Fronto-basal-ganglia circuits for selective stopping and braking

描述（由申请人提供）：该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。这对于以冲动和持续为特征的广泛的神经精神障碍具有重要意义。在美国，这些疾病的经济和社会成本是惊人的。更好地理解人们如何控制自己来自停止信号范式，其中受试者必须偶尔停止启动的反应。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。它在物种间具有高度可翻译性，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，在标准停止信号范例中测量的停止形式作为真实的世界控制的模型具有一些局限性，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（即停止一种倾向，而不是其他倾向）。我们最近提出了一种新的行为学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）来分离用于全局停止的额基底神经节脑回路和用于选择性停止的脑回路。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局性和选择性停止之间的差异。我们将在癫痫患者中使用皮层脑电图（ECoG），以解决目标监测和反应抑制功能如何在前额叶皮层中相互作用，以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，这种控制形式可以防止响应而不完全取消它-更类似于“刹车”。第二个目的是研究刹车的神经机制及其与停车的关系。我们将使用功能磁共振成像，TMS和ECoG的所有三种方法。我们预计刹车会像停车一样激活相同的大脑系统，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，以及它与刹车的关系。这将增强和扩大认知控制机制的理解，并与许多不同的条件有关，包括强迫症，注意力缺陷多动障碍，图雷特综合征和药物滥用问题-所有这些都以失去对特定反应倾向的目标驱动控制为特征。公共卫生相关性：这个提议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。这将有助于更好地理解认知控制的机制。这对于诸如强迫症、注意力缺陷多动障碍、图雷特综合征和药物滥用问题之类的疾病是重要的，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.