Functional and effective connectivity alterations relate to cognitive performance in aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder.

The neural mechanisms underlying cognitive dysfunction in aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4 + NMOSD) remain unclear. Functional connectivity (FC) studies have revealed network-level alterations, but little is known about the effective interactions that support compensatory reorganization. To address this gap, we investigated how alterations in functional and effective connectivity within large-scale networks relate to cognitive performance in AQP4 + NMOSD. To this end, 20 AQP4 + NMOSD patients and 20 age- and sex-matched healthy controls underwent 3-T structural MRI and resting-state functional MRI. Seed-based and region-of-interest connectivity analyses focused on the default mode network and ventral attention network. Directional interactions were assessed using dynamic causal modelling (DCM). Cognitive performance was evaluated with the Brief International Cognitive Assessment for Multiple Sclerosis and the Controlled Oral Word Association Test (COWAT). Overall, cognition was quite preserved in patients, except for reduced COWAT scores. Functional connectivity analyses revealed increased intra-network functional connectivity but decreased anterior-posterior default mode network integration. Dynamic causal modelling showed asymmetric prefrontal-posterior interactions, with stronger top-down excitatory influences from prefrontal to posterior regions. Taken together, these findings indicate that AQP4 + NMOSD patients exhibit altered functional brain organization despite relatively preserved cognition, suggesting a pattern of large-scale network reorganization that may support cognitive performance.