Assessing the contribution of a subcortical circuit for express visuomotor responses

视觉是人类用来识别外部环境中物体的主要感官。许多日常动作都需要将视觉信息转化为适当的肌肉活动模式。这种从视觉到运动的转变可以发生得非常快：快速眼跳或颈部或四肢肌肉募集的最早阶段可以在视觉目标开始后100ms内发生。我的研究项目试图了解大脑是如何产生如此快速的反应的。我们假设，表达反应，无论是在眼睛、头部或肢体产生的，都是由起源于上丘(SC)的共同顶盖-网状-脊髓通路启动的。为了测试这一点，我们建议在人类和非人类灵长类动物(NHP)中进行互补的行为和神经生理学实验。在项目1中，我们将测量眼睛运动以及颈部和上肢肌肉的活动，同时人类在过去的发现拨款期间开发的一项新的新兴目标任务中，执行视觉引导的触角。在这项任务中，受试者试图抓住从障碍物后面出现的移动目标。在这项任务中，几乎每个受试者的上肢肌肉都会产生快速反应，这使我们能够评估眼睛、头部和四肢的快速反应的逐个受试者和逐个试验的相关性。我们还将测试通过网状脊髓系统产生短潜伏期反应的令人震惊的声音刺激是否影响表达反应的时间和/或幅度。最后，由于网状脊髓系统是双侧投射的，我们将研究在一个修改的任务中，受试者选择使用哪只手臂来捕捉新出现的目标，是否双侧表达了上肢的表达反应。项目1中的工作只能间接测试潜在的神经机制。在项目2中，我们将研究在执行新出现的目标任务的NHP中表达反应的神经生理学，记录眼睛、颈部和肢体的反应，就像人类一样。然后我们将从SC记录，以评估目标出现后的信号计时以及相对于眼睛、头部和肢体的表达反应。最后，我们将对SC失活通常会改变眼睛、头部和肢体的表达反应的预测进行因果检验。长期以来，人们一直认识到，神经回路的层次结构有助于自愿的视觉引导动作，脊髓和脑干回路与皮质回路协同作用，以确保采取与背景相适应的动作。通过利用我们开发的一种新的行为任务来可靠地唤起表达反应，我们现在可以测试在表达反应中系统发育保守的组织网状脊髓回路在很大程度上没有被认识到的作用。这项工作最终将有助于更好地理解皮层和皮质下回路如何在动态和不确定的世界中协同工作，在时间至关重要的情况下产生与背景相适应的动作。

Vision is the main sense humans use to identify objects in the external environment. Many everyday actions require a transformation of visual information into the appropriate patterns of muscle activity. Such visual-to-motor transformations can occur remarkably fast: express saccades or the earliest phase of neck or limb muscle recruitment can occur within 100 ms of visual target onset. My research program seeks to understand how the brain generates such rapid responses. We hypothesize that express responses, be they generated at the eye, head, or limb, are initiated by a common tecto-reticulo-spinal pathway originating in the superior colliculus (SC). To test this, we propose complementary behavioural and neurophysiological experiments in humans and non-human primates (NHPs). In Project 1, we will measure eye movements and the activity of neck and upper limb muscles while humans perform visually-guided reaches in a novel emerging target task developed during the past Discovery Grant. In this task, subjects try to catch a moving target that emerges from behind a barrier. Express responses are produced on upper limb muscles in virtually every subject in this task, allowing us to assess subject-by-subject and trial-by-trial correlations of express responses across the eyes, head, and limb. We will also test whether startling acoustic stimuli, which engender short-latency responses via the reticulospinal system, influence the timing and/or magnitude of express responses. Finally, since the reticulospinal system projects bilaterally, we will examine whether express responses in the upper limb are expressed bilaterally in a modified task where subjects choose which arm to use to catch the emerging target. The work in Project 1 can only indirectly test underlying neural mechanisms. In Project 2, we will examine the neurophysiology of express responses in NHPs performing the emerging target task, recording eye, neck, and limb responses as in humans. We will then record from the SC to assess signal timing after target emergence and relative to express responses at the eyes, head and limb. Finally, we will causally test the prediction that inactivation of SC should commonly modify express responses of the eyes, head, and limb. It has long been appreciated that a hierarchy of neural circuits contributes to voluntary visually-guided actions, with spinal cord and brainstem circuits acting in concert with cortical circuits to ensure contextually-appropriate actions. By leveraging a novel behavioural task that we developed to reliably evoke express responses, we can now test the contribution of a largely unappreciated role for a phylogenetically-conserved tecto-reticulo-spinal circuit in express responses. This work will ultimately contribute to a better understanding of how cortical and subcortical circuits work together in a dynamic and uncertain world to generate contextually-appropriate actions when time is of the essence.