Fronto-basal-ganglia circuits for selective stopping and braking

摘要 这一建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。这对广泛的神经精神障碍有很大的意义。 以冲动和坚持不懈为特点。在美国，这些项目的经济和社会成本 混乱是令人震惊的。更好地理解人们是如何控制自己的，从一开始就是这样- 信号范式，在这种范式中，受试者必须偶尔停止启动的反应。神经体系结构 标准的停车信号范例中的停车形式已经被很好地理解了。它是 高度可跨物种翻译，它已被证明是认知控制的一个非常有用的生物标志物 许多神经精神障碍的损害。然而，在标准中衡量的停车形式 停车信号模式作为现实世界控制的模型有一些局限性，因为它似乎具有 对马达系统的全球影响。然而，一个人控制不适当的冲动的能力需要 控制的选择性(即停止一种趋势，而不是其他趋势)。我们最近提出了一项新的 研究选择性停车的行为学方法。这项建议的第一个目的是研究神经 选择性停车的机制。我们将在健康人群中使用功能磁共振成像(FMRI) 志愿者将额基底节脑环分离为全局性停顿和选择性停顿 停下来。我们将使用经颅磁刺激(TMS)来检查 以及通过识别对初级运动皮质中运动表征的影响来选择性停止。我们会 在接受癫痫评估的患者中使用皮质脑电图仪(ECoG)来解决大脑皮质功能如何 目标监控和反应抑制在前额叶皮质相互作用，允许受试者停下来 有选择地。ECOG提供了独特的时空分辨率来解决人类的这个问题。此外 “停止”，现实世界的控制也需要一种控制形式，防止在没有取消的情况下做出响应 完全--一种更类似于“刹车”的东西。这项建议的第二个目的是研究神经 制动机理及其与停车的关系。我们将使用所有这三种方法：fMRI、TMS和 ECG。我们预计刹车会招募到与停止相同的大脑系统，但不会取消马达 完全输出。总而言之，这些研究将提供一种新的神经系统模型，说明如何选择 停车是可能的，以及它与刹车的关系。这将增进和扩大对 认知控制机制，与许多不同的情况有关，包括强迫症 精神障碍，注意力缺陷多动障碍，抽动症和药物滥用问题- 所有的特征都是失去了对特定反应倾向的目标驱动的控制。

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.