Modulating Inhibitory Action Control Systems With Subthalamic Nucleus Stimulation

通过丘脑底核刺激调节抑制作用控制系统

• 批准号: 10326398
• 负责人: Joseph S Neimat
• 金额: $ 32.59万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-01-15 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10326398
• 关键词: Aging; Attention deficit hyperactivity disorder; Automobile Driving; Basal Ganglia; Basal Ganglia Diseases; Behavior Control; Behavior Disorders; Bilateral; Brain; Characteristics; Clinical; Cognitive; Cognitive deficits; Communities; Conflict (Psychology); Contralateral; Coupled; Data; Deep Brain Stimulation; Development; Devices; Diffuse; Disease; Disease model; Dorsal; Electrodes; Forms Controls; Freezing; Frequencies; Functional disorder; Gilles de la Tourette syndrome; Goals; Grant; Human; Huntington Disease; Impairment; Individual; Intervention; Knowledge; Lead; Left; Link; Measures; Methods; Microelectrodes; Mind; Modeling; Monitor; Motor; Movement; Movement Disorders; Neurocognitive; Neurodegenerative Disorders; Neurologic; Neurons; Obsessive-Compulsive Disorder; Operating Rooms; Operative Surgical Procedures; Parkinson Disease; Patients; Performance; Physiology; Play; Postoperative Period; Process; Property; Publishing; Research; Role; STN stimulation; Side; Signal Transduction; Structure; Structure of subthalamic nucleus; Suggestion; System; Technology; Testing; Work; cognitive control; cognitive neuroscience; cognitive process; design; experience; experimental study; falls; implantation; improved; innovation; motor control; motor impulse; motor symptom; nervous system disorder; neural circuit; neurophysiology; neuropsychiatric disorder; neuropsychiatry; next generation; novel; novel strategies; programs; relating to nervous system; response; skills; theories; voltage

Neurological (Parkinson's and Huntington's diseases) and neuropsychiatric disorders (Attention-Deficit Hyperactivity Disorder, Tourette syndrome) associated with frontal-basal ganglia dysfunction are accompanied by deficits in stopping or suppressing actions. Action inhibition deficits can have devastating effects and have been linked to clinical motor symptoms (e.g., falling, freezing, dyskinetic movements), poor functional skills (e.g., driving), and behavioral disorders (e.g., poor impulse control). Unfortunately, there are few options for treatment deficits in inhibitory control. One potential way to modulate inhibitory control processes is direct stimulation of relevant neural circuitries. Specifically, it is possible to stimulate a key node in the brain's inhibitory control circuitry, the subthalamic nucleus (STN), and directly modulate inhibitory control capabilities, including improving them. The STN is linked to two distinct forms of inhibitory control: (1) a stopping control mechanism that rapidly inhibits an initiated or ongoing action (2) a conflict control mechanism that selectively suppresses strong initial motor impulses that conflict and interfere with goal-directed actions. Our recent work and preliminary data lead to the hypothesis that these control mechanisms can be directly modulated and improved by stimulating the STN in patients with Parkinson's disease (PD). Moreover, our preliminary findings are strongly suggestive that modulating these distinct forms of inhibitory control requires stimulating in different STN subterritories. Additionally, a proposed, but scarcely tested idea is that inhibitory control mechanisms involve a predominantly right hemisphere circuitry. These state of findings leads to our specific hypotheses that inhibitory control circuitries can be directly modulated and improved by stimulating in distinct subregions and hemispheres in the STN. We propose experiments to systematically test the precise relationship between STN neural circuitry and inhibitory action control mechanisms. We propose novel interrogations of STN substructures and neurophysiology to define links between inhibitory control mechanisms and STN subterritories and hemispheres. In Specific Aim 1, we use innovative electrode localization and stimulation methods (both post-operatively as well as in the operating room) to test the hypothesis that stimulating dorsal and ventral subregions in the left and right STN produce dissociable effects on stopping control and on conflict control mechanisms. In Specific Aim 2, we investigate the relationships between inhibitory control mechanisms and STN neurophysiology by recording single unit neural activity in bilateral STN during intraoperative placement of DBS electrodes in PD patients. While the cognitive neuroscience of inhibitory control deficits in PD will benefit directly from this work, the project is designed with broader applications in mind as the neurosurgical community explores how DBS in the STN and other basal ganglia structures can improve inhibitory control deficits in individuals with Huntington's disease, Tourette's syndrome, and other neuropsychiatric disorders associated with basal ganglia circuitry dysfunction.

神经系统疾病（帕金森病和亨廷顿病）和神经精神疾病（注意力缺陷 多动障碍，抽动秽语综合征）与额基底神经节功能障碍伴随 在阻止或抑制行为方面的缺陷。行动抑制缺陷可能具有破坏性的影响， 与临床运动症状有关（例如，跌倒、冻结、运动障碍）、功能性技能差 (e.g.,驾驶），和行为障碍（例如，冲动控制不良）。不幸的是， 抑制控制的治疗缺陷。调节抑制性控制过程的一种潜在方法是直接 刺激相关的神经回路。具体来说，刺激大脑中的一个关键节点是可能的。 抑制性控制回路，丘脑底核（subthalamic nucleus，简称STN），并直接调节抑制性控制能力， 包括改进它们。抑制性控制与两种不同形式的抑制性控制有关：（1）停止控制 一种快速抑制已发起或正在进行的行动的机制（2）一种冲突控制机制， 抑制强烈的初始运动冲动，这些冲动与目标导向的行动相冲突并干扰。我们最近的工作 初步的数据导致的假设，这些控制机制可以直接调制， 通过刺激帕金森病（PD）患者的大脑皮层，此外，我们的初步调查结果 强烈暗示，调节这些不同形式的抑制控制需要刺激不同的神经元， 所有的次区域。此外，一个被提出但几乎没有被验证的想法是，抑制性控制机制 主要涉及右半球回路。这些发现的状态导致我们的特定假设， 抑制性控制电路可以通过在不同的子区域中进行刺激来直接调节和改善， 大脑半球我们提出实验来系统地测试的精确关系， 神经回路和抑制性动作控制机制。我们提出了新的审讯的 亚结构和神经生理学来定义抑制性控制机制和神经元之间的联系， 分区和半球。在特定目标1中，我们使用创新的电极定位和刺激 方法（术后以及在手术室），以测试刺激背侧的假设， 左、右丘脑腹侧亚区对停止控制和冲突产生可分离的作用 控制机制。在具体目标2中，我们研究了抑制性控制机制之间的关系， 通过记录术中双侧脑干的单个神经元活动， 在PD患者中放置DBS电极。虽然认知神经科学的抑制控制缺陷， PD将直接受益于这项工作，该项目的设计考虑到更广泛的应用， 神经外科社区探讨了DBS在小脑和其他基底神经节结构中如何改善 患有亨廷顿病、图雷特综合征和其他疾病个体的抑制控制缺陷 与基底神经节电路功能障碍相关的神经精神障碍。

项目成果

Subthalamic Nucleus Subregion Stimulation Modulates Inhibitory Control.

• DOI: 10.1093/texcom/tgaa083
• 发表时间: 2020
• 期刊: Cerebral cortex communications
• 作者: van Wouwe NC;Neimat JS;van den Wildenberg WPM;Hughes SB;Lopez AM;Phibbs FT;Schall JD;Rodriguez WJ;Bradley EB;Dawant BM;Wylie SA
• 通讯作者: Wylie SA