Table_1_Modulation of Resting Connectivity Between the Mesial Frontal Cortex and Basal Ganglia.DOCX

Background: The mesial prefrontal cortex, cingulate cortex, and the ventral striatum are key nodes of the human mesial fronto-striatal circuit involved in decision-making and executive function and pathological disorders. Here we ask whether deep wide-field repetitive transcranial magnetic stimulation (rTMS) targeting the mesial prefrontal cortex (MPFC) influences resting state functional connectivity.
Methods: In Study 1, we examined functional connectivity using resting state multi-echo and independent components analysis in 154 healthy subjects to characterize default connectivity in the MPFC and mid-cingulate cortex (MCC). In Study 2, we used inhibitory, 1 Hz deep rTMS with the H7-coil targeting MPFC and dorsal anterior cingulate (dACC) in a separate group of 20 healthy volunteers and examined pre- and post-TMS functional connectivity using seed-based and independent components analysis.
Results: In Study 1, we show that MPFC and MCC have distinct patterns of functional connectivity with MPFC–ventral striatum showing negative, whereas MCC–ventral striatum showing positive functional connectivity. Low-frequency rTMS decreased functional connectivity of MPFC and dACC with the ventral striatum. We further showed enhanced connectivity between MCC and ventral striatum.
Conclusions: These findings emphasize how deep inhibitory rTMS using the H7-coil can influence underlying network functional connectivity by decreasing connectivity of the targeted MPFC regions, thus potentially enhancing response inhibition and decreasing drug-cue reactivity processes relevant to addictions. The unexpected finding of enhanced default connectivity between MCC and ventral striatum may be related to the decreased influence and connectivity between the MPFC and MCC. These findings are highly relevant to the treatment of disorders relying on the mesio-prefrontal-cingulo-striatal circuit.

背景：内侧前额叶皮层（mesial prefrontal cortex, MPFC）、扣带回皮层（cingulate cortex）与腹侧纹状体（ventral striatum）是人类内侧额纹状体环路（mesial fronto-striatal circuit）的关键节点，该环路参与决策执行功能与病理生理紊乱。本研究旨在探讨靶向内侧前额叶皮层的深部宽场重复性经颅磁刺激（deep wide-field repetitive transcranial magnetic stimulation, rTMS）是否会影响静息态功能连接（resting state functional connectivity）。
方法：研究1纳入154名健康受试者，采用静息态多回波与独立成分分析技术，对内侧前额叶皮层与中扣带回皮层（mid-cingulate cortex, MCC）的默认模式连接特征进行表征。研究2则纳入另一组20名健康志愿者，采用H7线圈靶向内侧前额叶皮层与背侧前扣带回（dorsal anterior cingulate, dACC），施加抑制性1Hz深部rTMS，并通过基于种子点分析与独立成分分析，检测TMS干预前后的功能连接变化。
结果：研究1结果显示，内侧前额叶皮层与中扣带回皮层具有截然不同的功能连接模式：内侧前额叶皮层-腹侧纹状体连接呈负相关，而中扣带回皮层-腹侧纹状体连接呈正相关。抑制性1Hz rTMS可降低内侧前额叶皮层与背侧前扣带回和腹侧纹状体之间的功能连接。此外，本研究还发现中扣带回皮层与腹侧纹状体之间的连接显著增强。
结论：本研究结果表明，采用H7线圈实施的抑制性深部rTMS可通过降低靶向内侧前额叶皮层区域的连接强度，调节相关环路的功能连接，从而潜在增强反应抑制能力并降低与成瘾相关的药物线索反应性过程。中扣带回皮层与腹侧纹状体之间默认模式连接的意外增强，可能与内侧前额叶皮层与中扣带回皮层之间的连接减弱及影响降低有关。上述研究结果对依赖内侧额-扣带回-纹状体环路的疾病治疗具有重要参考价值。