Abstract
BACKGROUND: Stroke is a leading cause of mortality and disability worldwide, with post-stroke cognitive impairment (PSCI) being a common complication that significantly impacts patients’ health and quality of life. However, the neural mechanisms underlying PSCI remain incompletely understood. This study seeks to employ functional near-infrared spectroscopy (fNIRS) to investigate cortical functional connectivity patterns in PSCI patients with different lesion sides. METHODS: This case-control study enrolled 26 healthy controls (HCs) and 50 PSCI patients following their initial stroke. Lesion locations identified by CT or MRI imaging categorized patients into left hemisphere (L-PSCI, n = 17), right hemisphere (R-PSCI, n = 13), and bilateral hemisphere stroke subgroups (Bi-PSCI, n = 20). Cognitive function was assessed using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Concurrently, fNIRS captured whole-brain oxygenated hemoglobin signals during an 8-minute resting state and Verbal Fluency Test (VFT) to examine the brain functional connectivity profiles and brain region activation of PSCI patients with diverse lesion locations. RESULTS: The results of ROI-to-ROI connectivity indicated significant differences between the PSCI subgroups and HCs, included LPF-RO, LP-RP, LP-LO, RP-LO, RP-RO, it mainly involves the parieto-occipital network and fronto-occipital network. And the correlation found LPR-RO, RPF-RO and RPF-LP positive correlated with the total score of MMSE, as well as its subscales of attention and orientation. Further graph theory analysis of functional differentiation and integration revealed Sigma, Gamma and Eg were significant differences between the PSCI Subgroups and HCs, Additionally, VFT analysis showed that during the VFT task, activation levels in the LP, RP, RPF, LPF and RO regions were significantly weaker in the PSCI Subgroups than HCs. In the correlation analysis, PRF, LP, and RO 3 ROIs were significantly positive correlated with the total score of MMSE, as well as its subscales of memory and orientation. CONCLUSIONS: In this real-world study, we observed PSCI patients with various lesion locations and found significant reductions in functional connectivity and activation of the parieto-occipital and fronto-occipital networks. Consequently, these networks may act as key targets for neuromodulation, and their targeted modulation could offer a novel and promising therapeutic approach for managing PSCI clinically. TRIAL REGISTRATION: The trial was registered in the Chinese Clinical Trial Registry under the registration number ChiCTR2300070580 on 17th April 2023 and was retrospectively registered. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12883-026-04827-3.