Neuroplasticity of the left dorsolateral prefrontal cortex in patients with treatment-resistant depression as indexed with paired associative stimulation: a TMS–EEG study

Author:

Kaneko Naotsugu12,Wada Masataka3,Nakajima Shinichiro3,Takano Mayuko34,Taniguchi Keita3,Honda Shiori3,Mimura Masaru3,Noda Yoshihiro3

Affiliation:

1. Department of Life Sciences , Graduate School of Arts and Sciences, , 3-8-1 Komaba, Meguro, Tokyo 153-8902 , Japan

2. The University of Tokyo , Graduate School of Arts and Sciences, , 3-8-1 Komaba, Meguro, Tokyo 153-8902 , Japan

3. Department of Neuropsychiatry, Keio University School of Medicine , 35 Shinanomachi, Shinjuku, Tokyo 160-8582 , Japan

4. Teijin Pharma Limited , 4-3-2 Asahigaoka, Hino, Tokyo 191-8512 , Japan

Abstract

Abstract Major depressive disorder affects over 300 million people globally, with approximately 30% experiencing treatment-resistant depression (TRD). Given that impaired neuroplasticity underlies depression, the present study focused on neuroplasticity in the dorsolateral prefrontal cortex (DLPFC). Here, we aimed to investigate the differences in neuroplasticity between 60 individuals with TRD and 30 age- and sex-matched healthy controls (HCs). To induce neuroplasticity, participants underwent a paired associative stimulation (PAS) paradigm involving peripheral median nerve stimulation and transcranial magnetic stimulation (TMS) targeting the left DLPFC. Neuroplasticity was assessed by using measurements combining TMS with EEG before and after PAS. Both groups exhibited significant increases in the early component of TMS-evoked potentials (TEP) after PAS (P < 0.05, paired t-tests with the bootstrapping method). However, the HC group demonstrated a greater increase in TEPs than the TRD group (P = 0.045, paired t-tests). Additionally, event-related spectral perturbation analysis highlighted that the gamma power significantly increased after PAS in the HC group, whereas it was decreased in the TRD group (P < 0.05, paired t-tests with the bootstrapping method). This gamma power modulation revealed a significant group difference (P = 0.006, paired t-tests), indicating an inverse relationship for gamma power modulation. Our findings underscore the impaired neuroplasticity of the DLPFC in individuals with TRD.

Funder

Japan Society for the Promotion of Science

Japan Research Foundation for Clinical Pharmacology

Naito Foundation

Takeda Science Foundation

Uehara Memorial Foundation

Daiichi Sankyo Scholarship Donation Program

Japan Agency for Medical Research and Development

Teijin Pharma Ltd

Inter Reha Co., Ltd

Watanabe Foundation and Daiichi Sankyo Scholarship Donation Program

Magventure Inc.

Publisher

Oxford University Press (OUP)

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