Frontoparietal network mediates the antidepressant effects of accelerated iTBS and cTBS: TMS-EEG study

Xianwei Che; Haoyang Zhao; Xinyi Ye; Shaoyong Ye; Zhen Zhen; Zhimin Huang; Ying Li; Shiyi Zhang; Pengfeng Xu; Xuanqiang Chen; Chaonan Jiang; Fen Pan; Honglin Luan; Jingkai Chen; Desheng Shang; Shaohua Hu; Yiheng Tu; Li Hu; Bernadette M Fitzgibbon; Paul B Fitzgerald; Robin F H Cash; Manli Huang

doi:10.1016/j.xcrm.2025.102470

Frontoparietal network mediates the antidepressant effects of accelerated iTBS and cTBS: TMS-EEG study

Cell Rep Med. 2025 Dec 16;6(12):102470. doi: 10.1016/j.xcrm.2025.102470. Epub 2025 Dec 3.

Authors

Xianwei Che¹, Haoyang Zhao², Xinyi Ye², Shaoyong Ye², Zhen Zhen³, Zhimin Huang³, Ying Li², Shiyi Zhang², Pengfeng Xu², Xuanqiang Chen², Chaonan Jiang², Fen Pan², Honglin Luan⁴, Jingkai Chen², Desheng Shang⁵, Shaohua Hu², Yiheng Tu⁶, Li Hu⁶, Bernadette M Fitzgibbon⁷, Paul B Fitzgerald⁸, Robin F H Cash⁹, Manli Huang¹⁰

Affiliations

¹ Department of Psychiatry, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Zhejiang Key Laboratory of Precision Psychiatry, Hangzhou 310003, China; Centre for Cognition and Brain Disorders, The Affiliated Hospital of Hangzhou Normal University, Hangzhou 310015, China.
² Department of Psychiatry, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Zhejiang Key Laboratory of Precision Psychiatry, Hangzhou 310003, China.
³ Centre for Cognition and Brain Disorders, The Affiliated Hospital of Hangzhou Normal University, Hangzhou 310015, China.
⁴ Department of Psychiatry, Wen Zhou Seventh People's Hospital, Wenzhou 325006, China.
⁵ Department of Radiology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
⁶ CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing, China.
⁷ School of Medicine and Psychology, The Australian National University, Canberra, ACT, Australia; Monarch Research Institute, Monarch Mental Health Group, Sydney, NSW, Australia.
⁸ School of Medicine and Psychology, The Australian National University, Canberra, ACT, Australia.
⁹ Department of Psychiatry, The University of Melbourne, Parkville, VIC, Australia; Department of Biomedical Engineering, The University of Melbourne, Parkville, VIC, Australia.
¹⁰ Department of Psychiatry, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Nanhu Brain-computer Interface Institute, Hangzhou 311100, China; Zhejiang Key Laboratory of Precision Psychiatry, Hangzhou 310003, China. Electronic address: huangmanli@zju.edu.cn.

Abstract

Accelerated intermittent and continuous theta burst stimulation (a-iTBS and a-cTBS) show strong efficacy for treatment-resistant depression (TRD), yet their neural mechanisms remain unclear. This study uses concurrent transcranial magnetic stimulation (TMS) and electroencephalography (TMS-EEG) to examine these mechanisms in 40 TRD patients and 40 healthy controls (HCs). TRD individuals demonstrate abnormal local cortical excitability at baseline, characterized by left hypoactivity and right disinhibition. A-iTBS increases left excitability, and a-cTBS increases right inhibition, and both normalize it to the level of HCs. Network analyses reveal that a-iTBS improves current propagation to the left inferior parietal lobule (IPL), correlating with a better antidepressant effect. Contrastingly, a-cTBS induces a widespread inhibition as indicated by current propagation over parietal cortices, with the left IPL being most prominent, and this also correlates with a better antidepressant effect. These findings outline the frontoparietal circuitry in TMS antidepressant effects and provide insights for optimizing treatment efficacy. This study was registered at the Chinese Clinical Trial Registry (ChiCTR2200055320).

Keywords: TMS-EEG; inferior parietal lobule; theta burst stimulation; treatment-resistant depression.

MeSH terms

Adult
Antidepressive Agents / therapeutic use
Depressive Disorder, Treatment-Resistant* / physiopathology
Depressive Disorder, Treatment-Resistant* / therapy
Electroencephalography* / methods
Female
Frontal Lobe* / physiopathology
Humans
Male
Middle Aged
Nerve Net* / physiopathology
Parietal Lobe* / physiopathology
Transcranial Magnetic Stimulation* / methods

Substances

Antidepressive Agents