Browsing by Author "George, Mark S"

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Open Access
Age-dependent white matter disruptions after military traumatic brain injury: Multivariate analysis results from ENIGMA brain injury.
(Human brain mapping, 2022-06) Bouchard, Heather C; Sun, Delin; Dennis, Emily L; Newsome, Mary R; Disner, Seth G; Elman, Jeremy; Silva, Annelise; Velez, Carmen; Irimia, Andrei; Davenport, Nicholas D; Sponheim, Scott R; Franz, Carol E; Kremen, William S; Coleman, Michael J; Williams, M Wright; Geuze, Elbert; Koerte, Inga K; Shenton, Martha E; Adamson, Maheen M; Coimbra, Raul; Grant, Gerald; Shutter, Lori; George, Mark S; Zafonte, Ross D; McAllister, Thomas W; Stein, Murray B; Thompson, Paul M; Wilde, Elisabeth A; Tate, David F; Sotiras, Aristeidis; Morey, Rajendra A
Mild Traumatic brain injury (mTBI) is a signature wound in military personnel, and repetitive mTBI has been linked to age-related neurogenerative disorders that affect white matter (WM) in the brain. However, findings of injury to specific WM tracts have been variable and inconsistent. This may be due to the heterogeneity of mechanisms, etiology, and comorbid disorders related to mTBI. Non-negative matrix factorization (NMF) is a data-driven approach that detects covarying patterns (components) within high-dimensional data. We applied NMF to diffusion imaging data from military Veterans with and without a self-reported TBI history. NMF identified 12 independent components derived from fractional anisotropy (FA) in a large dataset (n = 1,475) gathered through the ENIGMA (Enhancing Neuroimaging Genetics through Meta-Analysis) Military Brain Injury working group. Regressions were used to examine TBI- and mTBI-related associations in NMF-derived components while adjusting for age, sex, post-traumatic stress disorder, depression, and data acquisition site/scanner. We found significantly stronger age-dependent effects of lower FA in Veterans with TBI than Veterans without in four components (q < 0.05), which are spatially unconstrained by traditionally defined WM tracts. One component, occupying the most peripheral location, exhibited significantly stronger age-dependent differences in Veterans with mTBI. We found NMF to be powerful and effective in detecting covarying patterns of FA associated with mTBI by applying standard parametric regression modeling. Our results highlight patterns of WM alteration that are differentially affected by TBI and mTBI in younger compared to older military Veterans.
Open Access
Evidence of transcranial direct current stimulation-generated electric fields at subthalamic level in human brain in vivo.
(Brain stimulation, 2018-07) Chhatbar, Pratik Y; Kautz, Steven A; Takacs, Istvan; Rowland, Nathan C; Revuelta, Gonzalo J; George, Mark S; Bikson, Marom; Feng, Wuwei
BACKGROUND:Transcranial direct current stimulation (tDCS) is a promising brain modulation technique for several disease conditions. With this technique, some portion of the current penetrates through the scalp to the cortex and modulates cortical excitability, but a recent human cadaver study questions the amount. This insufficient intracerebral penetration of currents may partially explain the inconsistent and mixed results in tDCS studies to date. Experimental validation of a transcranial alternating current stimulation-generated electric field (EF) in vivo has been performed on the cortical (using electrocorticography, ECoG, electrodes), subcortical (using stereo electroencephalography, SEEG, electrodes) and deeper thalamic/subthalamic levels (using DBS electrodes). However, tDCS-generated EF measurements have never been attempted. OBJECTIVE:We aimed to demonstrate that tDCS generates biologically relevant EF as deep as the subthalamic level in vivo. METHODS:Patients with movement disorders who have implanted deep brain stimulation (DBS) electrodes serve as a natural experimental model for thalamic/subthalamic recordings of tDCS-generated EF. We measured voltage changes from DBS electrodes and body resistance from tDCS electrodes in three subjects while applying direct current to the scalp at 2 mA and 4 mA over two tDCS montages. RESULTS:Voltage changes at the level of deep nuclei changed proportionally with the level of applied current and varied with different tDCS montages. CONCLUSIONS:Our findings suggest that scalp-applied tDCS generates biologically relevant EF. Incorporation of these experimental results may improve finite element analysis (FEA)-based models.
Open Access
The assessment of resistance to antidepressant treatment: Rationale for the Antidepressant Treatment History Form: Short Form (ATHF-SF).
(Journal of psychiatric research, 2019-06) Sackeim, Harold A; Aaronson, Scott T; Bunker, Mark T; Conway, Charles R; Demitrack, Mark A; George, Mark S; Prudic, Joan; Thase, Michael E; Rush, A John
There is considerable diversity in how treatment-resistant depression (TRD) is defined. However, every definition incorporates the concept that patients with TRD have not benefited sufficiently from one or more adequate trials of antidepressant treatment. This review examines the issues fundamental to the systematic evaluation of antidepressant treatment adequacy and resistance. These issues include the domains of interventions deemed effective in treatment of major depressive episodes (e.g., pharmacotherapy, brain stimulation, and psychotherapy), the subgroups of patients for whom distinct adequacy criteria are needed (e.g., bipolar vs. unipolar depression, psychotic vs. nonpsychotic depression), whether trials should be rated dichotomously as adequate or inadequate or on a potency continuum, whether combination and augmentation strategies require specific consideration, and the criteria used to evaluate the adequacy of treatment delivery (e.g., dose, duration), trial adherence, and clinical outcome. This review also presents the Antidepressant Treatment History Form: Short-Form (ATHF-SF), a completely revised version of an earlier instrument, and details how these fundamental issues were addressed in the ATHF-SF.