Reduced resting-state brain functional network connectivity and poor regional homogeneity in patients with CADASIL

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) manifests principally as a suite of cognitive impairments, particularly in the executive domain. Executive functioning requires the dynamic coordination of neural activity over large-scale networks. It remains unclear whether changes in resting-state brain functional network connectivity and regional homogeneities (ReHos) underly the mechanisms of executive dysfunction evident in CADASIL patients.

In this study, 22 CADASIL patients and 44 matched healthy controls underwent resting-state functional magnetic resonance imaging (fMRI). Independent component analysis (ICA) was used to measure functional brain network connectivity, and ReHos were calculated to evaluate local brain activities. We used seed-based functional connectivity (FC) analyses to determine whether dysfunctional areas (as defined by ReHos) exhibited abnormal FC with other brain areas. Relationships among the mean intra-network connectivity z-scores of dysfunctional areas within functional networks, and cognitive scores were evaluated using Pearson correlation analyses.

Compared to the controls, CADASIL patients exhibited decreased intra-network connectivity within the bilateral lingual gyrus (LG) and the right cuneus (CU) (thus within the visual network [VIN)], and within the right precuneus (Pcu), inferior frontal gyrus (IFG), and precentral gyrus (thus within the frontal network [FRN]). Compared to the controls, patients also exhibited significantly lower ReHos in the right precuneus and cuneus (Pcu/CU), visual association cortex, calcarine gyri, posterior cingulate, limbic lobe, and weaker FC between the right Pcu/CU and the bilateral parahippocampal gyrus (PHG), and between the right Pcu/CU and the right postcentral gyrus. Notably, the mean connectivity z-scores of the bilateral LG and the right CU within the VIN were positively associated with compromised attention, calculation and delayed recall as revealed by tests of the various cognitive domains explored by the Mini-Mental State Examination.

The decreases in intra-network connectivity within the VIN and FRN and reduced local brain activity in the posterior parietal area suggest that patients with CADASIL may exhibit dysfunctional visuomotor behaviors (a hallmark of executive function), and that all visual information processing, visuomotor planning, and movement execution may be affected.