Lesion-Gradient Mapping in Semantic Aphasia: Comparisons of Observed and Simulated Effects of Stroke on Connectivity Gradients

Post-stroke semantic aphasia is characterised by multimodal semantic deficits and reflects disruption of a distributed brain network spanning frontal and temporal regions. Connectivity gradients, which capture key dimensions of whole-brain variation in functional connectivity, offer a promising framework for understanding the global impact of stroke on brain function. This study investigated whether changes in connectivity gradients following stroke can explain semantic aphasia deficits. First, we evaluated whether lesion-location and lesion-load information from structural MRI could predict the gradient changes observed in resting-state fMRI, as a proof-of-principle analysis. Second, we tested whether simulated gradient changes predict the severity of semantic impairment. Results show that post-stroke gradient changes simulated from structural MRI are correlated with actual changes in resting-state fMRI, particularly for the principal gradient that separates unimodal and heteromodal regions. Semantic deficits were related to simulated connectivity changes along this gradient: left prefrontal areas involved in controlled semantic retrieval exhibited stronger connectivity to unimodal cortex in patients with more severe deficits. Semantic deficits also correlated with changes in the second gradient, which distinguishes visual and motor cortex. Particularly, the right parahippocampal gyrus, typically visually biased--showed reduced visual connectivity in more impaired patients. These results help explain controlled semantic retrieval deficits in semantic aphasia. More broadly, the findings suggest that functional connectivity gradients capture post-stroke reorganisation of global brain networks linked to cognitive impairment, and that these changes can be estimated from structural MRI alone, enhancing clinical utility of gradient-based approaches. HighlightsO_LIFunctional connectivity gradients explain the multimodal impairments in semantic aphasia from a dimensional perspective, using the unimodal-transmodal and motor-visual axes. C_LIO_LIPost-stroke functional changes are explored through alterations in connectivity gradient patterns. C_LIO_LICortical lesion information from structural MRI can be used to simulate changes in connectivity gradients, offering potential clinical relevance. C_LI