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

Daphne Voineskos, Daniel M. Blumberger, Reza Zomorrodi, Nigel C. Rogasch, Faranak Farzan, George Foussias, Tarek K. Rajji, Zafiris J. Daskalakis

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23 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)477-486
Number of pages10
JournalBiological Psychiatry
Issue number6
Publication statusPublished or Issued - 15 Mar 2019
Externally publishedYes


  • EEG
  • Excitation
  • GABA
  • Inhibition
  • Major depressive disorder
  • TMS

ASJC Scopus subject areas

  • Biological Psychiatry

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