Brigham and Women's Hospital, Boston, MA, United States of America; Massachusetts General Hospital, Boston, MA, United States of America; Harvard Medical School, Boston, MA, United States of America.
Brigham and Women's Hospital, Boston, MA, United States of America; Harvard Medical School, Boston, MA, United States of America.
J Affect Disord. 2022 Feb 15;299:207-214. doi: 10.1016/j.jad.2021.12.005. Epub 2021 Dec 4.
Repetitive transcranial magnetic stimulation (rTMS) has established therapeutic efficacy for major depressive disorder (MDD). While translational research has focused primarily on understanding the mechanism of action of TMS on functional activation and connectivity, the effects on structural connectivity remain largely unknown especially when rTMS is applied using subject-specific brain targets. This study aims to use novel diffusion magnetic resonance imaging (dMRI) analysis to examine microstructural changes related to rTMS treatment response using a unique cohort of 21 patients with MDD treated using rTMS with subject-specific targets. White matter dMRI microstructural measures and clinical scores were captured before and after the full course of treatment. We defined disease-relevant fiber bundles connected to different subregions of the left prefrontal cortex and analyzed changes in diffusion properties as well as correlations between the changes of dMRI measures and the changes in Hamilton Depression Rating Scale (HAMD). No significant changes were observed in tracts connected to the TMS targets. rTMS significantly increased the extra-axonal free-water volume, fractional anisotropy and decreased the radial diffusivity in anterior-medial prefrontal fiber bundles but did not lead to raw changes in lateral prefrontal tracts. That said, the microstructural changes in the lateral prefrontal white matter were significantly correlated with treatment response. Moreover, pre-rTMS dMRI measures of the dorsal anterior cingulate cortex and lateral prefrontal cortex connections are correlated with changes in HAMD scores. Microstructural changes in the anterior-medial and lateral prefrontal white matter are potentially involved in treatment response to TMS, though further investigation is needed using larger datasets.
重复经颅磁刺激（rTMS）已被证实对治疗重度抑郁症（MDD）有效。尽管转化研究主要集中在理解 TMS 对功能激活和连通性的作用机制，但 rTMS 对结构连通性的影响在很大程度上仍不清楚，特别是当 rTMS 使用基于个体的大脑靶点进行应用时。本研究旨在使用新颖的弥散磁共振成像（dMRI）分析，使用一组独特的 21 名接受基于个体的大脑靶点 rTMS 治疗的 MDD 患者，检查与 rTMS 治疗反应相关的微观结构变化。在整个治疗过程前后，分别采集了患者的白质 dMRI 微观结构测量值和临床评分。我们定义了与左前额叶不同亚区相关的与疾病相关的纤维束，并分析了弥散性质的变化以及 dMRI 测量值的变化与汉密尔顿抑郁评定量表（HAMD）变化之间的相关性。与 TMS 靶点相连的束没有观察到明显的变化。rTMS 显著增加了前内侧前额叶纤维束中的细胞外自由水体积、各向异性分数，并降低了辐射状弥散率，但并未导致外侧前额叶束的原始变化。也就是说，外侧前额叶白质的微观结构变化与治疗反应显著相关。此外，背侧前扣带皮层和外侧前额叶连接的 dMRI 测量值与 HAMD 评分的变化相关。前内侧和外侧前额叶白质的微观结构变化可能与 TMS 的治疗反应有关，但需要使用更大的数据集进行进一步研究。
