Enhanced hippocampal-cortical functional connectivity following post-stroke cognitive impairment: a resting-state functional magnetic resonance imaging study.

BACKGROUND

Resting-state functional magnetic resonance imaging (rs-fMRI) method was employed to investigate the abnormal patterns of functional connectivity (FC) between hippocampus and whole brain in patients with post-stroke cognitive impairment (PSCI). The aim was to explore imaging biomarkers, providing imaging evidence for understanding neurocognitive mechanisms of PSCI and formulating targeted intervention strategies.

METHODS

A total of 42 patients with acute ischemic stroke (AIS) were recruited from The First Affiliated Hospital of Xinjiang Medical University between June 2025 to October 2025 in this retrospective cross-sectional study. Concurrently, 40 healthy controls (HCs) without a history of cognitive impairment (CI) were recruited from the community. All participants underwent structural magnetic resonance imaging (MRI) and rs-fMRI scans. Cognitive function in PSCI patients was assessed longitudinally at 3 months post-stroke using standardized neuropsychological instruments, including Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE). Seed-based FC analysis was performed using bilateral hippocampus as regions of interest (ROIs) to compute whole brain connectivity maps. Pearson partial correlation analyses were conducted to examine the associations between altered FC strengths and cognitive scores, controlling for potential confounding variables.

RESULTS

Compared with the HC group, PSCI patients exhibited significantly lower MoCA (Z=0.203, P<0.001) and MMSE (Z=0.129, P<0.001) scores. Enhanced FC was observed in PSCI patients between left hippocampus and left superior temporal pole (t=4.435, P<0.001), right frontal inferior opercular (t=5.079, P<0.001), left inferior parietal (t=4.310, P<0.001), and right superior frontal gyrus (t=3.870, P<0.001). Additionally, enhanced connectivity was found between right hippocampus and right frontal inferior opercular (t=4.246, P<0.001) as well as the right supramarginal gyrus (t=3.794, P=0.001). Pearson correlation analyses revealed that enhanced FC between right hippocampus and right frontal inferior opercular was positively correlated with both MMSE (r=0.467, P=0.001) and MoCA (r=0.434, P=0.003) scores.

CONCLUSIONS

The FC between hippocampus and cerebral cortex is enhanced in PSCI patients. Abnormal connection between hippocampus and right frontal inferior opercular can be used as a potential imaging biomarker to reveal the neurocognitive mechanism of PSCI. In the future, cognitive function can be optimized by regulating these regions.