Fronto-basal-ganglia circuits for selective stopping and braking

摘要 这项建议涉及到人们如何利用他们的目标来实现目标的神经结构。 控制不适当的冲动这对广泛的神经精神疾病具有重要意义 以冲动和固执为特点。在美国，这些措施的经济和社会成本 疾病是惊人的。更好地理解人们如何控制自己来自停止- 信号范式，受试者必须偶尔停止启动的反应。神经结构 标准停止信号范例中的停止形式的基础已经被很好地理解。是 它在不同物种之间具有高度的可翻译性，已被证明是认知控制的一个非常有用的生物标志物。 许多神经精神疾病的损害。然而，停止的形式衡量的标准， 停止信号范例作为真实的世界控制的模型有一些局限性，因为它似乎 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（即停止一种趋势而不是其他趋势）。我们最近提出了一项新的 行为学方法研究选择性停止。这项建议的第一个目的是研究神经 选择性停止的机制。我们将使用功能性磁共振成像（fMRI）在健康 志愿者将额基底神经节脑回路从选择性停止脑回路中分离出来， 停下来。我们将使用经颅磁刺激（TMS）检查全球之间的差异 以及通过识别初级运动皮层中的运动表征的影响来选择性地停止。我们将 在接受癫痫评估的患者中使用皮质电图（ECoG），以解决 目标监控和反应抑制在前额叶皮层中相互作用， 选择性地。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”，现实世界的控制也需要一种控制形式，防止响应而不取消它 更接近于“刹车”。这项建议的第二个目的是研究神经系统 制动机制及其与停车的关系。我们将使用功能磁共振成像，经颅磁刺激和 皮层脑电图我们预计刹车会像停车一样激活相同的大脑系统，但不会取消运动 完全输出。总之，这些研究将提供一个新的神经系统模型， 停止是可能的，以及它与制动的关系。这将提高和扩大对 认知控制机制，并与许多不同的条件，包括强迫症 注意力缺陷多动障碍，图雷特综合征，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。

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.