Dopamine Effects on Mesocorticolimbic Function in Parkinson Disease

项目总结 用于帕金森病(PD)治疗的多巴胺(DA)疗法包括左旋多巴和多巴胺 受体激动剂(DAA)药物。在大约15%-20%的帕金森病患者中，一种已知的行为综合征 因为可能会出现冲动性强迫行为(ICB)。这些行为的特点是增加了 强迫性参与某些行为，如性、饮食、赌博、购物和爱好。DAA使用， 比左旋多巴更与这种疾病有关。DaaS优先靶向D2样受体(D2/D3 多巴胺受体)，在中脑边缘和中皮质表达较多。 因此，这些行为被认为是中皮质边缘功能改变的结果。目前仍不清楚原因 某些患者易受ICB发展的影响，哪些具体的改变是基于奖励的决定- 造成这种疾病的原因是什么？边缘皮质的神经病理机制是什么？ 区域解释了这种脆弱性，以及DA治疗如何触发这些行为的表达。 该提案详细说明了一项培训和职业发展计划，使应聘者能够 在使用认知科学和DA神经成像工具方面的专业知识，以开发改进的治疗方法 患有神经退行性疾病的患者。这项工作是应聘者临床培训的直接延伸 以及博士后研究领域。该提案的具体目标是：(1)确定以下要素的特征 帕金森病患者冲动强迫行为背后的奖赏动机决策 患者，以及(2)检测帕金森病患者有无冲动的D2样受体 强迫行为。 职业培训方案通过侧重于发展认知方面的专门知识来补充研究目标。 科学和神经成像。这些目标通过跨学科的导师结构得到加强， 神经学、心理学和神经放射学，从而为研究DA功能和 生物学。此外，帕金森病的大量临床人群也进一步增加了临床研究的机会。 候选人机构的病人。通过专业课堂学习、外部学习相结合 机会，以及利用研究环境的机会，应聘者将把这些专业知识 改善帕金森病患者的治疗和预后。因此，未来的研究将集中在优化 为改善帕金森病患者的个体化治疗提供依据。

PROJECT SUMMARY Dopamine (DA) therapy used for the treatment of Parkinson Disease (PD) consists of Levodopa and Dopamine receptor Agonist (DAA) medications. In approximately 15-20% of PD patients, a behavioral syndrome known as Impulsive Compulsive Behavior (ICB) can arise. These behaviors are characterized by an increased and compulsive participation in certain behaviors, such as sex, eating, gambling, shopping, and hobbies. DAA use, more so than Levodopa, is associated with this disorder. DAAs preferentially target D2-like receptors (D2/D3 Dopamine receptors), which are expressed in greater number in the mesolimbic and mesocortical areas. These behaviors are thus thought to result from alterations to mesocorticolimbic function. It is still unclear why certain patients are susceptible to the development of ICB, what specific alterations to reward-based decision- making underlie the emergence of the disorder, what neuropathological mechanisms in mesocorticolimbic regions account for this vulnerability, and how DA therapy triggers the expression of these behaviors. This proposal details a training and career development plan that will enable the candidate to develop expertise in the use of cognitive science and DA neuroimaging tools in order develop improved treatments for patients with neurodegenerative disorders. This work is a direct extension of the candidates clinical training and postdoctoral area of research. The Specific Aims of the proposal are: (1) To characterize the elements of reward-motivated decision-making that underlie Impulsive Compulsive Behaviors in Parkinson Disease patients, and (2) To examine D2-like receptors in Parkinson Disease patients with and without Impulsive Compulsive Behaviors. The career training proposal complements the research aims by focusing on developing expertise in cognitive science and neuroimaging. These aims are enhanced by an interdisciplinary mentorship structure with Neurology, Psychology and Neuroradiology, thus providing important expertise in the study of DA function and biology. Also, the opportunities for clinical research are further enhanced by the large clinical population of PD patients at the candidates institution. Through a combination of specialized classroom learning, external learning opportunities, and utilization of the research environment opportunities, the candidate will translate this expertise into improved treatment and prognosis of patients with PD. Future studies will therefore focus on optimizing cognitive performance in PD patients, providing a basis for improved individulalized therapy for patients with PD.