Mechanisms of Visual Perception

描述（由申请人提供）：决策的神经生物学已经成为理解认知基础的基本大脑机制的模型平台。该领域的显著进展归功于其在人类和非人类灵长类动物视觉感知和视觉神经科学研究方面的强大定量和经验基础。因此，非人类灵长类动物的视觉感知决策已经开始揭示高级脑功能的关键原则及其潜在机制——感官证据的整合、灵活的时间和终止过程的设定标准。这些机制构成了复杂认知功能的基础。它们使正常的大脑“不困惑”：能够推理，优先考虑，推断原因和后果，为自己的想法指定作者，探索，避免分心并与环境互动。似乎有一天，影响大脑高级功能的疾病的治疗进展将依赖于操纵回路的能力，以影响这些机制的表达。本应用程序中提出的研究代表了朝这个方向迈出的一步。这三个科学目标是开发传统的电刺激工具和新兴的光激活工具（“光遗传学”），以在决策过程中操纵大脑活动。这些实验将阐明神经机制，解释导致选择的深思熟虑过程，这种选择是正确的可能性（即准确性），做出选择所需的时间（即反应时间），以及决策者在结果已知之前对选择的信心。第一个实验目的是研究电微刺激对猴子（M. mulatta）视觉皮层约100个神经元在困难感知决策中的影响。众所周知，在这种情况下，微刺激会影响选择和反应时间，但实验将首次评估这种操作是降低还是增强了对决策的信心。第二个和第三个目标是在相同的决策任务中引入新兴的“光遗传学”方法。这些实验利用了一种新的能力来诱导成年猕猴大脑中的神经元表达通道视紫红质（ChR2）和其他光敏离子泵。目的2考察光刺激对选择准确性和反应时间的影响。目的3概述了用光代替电流刺激神经元的置信度测量。这些研究有望阐明感知和决策的神经机制。此外，通过在猕猴中推进光遗传学方法，拟议的研究将有助于在比迄今为止可能的更精细的水平上研究复杂的神经机制。

DESCRIPTION (provided by applicant): The neurobiology of decision making has emerged as a model platform to understand fundamental brain mechanisms that underlie cognition. The remarkable progress in this area is attributed to its strong quantitative and empirical foundation in the study of visual perception and visual neuroscience in human and nonhuman primates. Thus, visual perceptual decision-making in nonhuman primates has begun to expose key principles of higher brain function and their underlying mechanisms - integration of sensory evidence, flexible timing, and setting criteria to terminate a process. These mechanisms comprise the rudiments of complex cognitive functions. They make a normal brain "not confused": able to reason, prioritize, infer causes and consequences, assign authorship to one's own thoughts, explore, avoid distractions and engage with the environment. It seems likely that advances in the treatments of diseases affecting higher brain function will one day rely on an ability to manipulate circuits in order to affect the expression of these mechanisms. The research proposed in this application represents a step in this direction. The three scientific aims develop traditional electrical stimulation tools and emerging light-activation tools ("optogenetics") for manipulating brain activity during decision making. The experiments will elucidate the neural mechanisms that explain the process of deliberation leading to a choice, the likelihood that such a choice is the correct one (i.e., accuracy), the amount of time it takes o make the choice (i.e., reaction time), and the confidence that a decision-maker has in a choice before the outcome is known. The first experimental aim examines the effect of electrical microstimulation of ~100 neurons in the visual cortex of a monkey (M. mulatta) during a difficult perceptual decision. Microstimulation is known to affect choice and reaction time in this setting, but the experiments will assess, for the first time, whether the manipulation reduces or enhances confidence in a decision. The second and third aims introduce emerging "optogenetic" methods in the same decision-making task. These experiments exploit a new capacity to induce neurons in the adult macaque brain to express channelrhodopsin (ChR2) and other light sensitive ion pumps. Aim 2 examines the effect of photostimulation on choice-accuracy and reaction-time. Aim 3 recapitulates the confidence measurements using light instead of electrical current to stimulate neurons. These studies promise to elucidate neural mechanisms of perception and decision-making. Moreover, by advancing optogenetic methods in the macaque, the proposed research will facilitate the study of sophisticated neural mechanisms at a more refined level than was hitherto possible.