Functional Connectivity Abnormalities of the Subgenual Anterior Cingulate Cortex: Implications for Transcranial Magnetic Stimulation in Depression
Author:
Chen XiaoORCID, Lu Bin, Wang Yu-Wei, Li Xue-Ying, Wang Zi-Han, Li Hui-Xian, Liao Yi-Fan, Blumberger Daniel M., Castellanos Francisco Xavier, Cao Li-Ping, Chen Guan-Mao, Chen Jian-Shan, Chen Tao, Chen Tao-Lin, Chen Yan-Rong, Cheng Yu-Qi, Chu Zhao-Song, Cui Shi-Xian, Cui Xi-Long, Deng Zhao-Yu, Gao Qing-Lin, Gong Qi-YongORCID, Guo Wen-Bin, He Can-Can, Hu Zheng-Jia-Yi, Huang Qian, Ji Xin-Lei, Jia Feng-Nan, Kuang Li, Li Bao-Juan, Li Feng, Li Tao, Li Xue, Lian Tao, Liu Xiao-Yun, Liu Yan-Song, Liu Zhe-Ning, Long Yi-Cheng, Lu Jian-Ping, Qiu Jiang, Shan Xiao-Xiao, Si Tian-Mei, Sun Peng-Feng, Wang Chuan-Yue, Wang Han-Lin, Wang Hua-Ning, Wang Xiang, Wang Ying, Wu Chen-Nan, Wu Xiao-Ping, Wu Xin-RanORCID, Wu Yan-Kun, Xie Chun-Ming, Xie Guang-Rong, Xie PengORCID, Xu Xiu-Feng, Xue Zhen-Peng, Yang Hong, Yang Jian, Yu Hua, Yu Yong-Qiang, Yuan Min-Lan, Yuan Yong-Gui, Zang Yu-Feng, Zhang Ai-Xia, Zhang Ke-Rang, Zhang Wei, Zhang Zi-Jing, Zhao Jing-Ping, Zhu Jia-Jia, Zuo Xi-Nian, Yan Chao-GanORCID,
Abstract
AbstractBackgroundThe subgenual anterior cingulate cortex (sgACC) plays a central role in the pathophysiology of major depressive disorder (MDD), and its functional interactive profile with the left dorsal lateral prefrontal cortex (DLPFC) is associated with transcranial magnetic stimulation (TMS) treatment outcomes. Nevertheless, 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 on an individual level is challenging because of the low signal-to-noise ratio and the poor replicability of individualized functional brain images.MethodsLeveraging a large multi-site cross-sectional sample (1660 MDD patients vs. 1341 healthy controls) from Phase II of the Depression Imaging REsearch ConsorTium (DIRECT), we systematically delineated case-control difference maps of sgACC-FC. Then, in a sample of 25 individuals with treatment-resistant depression who had received repetitive TMS (rTMS) treatment, we examined the relationship between case-control differences in FCs between sgACC and their specific TMS targets and treatment outcomes. Next, we tested whether the position of the group mean FC-based target (previously determined in healthy participants) differed in MDD patients. Finally, we developed a dual regression (DR) based approach to integrate group-level statistical maps with individual-level spontaneous brain activity to evaluate individualized TMS target localization in MDD. We tested this approach in a sample of 16 individuals who had received rTMS.ResultsWe found enhanced sgACC-DLPFC FC in MDD patients. The magnitude of case-control differences in FC between sgACC and TMS targets was related to clinical improvement. We found different peak sgACC anticorrelation locations in mean FC maps of MDD patients and HCs. More effective TMS targets were closer to individualized DR-based loci than to group-level targets.ConclusionIn summary, 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. The proposed individualized approach for TMS targeting has the potential to improve TMS treatment outcome and warrants prospective clinical trials.
Publisher
Cold Spring Harbor Laboratory
Cited by
2 articles.
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