Motor impairment and adaptation in a novel non-human primate model of internal capsule infarct

Sivakumar, S. S.; Anand, S. A.; Brawer, L.; Mellor, R. L.; Burkhalter, A.; Burton, H.; Brunner, P.; Bundy, D. T.; Leuthardt, E. C.; Moran, D. W.

doi:10.1101/2025.05.27.656471

bioRxiv · 10.1101/2025.05.27.656471

Motor impairment and adaptation in a novel non-human primate model of internal capsule infarct

Sivakumar, S. S.·Anand, S. A.·Brawer, L.·Mellor, R. L.·Burkhalter, A.·Burton, H.·Brunner, P.·Bundy, D. T.·Leuthardt, E. C.·Moran, D. W.

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Abstract

Loss of distal hand and finger control is among the most disabling consequences of stroke. Functional outcomes are typically worse when infarcts involve subcortical white matter tracts, particularly the internal capsule, yet most preclinical stroke models target cortical regions. To address this gap, we developed a non-human primate model of internal capsule infarct using stereotactically guided endothelin-1 injections to disrupt descending fibers from the primary motor cortex hand area. Serial structural and diffusion MRI, along with histology, confirmed subcortical infarcts centered on the targeted white matter region with no apparent cortical involvement. Motor function was assessed pre- and post-infarct using a joystick-based center-out task (proximal forelimb control) and a Kluver board task (distal forelimb control). Animals exhibited variable impairments in proximal function and consistent post-infarct deficits in distal function, including reduced contralesional hand use, longer retrieval time, and increased in-well digit flexions. One animal showed mild post-infarct impairment and the smallest lesion, highlighting that this model reflects inter-individual differences in infarct size and functional outcome as seen in human subcortical stroke. In contrast, the other two animals developed a compensatory wrist-extended posture on the Kluver board task by 4 weeks post-infarct, which stabilized the hand and enabled improved digit flexion. Incorporating this behavioral adaptation into statistical models improved prediction of motor performance. The observed adaptation may have drawn on spared corticospinal output pathways, allowing animals to re-engage pre-existing motor routines to perform the retrieval. While future studies may benefit from ethologically relevant tasks to further elucidate such adaptations, findings from this study recapitulate key features of human subcortical stroke, including persistent distal motor deficits and emergence of adaptive motor strategies. By combining precise lesioning, longitudinal imaging, and detailed behavioral analysis, this model provides a translationally oriented platform for studying white matter stroke mechanisms and evaluating interventions that promote functional recovery.

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Sivakumar, S. S., Anand, S. A., Brawer, L., Mellor, R. L., Burkhalter, A., Burton, H., Brunner, P., Bundy, D. T., Leuthardt, E. C., Moran, D. W.. 2025-06-01. Motor impairment and adaptation in a novel non-human primate model of internal capsule infarct. https://doi.org/10.1101/2025.05.27.656471

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