Aphasia is a language problem that often happens after a stroke, but scientists still don’t fully understand why some people have more severe symptoms than others. One known factor is where the brain damage (lesion) occurs, but researchers have not studied much about how genes in those brain areas might play a role. In this study, we developed and tested a new method called gene-expression lesion-symptom mapping (GLSM). This approach looks at how stroke damage overlaps with brain regions that have high expression of certain genes. We focused on the FOXP2 gene, which has been linked to communication, and studied 91 people with long-term aphasia after a stroke in the left side of the brain. We found that people with damage in areas where FOXP2 is highly expressed had worse language problems compared to those with damage in areas where FOXP2 expression was lower.

Our results show that including gene expression, like FOXP2, helps explain aphasia severity better than looking at lesion location alone. This suggests that GLSM can give new insights into how brain damage and genetics work together to affect language recovery after stroke. By connecting stroke lesions with gene activity, this method could help researchers and health care providers better understand why language problems vary so much between patients. In the future, GLSM may even guide more personalized treatments to improve recovery for stroke survivors.

This work was a collaboration between the College of Health Professions, MUSC and USC Departments of Psychology, Communication Sciences and Disorders, Drug Discovery and Biomedical Sciences and Neurology.

Gene expression-based lesion-symptom mapping: FOXP2 and language impairments after stroke.Wilmskoetter J, Kristinsson S, Rangus I, Busby N, Rorden C, den Ouden D, Newman-Norlund R, Banister C, Riccardi N, Teghipco A, Newman-Norlund S, Fridriksson J, Bonilha L. J Neurosci. 2025 Nov 7:e0413252025. doi: 10.1523/JNEUROSCI.0413-25.2025. Online ahead of print. PMID: 41203433