Neurophysiology of response inhibition in PD

 描述(申请人提供)：帕金森病(PD)是一种破坏性的神经退行性疾病，影响大约100万美国人。这种疾病会造成运动以及认知和行为方面的问题。对于这种疾病的运动方面，有有效的治疗方法。然而，我们对思维和行为问题背后的大脑变化知之甚少，因此，这些症状得不到治疗。这一职业发展奖将为弗洛登博士提供更多的培训和研究机会，以提高她的临床研究技能，以解决这一差距。她是一位在认知神经科学研究方面有经验的临床神经心理学家。她的长期目标是建立一个程序性的研究机构，以表征与帕金森病相关的认知和行为障碍的电生理学基础。她将利用这些知识来设计方法来调节帕金森病患者的这些电生理异常，从而将相关的认知和行为损害降至最低。这一奖项将帮助她通过结构化的培训计划实现这些目标，其中包括神经生理学、生物电学和计算神经科学技术方面的正式课程工作，以及参与相关的研讨会和实验室工作。她还将接受额外的拨款撰写以及临床试验研究的设计和管理方面的培训，以促进她未来的翻译工作。构成当前应用基础的研究项目是对单个脑细胞和多个脑细胞在反应抑制期间发生的活动变化的研究，这是一种特定的认知过程， 在帕金森病中受损，但对控制行为很重要。在治疗帕金森病运动症状的脑深部刺激手术中，这种活动是通过放置在重要大脑区域丘脑底核(STN)的电极来测量的。这将是第一次测量人类STN在反应抑制期间的单细胞放电率的研究。我们假设a)反应抑制特异性细胞将在STN的特定区域被观察到，以及b)异常的认知和运动信号将被那些选定的STN区域中不同频段的群体活动差异编码。如果这些假设是正确的，这将为开发空间和频率定制的刺激疗法以改善认知功能铺平道路。无论结果如何，这项研究的结果将代表着我们对帕金森病认知障碍的电生理机制的认识取得了重大进展。

 DESCRIPTION (provided by applicant): Parkinson disease (PD) is a devastating neurodegenerative disease that affects approximately one million Americans. The disease creates problems with movement as well as with cognition and behavior. Effective treatments are available for the movement aspects of the disease. However, we understand much less about the changes in the brain that underlie the thinking and behavior problems and, as such, these symptoms go untreated. This Career Development Award will provide additional training and research opportunities for Dr. Floden to advance her clinical research skills in order to address this disparity. She is a clinical neuropsychologist with experience in cognitive neuroscience research. Her long term goal is to establish a programmatic body of research that characterizes the electrophysiological basis of cognitive and behavioral impairments associated with PD. She will use this knowledge to design methods to modulate these electrophysiological abnormalities in PD and thereby minimize the associated cognitive and behavioral impairments. This award will aid her in achieving these goals through a structured training plan that includes formal course work in neurophysiology, bioelectricity, and computational neuroscience techniques, as well as participation in relevant seminars and laboratory work. She will also receive additional training in grant writing and the design and administration of clinical trials research to facilitate her future translational work. The research project that forms the foundation of the current application is a study of the activity changes in single brain cells and populations of brain cells that occur during response inhibition, a specific cognitive process that is impaired in PD but important for controlling behavior. This activity is measured from electrodes that are placed in an important brain region called the Subthalamic Nucleus (STN) during Deep Brain Stimulation surgery for treatment of motor symptoms in Parkinson disease. This will be the first study to measure single cell firing rates in the human STN during response inhibition. We hypothesize that a) response inhibition-specific cells will be observed in select regions of the STN and b) abnormal cognitive and motor signals will be differentially coded by population activity in distinct frequency bands in those select STN regions. If these hypotheses are correct, this would pave the way to development of spatial- and frequency- tailored stimulation treatments to improve cognitive function. Regardless of the outcome, the findings from this study will represent a significant advance in our knowledge of the electrophysiological mechanisms of cognitive impairment in PD.