Reduced signal propagation elicited by frontal transcranial magnetic stimulation is associated with oligodendrocyte abnormalities in treatment-resistant depression

Masataka Wada, Shinichiro Nakajima, Shiori Honda, Mayuko Takano, Keita Taniguchi, Sakiko Tsugawa, Yu Mimura, Nanao Hattori, Shinsuke Koike, Reza Zomorrodi, Daniel M. Blumberger, Zafiris J. Daskalakis, Masaru Mimura, Yoshihiro Noda

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The efficacy of repetitive transcranial magnetic stimulation (rTMS) to the left dorsolateral prefrontal cortex (dlPFC) has been established in patients with treatment-resistant depression (TRD), suggesting that alterations in signal propagation from the left dlPFC to other brain regions may be linked to the pathophysiology of TRD. Alterations at the cellular level, including dysfunction of oligodendrocytes, may contribute to these network abnormalities. The objectives of the present study were to compare signal propagation from the left dlPFC to other neural networks in patients with TRD and healthy controls. We used TMS combined with electroencephalography to explore links between cell-specific gene expression and signal propagation in TRD using a virtual-histology approach. Methods: We examined source-level estimated signal propagation from the left dlPFC to the 7 neural networks in 60 patients with TRD and 30 healthy controls. We also calculated correlations between the interregional profiles of altered signal propagation and gene expression for 9 neural cell types derived from the Allen Human Brain Atlas data set. Results: Signal propagation from the left dlPFC to the salience network was reduced in the θ and α bands in patients with TRD (p = 0.0055). Furthermore, this decreased signal propagation was correlated with cellspecific gene expression of oligodendrocytes (p < 0.000001). Limitations: These results show only part of the pathophysiology of TRD, because stimulation was limited to the left dlPFC. Conclusion: Reduced signal propagation from the left dlPFC to the salience network may represent a pathophysiological endophenotype of TRD; this finding may be associated with reduced expression of oligodendrocytes.

Original languageEnglish
Pages (from-to)E325-E335
JournalJournal of Psychiatry and Neuroscience
Volume47
Issue number5
DOIs
Publication statusPublished - 2022

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry
  • Pharmacology (medical)

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