Orbitofrontal cortex-hippocampus potentiation mediates relief for depression: A randomized double-blind trial and TMS-EEG study

Sizhu Han; Xing-Xing Li; Shuochi Wei; Di Zhao; Jinjun Ding; Yongming Xu; Chang Yu; Zan Chen; Dong-Sheng Zhou; Ti-Fei Yuan

doi:10.1016/j.xcrm.2023.101060

Orbitofrontal cortex-hippocampus potentiation mediates relief for depression: A randomized double-blind trial and TMS-EEG study

Cell Rep Med. 2023 Jun 20;4(6):101060. doi: 10.1016/j.xcrm.2023.101060. Epub 2023 May 31.

Authors

Sizhu Han¹, Xing-Xing Li², Shuochi Wei², Di Zhao³, Jinjun Ding³, Yongming Xu², Chang Yu², Zan Chen², Dong-Sheng Zhou⁴, Ti-Fei Yuan⁵

Affiliations

¹ Department of Psychiatry, Ningbo Kangning Hospital, Ningbo 315201, China; Shanghai Key Laboratory of Psychotic Disorders, Brain Health Institute, National Center for Mental Disorders, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai 200030, China.
² Department of Psychiatry, Ningbo Kangning Hospital, Ningbo 315201, China.
³ Shanghai Key Laboratory of Psychotic Disorders, Brain Health Institute, National Center for Mental Disorders, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai 200030, China.
⁴ Department of Psychiatry, Ningbo Kangning Hospital, Ningbo 315201, China. Electronic address: wyzhouds@sina.com.
⁵ Shanghai Key Laboratory of Psychotic Disorders, Brain Health Institute, National Center for Mental Disorders, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai 200030, China; Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226019, China. Electronic address: tifei.yuan@smhc.org.cn.

Abstract

It has been 15 years since repetitive transcranial magnetic stimulation (rTMS) targeting the dorsolateral prefrontal cortex (DLPFC) was approved by the FDA for clinical depression treatment. Yet, the underlying mechanisms for rTMS-induced depression relief are not fully elucidated. This study analyzes TMS-electroencephalogram (EEG) data from 64 healthy control (HC) subjects and 53 patients with major depressive disorder (MDD) before and after rTMS treatment. Prior to treatment, patients with MDD have lower activity in the DLPFC, the hippocampus (HPC), the orbitofrontal cortex (OFC), and DLPFC-OFC connectivity compared with HCs. Following active rTMS treatment, patients with MDD show a significant increase in the DLPFC, HPC, and OFC. Notably, the increase in HPC activity is specifically associated with amelioration of depressive symptoms but not anxiety or sleep quality. The orbitofrontal-hippocampal pathway plays a crucial role in mediating depression relief following rTMS treatment. These findings suggest potential alternative targets for brain stimulation therapy against depression (chictr.org.cn: ChiCTR2100052007).

Keywords: brain stimulation; circuit; depression; hippocampus; orbital.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Depression / therapy
Depressive Disorder, Major* / etiology
Depressive Disorder, Major* / therapy
Electroencephalography
Hippocampus
Humans
Prefrontal Cortex
Transcranial Magnetic Stimulation / adverse effects