The Influence of Contralesional Brain Age Gradients on Chronic Stroke Aphasia Severity and Treatment Response.

The adult brain follows normative aging trajectories, yet stroke abruptly disrupts this process. Beyond the focal lesion, undamaged regions can deviate from expected aging due to diaschisis or pre-existing vulnerabilities, reflecting tissue health that may constrain recovery. Chronic post-stroke aphasia, a persistent language disorder, shows wide individual variability in severity and treatment response, and these differences are not fully captured by lesion characteristics or demographic factors. Further, prior imaging biomarkers have been difficult to scale because they rely on specialized acquisitions or nonstandardized analytical pipelines. Here, we used a standardized, lifespan-informed brain age model (volBrain) trained on large public datasets to quantify regional deviations from normative aging using only routine structural MRI (T1-weighted). In 188 individuals with chronic stroke (67 female, 121 male), regional aging deviations in the contralesional hemisphere explained aphasia severity beyond lesion volume, lesion location, and basic demographics. In a treated subgroup, baseline brain aging patterns also predicted language gains that persisted 6 months after therapy, indicating prognostic value. By characterizing how individual brains diverge from expected aging, this approach captures variation in tissue integrity that is relevant for both impairment and recovery. This provides a scalable framework that can be integrated across sites and studies, linking normative aging models with post-stroke prognostics and informing precision neurorehabilitation.