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

项目总结 90%的帕金森病(PD)患者存在言语和吞咽障碍 吸入性肺炎是这一患者群体的主要死亡原因。当当前 药物和手术干预在缓解帕金森病的一般肢体运动症状方面是有效的，他们 未能为皮质球束控制的颅运动功能提供显著的益处，例如 说话和吞咽。这表明，颅脑运动和肢体运动障碍是由不同的 帕金森病的潜在神经病理，然而，这些差异的性质目前还不清楚。这个 这项提议的中心目标是研究调节皮质球蛋白的神经机制的差异。 在帕金森病动物模型中对比皮质脊髓损伤。使用皮质内微刺激和 综合行为测试组合，包括头运动和肢体运动任务，建议 研究将(1)确定单侧和双侧纹状体多巴胺耗竭的不同影响。 头颅和四肢运动功能以及皮质球和皮质脊髓回路；(2)确定区别 帕金森病患者对靶向运动康复和多巴胺替代治疗的反应 治疗；以及(3)确定靶向运动康复和多巴胺替代的不同效果 皮质球和皮质脊髓环路的完整性治疗。这一结果有可能指导 神经生物学知情疗法的发展，专门针对可以 被转化为人类患者群体。更有效的颅运动功能障碍的治疗策略 在PD中将提高患者的生活质量，降低个人医疗保健成本，最终导致吸入性肺炎 这种疾病人群中的发病率。

PROJECT SUMMARY 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.