Hypoperfusion-related functional abnormalities of middle cerebral artery stenotic-occlusive disease

Unilateral asymptomatic middle cerebral artery stenosis or occlusion (MCAs/o) is an ideal human model for investigating the neural consequences of chronic cerebral hypoperfusion. Using a discovery-validation approach, this study aimed to characterize functional abnormalities in hypoperfused brain regions of unilateral MCAs/o and assess their neurobehavioral implications. In a discovery cohort comprising 41 patients with unilateral MCAs/o and 30 matched controls, patients exhibited significantly impaired performance on bilateral grooved pegboard tests (GPT, p<0.05). Arterial spin labeling identified hypoperfused regions with prolonged arterial transit time. These regions showed increased intraregional regional homogeneity (ReHo) and functional connectivity (FC), and decreased extraregional FC (FDR-p<0.05). A machine-learning model integrated these functional imaging features into a hypoperfusion-functional abnormality index (HFAi), which effectively detected early functional abnormalities in MCAs/o patients (AUC=0.978) and correlated significantly with GPT performance (p<0.01). Validation in an independent cohort (20 MCAs/o patients and 18 controls) confirmed these findings, demonstrating consistent identification of early functional abnormalities (AUC=0.861) and correlation between HFAi and GPT scores (p<0.05). Our results indicate that unilateral MCAs/o increased local neural synchronization coupled with reduced global functional integration, suggesting a shift toward isolated neural processing. These hypoperfusion-related functional abnormalities are closely linked to neurobehavioral alterations and can be objectively quantified.