# Network Disconnection Syndrome in Unruptured Brain Arteriovenous Malformations: A Multimodal Connectome Study

## TL;DR

This study finds that cognitive issues in brain arteriovenous malformations are caused by disrupted white matter connections, not just lesion size.

## Contribution

The study introduces a new framework linking structural disconnection to cognitive decline in unruptured brain AVMs.

## Key findings

- Global white matter disconnection, not lesion volume, best predicts cognitive decline in bAVM patients.
- Increased inter-hemispheric synchronization fails to compensate for structural damage in high-order brain networks.
- Structure–function decoupling in association networks correlates with executive and memory impairments.

## Abstract

Cognitive impairment is a critical yet poorly understood complication of brain arteriovenous malformations (bAVM). While traditionally attributed to hemodynamic “steal” or focal tissue destruction, it remains unclear whether cognitive variability correlates with gross structural pathology or broader network disruption.

We recruited consecutive patients with unruptured bAVM at Huashan Hospital and matched healthy controls (2017–2020). We integrated lesion frequency mapping, surface‐based morphometry, and Network Diffusion Modeling (NDM) to dissect the structure–function relationship in a cohort of bAVM patients compared to matched controls. We systematically evaluated the predictive value of three distinct damage metrics—gross lesion load, cortical morphological remodeling, and white matter structural connectivity—on global and domain‐specific cognitive performance.

Patients with bAVM exhibited significantly reduced global efficiency in structural networks (p < 0.05), which was a stronger predictor of cognitive decline than lesion volume. In contrast, global functional network topology was largely preserved. Although local functional reorganization was observed, characterized by increased inter‐hemispheric synchronization, these adaptations did not prevent cognitive deficits. Notably, increased structure–function decoupling within high‐order association networks (including frontoparietal and ventral attention systems) was significantly associated with executive and memory impairment.

Cognitive dysfunction in bAVM represents a disconnection syndrome caused by the disruption of long‐range white matter tracts rather than local cortical pathology. The dissociation between structural damage and functional compensation highlights the limitations of conventional volumetric assessment. Preoperative connectome mapping, particularly of white matter integrity, may improve risk stratification and functional preservation strategies.

This study challenges the traditional reliance on lesion size, demonstrating that cognitive impairment in unruptured bAVMs is fundamentally driven by global white matter disconnection. We identified a critical “structure–function decoupling,” where compensatory reorganization fails once the underlying structural scaffold collapses. These findings highlight a physiological “ceiling of plasticity,” advocating for a paradigm shift toward tract‐sparing strategies in preoperative planning.