Repetitive transcranial magnetic stimulation regulate brain networks effective connectivity patterns in the spectrum of preclinical Alzheimer's disease

Background: Subjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI) are considered as the spectrum of preclinical Alzheimer's disease (AD), with abnormal brain network connectivity as the main neuroimaging features. Repetitive transcranial magnetic stimulation (rTMS) has been proven to be an effective non-invasive technique for neuropsychiatric disorders. This article aims to explore whether precuneus (PCUN)-targeted rTMS can regulate the effective connectivity of the default mode network (DMN) and the executive control network (CEN), thereby improving cognitive function. Methods This study included 86 healthy controls (HCs), 72 SCDs, and 86 aMCIs. Among them, 10 SCDs and 11 aMCIs received a 2-week rTMS course of 5-day, once-daily. Cross-sectional analysis with the spectral dynamic causal model (spDCM) was used to analyze the DMN and CEN effective connectivity patterns of the three groups. Afterwards, longitudinal analysis was conducted on the changes in effective connectivity patterns and cognitive function before and after rTMS for SCD and aMCI, and the correlation between them was analyzed. Results Cross-sectional analysis showed that there were different effective connectivity patterns in the DMN and CEN in the three groups. Longitudinal analysis showed that the effective connectivity pattern of the SCD changed, accompanied by episodic memory improved. Correlation analysis showed that effective connectivity from the left angular gyrus (ANG) to the anterior cingulate gyrus (ACG) and the ANG.R to the right middle frontal gyrus (MFG) was negatively correlated with visuospatial and executive function, respectively. In the aMCI, episodic memory and executive function improved, while the effective connectivity pattern remained unchanged. Conclusions This study demonstrates that PCUN-targeted rTMS of SCD regulating the abnormal effective connectivity patterns of DMN and CEN improves cognition function, while in aMCI possibly through other mechanisms. Our findings further suggest that rTMS are more effective at preventing or delaying disease progression earlier in the AD spectrum. Trial registration CCTR, ChiCTR2000034533. Registered 9 July 2020 - Retrospectively registered, http://www.chictr.org.cn