Investigating Inhibitory Control Networks in Parkinson's Disease

项目概述：该项目的总体目标是为申请者J.Nicole Bentley，MD提供合适的 资源和指导，以发展技能，从而在以下领域走上研究独立的道路 认知障碍的神经调节。这项建议侧重于背外侧前额叶皮质的作用。 (DLPFC)在帕金森病(PD)患者中的认知改变 清醒深部脑刺激(DBS)手术期间的皮质下录音。认知障碍是一种常见的 帕金森氏病(PD)的非运动症状，影响四分之一的新诊断患者，甚至更多 超过80%的患者在病程中。尽管它很普遍，但治疗选择很少。 不幸的是，帕金森病运动症状的主要治疗方法，如多巴胺能药物和高... 频率深部脑刺激(DBS)并没有改善，在某些情况下甚至会恶化认知 症状。最近的证据表明，帕金森病患者的前额叶theta频率振荡活动减少 与认知受损有关，特别是在抑制控制领域。考虑到它的密度 连接到基底节和运动前区，DLPFC-基底节网络的神经调节可以 增强帕金森病患者认知功能障碍的因素。我们新的初步数据显示DLPFC和皮质下 术中测量抑制的SIMON任务中的功率调制和相位-幅度耦合 控制，而突增的theta频率DBS调制DLPFC theta功率。在此，我们建议研究(1) 同步记录PD清醒患者DLPFC和苍白球内脑局灶场电位 在Simon任务中，以及(2)对比来自DBS电极的连续和间歇的theta刺激 GPI以确定对行为和电生理测量的影响。鉴于流行率不断上升 由于认知障碍和缺乏可用的治疗方法，迫切需要促进这种发展 临床神经学家对此感兴趣。作为一名专门研究神经调节的神经外科医生， 本特利是担任这一职务的理想人选。她已经组建了一支多学科、多机构的 将为科学和职业发展提供指导和支持的专家导师团队 这项提议的目的。她和她的导师设计了一项职业发展计划，其中包括认知 神经科学、计算神经科学和信号处理技术。这些培训目标将是 结合高三级运动障碍的功能神经外科实践 阿拉巴马大学伯明翰分校。凭借该机构在研究计算、生物统计学、 工程学和神经生理学，这项建议将确保本特利博士为进入 通过完成这一奖项来实现研究的独立性。

Project Summary: The overall goal of this project is to provide applicant J. Nicole Bentley, MD appropriate resources and mentorship to develop skills allowing a path to research independence in the field of neuromodulation for cognitive disorders. This proposal focuses on the role of dorsolateral prefrontal cortex (DLPFC) in altered cognition in Parkinson’s disease (PD) patients with simultaneous intracranial cortical and subcortical recordings during awake deep brain stimulation (DBS) surgery. Cognitive impairment is a common non-motor symptom of Parkinson’s disease (PD), affecting one-quarter of newly diagnosed patients, and more than 80% of patients over the course of the disease. Despite its prevalence, very few treatment options exist. Unfortunately, mainstay treatments for motor symptoms of PD such as dopaminergic medications and high- frequency deep brain stimulation (DBS) do not improve and in some instances can even worsen cognitive symptoms. Recent evidence in PD patients suggests that reduced prefrontal theta frequency oscillatory activity is associated with impaired cognition, specifically evident in the domain of inhibitory control. Given its dense connections to basal ganglia and pre-motor areas, neuromodulation of the DLPFC-basal ganglia network could enhance elements of cognitive dysfunction in PD. Our novel preliminary data shows DLPFC and subcortical power modulation and phase-amplitude coupling during an intraoperative Simon task measuring inhibitory control, and that bursting theta-frequency DBS modulates DLPFC theta power. Here we propose studies to (1) simultaneously record DLPFC and globus pallidus interna (GPi) local field potentials (LFPs) in awake PD patients during the Simon task, and (2) contrast continuous and intermittent theta stimulation from the DBS electrode at the GPi to determine the effect on behavioral and electrophysiologic measures. Given the increasing prevalence of cognitive impairment and the dearth of available treatments, there is an urgent need to foster the development of clinician-neuroscientists with this interest. As a neurosurgeon with specialization in neuromodulation, Dr. Bentley is an ideal candidate to serve in this role. She has assembled a multi-disciplinary and multi-institutional team of expert mentors who will provide guidance and support towards the scientific and career development aims of this proposal. She and her mentors have designed a career development plan consisting of cognitive neuroscience, computational neuroscience, and signal processing techniques. These training aims will be combined with the high volume of a tertiary movement disorders functional neurosurgery practice at the University of Alabama, Birmingham. With the institution’s robust resources in research computing, biostatistics, engineering, and neurophysiology, this proposal will ensure that Dr. Bentley is well-prepared for progressing to research independence by the completion of this award.