Liu Meng, Ren-Li Ren, Sun Jin Nan, Yeo Janelle S Y, Ma Jing, Yan Jia-Xin, Tu Zhao-Xi, Li Yun-Xia
Department of Neurology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China.
Department of Neurology, Shanghai Changhai Hospital, the Second Military Medical University Shanghai, P.R., Shanghai, China.
CNS Neurosci Ther. 2025 Mar;31(3):e70301. doi: 10.1111/cns.70301.
Visual working memory (VWM), which is an essential component of higher cognitive processes, declines with age and is associated with the progression from amnestic mild cognitive impairment (aMCI) to Alzheimer's disease (AD). Cognitive impairment, particularly in VWM, is prominent in aMCI and may indicate disease progression. This study investigates the cognitive neural mechanisms responsible for VWM impairment in aMCI, with a focus on identifying the VWM processing stages affected. The study targets the dorsolateral prefrontal cortex (DLPFC) for repetitive transcranial magnetic stimulation (rTMS) to investigate its influence on VWM in aMCI patients. The role of the DLPFC in the top-down control of VWM processing is central to understanding rTMS effects on the stages of information processing in aMCI-related VWM impairments.
A 7-day rTMS intervention was performed in 25 aMCI patients and 15 healthy elderly controls to investigate its effects on VWM and cognitive functions. Tasks included VWM change detection, digital symbol transformation, and the Stroop task for attention and executive functions. EEG analyses consisting of ERP, ERSP, and functional connectivity (wPLI) were integrated. The first part of the study addressed the cognitive neural mechanism of VWM impairment in aMCI and differentiated the processing stages using EEG. The second part investigated the effects of rTMS on EEG processing at different VWM stages and revealed cognitive neural mechanisms that improve visual working memory in aMCI.
The results indicated a significant deterioration of VWM tasks in aMCI, especially in accuracy and memory capacity, with prolonged reaction time and increased duration of the Stroop task. In the VWM memory encoding phase, N2pc amplitude, α-oscillation in the parieto-occipital region, and θ-band synchronization in the frontoparietal connectivity decreased. Conversely, rTMS improved N2pc amplitude, α-oscillation, and θ-band synchronization, which correlated with improved frontoparietal connectivity, parieto-occipital α-oscillation, and attentional capacity.
Patients with aMCI experience significant deterioration in VWM function, particularly during the encoding phase. This deterioration manifests in reduced accuracy and capacity of memory performance, accompanied by a significant decrease in N2pc amplitude, alpha oscillations, and theta-band connectivity in frontoparietal and fronto-occipital brain regions. rTMS proves to be a promising intervention that improves VWM, attention, and executive functions. In particular, it supports attention during target selection by increasing N2pc amplitude during encoding, enhancing alpha oscillations for better suppression of irrelevant information, and increasing synchronization in frontoparietal and occipital functional connectivity, which ultimately improves visual working memory.
视觉工作记忆（VWM）是高级认知过程的重要组成部分，随年龄增长而衰退，且与从遗忘型轻度认知障碍（aMCI）进展为阿尔茨海默病（AD）相关。认知障碍，尤其是VWM方面的障碍，在aMCI中很突出，可能预示着疾病进展。本研究调查了aMCI中VWM损害的认知神经机制，重点是确定受影响的VWM加工阶段。该研究针对背外侧前额叶皮层（DLPFC）进行重复经颅磁刺激（rTMS），以研究其对aMCI患者VWM的影响。DLPFC在VWM加工的自上而下控制中的作用对于理解rTMS对aMCI相关VWM损害中信息加工阶段的影响至关重要。
对25例aMCI患者和15名健康老年对照进行为期7天的rTMS干预，以研究其对VWM和认知功能的影响。任务包括VWM变化检测、数字符号转换以及用于注意力和执行功能的Stroop任务。整合了包括事件相关电位（ERP）、事件相关谱功率（ERSP）和功能连接（加权相位滞后指数，wPLI）的脑电图分析。研究的第一部分探讨了aMCI中VWM损害的认知神经机制，并使用脑电图区分加工阶段。第二部分研究了rTMS在不同VWM阶段对脑电图加工的影响，并揭示了改善aMCI患者视觉工作记忆的认知神经机制。
结果表明，aMCI患者的VWM任务显著恶化，尤其是在准确性和记忆容量方面，反应时间延长，Stroop任务持续时间增加。在VWM记忆编码阶段，N2pc波幅、顶枕区的α振荡以及额顶连接中的θ波段同步性降低。相反，rTMS改善了N2pc波幅、α振荡和θ波段同步性，这与额顶连接性改善、顶枕α振荡和注意力容量提高相关。
aMCI患者的VWM功能显著恶化，尤其是在编码阶段。这种恶化表现为记忆表现的准确性和容量降低，同时额顶和额枕脑区的N2pc波幅、α振荡和θ波段连接性显著降低。rTMS被证明是一种有前景的干预措施，可改善VWM、注意力和执行功能。特别是，它通过在编码期间增加N2pc波幅来支持目标选择过程中的注意力，增强α振荡以更好地抑制无关信息，并增加额顶和枕叶功能连接的同步性，最终改善视觉工作记忆。
