Dissociating the Neural Substrates of Cranial and Limb Motor Impairment in an Ani

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DESCRIPTION (provided by applicant): Speech and swallowing impairments occur in 90% of individuals with Parkinson's Disease (PD) and aspiration pneumonia constitutes the leading cause of death in this patient population. While current pharmacological and surgical interventions are effective in alleviating general limb motor symptoms of PD, they have failed to provide significant benefit for cranial motor functions controlled by corticobulbar tracts such as speech and swallowing. This suggests that cranial motor and limb motor deficits are mediated by different underlying neural pathologies in PD, however the nature of these differences are not currently understood. The central goal of this proposal is to investigate differences in the neural mechanisms mediating corticobulbar versus corticospinal impairments in an animal model of PD. Using intracorticial microstimulation and a comprehensive behavioral testing battery consisting of both cranial motor and limb motor tasks, the proposed studies will (1) determine the differential effects of unilateral versus bilateral striatal dopamine depletion on cranial and limb motor function and corticobulbar and corticospinal circuits; (2) determine the differential responses of cranial and limb motor function in PD to targeted motor rehabilitation and dopamine replacement therapy; and (3) determine the differential effects of targeted motor rehabilitation and dopamine replacement therapy on the integrity of corticobulbar and corticospinal circuits. The results have the potential to guide the development of neurobiologically informed therapies that specifically target cranial motor impairment that can be translated to the human patient population. More effective treatment strategies of cranial motor dysfunction in PD will improve patient quality of life; reduce individual health care cost, aspiration pneumonia and ultimately morbidity in this disease population. PUBLIC HEALTH RELEVANCE: The results will provide direct insight into the neural mechanisms mediating oral motor impairments in PD and have clear implications for the development of novel, effective and neurobiologically informed treatments that specifically target cranial motor impairment in PD. Better treatment strategies for speech and swallowing dysfunction in PD will lead to improvements in quality of life and reductions in individual health care costs, total economic burden, caregiver burden, aspiration pneumonia and ultimately mortality in this disease population.