“Cortical electrophysiology of response inhibition and implications for DBS therapy in patients

Ø 反应抑制的皮层电生理学及其对患者 DBS 治疗的影响

• 批准号: 10495230
• 负责人: Svjetlana Miocinovic
• 金额: $ 38.72万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-29 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10495230
• 关键词: Affect; Age; Area; Attention; Basal Ganglia; Behavior; Behavioral; Behavioral inhibition; Biophysics; Brain; Characteristics; Clinical; Clinical Research; Cognition; Cognitive; Computer Models; Conflict (Psychology); Cues; Data; Deep Brain Stimulation; Devices; Disease; Electrocorticogram; Electrodes; Electroencephalography; Electrophysiology (science); Emergency Situation; Evaluation; Evoked Potentials; Frequencies; Functional disorder; Gait; Impairment; Implant; Implantation procedure; Impulsivity; Knowledge; Lateral; Lead; Levodopa; Location; Maps; Measurement; Measures; Methods; Motor; Movement; Neuropsychological Tests; Neuropsychology; Operative Surgical Procedures; Outcome; Parkinson Disease; Pathway interactions; Patients; Performance; Persons; Pharmaceutical Preparations; Physiology; Postoperative Period; Prefrontal Cortex; Proactive Inhibition; Procedures; Process; Reactive Inhibition; Research; Resolution; Role; STN stimulation; Sampling; Scalp structure; Signal Transduction; Structure of subthalamic nucleus; Task Performances; Testing; Universities; base; behavior measurement; behavioral outcome; behavioral study; biophysical model; catalyst; cognitive impairment in Parkinson' s; design; dopamine replacement therapy; electric field; executive function; experimental study; frontal lobe; implantation; member; motor control; motor deficit; motor symptom; novel; patient oriented; patient subsets; predictive modeling; recruit; response; sex; side effect

Project Summary – Project 4 Parkinson’s disease (PD) is associated with behavioral impulsivity and deficits in motor control which result in an inability to cancel planned actions or stop ongoing movements. These behaviors are affected by deep brain stimulation (DBS) and levodopa treatment. The prefrontal cortex and its connections to the subthalamic nucleus (STN), the main target of DBS therapy for PD, have been implicated in the control of these ‘response inhibition’ functions. It has been proposed that modulation of prefrontal-STN connections by DBS can change response inhibition behavior, but clinical studies of this interaction have been conflicting, and clinical programming of DBS devices continues to focus on the optimization of the motoric outcome of DBS, with little attention to the potential changes in cognition and behavior which may result from DBS. The effects of dopaminergic medications on motor response inhibition are also not well understood. While large-scale changes such as outright compulsive disorders are often recognized, more subtle shifts in behavior are not usually acknowledged. The proposed experiments will study the pathophysiologic underpinning of response inhibition abnormalities in PD, asking which cortical mechanisms are engaged in different aspects of motor inhibitory control (proactive vs reactive; discrete vs continuous) in patients off and on levodopa therapy, compared to healthy controls, and examine whether the effects of STN DBS on response inhibition correlates with the degree of activation of the prefrontal cortico-STN pathway. We will use invasive and non-invasive electrophysiology methods, as well as computa- tional modeling. We will study patients longitudinally (before, during and after DBS procedures) and measure their performance and cortical activity while they perform two response inhibition tasks. We will define the degree of prefrontal cortico-STN pathway activation by different stimulation settings, using both direct electrophysiologic recordings (subcortico-cortical evoked potentials) and state-of-the-art computational biophysical models. We will also study how behavior and the underlying electrophysiologic activity change with levodopa treatment, and how these alterations relate to the results of standard clinical neuropsychological tests. In addition to the PD patients, we will study control subjects to understand to what extent changes in PD differ from healthy behavior and physiology. We hypothesize that the stimulation location and the extent of stimulation field produced by STN- DBS determine the degree of prefrontal cortex engagement and impact the patient’s ability to inhibit actions. We postulate that by developing a detailed understanding of how these changes arise, both locally and throughout the cognitive and motor networks, we can design stimulation strategies that maximize motor benefit and minimize negative behavioral side effects of DBS. Successful completion of the proposed studies will thus inform DBS targeting and programming strategies. The proposed Catalyst clinical study will synergize with the other Udall Center components by focusing on cortical electrophysiology and exploring cortical-subcortical interactions that lead to motor/cognitive dysfunction in PD, specifically as it relates to STN-DBS.

项目摘要 - 项目4 帕金森氏病（PD）与行为冲动有关，并在运动控制中定义 无法取消计划的行动或停止正在进行的动作。这些行为受到深脑的影响 刺激（DB）和左旋多巴治疗。前额叶皮层及其与丘脑下核的连接 （STN）是DBS治疗PD的主要靶标，在控制这些“反应抑制”时已暗示 功能。已经提出，DBS对额叶-STN连接的调制可以改变响应 抑制行为，但是对这种相互作用的临床研究一直存在冲突，DBS的临床编程 设备继续专注于DBS的摩托车结果的优化，而很少关注潜力 DBS可能导致的认知和行为变化。多巴胺能药物对 运动反应抑制也不是很好的理解。而大规模的变化，例如完全强迫性 疾病经常被认可，行为的更微妙的转变通常不承认。提议 实验将研究PD反应抑制异常的病理生理基础，询问 哪些皮质机制参与运动抑制性控制的不同方面（主动与反应性； 与健康对照组相比 STN DBS对响应抑制的影响是否与前额叶的激活程度相关 Cortico-Stn途径。我们将使用侵入性和非侵入性电生理方法，以及计算 建模。我们将纵向研究患者（在DBS手术之前，之中和之后），并测量 他们的性能和皮质活动在执行两个响应抑制任务时。我们将定义学位 使用两种直接电生理学 记录（亚皮层皮层诱发电位）和最先进的计算生物物理模型。我们将 还研究行为和潜在的电生理活性如何随左旋多巴处理而变化，以及如何改变 这些改变与标准临床神经心理学测试的结果有关。除了PD患者， 我们将研究控制受试者，以了解PD的变化在多大程度上与健康行为不同和 生理。我们假设刺激位置和STN-产生的刺激场的程度 DBS确定了前额叶皮层的参与程度，并影响患者抑制作用的能力。我们 假设通过对这些变化的详细了解，无论是在本地和整个过程中都会出现的 认知和电动机网络，我们可以设计模拟策略，以最大程度地提高运动益处并最大程度地减少 DBS的负行为副作用。因此，成功完成拟议的研究将为DBS提供通知 定位和编程策略。拟议的催化剂临床研究将与其他Udall协同作用 通过关注皮质电生理学并探索皮质皮质相互作用来通过中心组件 导致PD中的运动/认知功能障碍，特别是与STN-DB有关。