Transcranial magnetic stimulation neurophysiology of patients with major depressive disorder: A systematic review and meta-analysis

Megumi Kinjo, Masataka Wada, Shinichiro Nakajima, Sakiko Tsugawa, Tomomi Nakahara, Daniel M. Blumberger, Masaru Mimura, Yoshihiro Noda

Research output: Contribution to journalReview articlepeer-review

8 Citations (Scopus)


Major depressive disorder (MDD) is a mental illness with high socio-economic burden, but its pathophysiology has not been fully elucidated. Recently, the cortical excitatory and inhibitory imbalance hypothesis and neuroplasticity hypothesis have been proposed for MDD. Although several studies have examined the neurophysiological profiles in MDD using transcranial magnetic stimulation (TMS), a meta-analysis of TMS neurophysiology has not been performed. The objective of this study was to compare TMS-electromyogram (TMS-EMG) findings between patients with MDD and healthy controls (HCs). To this end, we examined whether patients with MDD have lower short-interval cortical inhibition (SICI) which reflects gamma-aminobutyric acid (GABA)A receptor-mediated activity, lower cortical silent period (CSP) which represents GABAB receptor-mediated activity, higher intracortical facilitation (ICF) which reflects glutamate N-methyl-D-aspartate receptor-mediated activity, and the lower result of paired associative stimulation (PAS) paradigm which shows the level of neuroplasticity in comparison with HC. Further, we explored the effect of clinical and demographic factors that may influence TMS neurophysiological indices. We first searched and identified research articles that conducted single- or paired-pulse TMS-EMG on patients with MDD and HC. Subsequently, we extracted the data from the included studies and meta-analyzed the data with the comprehensive meta-analysis software. Patients with MDD were associated with lower SICI, lower CSP, potentially higher ICF, and lower PAS compared with HC. Our results confirmed the proposed hypotheses, suggesting the usefulness of TMS neurophysiology as potential diagnostic markers of MDD.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalPsychological Medicine
Issue number1
Publication statusPublished - 2021 Jan


  • TMS neurophysiology
  • cortical excitability
  • cortical inhibition
  • excitatory and inhibitory imbalance hypothesis
  • major depressive disorder
  • neuroplasticity hypothesis

ASJC Scopus subject areas

  • Applied Psychology
  • Psychiatry and Mental health


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