Department of Neurology, Drum Tower Hospital, Medical School and The State Key Laboratory of Pharmaceutical Biotechnology, Institute of Brain Science, Nanjing University, Nanjing, China.
Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
CNS Neurosci Ther. 2023 Aug;29(8):2267-2280. doi: 10.1111/cns.14177. Epub 2023 Mar 21.
Neuro-navigated repetitive transcranial magnetic stimulation (rTMS) is effective in alleviating cognitive deficits in Alzheimer's disease (AD). However, the strategy for target determination and the mechanisms for cognitive improvement remain unclear.
One hundred and thirteen elderly subjects were recruited in this study, including both cross-sectional (n = 79) and longitudinal experiments (the rTMS group: n = 24; the sham group: n = 10). The cross-sectional experiment explored the precise intervention target based on the cortical-hippocampal network. The longitudinal experiment investigated the clinical efficacy of neuro-navigated rTMS treatment over a four-week period and explored its underlying neural mechanism using seed-based and network-based analysis. Finally, we applied connectome-based predictive modeling to predict the rTMS response using these functional features at baseline.
RTMS at a targeted site of the left angular gyrus (MNI: -45, -67, 38) significantly induced cognitive improvement in memory and language function (p < 0.001). The improved cognition correlated with the default mode network (DMN) subsystems. Furthermore, the connectivity patterns of DMN subsystems (r = 0.52, p = 0.01) or large-scale networks (r = 0.85, p = 0.001) at baseline significantly predicted the Δ language cognition after the rTMS treatment. The connectivity patterns of DMN subsystems (r = 0.47, p = 0.019) or large-scale networks (r = 0.80, p = 0.001) at baseline could predict the Δ memory cognition after the rTMS treatment.
These findings suggest that neuro-navigated rTMS targeting the left angular gyrus could improve cognitive function in AD patients. Importantly, dynamic regulation of the intra- and inter-DMN at baseline may represent a potential predictor for favorable rTMS treatment response in patients with cognitive impairment.
神经导航重复经颅磁刺激（rTMS）在缓解阿尔茨海默病（AD）患者的认知缺陷方面是有效的。然而，目标确定的策略和认知改善的机制仍不清楚。
本研究共纳入 113 名老年人，包括横断面（n=79）和纵向实验（rTMS 组：n=24；假刺激组：n=10）。横断面实验基于皮质-海马网络探索了精确的干预靶点。纵向实验在四周的时间内观察神经导航 rTMS 治疗的临床疗效，并使用种子和网络分析来探索其潜在的神经机制。最后，我们应用连接组学预测模型，使用基线时的这些功能特征来预测 rTMS 的反应。
刺激左角回（MNI：-45，-67，38）的 rTMS 可显著改善记忆和语言功能的认知（p<0.001）。改善的认知与默认模式网络（DMN）亚系统相关。此外，DMN 亚系统（r=0.52，p=0.01）或基线时的大尺度网络（r=0.85，p=0.001）的连接模式显著预测了 rTMS 治疗后的语言认知的Δ值。DMN 亚系统（r=0.47，p=0.019）或大尺度网络（r=0.80，p=0.001）的连接模式可预测 rTMS 治疗后的记忆认知的Δ值。
这些发现表明，神经导航 rTMS 靶向左角回可以改善 AD 患者的认知功能。重要的是，基线时 DMN 内和 DMN 间的动态调节可能代表认知障碍患者对 rTMS 治疗反应良好的潜在预测因子。
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