biostudies-literatureUnknown7(5)Zou YUnilateral 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, <i>P</i> < 0.05). Arterial spin labelling identified hypoperfused regions with prolonged arterial transit time. These regions showed increased intraregional regional homogeneity and functional connectivity (FC), and decreased extraregional FC (FDR-<i>P</i> < 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 (<i>P</i> < 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 (<i>P</i> < 0.05). Our results indicate that unilateral MCAs/o increased local neural synchronization coupled with reduced global functional integration, suggesting a shift towards isolated neural processing. These hypoperfusion-related functional abnormalities are closely linked to neurobehavioral alterations and can be objectively quantified.Brain communicationsfcaf393https://www.ebi.ac.uk/biostudies/studies/S-EPMC12560163biostudies-literatureHypoperfusion-related functional abnormalities of middle cerebral artery stenotic-occlusive disease.PMC12560163Si QFan XLiu LCheng ALiu NLi MZou YLiu YGuo HZhang XLiu CZhou HXu WfalseHypoperfusion-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, <i>P</i> < 0.05). Arterial spin labelling identified hypoperfused regions with prolonged arterial transit time. These regions showed increased intraregional regional homogeneity and functional connectivity (FC), and decreased extraregional FC (FDR-<i>P</i> < 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 (<i>P</i> < 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 (<i>P</i> < 0.05). Our results indicate that unilateral MCAs/o increased local neural synchronization coupled with reduced global functional integration, suggesting a shift towards isolated neural processing. These hypoperfusion-related functional abnormalities are closely linked to neurobehavioral alterations and can be objectively quantified.2025-01-01T00:00:00Z20252026-06-05T07:38:10.618Z2026-05-14T03:12:49.982ZS-EPMC125601634116477910.1093/braincomms/fcaf393