Fronto-basal-ganglia circuits for selective stopping and braking

描述（由申请人提供）：这个提案解决了人们如何能够利用他们的目标来控制不适当的冲动的神经结构。这对于以冲动和坚持为特征的广泛的神经精神疾病具有重要意义。在美国，这些疾病的经济和社会成本是惊人的。通过停止信号范式，我们可以更好地理解人们是如何控制自己的，在这种范式中，受试者必须偶尔停止一种发起的反应。在标准停止信号范式中，停止形式背后的神经结构已经被很好地理解了。它具有高度的跨物种可翻译性，并且已被证明是许多神经精神疾病中认知控制障碍的非常有用的生物标志物。然而，在标准停止信号范式中测量的停止形式作为现实世界控制模型有一些局限性，因为它似乎对运动系统具有全局影响。然而，一个人控制不适当冲动的能力需要控制的选择性（即阻止一种倾向而不是其他倾向）。我们最近提出了一种新的行为方法来研究选择性停止。本研究的第一个目的是研究选择性停止的神经机制。我们将在健康志愿者中使用功能性磁共振成像（fMRI）分离用于全局停止和选择性停止的额基底神经节脑回路。我们将使用经颅磁刺激（TMS）通过识别对初级运动皮层中运动表征的影响来检查全面停止和选择性停止之间的差异。我们将在接受癫痫评估的患者中使用皮质电图（ECoG）来研究目标监测和反应抑制功能如何在前额皮质中相互作用，从而允许受试者选择性地停止。ECoG提供了独特的时空分辨率来解决人类的这个问题。除了“停止”之外，现实世界的控制还需要一种控制形式，即在不完全取消响应的情况下阻止响应——这更类似于“刹车”。本研究的第二个目的是研究制动的神经机制及其与停车的关系。我们将使用fMRI、TMS和ECoG这三种方法。我们预计，刹车会激活与停车相同的大脑系统，但不会完全取消运动输出。总之，这些研究将提供一个新的神经系统模型，说明选择性停车是如何可能的，以及它与制动的关系。这将增强和扩展对认知控制机制的理解，并与许多不同的疾病相关，包括强迫症、注意缺陷多动障碍、妥瑞氏综合征和药物滥用问题——所有这些疾病的特征都是失去对特定反应倾向的目标驱动控制。与公共健康相关：该建议阐述了人们如何能够利用目标来控制不适当冲动的神经结构。这将有助于更好地理解认知控制的机制。这对于强迫症、注意缺陷多动障碍、图雷特综合症和药物滥用问题等疾病很重要，这些疾病的特征都是失去对特定反应倾向的目标驱动控制。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: This proposal addresses the neural architecture underlying how people are able to use their goals to control inappropriate urges. This will contribute to a better understanding of mechanisms of cognitive control. This is important for disorders such as Obsessive Compulsive Disorder, Attention Deficit Hyperactivity Disorder, Tourette's syndrome and substance abuse problems, which are all characterized by a loss of goal-driven control over particular response tendencies.