Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.