Functional connectivity associated with motor recovery after internal capsule lesions

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Project Summary Stroke survivors face significant long-term health consequences, with rehabilitation being essential to improve their recovery and quality of life. Currently, patients who do not restore motor function after 3-6 months are unlikely to show further recovery. Lesions with white matter tract involvement typically correlate with worse outcomes. For example, corticospinal tract lesions (CST) lesions produce worse motor deficiencies and portend poor functional recovery. Brain-computer interface mediated stroke rehabilitation (BCI-SR) can be a powerful rehabilitation tool. In BCI-SR, a patient learns to modulate localized brain activity that is recorded by electrodes. This can be used to control an orthosis to move the paretic limb. Most BCI systems utilize signals from affected hemisphere, attempting to drive plasticity in injured cortex. However, residual brain function after stroke limits BCI-SR efficacy, making ipsilesional BCI difficult to use in patients with the worst injuries. In humans, contralesional BCI-SR devices have used the uninjured hemisphere to drive further rehabilitation after the traditional plateau in motor function recovery. Clinical predictions of functional outcome after stroke are imprecise. Resting state functional connectivity (rsFC) measures the correlation of blood oxygen level-depending (BOLD) fluctuations at rest across the brain, providing a powerful tool to study brain network remodeling after stroke. However, human studies investigating brain remodeling after a stroke typically include patients with diverse lesions and do not have access to baseline measurements that allow rsFC comparison pre- and post-stroke. Animal studies could address both issues by enabling the generation of replicable, homogenous, and specific infarcts and by allowing collection of baseline measurements prior to infarct generation. There is also an absence of adequate animal studies characterizing rsFC changes associated with BCI rehabilitation strategies. Our project goal is to further characterize rsFC changes associated with CST lesions and test a BCI-mediated rehabilitation strategy after motor recovery plateaus. We will generate uniform lesions in the CST of six Rhesus macaques and after three months of natural recovery, drive contralesional BCI-SR. In each primate, we will collect resting-state functional MRI at baseline before lesioning, after CST lesioning, and during contralesional BCI-SR. We will then identify acute and chronic changes in rsFC that correspond with CST lesioning, innate recovery, and brain-computer-interface mediated rehabilitation. Through these approaches, we seek to validate the efficacy of a novel stroke rehabilitation strategy while providing insight into recovery-associated changes in rsFC.