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, Bin Lü, Yuwei Wang, Xue-Ying Li, Zihan Wang, Hui-Xian Li, Yifan Liao, Daniel M. Blumberger, F. Xavier Castellanos, Eduardo A. Garza‐Villarreal, Liping Cao, Guanmao Chen, Jiangshan Chen, Tao Chen, Tao-Lin Chen, Yan-Rong Chen, Yu-Qi Cheng, Zhaosong Chu, Shi‐Xian Cui, Xilong Cui, Zhao‐Yu Deng, Qinglin Gao, Qiyong Gong, Wen-Bin Guo, Cancan He, Zheng-Jia-Yi Hu, Qian Huang, Xinlei Ji, Feng-Nan Jia, Li Kuang, Baojuan Li, Feng Li, Tao Li, Li Xue, Tao Lian, Xiaoyun Liu, Yan-Song Liu, Zhe-Ning Liu, Yi-Cheng Long, Jian‐Ping Lu, Jiang Qiu, Xiaoxiao Shan, Tian-Mei Si, Peng-Feng Sun, Chuanyue Wang, Hanlin Wang, Xiang Wang, Ying Wang, Chen-Nan Wu, Xiaoping Wu, Xin-Ran Wu, Yankun Wu, Chunming Xie, Guangrong Xie, Peng Xie, Xiu-Feng Xu, Zhenpeng Xue, Hong Yang, Jian Yang, Hua Yu, Yongqiang Yu, Minlan Yuan, Yonggui Yuan, Yu‐Feng Zang, Ai‐Xia Zhang, Kerang Zhang, Wei Zhang, Zijing Zhang, Jingping Zhao, Jiajia Zhu, Xi‐Nian Zuo, Chao‐Gan Yan, Xiao Chen, Li-Ping Cao, Wei Chen, Yu-Qi Cheng, Yi-Ru Fang, Qiyong Gong, Wen-Bin Guo, Li Kuang, Baojuan Li, Tao Li, Yan-Song Liu, Zhe-Ning Liu, Jian‐Ping Lu, Qing-Hua Luo, Hua-Qing Meng, Dai-Hui Peng, Jiang Qiu, Yue-Di Shen, Tian-Mei Si, Yan-Qing Tang, Chuan-Yue Wang, Fei Wang, Hua-Ning Wang, Kai Wang, Xiang Wang, Ying Wang, Xiaoping Wu, Chunming Xie
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.