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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 &amp;lt; 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-P &amp;lt; 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 &amp;lt; 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 &amp;lt; 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.<\/jats:p>","DOI":"10.1093\/braincomms\/fcaf393","type":"journal-article","created":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T12:32:45Z","timestamp":1760358765000},"source":"Crossref","is-referenced-by-count":1,"title":["Hypoperfusion-related functional abnormalities of middle cerebral artery stenotic-occlusive disease"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7150-4167","authenticated-orcid":false,"given":"Yinxi","family":"Zou","sequence":"first","affiliation":[{"name":"Department of Neurology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100730 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