Indexing Cortical Reactivity with TMS in Major Depressive Disorder and Response to Therapeutic Brain Stimulation
Year: 2019
Type: paratext
Abstract: The neuropathophysiology of Major Depressive Disorder (MDD) appears to be linked to aberrant cortical inhibition and excitation. These processes are mediated by -amino butyric acid (GABA) and glutamate, the main inhibitory and excitatory neurotransmitters of the cortex, and modified by therapeutic brain stimulation, such as electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS). Cortical inhibition and excitation can be indexed via transcranial magnetic stimulation, affording high potential as biomarkers of illness state and response to brain stimulation. When combined with electromyography (TMS-EMG), the motor cortex response is assessed. When combined with electroencephalography (TMS-EEG), TMS indexes cortical inhibition and excitation over other cortical regions, more closely associated with MDD. In study one, cortical inhibition was indexed with TMS-EMG over the motor cortex before and after a course of ECT. A TMS-EMG measure of GABAB receptor-mediated cortical inhibition, the cortical silent period, was shorter at baseline in patients who responded to ECT, when compared to the non-responder group. Contrary to evidence, neither cortical silent period nor short interval cortical inhibition (both TMS-EMG measures of cortical inhibition) were altered by a course of ECT. In study two, TMS-EEG indexed cortical inhibition and excitation over the dorsolateral prefrontal cortex (DLPFC) in healthy subjects and patients with MDD. MDD patients had larger TMS-EEG amplitudes of markers of cortical inhibition (N45 and N100) and excitation (P60 and GMFA Area Under the Curve). In fact, the N45 predicted illness state with high accuracy, and N100 was associated with illness severity. In study three, DLPFC response to rTMS was indexed via TMS-EEG in patients recruited for a trial comparing active rTMS to sham rTMS. Sham rTMS did not alter TMS-EEG markers. Active rTMS resulted in differences in the markers of cortical inhibition. The N100 amplitude, a marker associated with GABAB receptor mediated inhibition, decreased in amplitude after rTMS in association with improvement in depressive symptoms. Moreover, a local dampening of cortical activity over the DLPFC, where rTMS was applied, was noted only with active rTMS. TMS markers of cortical inhibition and excitation therefore demonstrate high potential as biomarkers of MDD and response to therapeutic brain stimulation.
Source: TSpace (University of Toronto)
Author: Daphne Voineskos
Language: English
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W3089982597