Neuronal mechanisms of response inhibition during decision making

描述(由申请者提供)：几十年来，人们一直致力于研究我们是否有能力控制我们是否采取行动以及采取什么行动，但还没有神经科学研究测试这两种至关重要的认知功能是如何协同工作的。这项研究将是第一个专门针对 彻底测试这一点，从行为到大脑。总体假设是，不同的神经元池独立执行这两个过程。反应抑制是执行控制的一种形式，在需要取消迫在眉睫的行动时使用。它已经被广泛使用停止信号范例进行研究，现在被诊断为许多精神和神经疾病。这项任务通常需要对选择刺激做出反应，但又要抑制 当出现不频繁的停止信号时的响应。取消响应的难度随选择刺激和随后的停止信号之间的延迟而变化，即停止信号延迟(SSD)。对于较短的SSD，抑制更容易。竞争模型将任务的性能解释为随机GO和STOP进程之间的竞争。如果GO进程在停止进程之前完成，则会做出响应，但如果停止进程首先完成，则不会进行响应。该模型考虑了正确和错误响应时间(RTS)，并提供了估计隐蔽停止过程持续时间的方法。对恒河猴进行的一项眼跳停止任务发现，额叶眼场(FEF)中的Go和Stop过程与神经元相关。这些神经数据将种族模型从认知过程模型提炼为大脑机制模型。然而，该模型以及猴子的相关行为和单神经元数据将眼跳定位于单个目标。几乎所有的人类停车信号研究都使用了选择RT任务，在该任务中，受试者辨别一个选择刺激以做出反应。认知和神经竞赛模型都缺乏对选择RT任务所需的范畴决定的解释。分类决策的神经元基础已被广泛探索，但很少与反应抑制的神经元基础相联系。决策研究通常使用两种选择的强迫选择任务。漂移扩散模型将决策解释为选择边界之间的扩散过程。已经在FEF中发现了扩散的神经元相关性。这一建议的主要研究目标是将行为决策和神经决策整合到反应抑制的种族模型中。其目的是(1)通过记录执行选择RT停止信号任务的猕猴FEF中的神经活动来探索反应抑制和决策的神经机制，以及(2)建立一个整合了反应抑制和决策并解释行为和神经生理学的模型。这项建议的第一个主要培训目标是在以往经验的基础上扩大申请人的神经生理学技能集。第二个主要培训目标是获得使用随机累加器进行认知建模的专业知识。这项研究培训加上专业发展活动，将为申请者成为视觉神经科学独立研究人员的长期目标奠定基础。

DESCRIPTION (provided by applicant): Decades of research have been devoted to our ability to control whether we act and which action to make, but no neuroscience research has tested how these two vital cognitive functions work together. This study will be the first to specifically and thoroughly test this, from behavior to brain. The overall hypothesis is that distinct pools of neurons independently implement the two processes. Response inhibition is a form of executive control, exercised when an imminent action needs to be canceled. It has been extensively studied using the stop signal paradigm, and is now diagnostic for many psychiatric and neurological disorders. The task typically requires responding to a choice stimulus, but inhibiting the response when an infrequent stop signal is presented. The difficulty of canceling a response varies with the delay between the choice stimulus and subsequent stop signal, the stop signal delay (SSD). Inhibition is easier for shorter SSDs. The race model explains performance of the task as a race between stochastic GO and STOP processes. If the GO process finishes before the STOP process, a response is made, but if the STOP process finishes first the response is withheld. The model accounts for correct and error response times (RTs) and provides ways to estimate the duration of the covert stopping process. A saccade stop task with rhesus macaques found neuronal correlates of the GO and STOP processes in the frontal eye field (FEF). These neural data refined the race model from a cognitive process model into a brain mechanism model. However, the model and the associated behavior and single neuron data in monkeys addressed saccades to single targets. Nearly all stop signal studies in humans have used choice RT tasks, in which subjects discriminate a choice stimulus to respond. Both cognitive and neural race models lack an account of the categorical decision required by choice RT tasks. The neuronal basis of categorical decision-making has been explored extensively but has made little contact with the neuronal basis of response inhibition. Decision-making studies typically use a two-alternative forced choice task. Drift diffusion models explain decisions as a diffusion process between choice boundaries. Neuronal correlates of the diffusion have been found in FEF. The major research goal of this proposal is to integrate behavioral and neural decision making into the race model of response inhibition. The aims are (1) to explore neuronal mechanisms underlying response inhibition and decision making by recording neural activity in FEF of macaque monkeys performing a choice RT stop signal task, and (2) to develop a model that integrates response inhibition and decision-making and accounts for behavior and neurophysiology. The first major training goal of this proposal is to expand the applicant's neurophysiological skill set, building on previous experience. The second major training goal is to acquire expertise in cognitive modeling with stochastic accumulators. This research training coupled with professional development activities will build the foundation for the applicant's long-term goal of becoming an independent researcher in visual neuroscience.