Biology subjects

George, M. S.

Publications and source records attributed to George, M. S..

5 recordsLinked to original sources

bioRxiv2026

Toward an Objective Assessment of Fight-or-Flight System Function in Anxiety Disorders: Startle Reflex Modulation in Threat Coping Contexts as a Candidate Neurophysiological Marker of Disrupted Defense System Operation

Background: As a key mechanism of disorder, clinical anxiety changes how a defensive motivation system functions in active threat coping contexts. Building on initial evidence that a lab-based escape/avoid preparation task is sensitive to disruptions in underlying defensive activation, current research moved toward implementation as a clinical assessment by testing if task responding predicts symptoms in anxiety treatment seekers. Methods: In our escape/avoid task, unpleasant images are shown after 5.5-second cues that indicate if the upcoming image can be prevented (avoid context), terminated after onset (escape context), or not controlled (no-control comparator). To assess defensive activation during response preparation/threat anticipation, a startle reflex indicator of such activation is probed during each cue. Guided by prior data, 125 individuals were classified into groups based on whether startle was enhanced 1) in a no-control, relative to avoid, context, and 2) in an escape, relative to avoid, context. To test clinical correlates, anxiety (State-Trait Anxiety Inventory), depression (Beck Depression Inventory), and worry (Penn State Worry Questionnaire) were then compared across response groups. Results: Anxiety and worry were higher in participants with enhanced no-control and escape startle than in participants with enhanced no-control but not escape startle. Further, depression was higher in participants with under-enhancement of no-control startle than other groups. Finally, when comparing startle-based profiles to canonical questionnaire cut-off score-based groups, ~54-63% convergence emerged. Conclusions: Defensive profiling in escape/avoid contexts shows promise as a prognostic indicator, but a need to continue improving is also indicated. Possibilities to improve predictiveness and reliability are discussed.

neuroscience↗

bioRxiv2022

Functional and effective connectivity between dorsolateral prefrontal and subgenual anterior cingulate cortex depends on the timing of transcranial magnetic stimulation relative to the phase of prefrontal alpha EEG

BACKGROUNDThe communication through coherence model posits that brain rhythms are synchronized across different frequency bands and that effective connectivity strength between interacting regions depends on their phase relation. Evidence to support the model comes mostly from electrophysiological recordings in animals while evidence from human data is limited. METHODSHere, an fMRI-EEG-TMS (fET) instrument capable of acquiring simultaneous fMRI and EEG during noninvasive single pulse TMS applied to dorsolateral prefrontal cortex (DLPFC) was used to test whether prefrontal EEG alpha phase moderates TMS-evoked top-down influences on subgenual, rostral and dorsal anterior cingulate cortex (ACC). Results in healthy volunteers (n=11) were compared to those from patients with major depressive disorder (MDD) (n=17) collected as part of a ongoing clinical trial investigation. RESULTSIn both groups, TMS-evoked functional connectivity between DLPFC and subgenual ACC (sgACC) depended on the EEG alpha phase. TMS-evoked DLPFC to sgACC effective connectivity (EC) was moderated by EEG alpha phase in healthy volunteers, but not in the MDD patients. Top-down EC was inhibitory for TMS onsets during the upward slope of the alpha wave relative to TMS timed to the downward slope of the alpha wave. Prefrontal EEG alpha phase dependent effects on TMS-evoked fMRI BOLD activation of the rostral anterior cingulate cortex were detected in the MDD patient group, but not in the healthy volunteer group. DISCUSSIONResults demonstrate that TMS-evoked top-down influences vary as a function of the prefrontal alpha rhythm, and suggest clinical applications whereby TMS is synchronized to the brains internal rhythms in order to more efficiently engage deep therapeutic targets.

neuroscience↗

bioRxiv2021

Optimizing transcranial direct current stimulation (tDCS) electrode position, size, and distance doubles the on-target cortical electric field: Evidence from 3000 Human Connectome Project models

Transcranial direct current stimulation (tDCS) is a widely used noninvasive brain stimulation technique with mixed results and no FDA-approved therapeutic indication to date. So far, thousands of published tDCS studies have placed large scalp electrodes directly over the intended brain target and delivered the same stimulation intensity to each person. Inconsistent therapeutic results may be due to insufficient cortical activation in some individuals and the inability to determine an optimal dose. Here, we computed 3000 MRI-based electric field models in 200 Human Connectome Project (HCP) participants, finding that the largely unexamined variables of electrode position, size, and between-electrode distance significantly impact the delivered cortical electric field magnitude. At the same scalp stimulation intensity, smaller electrodes surrounding the neural target deliver more than double the on-target cortical electric field while stimulating only a fraction of the off-target brain regions. This new optimized tDCS method can ensure sufficient cortical activation in each person and could produce larger and more consistent behavioral effects in every prospective research and transdiagnostic clinical application of tDCS.

neuroscience↗

bioRxiv2020

Assessing the Intra- and Inter-Subject Reliability of the Perturbational Complexity Index (PCI) of Consciousness for Three Brain Regions Using TMS-EEG

BackgroundThe perturbational complexity index (PCI) is a useful measure of consciousness that combines transcranial magnetic stimulation (TMS) with electroencephalography (EEG). However, the PCI has not been assessed for reliability between sessions nor is there a clear best stimulation target to acquire a PCI. Objective/HypothesisWe assessed the reliability of within-subject PCIs between 3 sessions with stimulation over the same premotor, motor, and parietal targets between visits, hypothesizing that we could determine a most reliable TMS-EEG target to acquire PCIs in healthy, conscious adults. MethodsPCIs were acquired for 9 participants (5 women) over 3 sessions within a week. A 64 channel EEG system was used with all electrode impedances [≤] 10k{Omega}. Premotor, motor, and parietal stimulation targets were identified using a real-time Matlab graphical user interface (GUI). Neuronavigation using an MRI-template brain ensured that every TMS pulse was delivered within 3.0mm and 5{degrees} of the stimulation target. ResultsPremotor, motor, and parietal PCIs all had significant PCIs (all p < 0.05). However, parietal and motor PCIs had excellent reliability (ICCs = 0.927 and 0.857 respectively) whereas premotor PCIs had good reliability (ICC = 0.737). PCIs were similar between brain sites within each subject in a single visit, but with only a moderate effect (p = 0.024, ICC = 0.480). PCIs on a group level did not differ between brain sites (p = 0.589). ConclusionsThe PCI is a reliable measure over this timeframe within each subject for single brain targets. PCIs for parietal and motor sites are most similar between visits. Due to only moderate similarity between PCIs from three brain sites within each session, PCIs should be acquired over at least two brain sites, with parietal and motor regions as the top candidates.

neuroscience↗

bioRxiv2019

Transcranial Electrical Stimulation Motor Threshold Combined with Reverse-Calculated Electric Field Modeling Can Determine Individualized tDCS Dosage

BackgroundUnique amongst brain stimulation tools, transcranial direct current stimulation (tDCS) currently lacks an easy method for individualizing dosage.\n\nObjectiveCan one individually dose tDCS? We developed a novel method of reverse-calculating electric-field (E-field) models based on Magnetic Resonance Imaging (MRI) scans that can determine individualized tDCS dose. We also sought to develop an MRI-free method of individualizing tDCS dose by measuring transcranial magnetic stimulation (TMS) motor threshold (MT) and single pulse, suprathreshold transcranial electrical stimulation (TES) MT and regressing it against E-field modeling.\n\nMethodsIn 29 healthy adults, we acquired TMS MT, TES MT, and structural MRI scans with a fiducial marking the motor hotspot. We then computed a \"reverse-calculated tDCS dose\" of tDCS applied at the scalp needed to cause a 1.00V/m E-field at the cortex. Finally, we examined whether the predicted E-field values correlated with each participants measured TMS MT or TES MT.\n\nResultsWe were able to determine a reverse-calculated tDCS dose for each participant. The Transcranial Electrical Stimulation MT, but not the Transcranial Magnetic Stimulation MT, significantly correlated with the calculated tDCS dose determined by E-field modeling (R2 = 0.509, p < 0.001).\n\nConclusionsReverse-calculation E-field modeling, alone or in combination with TES MT, shows promise as a method to individualize tDCS dose. The large range of the reverse-calculated tDCS doses between subjects underscores the likely need to individualize tDCS dose. If these results are confirmed in future studies, TES MT may evolve into an inexpensive and quick method to individualize tDCS dose.

neuroscience↗