Severe asymptomatic carotid stenosis is associated with robust reductions in homotopic functional connectivity

Severe (>70% narrowing) asymptomatic carotid stenosis (SACS) is associated with cognitive impairment and future strokes, and connectivity basis for the remote brain consequences is poorly understood. Here we explored homotopic connectivity and parenchymal lesions measured by multimodal magnetic resonance imaging (MRI) parameters in patients with SACS. Twenty-four patients with SACS (19 males/5 females; 64.25 ± 7.18 years), 24 comorbidities-matched controls (19 males/5 females; 67.16 ± 6.10 years), and an independent sample of elderly healthy controls (39 females/45 males; 57.92 ± 4.94 years) were included. Homotopic functional connectivity (FC) of resting-state functional MRI and structural connectivity (SC) of deterministic tractography were assessed. Arterial spin labeling based cerebral perfusion, susceptibility weighted imaging based microhemorrhagic lesions, and T2-weighted white matter hyperintensities were also quantified. Significant and robust homotopic reductions (validated by the independent dataset and support vector machine-based machine learning) were identified in the Perisylvian fissure in patients with SACS (false discovery rate corrected, voxel p < 0.05). These involved regions span across several large-scale brain systems, which include the somatomotor, salience, dorsal attention, and orbitofrontal-limbic networks. This significantly reduced homotopic FC can be partially explained by the corrected white matter hyperintensity size. Further association analyses suggest that the decreased homotopic FC in these brain regions is most closely associated with delayed memory recall, sensorimotor processing, and other simple cognitive functions. Together, these results suggest that SACS predominately affects the lower-order brain systems, while higher-order systems, especially the topographies of default mode network, are least impacted initially, but may serve as a hallmark precursor to vascular dementia. Thus, assessment of homotopic FC may provide a means of noninvasively tracking the progression of downstream brain damage following asymptomatic carotid stenosis.