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.
A wide range of cognitive functions depend on brain mechanisms that support decision-making. Restoring these mechanisms will likely play an essential role in future treatments of brain disorders affecting cognition. The proposed research moves a step in this direction by introducing new tools to manipulate brain activity with light during decision making, thereby advancing our understanding of normal brain function and the capacity to alter brain circuitry.
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