Altered Transcranial Magnetic Stimulation–Electroencephalographic Markers of Inhibition and Excitation in the Dorsolateral Prefrontal Cortex in Major Depressive Disorder.

Abstract Background The neurophysiology of major depressive disorder (MDD) has become a particular focus of transcranial magnetic stimulation (TMS) investigational studies. TMS combined with electroencephalography (TMS-EEG) affords a window to directly measure evoked activity from the dorsolateral prefrontal cortex (DLPFC), which is of considerable interest in MDD. Our study examined TMS-EEG responses from the DLPFC in persons with MDD compared with those in healthy participants. Specifically, we examined TMS-EEG markers linked to inhibitory and excitatory neurophysiological processes and their balance. Methods In all, 30 participants with MDD and 30 age- and sex-matched healthy participants underwent single-pulse TMS-EEG to assess inhibition and excitation from DLPFC. TMS-EEG waveforms were analyzed through global mean field amplitude. Results MDD participants demonstrated abnormalities in TMS-EEG markers in the DLPFC. Inhibitory measures—N45 and N100—were larger in the MDD group than in healthy participants (N45 [ t = −4.894, p <.001] and N100 [ t = −3.496, p =.001]). In a receiver operating characteristic analysis, N45 amplitude predicted depression illness state with 80% sensitivity, 73.3% specificity, and 76.6% accuracy (area under the curve = 0.829, p <.001). The global mean field amplitude area under the curve, a neurophysiological measure of cortical reactivity, was significantly larger in persons with MDD (t = −3.114, p =.003), as was P60 (t = −3.260, p =.002). In healthy participants, there was a positive correlation between inhibitory N45 and excitatory global mean field amplitude area under the curve (r =.711, p <.001) that was not present in persons with MDD (r =.149, p =.43), demonstrating a potential imbalance between inhibition and excitation in MDD. Conclusions As the TMS-EEG waveform and its components index inhibitory and excitatory activity from the cortex, our results suggest abnormalities in these neurophysiological processes of DLPFC in persons with MDD. [ABSTRACT FROM AUTHOR]