Reorganisation of Functional Connectivity Gradients in Post-Stroke Aphasia

Abstract

Aphasia after stroke arises from focal damage to language-relevant cortex but is accompanied by widespread alterations in functional connectivity. In 60 stroke survivors, we related principal component-derived language scores to both lesion location and stroke-related changes in resting-state functional organisation, combining structural lesion-symptom mapping with a gradient-based approach. Structural lesion-symptom mapping identifies which damaged regions are associated with specific language impairments but does not capture how surviving cortex is reconfigured within the brains large-scale architecture. In contrast, lesion-gradient mapping characterises whole-brain connectivity gradients - data-driven axes that summarise the principal patterns of variation in cortical connectivity - and quantifies how behavioural variation relates to displacement of structurally intact regions along these intrinsic axes. Stroke was associated with altered positioning of cortical regions along the gradient separating default mode and control networks. Notably, the position of the left inferior frontal gyrus along this axis predicted dissociable language outcomes: displacement toward default mode connectivity patterns was associated with better speech but poorer writing performance. This opposing behavioural profile suggests that inferior frontal cortex contributes to language through flexible large-scale coupling, with distinct coupling regimes differentially supporting spoken and written production. These findings indicate that gradient-based mapping provides a mechanistic link between focal tissue damage and distributed behavioural consequences by revealing systematic reorganisation of macroscale functional architecture beyond the lesion site.