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

## TL;DR

This study finds that brain regions with reduced blood flow due to middle cerebral artery issues show stronger local activity but weaker connections elsewhere, which can be measured to assess cognitive risks.

## Contribution

The study introduces and validates a new index to quantify hypoperfusion-related functional brain changes in middle cerebral artery stenosis–occlusion.

## Key findings

- Hypoperfused brain regions show increased local neural synchronization and decreased global connectivity.
- The hypoperfusion-functional abnormality index effectively detects early functional abnormalities and correlates with cognitive performance.
- Findings were validated in an independent cohort, showing consistent results.

## Abstract

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 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 < 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 towards isolated neural processing. These hypoperfusion-related functional abnormalities are closely linked to neurobehavioral alterations and can be objectively quantified.

Zou et al. report that in unilateral asymptomatic middle cerebral artery stenosis–occlusion, chronically under-perfused regions show stronger local synchrony but weaker long-range connectivity. They develop and validate a hypoperfusion-functional abnormality index quantifying these changes, which relates to individual cognitive differences, highlighting a reproducible marker for personalized risk assessment.

Graphical Abstract