Subgenual anterior cingulate cortex functional connectivity abnormalities in depression: insights from brain imaging big data and precision-guided personalized intervention via transcranial magnetic stimulation

Xiao Chen¹, Bin Lu², Yu-Wei Wang¹, Xue-Ying Li¹, Zi-Han Wang¹, Hui-Xian Li³, Yi-Fan Liao¹, Daniel M Blumberger⁴, Francisco Xavier Castellanos⁵, Eduardo A Garza-Villarreal⁶, Li-Ping Cao⁷, Guan-Mao Chen⁸, Jian-Shan Chen⁷, Tao Chen⁹, Tao-Lin Chen¹⁰, Yan-Rong Chen¹¹, Yu-Qi Cheng¹², Zhao-Song Chu¹², Shi-Xian Cui¹³, Xi-Long Cui¹⁴, Zhao-Yu Deng¹, Qing-Lin Gao¹, Qi-Yong Gong¹⁰, Wen-Bin Guo¹⁴, Can-Can He¹⁵, Zheng-Jia-Yi Hu¹³, Qian Huang¹⁶, Xin-Lei Ji¹⁴, Feng-Nan Jia¹⁷, Li Kuang¹⁶, Bao-Juan Li¹⁸, Feng Li¹⁹, Tao Li²⁰, Xue Li¹, Tao Lian¹, Xiao-Yun Liu²¹, Yan-Song Liu¹⁷, Zhe-Ning Liu¹⁴, Yi-Cheng Long¹⁴, Jian-Ping Lu²², Jiang Qiu²³, Xiao-Xiao Shan¹⁴, Tian-Mei Si²⁴, Peng-Feng Sun²⁵, Chuan-Yue Wang¹⁹, Han-Lin Wang¹³, Xiang Wang¹⁴, Ying Wang⁸, Chen-Nan Wu¹, Xiao-Ping Wu²⁵, Xin-Ran Wu²³, Yan-Kun Wu²⁴, Chun-Ming Xie¹⁵, Guang-Rong Xie¹⁴, Peng Xie²⁶, Xiu-Feng Xu¹², Zhen-Peng Xue²², Hong Yang⁹, Jian Yang²⁷, Hua Yu²⁰, Yong-Qiang Yu²⁸, Min-Lan Yuan²⁹, Yong-Gui Yuan²¹, Yu-Feng Zang³⁰, Ai-Xia Zhang³¹, Ke-Rang Zhang³¹, Wei Zhang²⁹, Zi-Jing Zhang¹, Jing-Ping Zhao¹⁴, Jia-Jia Zhu²⁸, Xi-Nian Zuo³²; DIRECT Consortium; Hua-Ning Wang¹⁸, Chao-Gan Yan³³

Collaborators, Affiliations

Collaborators

Affiliations

¹ State Key Laboratory of Cognitive Science and Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing 100049, China.
² State Key Laboratory of Cognitive Science and Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing 100049, China; Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, 6525 EN, Netherland.
³ The Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
⁴ Temerty Centre for Therapeutic Brain Intervention, Campbell Family Research Institute, Centre for Addiction and Mental Health, Toronto, M6J1H4, Canada; Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, M5S1A1, Canada.
⁵ Department of Child and Adolescent Psychiatry, NYU Grossman School of Medicine, New York, NY, 10016, USA; Nathan Kline Institute for Psychiatric Research, Orangeburg, SC, 10962, USA.
⁶ Instituto de Neurobiologia, Universidad Nacional Autonoma de Mexico camus Juriquilla, Queretaro, 7630, Mexico.
⁷ Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou 510370, China.
⁸ The First Affiliated Hospital of Jinan University, Guangzhou 250024, China.
⁹ Department of Radiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310058, China.
¹⁰ Department of Radiology and Huaxi MR Research Center (HMRRC), Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital of Sichuan University, Chengdu 610041, China; Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu 610041, China.
¹¹ State Key Laboratory of Cognitive Science and Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China; Magnetic Resonance Imaging Research Center, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China.
¹² Department of Psychiatry, First Affiliated Hospital of Kunming Medical University, Kunming 650032, China.
¹³ State Key Laboratory of Cognitive Science and Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China; Sino-Danish College, University of Chinese Academy of Sciences, Beijing 101408, China; Sino-Danish Center for Education and Research, Graduate University of Chinese Academy of Sciences, Beijing 101408, China.
¹⁴ Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, China.
¹⁵ Department of Neurology, Affiliated ZhongDa Hospital of Southeast University, Nanjing 210009, China.
¹⁶ Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400042, China.
¹⁷ Department of Clinical Psychology, Suzhou Psychiatric Hospital, The Affiliated Guangji Hospital of Soochow University, Suzhou 215003, China.
¹⁸ Xijing Hospital of Air Force Military Medical University, Xi'an 710032, China.
¹⁹ Beijing Anding Hospital, Capital Medical University, Beijing 100120, China.
²⁰ Affiliated Mental Health Center & Hangzhou Seventh People's Hospital, Zhejiang University School of Medicine, Hangzhou 310063, China; Mental Health Center and Psychiatric Laboratory, West China Hospital of Sichuan University, Chengdu 610044, China.
²¹ Department of Psychosomatics and Psychiatry, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China.
²² Shenzhen Kangning Hospital, Shenzhen 518020, China.
²³ Faculty of Psychology, Southwest University, Chongqing 400715, China.
²⁴ National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital) & Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing 100191, China.
²⁵ Xi'an Central Hospital, Xi'an 710004, China.
²⁶ Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Neurobiology, Chongqing 400000, China; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400042, China.
²⁷ Chongqing Key Laboratory of Neurobiology, Chongqing 400000, China.
²⁸ Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Research Center of Clinical Medical Imaging, Hefei 230032, China; Anhui Provincial Institute of Translational Medicine, Hefei 230032, China.
²⁹ West China Hospital of Sichuan University, Chengdu 610044, China.
³⁰ Center for Cognition and Brain Disorders, The Affiliated Hospital of Hangzhou Normal University, Hangzhou 310018, China; Zhejiang Key Laboratory for Research in Assessment of Cognitive Impairments, Hangzhou 310000, China.
³¹ First Hospital of Shanxi Medical University, Taiyuan 030001, China.
³² Developmental Population Neuroscience Research Center, IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing 100091, China; National Basic Science Data Center, Beijing 100038, China.
³³ State Key Laboratory of Cognitive Science and Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing 100049, China; Sino-Danish College, University of Chinese Academy of Sciences, Beijing 101408, China; Sino-Danish Center for Education and Research, Graduate University of Chinese Academy of Sciences, Beijing 101408, China; Department of Psychological and Cognitive Sciences, Tsinghua University, Beijing 100084, China; Research Center for Culture and Psychology, Tsinghua University, Beijing 100084, China. Electronic address: yancg@tsinghua.edu.cn.

PMID: 40628558
DOI: 10.1016/j.scib.2025.05.042

Free article

Subgenual anterior cingulate cortex functional connectivity abnormalities in depression: insights from brain imaging big data and precision-guided personalized intervention via transcranial magnetic stimulation

Xiao Chen et al. Sci Bull (Beijing). 2025.

Free article

. 2025 Aug 30;70(16):2676-2690.

doi: 10.1016/j.scib.2025.05.042. Epub 2025 Jun 4.

Authors

Collaborators

Affiliations

¹ State Key Laboratory of Cognitive Science and Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing 100049, China.
² State Key Laboratory of Cognitive Science and Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing 100049, China; Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, 6525 EN, Netherland.
³ The Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
⁴ Temerty Centre for Therapeutic Brain Intervention, Campbell Family Research Institute, Centre for Addiction and Mental Health, Toronto, M6J1H4, Canada; Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, M5S1A1, Canada.
⁵ Department of Child and Adolescent Psychiatry, NYU Grossman School of Medicine, New York, NY, 10016, USA; Nathan Kline Institute for Psychiatric Research, Orangeburg, SC, 10962, USA.
⁶ Instituto de Neurobiologia, Universidad Nacional Autonoma de Mexico camus Juriquilla, Queretaro, 7630, Mexico.
⁷ Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou 510370, China.
⁸ The First Affiliated Hospital of Jinan University, Guangzhou 250024, China.
⁹ Department of Radiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310058, China.
¹⁰ Department of Radiology and Huaxi MR Research Center (HMRRC), Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital of Sichuan University, Chengdu 610041, China; Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu 610041, China.
¹¹ State Key Laboratory of Cognitive Science and Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China; Magnetic Resonance Imaging Research Center, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China.
¹² Department of Psychiatry, First Affiliated Hospital of Kunming Medical University, Kunming 650032, China.
¹³ State Key Laboratory of Cognitive Science and Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China; Sino-Danish College, University of Chinese Academy of Sciences, Beijing 101408, China; Sino-Danish Center for Education and Research, Graduate University of Chinese Academy of Sciences, Beijing 101408, China.
¹⁴ Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, China.
¹⁵ Department of Neurology, Affiliated ZhongDa Hospital of Southeast University, Nanjing 210009, China.
¹⁶ Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400042, China.
¹⁷ Department of Clinical Psychology, Suzhou Psychiatric Hospital, The Affiliated Guangji Hospital of Soochow University, Suzhou 215003, China.
¹⁸ Xijing Hospital of Air Force Military Medical University, Xi'an 710032, China.
¹⁹ Beijing Anding Hospital, Capital Medical University, Beijing 100120, China.
²⁰ Affiliated Mental Health Center & Hangzhou Seventh People's Hospital, Zhejiang University School of Medicine, Hangzhou 310063, China; Mental Health Center and Psychiatric Laboratory, West China Hospital of Sichuan University, Chengdu 610044, China.
²¹ Department of Psychosomatics and Psychiatry, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China.
²² Shenzhen Kangning Hospital, Shenzhen 518020, China.
²³ Faculty of Psychology, Southwest University, Chongqing 400715, China.
²⁴ National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital) & Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing 100191, China.
²⁵ Xi'an Central Hospital, Xi'an 710004, China.
²⁶ Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Neurobiology, Chongqing 400000, China; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400042, China.
²⁷ Chongqing Key Laboratory of Neurobiology, Chongqing 400000, China.
²⁸ Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Research Center of Clinical Medical Imaging, Hefei 230032, China; Anhui Provincial Institute of Translational Medicine, Hefei 230032, China.
²⁹ West China Hospital of Sichuan University, Chengdu 610044, China.
³⁰ Center for Cognition and Brain Disorders, The Affiliated Hospital of Hangzhou Normal University, Hangzhou 310018, China; Zhejiang Key Laboratory for Research in Assessment of Cognitive Impairments, Hangzhou 310000, China.
³¹ First Hospital of Shanxi Medical University, Taiyuan 030001, China.
³² Developmental Population Neuroscience Research Center, IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing 100091, China; National Basic Science Data Center, Beijing 100038, China.
³³ State Key Laboratory of Cognitive Science and Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing 100049, China; Sino-Danish College, University of Chinese Academy of Sciences, Beijing 101408, China; Sino-Danish Center for Education and Research, Graduate University of Chinese Academy of Sciences, Beijing 101408, China; Department of Psychological and Cognitive Sciences, Tsinghua University, Beijing 100084, China; Research Center for Culture and Psychology, Tsinghua University, Beijing 100084, China. Electronic address: yancg@tsinghua.edu.cn.

PMID: 40628558
DOI: 10.1016/j.scib.2025.05.042

Abstract

The subgenual anterior cingulate cortex (sgACC) plays a central role in the pathophysiology of major depressive disorder (MDD). Its functional interactive profile with the left dorsal lateral prefrontal cortex (DLPFC) is associated with transcranial magnetic stimulation (TMS) treatment outcomes. Previous research on sgACC functional connectivity (FC) in MDD has yielded inconsistent results, partly due to small sample sizes and limited statistical power. Furthermore, calculating sgACC-FC to target TMS individually is challenging. We used a large multi-site cross-sectional sample (1660 patients with MDD vs. 1341 healthy controls) from Phase II of the Depression Imaging REsearch ConsorTium (DIRECT) to systematically delineate case-control difference maps of sgACC-FC. We explored the potential impact of group-level abnormality profiles on TMS target localization and clinical efficacy. Next, we developed an MDD big data-guided, individualized TMS targeting algorithm to integrate group-level statistical maps with individual-level brain activity to individually localize TMS targets. We found enhanced sgACC-DLPFC FC in patients with MDD compared with healthy controls (HC). These group differences altered the position of the sgACC anti-correlation peak in the left DLPFC. We showed that the magnitude of case-control differences in the sgACC-FC was related to clinical improvement in two independent clinical samples. This targeting algorithm may generate targets demonstrating stronger associations with clinical efficiency than group-level targets. We reliably delineated MDD-related abnormalities of sgACC-FC profiles in a large, independently ascertained sample and demonstrated the potential impact of such case-control differences on FC-guided localization of TMS targets.

Keywords: Dual regression; Functional connectivity; Individualization; Major depressive disorder; Subgenual anterior cingulate cortex; Transcranial magnetic stimulation.

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Subgenual anterior cingulate cortex functional connectivity abnormalities in depression: insights from brain imaging big data and precision-guided personalized intervention via transcranial magnetic stimulation

Collaborators

Affiliations

Subgenual anterior cingulate cortex functional connectivity abnormalities in depression: insights from brain imaging big data and precision-guided personalized intervention via transcranial magnetic stimulation

Authors

Collaborators

Affiliations

Abstract

MeSH terms

LinkOut - more resources

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