was observed, which is roughly a 10% increase from baseline. Visual hemifield stimulation generated a measurable blood velocity response only in the contralateral cerebral hemisphere, indicating that systemic physiological changes occurring with stimulation cannot account for the observed response, suggesting that they instead reflect neurovascular coupling initiated in the visual cortex. The observed arterial blood velocity response is consistent with a downstream reduction in microvascular resistance and may represent a passive response rather than an active vessel dilation at the targeted arterial segment. The proposed method has the potential to extend the capability of commonly used approaches, such as fTCD, in clinical applications.

    View details for DOI 10.1162/IMAG.a.148

    View details for PubMedID 40959705

    View details for PubMedCentralID PMC12434382

  • Transcranial Magnetic Stimulation and H<SUP>1</SUP>-Magnetic Resonance Spectroscopy Measures of Excitation and Inhibition Following Lorazepam Administration NEUROSCIENCE Ferland, M., Therrien-Blanchet, J., Proulx, S., Klees-Themens, G., Bacon, B., Vu, T., Theoret, H. 2021; 452: 235-246

    Abstract

    This study aimed at better understanding the neurochemistry underlying transcranial magnetic stimulation (TMS) and magnetic resonance spectroscopy (MRS) measurements as it pertains to GABAergic activity following administration of allosteric GABAA receptor agonist lorazepam. Seventeen healthy adults (8 females, 26.0 ± 5.4 years old) participated in a double-blind, crossover, placebo-controlled study, where participants underwent TMS and MRS two hours after drug intake (placebo or lorazepam; 2.5 mg). Neuronavigated TMS measures reflecting cortical inhibition and excitation were obtained in the left primary motor cortex. Sensorimotor cortex and occipital cortex MRS data were acquired using a 3T scanner with a MEGA-PRESS sequence, allowing water-referenced [GABA] and [Glx] (glutamate + glutamine) quantification. Lorazepam administration decreased occipital [GABA], decreased motor cortex excitability and increased GABAA-receptor mediated motor cortex inhibition (short intracortical inhibition (SICI)). Lorazepam intake did not modulate sensorimotor [GABA] and TMS measures of intra-cortical facilitation, long-interval cortical inhibition, cortical silent period, and resting motor threshold. Furthermore, higher sensorimotor [GABA] was associated with higher cortical inhibition (SICI) following lorazepam administration, suggesting that baseline sensorimotor [GABA] may be valuable in predicting pharmacological or neuromodulatory treatment response. Finally, the differential effects of lorazepam on MRS and TMS measures, with respect to GABA, support the idea that TMS measures of cortical inhibition reflect synaptic GABAergic phasic inhibitory activity while MRS reflects extrasynaptic GABA.

    View details for DOI 10.1016/j.neuroscience.2020.11.011

    View details for Web of Science ID 000604587200004

    View details for PubMedID 33246064

  • Longitudinal assessment of <SUP>1</SUP>H-MRS (GABA and Glx) and TMS measures of cortical inhibition and facilitation in the sensorimotor cortex EXPERIMENTAL BRAIN RESEARCH Ferland, M., Therrien-Blanchet, J., Lefebvre, G., Klees-Themens, G., Proulx, S., Theoret, H. 2019; 237 (12): 3461-3474

    Abstract

    The purpose of the present study was to investigate the long-term stability of water-referenced GABA and Glx neurometabolite concentrations in the sensorimotor cortex using MRS and to assess the long-term stability of GABA- and glutamate-related intracortical excitability using transcranial magnetic stimulation (TMS). Healthy individuals underwent two sessions of MRS and TMS at a 3-month interval. A MEGA-PRESS sequence was used at 3 T to acquire MRS signals in the sensorimotor cortex. Metabolites were quantified by basis spectra fitting and metabolite concentrations were derived using unsuppressed water reference scans accounting for relaxation and partial volume effects. TMS was performed using published standards. After performing stability and reliability analyses for MRS and TMS, reliable change indexes were computed for all measures with a statistically significant test-retest correlation. No significant effect of time was found for GABA, Glx and TMS measures. There was an excellent ICC and a strong correlation across time for GABA and Glx. Analysis of TMS measure stability revealed an excellent ICC for rMT CSP and %MSO and a fair ICC for 2 ms SICI. There was no significant correlation between MRS and TMS measures at any time point. This study shows that MRS-GABA and MRS-Glx of the sensorimotor cortex have good stability over a 3-month period, with variability across time comparable to that reported in other brain areas. While resting motor threshold, %MSO and CSP were found to be stable and reliable, other TMS measures had greater variability and lesser reliability.

    View details for DOI 10.1007/s00221-019-05691-z

    View details for Web of Science ID 000504322600033

    View details for PubMedID 31734787

  • Temporary monocular occlusion facilitates binocular fusion during rivalry JOURNAL OF VISION Sheynin, Y., Proulx, S., Hess, R. F. 2019; 19 (5): 23

    Abstract

    A few hours of monocular patching temporarily enhances the deprived eye's contribution to binocular vision, constituting a form of adult brain plasticity. Although the mechanism for this plasticity is currently unknown, several imaging studies present evidence that monocular deprivation achieves its effects by changing excitatory-inhibitory balance in the visual cortex. Much of the past work on adult monocular patching utilized binocular rivalry to quantify the patching-induced shift in perceptual eye dominance, extracting periods of exclusive visibility (in which one eye's signal is suppressed from perception) to assess each eye's contribution to binocular vision while overlooking the occurrence of mixed visibility (in which information from both eyes is combined). In this paper, we discuss two experiments to investigate the effects of short-term monocular occlusion on the relative predominance of mixed and exclusive percepts during binocular rivalry. In addition to the known perceptual eye-dominance shift, we hypothesized patching would also increase the perception of mixtures during rivalry due to deprivation-induced changes in excitatory-inhibitory balance. Our data point to two previously unknown effects of monocular deprivation: (a) a significant increase in the overall fraction and median duration of mixed visibility during rivalry that is detectable up to at least an hour after removing the patch and (b) the overall fraction of superimposition; rather than piecemeal, mixed percepts are specifically enhanced after monocular deprivation. In addition to strengthening the contribution of the deprived eye, our results show that temporary monocular patching enhances the visibility of fused binocular percepts, likely the result of attenuated interocular inhibition.

    View details for DOI 10.1167/19.5.23

    View details for Web of Science ID 000469497000023

    View details for PubMedID 31136647

  • Increased Myo-Inositol in Primary Motor Cortex of Contact Sports Athletes without a History of Concussion JOURNAL OF NEUROTRAUMA Lefebvre, G., Chamard, E., Proulx, S., Tremblay, S., Halko, M., Soman, S., de Guise, E., Pascual-Leone, A., Theoret, H. 2018; 35 (7): 953-962

    Abstract

    The objective of the study was to determine whether repetitive hits to the head at a subclinical level are associated with structural and functional brain abnormalities and whether these effects are influenced by high levels of fitness associated with intense physical activity. Seventy-two college students were recruited: 24 nonathletic, 24 athletes practicing a varsity contact sport, and 24 athletes practicing a varsity noncontact sport. They were recruited for a neuropsychological evaluation and a magnetic resonance imaging session that included magnetic resonance spectroscopy of primary motor cortex (M1) and prefrontal cortex and susceptibility-weighted imaging. There was no evidence for reduced cognitive performance or presence of micro bleeds in contact sports athletes. Abnormalities in contact sports athletes were found for myo-inositol concentration (mIns) in M1, where levels were significantly higher compared with noncontact sports athletes (p = 0.016) and nonathletes (p = 0.029). In prefrontal cortex, glutamate + glutamine (Glx) was significantly reduced in contact sports athletes compared with noncontact sports athletes (p = 0.016), and a similar reduction was observed for gamma-aminobutyric acid (GABA) levels (p = 0.005). Varsity contact sports are associated with area-specific alterations in mIns concentration in the primary motor cortex. In the prefrontal cortex, high levels of fitness could modulate the effects of head impact exposure on prefrontal metabolite concentration. Indeed, although athletes in contact and noncontact sports show different neurometabolic profiles, they do not differ from sedentary controls.

    View details for DOI 10.1089/neu.2017.5254

    View details for Web of Science ID 000424833600001

    View details for PubMedID 29279021

    View details for PubMedCentralID PMC5865614

  • GABA and glutamate levels correlate with MTR and clinical disability: Insights from multiple sclerosis. NeuroImage Nantes, J. C., Proulx, S., Zhong, J., Holmes, S. A., Narayanan, S., Brown, R. A., Hoge, R. D., Koski, L. 2017

    Abstract

    Converging areas of research have implicated glutamate and γ-aminobutyric acid (GABA) as key players in neuronal signalling and other central functions. Further research is needed, however, to identify microstructural and behavioral links to regional variability in levels of these neurometabolites, particularly in the presence of demyelinating disease. Thus, we sought to investigate the extent to which regional glutamate and GABA levels are related to a neuroimaging marker of microstructural damage and to motor and cognitive performance. Twenty-one healthy volunteers and 47 people with multiple sclerosis (all right-handed) participated in this study. Motor and cognitive abilities were assessed with standard tests used in the study of multiple sclerosis. Proton magnetic resonance spectroscopy data were acquired from sensorimotor and parietal regions of the brains' left cerebral hemisphere using a MEGA-PRESS sequence. Our analysis protocol for the spectroscopy data was designed to account for confounding factors that could contaminate the measurement of neurometabolite levels due to disease, such as the macromolecule signal, partial volume effects, and relaxation effects. Glutamate levels in both regions of interest were lower in people with multiple sclerosis. In the sensorimotor (though not the parietal) region, GABA concentration was higher in the multiple sclerosis group compared to controls. Lower magnetization transfer ratio within grey and white matter regions from which spectroscopy data were acquired was linked to neurometabolite levels. When adjusting for age, normalized brain volume, MTR, total N-acetylaspartate level, and glutamate level, significant relationships were found between lower sensorimotor GABA level and worse performance on several tests, including one of upper limb motor function. This work highlights important methodological considerations relevant to analysis of spectroscopy data, particularly in the afflicted human brain. These findings support that regional neurotransmitter levels are linked to local microstructural integrity and specific behavioral abilities that can be affected in diseases such as multiple sclerosis.

    View details for DOI 10.1016/j.neuroimage.2017.01.033

    View details for PubMedID 28131894

  • The effects of bi-hemispheric M1-M1 transcranial direct current stimulation on primary motor cortex neurophysiology and metabolite concentration RESTORATIVE NEUROLOGY AND NEUROSCIENCE Tremblay, S., Lafleur, L., Proulx, S., Beaule, V., Latulipe-Loiselle, A., Doyon, J., Marjanska, M., Theoret, H. 2016; 34 (4): 587-602

    Abstract

    The aim of the present study was to assess, in healthy individuals, the impact of M1-M1 tDCS on primary motor cortex excitability using transcranial magnetic stimulation and sensorimotor metabolite concentration using 1H-MRS.For both experiments, each participant received the three following interventions (20 min tDCS, 1 mA): left-anodal/right-cathodal, left-cathodal/right-anodal, sham. The effects of tDCS were assessed via motor evoked potentials (experiment 1) and metabolite concentrations (experiment 2) immediately after and 12 minutes following the end of stimulation and compared to baseline measurement.No effect of M1-M1 tDCS on corticospinal excitability was found. Similarly, M1-M1 tDCS did not significantly modulate metabolite concentrations. High inter-subject variability was noted. Response rate analysis showed a tendency towards inhibition following left-anodal/right-cathodal tDCS in 50% of participants and increased GABA levels in 45% of participants.In line with recent studies showing important inter-subject variability following M1-supraorbital tDCS, the present data show that M1-M1 stimulation is also associated with large response variability. The absence of significant effects suggests that current measures may lack sensitivity to assess changes in M1 neurophysiology and metabolism associated with M1-M1 tDCS.

    View details for DOI 10.3233/RNN-150569

    View details for Web of Science ID 000383190100010

    View details for PubMedID 27232951

    View details for PubMedCentralID PMC9924828