Neurophysiology of response inhibition in PD

 描述（由申请人提供）：帕金森病（PD）是一种破坏性的神经退行性疾病，影响约一百万美国人。这种疾病会造成运动以及认知和行为方面的问题。有效的治疗方法可用于疾病的运动方面。然而，我们对大脑的变化了解得很少，这些变化是思维和行为问题的基础，因此，这些症状得不到治疗。该职业发展奖将为弗洛登博士提供额外的培训和研究机会，以提高她的临床研究技能，以解决这一差距。她是一位临床神经心理学家，在认知神经科学研究方面有丰富的经验。她的长期目标是建立一个程序化的研究机构，以表征与PD相关的认知和行为障碍的电生理基础。她将利用这些知识来设计方法来调节PD中的这些电生理异常，从而最大限度地减少相关的认知和行为障碍。该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，生物电和计算神经科学技术的正式课程，以及参与相关研讨会和实验室工作。她还将接受补助金写作和临床试验研究的设计和管理方面的额外培训，以促进她未来的翻译工作。形成当前应用基础的研究项目是对反应抑制期间发生的单个脑细胞和脑细胞群体的活动变化的研究，反应抑制是一种特定的认知过程， 在PD中受损但对控制行为很重要。这种活动是通过在脑深部电刺激手术期间放置在称为丘脑底核（Subthalamic Nucleus，简称ENA）的重要大脑区域的电极来测量的，该手术用于治疗帕金森病的运动症状。这将是第一项测量人类大脑中反应抑制期间单细胞放电率的研究。我们假设a）在特定的脑皮层区域会观察到反应抑制特异性细胞，B）在这些特定的脑皮层区域，异常的认知和运动信号会被不同频带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治疗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我们对PD认知障碍电生理机制的认识的重大进展。

 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.