Gray matter and white matter functional connectivity changes induced by rTMS concurrent with cognitive training in Alzheimer’s disease

IF 3.7 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin Pub Date : 2025-06-03 DOI:10.1016/j.brainresbull.2025.111418

Jicheng Fang , Yan Shi , Li Ba , Min Zhang , Muwei Li , Ning Zheng , Yuanyuan Qin , Wenzhen Zhu

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引用次数: 0

Abstract

Background and purpose

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.

Methods

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.

Results

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, η²=0.401) and right inferior temporal gyrus (ITG) (F=11.784, p = 0.004, η²=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, η²=0.464). The FC between left DLPFC and right cerebral peduncle (CBRP) demonstrated significant time main effect (F=15.569, p = 0.001, η²=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.

Conclusion

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.

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阿尔茨海默病认知训练并发rTMS诱导的灰质和白质功能连通性改变

背景与目的重复性经颅磁刺激（rTMS）主要针对灰质（GM），显示出改善阿尔茨海默病（AD）患者认知功能的希望。然而，rTMS对白质（WM）的影响仍然知之甚少。本研究旨在探讨rTMS诱导的GM和WM的功能连通性（FC）变化，并探讨其与疾病临床表现的关系。方法选取16例轻中度AD患者，随机分为真rTMS组（n = 8）和假rTMS组（n = 8）。两组患者均接受认知训练和rTMS联合治疗。真实rTMS组接受10 Hz的刺激，目标是左背外侧前额叶皮层（DLPFC），然后是左外侧颞叶（LTL），每次持续20 分钟，每天4周，而假性rTMS组线圈定位为90°角。对每位受试者治疗前后的82个GM区和48个WM束的静息状态BOLD信号取平均时间序列。我们使用2 × 2因子设计分析静息状态fMRI数据，其中“时间”为受试者内因子，“组”为受试者间因子。结果在82个GM区域的分析中，以左侧LTL为种子时，右侧腹侧后扣带皮层（vPCC）（F=9.356, p = 0.009,η2=0.401）和右侧颞下回（ITG）（F=11.784, p = 0.004,η2=0.457）出现了显著的时间主效应。在48个WM束的分析中，当以左侧DLPFC为种子时，右侧扣带（海马部分，CGH）存在显著的时间× 组相互作用（F=12.123, p = 0.004,η2=0.464）。左DLPFC与右脑脚（CBRP）间FC表现出显著的时间主效应（F=15.569, p = 0.001,η2=0.527）。此外，左侧DLPFC和右侧CGH之间的FC与MMSE评分变化显著相关（r = -0.610,p = 0.027），反映治疗后认知改善。结论目前的研究表明，当rTMS与认知训练相结合时，可以同时调节轻度至中度AD患者GM和WM的功能活动，这与认知改善有关。值得注意的是，大脑边缘系统似乎在促进这一治疗过程中起着关键作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Brain Research Bulletin 医学-神经科学

CiteScore

6.90

自引率

2.60%

发文量

253

审稿时长

67 days

期刊介绍： The Brain Research Bulletin (BRB) aims to publish novel work that advances our knowledge of molecular and cellular mechanisms that underlie neural network properties associated with behavior, cognition and other brain functions during neurodevelopment and in the adult. Although clinical research is out of the Journal''s scope, the BRB also aims to publish translation research that provides insight into biological mechanisms and processes associated with neurodegeneration mechanisms, neurological diseases and neuropsychiatric disorders. The Journal is especially interested in research using novel methodologies, such as optogenetics, multielectrode array recordings and life imaging in wild-type and genetically-modified animal models, with the goal to advance our understanding of how neurons, glia and networks function in vivo.