Fronto-basal-ganglia circuits for selective stopping and braking

用于选择性停止和制动的额基底神经节回路

• 批准号: 8264210
• 负责人: Adam Robert Aron
• 金额: $ 31.65万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-15 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8264210
• 关键词: Address; Affect; Architecture; Attention deficit hyperactivity disorder; Basal Ganglia; Behavioral; Biological Markers; Biological Models; Brain; Bypass; Corpus striatum structure; Crime; Disease; Electrocorticogram; Epilepsy; Food; Forms Controls; Functional Magnetic Resonance Imaging; Future; Gilles de la Tourette syndrome; Goals; Human; Impairment; Impulse Control Disorders; Impulsivity; Inferior frontal gyrus; Measures; Methods; Middle frontal gyrus structure; Modeling; Monitor; Motor; Motor Cortex; Motor output; Obsessive-Compulsive Disorder; Output; Participant; Patients; Persons; Pharmaceutical Preparations; Prefrontal Cortex; Public Health; Recruitment Activity; Research; Research Personnel; Resolution; Self-control as a personality trait; Short-Term Memory; Signal Transduction; Smoking; Structure; Structure of subthalamic nucleus; Substance abuse problem; System; Testing; Transcranial magnetic stimulation; United States; Violence; Work; base; cognitive control; cost; healthy volunteer; neuromechanism; neuropsychiatry; novel; prevent; psychologic; relating to nervous system; response; spatiotemporal

ABSTRACT This proposal addresses the neural architecture underlying how people are able to use their goals to control inappropriate urges. This has large significance for a wide range of neuropsychiatric disorders characterized by impulsivity and perseveration. In the United States, the financial and societal cost of these disorders is staggering. Better understanding how people control themselves has come from the stop- signal paradigm, in which subjects must occasionally stop an initiated response. The neural architecture underlying the form of stopping in the standard stop-signal paradigm is already quite well understood. It is highly translatable across species and it has proven a very useful biomarker for cognitive control impairments in many neuropsychiatric disorders. However, the form of stopping measured in the standard stop-signal paradigm has some limitations as a model for real world control because it appears to have global effects on the motor system. Yet a person's ability to control an inappropriate urge requires selectivity of the control (i.e. to stop one tendency but not others). We have recently proposed a new behavioral method to study selective stopping. The first aim of this proposal is to study the neural mechanisms of selective stopping. We will use functional Magnetic Resonance Imaging (fMRI) in healthy volunteers to dissociate the fronto-basal-ganglia brain circuits for global stopping from those for selective stopping. We will use Transcranial Magnetic Stimulation (TMS) to examine the difference between global and selective stopping by identifying effects on motor representations in the primary motor cortex. We will use Electrocorticography (ECoG) in patients being evaluated for epilepsy to address how the functions of goal monitoring and response inhibition interact in the prefrontal cortex to allow a subject to stop selectively. ECoG provides unique spatiotemporal resolution to address this question in humans. Besides "stopping", real-world control also requires a form of control that prevents responding without canceling it completely -something more akin to 'braking'. The second aim of this proposal is to study the neural mechanisms of braking and their relation with stopping. We will use all three methods of fMRI, TMS and ECoG. We anticipate that braking recruits the same brain systems as stopping, but without canceling motor output completely. Together, these studies will provide a novel neural-systems model for how selective stopping is possible and for how it relates to braking. This will enhance and expand understanding of cognitive control mechanisms, and is relevant for many diverse conditions including Obsessive Compulsive Disorder, Attention Deficit Hyperactivity Disorder, Tourette's syndrome, and substance abuse problems - all characterized by a loss of goal-driven control over particular response tendencies.

抽象的 该提案解决了人们如何利用他们的目标来实现目标的神经架构 控制不适当的冲动。这对于广泛的神经精神疾病具有重要意义 特点是冲动和坚持。在美国，这些措施的财务和社会成本 疾病是惊人的。更好地理解人们如何控制自己来自于停止—— 信号范式，其中受试者必须偶尔停止发起的反应。神经架构 标准停止信号范式中停止形式的基本原理已经得到很好的理解。这是 跨物种高度可翻译，已被证明是认知控制非常有用的生物标志物 许多神经精神疾病的损伤。然而，标准中测量的停止形式 停止信号范式作为现实世界控制的模型有一些局限性，因为它似乎有 对运动系统的整体影响。然而，一个人控制不适当冲动的能力需要 控制的选择性（即阻止一种趋势而不是其他趋势）。我们最近提出了一个新的 研究选择性停止的行为方法。该提案的第一个目标是研究神经网络 选择性停止机制。我们将在健康方面使用功能性磁共振成像（fMRI） 志愿者将用于全局停止的额叶-基底节-神经节大脑回路与用于选择性停止的大脑回路分离 停止。我们将使用经颅磁刺激（TMS）来检查全球之间的差异 通过识别对初级运动皮层运动表征的影响来选择性停止。我们将 在接受癫痫评估的患者中使用皮质电图（ECoG）来了解皮质功能如何 目标监控和反应抑制在前额叶皮层相互作用，让受试者停下来 有选择地。 ECoG 提供独特的时空分辨率来解决人类的这个问题。除了 “停止”，现实世界的控制还需要一种控制形式，在不取消响应的情况下阻止响应 完全-更类似于“制动”的东西。该提案的第二个目标是研究神经网络 制动机制及其与停止的关系。我们将使用 fMRI、TMS 和 生态图。我们预计刹车会调动与停车相同的大脑系统，但不会取消运动 输出完全。总之，这些研究将为如何选择性地提供一种新颖的神经系统模型 停止是可能的，以及它与制动的关系。这将增强和扩大对 认知控制机制，与许多不同的条件相关，包括强迫症 精神障碍、注意力缺陷多动障碍、抽动秽语综合症和药物滥用问题 - 所有这些的特点都是失去对特定反应倾向的目标驱动的控制。