Table_1_Functional Remodeling Associated With Language Recovery After Repetitive Transcranial Magnetic Stimulation in Chronic Aphasic Stroke.DOCX

BackgroundRepetitive transcranial magnetic stimulation (rTMS) has shown promising efficacy in improving the language functions in poststroke aphasia. However, randomized controlled trials were lacking to investigate the rTMS-related neuroimaging changes underlying the therapeutic effects on language improvement in chronic aphasia.
ObjectiveIn this study, we aimed to evaluate the effects of low-frequency rTMS (LF-rTMS) on chronic poststroke aphasia. We hypothesized that the deactivation of the right pars triangularis could restore the balance of interhemispheric inhibition and, hence, facilitated the functional remodeling of language networks in both the hemispheres. Furthermore, the rTMS-induced functional reorganization should underpin the language recovery after rTMS.
MethodsA total of 33 patients (22 males; age: 58.70 ± 13.77 years) with chronic stroke in the left hemisphere and nonfluent aphasia were recruited in this randomized double-blinded study. The ratio of randomization between the rTMS and sham groups is 17:16. All the patients received real 1-Hz rTMS or sham stimulation (placebo coil delivered < 5% of magnetic output with similar audible click-on discharge) at the right posterior pars triangularis for 10 consecutive weekdays (stroke onset to the first stimulation: 10.97 ± 10.35 months). Functional connectivity of language networks measured by resting-state fMRI was calculated and correlated to the scores of the Concise Chinese Aphasia Test by using the stepwise regression analysis.
ResultsAfter LF-rTMS intervention, significant improvement in language functions in terms of comprehension and expression abilities was observed compared with the sham group. The rTMS group showed a significant decrease of coupling strength between right pars triangularis and pars opercularis with a strengthened connection between right pars orbitalis and angular gyrus. Furthermore, the LF-rTMS significantly enhanced the coupling strength associated with left Wernicke area. Results of regression analysis showed that the identified functional remodeling involving both the hemispheres could support and predict the language recovery after LF-rTMS treatment.
ConclusionWe reported the therapeutic effects of LF-rTMS and corresponding functional remodeling in chronic poststroke aphasia. Our results provided neuroimage evidence reflecting the rebalance of interhemispheric inhibition induced by LF-rTMS, which could facilitate future research in the refinement of rTMS protocol to optimize the neuromodulation efficacy and benefit the clinical management of patients with stroke.

【背景】重复经颅磁刺激（repetitive transcranial magnetic stimulation，rTMS）在改善卒中后失语症患者语言功能方面已展现出可观的疗效。然而，目前尚缺乏随机对照试验，来探究慢性失语症患者中，rTMS治疗语言功能改善背后的神经影像学变化机制。
【目的】本研究旨在评估低频重复经颅磁刺激（low-frequency rTMS，LF-rTMS）对慢性卒中后失语症的干预效果。我们提出假说：右侧额下回三角部的去激活可恢复半球间抑制平衡，进而促进双侧大脑半球语言网络的功能重塑；此外，rTMS诱导的功能重组应是rTMS治疗后语言功能恢复的基础。
【方法】本项随机双盲研究共纳入33例左侧半球慢性卒中合并非流利型失语症患者（22例男性，年龄58.70±13.77岁）。rTMS组与假刺激组的随机分配比例为17:16。所有患者于右侧额下回后三角部接受连续10个工作日的1Hz真实rTMS或假刺激（假刺激线圈的磁输出功率低于5%，且伴有类似的可闻放电声响），从卒中发病至首次刺激的间隔时间为10.97±10.35个月。通过静息态功能磁共振成像（resting-state fMRI）采集数据并计算语言网络的功能连接，采用逐步回归分析将连接参数与简明中文失语症测验（Concise Chinese Aphasia Test）得分进行关联。
【结果】与假刺激组相比，低频rTMS干预后，患者的语言理解与表达能力均出现显著改善。rTMS组的右侧额下回三角部与岛盖部之间的连接耦合强度显著降低，同时右侧额下回眶部与角回之间的连接显著增强。此外，低频rTMS显著增强了与左侧韦尼克区（Wernicke area）相关的连接耦合强度。回归分析结果显示，本研究鉴定出的双侧大脑半球功能重塑，可支持并预测低频rTMS治疗后的语言功能恢复。
【结论】本研究报道了低频rTMS对慢性卒中后失语症的治疗效果及其伴随的功能重塑现象。本研究结果提供了神经影像学证据，揭示了低频rTMS诱导的半球间抑制平衡重建机制，可为未来优化rTMS方案以提升神经调控疗效、改善卒中患者的临床管理提供参考依据。