Interhemispheric Communication and Compensation in Peripheral Nerve Injury

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Use of the non-dominant left hand is critical for individuals who suffer chronic impairment of the dominant right hand due to unilateral conditions such as peripheral nerve injury. (This project will study right-handed individuals, and thus uses "right hand" instead of "dominant hand.") Most rehabilitation focuses on restoration of function, but many patients never achieve this: 64,000 people per year in the USA have nerve injury to the right hand but achieve satisfactory recovery, and these patients must learn to compensate by using the left hand. However, the neural mechanisms of left hand compensation remain unknown. Our preliminary data suggest that compensation involves interhemispheric mechanisms: the left hemisphere's mechanisms are recruited to support the ipsilateral left hand. However, this mechanism has never been assessed with neuroimaging during the left hand precision movements that would engage such a mechanism, nor in the context of hand usage choices (left vs. right) during unconstrained reach-to-grasp action. Our short-term goal is to identify interhemispheric mechanisms that support left hand compensation (both performance and use), and determine whether the mechanisms arise from cortical asymmetry for movement (hand dominance). This will provide the foundation for our long-term goal to develop and target therapies to improve compensation for patients who face challenges to rehabilitation due to chronic right hand impairment. Our patients will be individuals with chronic forced use of the left hand due to unilateral upper extremity peripheral nerve injury. We will compare them with healthy patients in one fMRI study with 3 Aims: Aim 1: identify interhemispheric mechanisms that support left hand performance after right hand injury. We expect left hemisphere activity to correlate with left hand performance in fMRI, in patients > controls. Aim 2: identify interhemispheric mechanisms that support left hand usage after right hand injury. We expect left hemisphere activity to correlate with left hand usage outside fMRI, in patients > controls. Aim 3: determine whether the interhemispheric mechanisms arise from cortical asymmetry. We expect the mechanism to depend on hemisphere-specific specializations. Specifically, for patients who retain some function of their injured right hand, we expect that ipsilateral brain involvement will be demand-correlated during left hand action > during right hand action. These findings will establish a mechanistic understanding of the interhemispheric cortical mechanisms of left hand compensation. These mechanisms are the necessary foundation for future development of interventions such as targeted neuromodulation, and precision-medicine prediction of which patients will benefit from compensatory therapy. Moreover, our findings will establish a healthy-brain mechanism for the changes following chronic forced use of the LH, which can serve as a baseline for future studies of central nervous system conditions (e.g. stroke) that include chronic forced use.