M11. ALTERED TRANSCRANIAL MAGNETIC STIMULATION ELECTROENCEPHALOGRAPHIC MARKERS IN SCHIZOPHRENIA

Abstract

BackgroundCortical inhibition is a neurophysiological process in which cortical gamma-aminobutyric acid (GABA) inhibitory interneurons modulate the activity of pyramidal neurons in the cerebral cortex. Multiple lines of evidence, including neurophysiological and neuropathological, report that individuals with schizophrenia have deficits in cortical inhibition. Combining transcranial magnetic stimulation (TMS) with electroencephalography is a reliable approach to measure inhibitory processes in the cortex. The overall waveform produced by TMS-EEG may index cortical reactivity as a whole and previous investigations have linked the N45 component peak and the N100 component peak with GABA-A and GABA-B inhibitory neurotransmission, respectively. The aim of this study was to stimulate the DLPFC with TMS and examine resultant differences in the TMS-EEG waveform peaks between patients with schizophrenia and healthy subjects. We hypothesized that individuals with schizophrenia will have smaller TMS-evoked potentials, specifically the amplitudes of the N100 and N45 components, those previously related to GABA-ergic inhibition.MethodsWe applied TMS over the left DLPFC and recorded EEG activity in 48 healthy subjects (mean age: 33.8±5.3) and 46 patients with schizophrenia (mean age: 43.3±6.4). Monophasic TMS pulses were administered using a 7-cm figure-of-8 coil, and two Magstim 200 stimulators connected via a Bistim module. Single pulse TMS was administered over the left DLPFC with 100 total pulses, which were delivered every 5s. Resultant waveforms were extracted and analyzed through custom MATLAB scripts. The TMS-evoked potential waveform was examined through Global Mean Field Amplitude (GMFA) analysis of waveform peaks in each the two groups. Normality of the distribution of each variable was assessed and a Mann Whitney U test was then performed for each variable of interest to assess differences between groups.ResultsIndividuals in the schizophrenia group demonstrated smaller measures of cortical inhibition in the DLPFC. Specifically, smaller amplitudes of the N45 (U=724.00, p=0.004) and N100 peaks (U=831.00, p=0.039), although the overall AUC of the waveform did not differ between groups (U=969.00, p=0.307). Further analysis is underway to examine medication and symptom cluster effects.DiscussionThese results demonstrate novel findings of deficits in both GABA-A and GABA-B associated measures of cortical inhibition as indexed by single pulse TMS-EEG. This reinforces previous evidence from different research modalities demonstrating overall GABAergic inhibitory deficits in schizophrenia, and specifically provides new support which confirms recent findings of aberrant GABA-Aergic inhibitory neurotransmission in schizophrenia.