Correlations of brain functional connectivity and white matter microstructure alterations with cognitive impairment in patients with white matter hyperintensities of presumed vascular origin: a MRI study

Abstract

Objective To investigate the alterations in voxel-mirrored homotopic connectivity (VMHC) of brain regions, association loop connectivity, and white matter microstructure in patients with white matter hyperintensities (WMH) of presumed vascular origin, and analyze the pathological basis of cognitive impairment in WMH patients. Methods A prospective study was performed; 75 WMH patients (WMH group) admitted to Jiangsu Shengze Hospital Affiliated to Nanjing Medical University from January 2023 to September 2024 and 67 volunteers without obvious brain diseases (control group) recruited during the same period were enrolled. General data of these participants, and scores of neuropsychological scales such as mini-mental state examination (MMSE), frontal assessment battery (FAB), and trail making test (TMT) were compared between the two groups. Resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) data of all participants were collected; rs-fMRI data were then analyzed using VMHC algorithm to calculate and conform the brain regions with significantly different VMHC between the two groups, and these regions were used as seed points to perform functional connectivity with the whole brain; Pearson correlation analyses of VMHC and functional connectivity in these brain regions with scores of neuropsychological scales were performed. DTI data were processed using tract-based spatial statistics (TBSS) method to calculate and conform the brain regions with significantly different diffusion parameters of fiber tracts between the two groups; Pearson correlation analyses of diffusion parameters of the fiber tracts in these brain regions with scores of neuropsychological scales were performed. Results (1) Comparison of general data and neuropsychological scale scores: proportion of participants with hypertension history was significantly different between the two groups (P<0.05); scores of TMT-A, TMT-B, and Stroop C scales in the WMH group were significantly higher than those in the control group (P<0.05). (2) Comparison of VMHC and seed point functional connectivity: compared with that in the control group, the VMHC in bilateral middle occipital gyrus, visual cortex, medial occipitotemporal gyrus, insula, and postcentral gyrus of the WMH group were statistically lower (P<0.05). Compared with that in the control group, functional connectivity of right visual cortex with right middle temporal gyrus, bilateral precuneus, and right dorsolateral superior frontal gyrus in the WMH group was significantly weakened, and functional connectivity of right postcentral gyrus with right medial occipitotemporal gyrus, left middle temporal gyrus, left visual cortex, and left postcentral gyrus was statistically weakened (P<0.05). In the WMH group, the VMHC of bilateral insula was negatively correlated with TMT-B score (r=-0.381, P<0.001), and functional connectivity between right visual cortex and right dorsolateral superior frontal gyrus was negatively correlated with Stroop C score (r=-0.401, P<0.001). (3) TBSS results: the diffusion parameters of the anterior corona radiata, superior corona radiata, corpus callosum, superior longitudinal fasciculus, and posterior thalamic radiation were statistically significant between the two groups (P<0.05). In the WMH group, the fractional anisotropy in the genu of the corpus callosum was positively correlated with Stroop C score (r=0.426, P<0.001), radial diffusivity was negatively correlated with Stroop C score (r=-0.376, P<0.001), and mean diffusivity of the left anterior corona radiata was negatively correlated with TMT-A score (r=-0.443, P<0.001). Conclusion WMH patients have decreased coordination in homotopic brain regions and weakened functional connectivity of association loops, with widely distributed white matter microstructure damages, which may be involved in the neuropathological process of cognitive impairment.