new research in lancet digital health It suggests that the brain may respond to stroke in surprising ways. Researchers at the USC Mark and Mary Stevens Neuroimaging and Informatics Institute (Stevens INI) have found that people who become severely disabled after a stroke may show signs of “youthful” brain structure in undamaged areas. This likely reflects how the brain adapts and reorganizes after injury.
This study was conducted as part of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Stroke Recovery Working Group. Scientists analyzed brain scans from more than 500 stroke survivors collected at 34 research centers in eight countries. By applying a deep learning model trained on tens of thousands of MRI scans, the research team estimated the ‘brain age’ of different regions in each hemisphere and examined how stroke affects both structure and recovery.
“We found that major strokes accelerate aging in the damaged hemisphere, but paradoxically the other side of the brain appears younger,” said Ho-Sung Kim, Ph.D., associate professor of research neurology at the Keck School of Medicine at the University of Southern California and co-senior author of the study. “This pattern suggests that the brain may be reorganizing itself and activating intact networks to compensate for lost function.”
AI reveals brain rewiring after stroke
To perform the analysis, the researchers used a type of artificial intelligence called a graph convolutional network. The system estimated the biological age of 18 brain regions based on MRI data. This predicted age was then compared to each person’s actual age. This is a measure known as brain-predicted age difference (brain-PAD) and serves as an indicator of brain health.
When these brain age measurements were compared with motor function scores, a clear pattern emerged. Stroke survivors with severe motor impairment showed younger-than-expected brain ages in regions contralateral to the injury site, even after more than 6 months of rehabilitation. This effect was particularly strong in the fronto-parietal network, which plays a key role in motor planning, attention, and coordination.
“These findings suggest that when stroke damage causes further loss of motor skills, undamaged areas on the opposite side of the brain may adapt to compensate,” Professor Kim explained. “We observed this in the contralesional fronto-parietal network, which exhibits a more ‘youthful’ pattern and is known to support motor planning, attention and coordination. Rather than indicating complete motor recovery, this pattern may reflect the brain’s attempt to adjust when the damaged motor system no longer functions normally. This provides a new way to look at neuroplasticity that has not been captured by traditional imaging.”
Big data reveals hidden patterns
The study relied on ENIGMA, a global collaboration that integrates data from more than 50 countries to better understand the brain in different settings. By standardizing MRI data and clinical information from many research groups, the team created the largest stroke neuroimaging dataset of its kind.
“By pooling data from hundreds of stroke survivors around the world and applying cutting-edge AI, we are able to detect subtle patterns in brain reorganization that are invisible in small studies. These findings about regional differences in brain aging in chronic stroke may ultimately guide individualized rehabilitation strategies,” said Arthur W. Toga, Ph.D., Stevens INI Director and USC Professor.
Towards personalized stroke recovery
The researchers plan to continue this study by following patients over time, from the early stages after stroke through long-term recovery. Tracking how aging patterns and structural changes in the brain progress may help doctors tailor treatments to each person’s unique recovery process, with the aim of improving treatment outcomes and quality of life.
Watch this video created by Stevens INI to learn more about the connection between contralesional neuroplasticity and movement disorders.
The study, “MRI-based deep learning prediction of regional brain age reveals contralesional neuroplasticity associated with severe motor deficits in chronic stroke: the global ENIGMA study,” was funded by National Institutes of Health (NIH) grant R01 NS115845 and supported by international collaborators including the University of British Columbia, Monash University, Emory University, and the University of Oslo.
