Fang Jicheng, Shi Yan, Ba Li, Zhang Min, Li Muwei, Zheng Ning, Qin Yuanyuan, Zhu Wenzhen
Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Brain Res Bull. 2025 Aug;228:111418. doi: 10.1016/j.brainresbull.2025.111418. Epub 2025 Jun 3.
Primarily by targeting the gray matter (GM), repetitive transcranial magnetic stimulation (rTMS) has shown promise in improving cognitive function in individuals with Alzheimer's disease (AD). However, the impact of rTMS on white matter (WM) remains poorly understood. This study aimed to investigate the functional connectivity (FC) changes in both GM and WM induced by rTMS, and explore their relationship with the clinical manifestation of the disease.
Sixteen patients with mild to moderate AD were enrolled and randomly assigned to either the real rTMS group (n = 8) or the sham treatment group (n = 8). Both groups received cognitive training in combination with rTMS. The real rTMS group received 10 Hz stimulation targeting the left dorsolateral prefrontal cortex (DLPFC) followed by the left lateral temporal lobe (LTL), with each session lasting 20 min per day for 4 weeks, while sham with the coil positioned at a 90° angle. Resting-state BOLD signals were averaged to generate mean time series for each of the 82 GM regions and 48 WM bundles, both before and after treatment for each subject. We analyzed the resting-state fMRI data by using a 2 × 2 factorial design with "time" as the within-subjects factor and "group" as the between-subjects factor.
In the analysis of 82 GM regions, when using left LTL as the seed, significant time main effect was observed in right ventral Posterior cingulate cortex (vPCC) (F=9.356, p = 0.009, η=0.401) and right inferior temporal gyrus (ITG) (F=11.784, p = 0.004, η=0.457). In the analysis of 48 WM bundles, when using left DLPFC as the seed, significant time × group interactions were found in right cingulum (hippocampus part, CGH) (F=12.123, p = 0.004, η=0.464). The FC between left DLPFC and right cerebral peduncle (CBRP) demonstrated significant time main effect (F=15.569, p = 0.001, η=0.527). Moreover, the FC between left DLPFC and right CGH was significantly correlated with MMSE scores changes (r = -0.610, p = 0.027), reflecting cognitive improvements after treatment.
The current study suggested that rTMS, when combined with cognitive training, can concurrently modulate functional activities in both GM and WM in patients with mild to moderate AD, which are associated with cognitive improvements. Notably, the limbic system appears to play a pivotal role in facilitating this therapeutic process.
重复经颅磁刺激（rTMS）主要作用于灰质（GM），在改善阿尔茨海默病（AD）患者认知功能方面已显示出前景。然而，rTMS对白质（WM）的影响仍知之甚少。本研究旨在探讨rTMS诱导的GM和WM功能连接（FC）变化，并探索它们与疾病临床表现的关系。
招募16例轻度至中度AD患者，随机分为真rTMS组（n = 8）和假治疗组（n = 8）。两组均接受认知训练并结合rTMS。真rTMS组接受针对左侧背外侧前额叶皮质（DLPFC）随后是左侧颞叶外侧（LTL）的10Hz刺激，每天每次刺激持续20分钟，共4周，而假刺激时线圈以90°角放置。在每个受试者治疗前后，对静息态BOLD信号进行平均，以生成82个GM区域和48个WM束中每一个的平均时间序列。我们采用2×2析因设计分析静息态fMRI数据，“时间”作为组内因素，“组”作为组间因素。
在对82个GM区域的分析中，以左侧LTL为种子时，在右侧腹侧后扣带回皮质（vPCC）（F = 9.356，p = 0.009，η = 0.401）和右侧颞下回（ITG）（F = 11.784，p = 0.004，η = 0.457）观察到显著的时间主效应。在对48个WM束的分析中，以左侧DLPFC为种子时，在右侧扣带（海马部分，CGH）发现显著的时间×组交互作用（F = 12.123，p = 0.004，η = 0.464）。左侧DLPFC与右侧脑桥（CBRP）之间的FC表现出显著的时间主效应（F = 15.569，p = 0.001，η = 0.527）。此外，左侧DLPFC与右侧CGH之间的FC与MMSE评分变化显著相关（r = -0.610，p = 0.027），反映了治疗后的认知改善。
当前研究表明，rTMS与认知训练相结合时，可同时调节轻度至中度AD患者GM和WM的功能活动，这与认知改善相关。值得注意的是，边缘系统似乎在促进这一治疗过程中起关键作用。
