Precuneus-to-hippocampus connectivity links LTP-like plasticity to cognitive function in subjective cognitive decline...

Disruptions in synaptic plasticity and alterations in effective connectivity (EC) involving the hippocampus and amygdala are hallmarks of early Alzheimer's disease (AD). However, the interplay between these neurophysiological changes and their relationships with cognitive functions in subjective cognitive decline (SCD) and mild cognitive impairment (MCI) remains poorly understood.

Transcranial magnetic stimulation (TMS) and resting-state functional magnetic resonance imaging (rs-fMRI) were used to assess long-term potentiation (LTP)-like plasticity and EC involving the amygdala and hippocampus in 34 individuals with SCD, 27 with MCI, and 35 healthy controls (HC). Between-group differences in cognitive performance, EC alterations, and LTP-like plasticity were examined and their relationships were assessed via correlation and mediation analyses.

Both SCD and MCI groups exhibited disrupted EC between the amygdala/hippocampus and the inferior occipital gyrus (IOG), inferior parietal lobule (IPL), medial frontal lobe (MFL), and precuneus. Also, both LTP-5min and LTP-10min were significantly reduced in MCI group compared to SCD and HC groups. Importantly, EC from the left hippocampus to the IPL and from the IPL, MFL, and precuneus to the hippocampus was correlated with memory and executive functions. Moreover, precuneus-to-hippocampus EC was positively correlated with LTP-10min and mediated the relationship between LTP-like plasticity and cognitive performance.

This study provides novel evidence that precuneus-to-hippocampus EC mediates the link between synaptic plasticity and cognitive function in SCD and MCI, suggesting the precuneus-hippocampus pathway as a promising target for early diagnosis and intervention.