The neurobiology of choice behavior has been intensely studied with laboratory tasks in which a subject makes a perceptual judgement and indicates the result with a motor action. Combined psychophysical and neurophysiological experiments have thus characterized perceptual decision-making capacity as a function of signal quality, strength, and subjective value, and have revealed many of the underlying neural circuits and their specific roles. However, the fundamental question of timing has been much harder to tackle: how long does it take to make a perceptual judgment, versus executing a motor action to report that judgment? At what point in time is a subject committed to a particular choice, and what neural mechanisms determine that? These issues are relevant to many real-life situations that require quick choices; for instance, when a driver sees a traffic light and must rapidly decide whether to step on the brake or the accelerator, depending on the light's color. But making accurate timing measurements is complicated because they are affected by numerous sensory and motor factors, such as readiness, motivation, task difficulty and speed-accuracy trade-offs. Consequently, current knowledge about the temporal dynamics of perceptual decision-making is rather crude. The PIs in this project recently developed a task that eliminates these confounds and produces a new psychophysical measure, the tachometric curve, which isolates a subject's perceptual processing capacity and quantifies it with unprecedented temporal resolution. They have also constructed a computational model that reproduces the subjects' behavior with great detail. The new paradigm and the model will be used jointly to investigate the timing of perceptual judgments and its neural basis. Specific model predictions will be tested via single-neuron recording and microstimulation within the Frontal Eye Field (FEF) of monkeys trained to perform the task under a variety of conditions. There are three specific aims. Aim 1: To test the hypothesis that changes in perceptual processing speed are manifested as changes in the slope of the tachometric curve (psychophysically) and in the acceleration of the oculomotor activity associated with a saccadic choice (neurally). According to the model, the tachometric curve and the oculomotor activity associated with saccadic choices should depend in specific ways on perceptual difficulty. To measure this dependency, subjects will perform 3 versions of the same choice task that will vary in perceptual difficulty according to different stimulus features to be discriminated. Aim 2: To test the hypothesis that when perceptual processing speed remains constant, both the slope of the tachometric curve and the acceleration of the oculomotor activity will stay constant as well, even if other measures of psychophysical performance do change. These experiments are thus complementary to those of Aim 1. Subjects will perform 4 variants of the choice task in which perceptual difficulty will be fixed but the likelihoods and rewards associated with the two possible motor responses will vary. The subject's performance level, reaction times and proportions of choices are expected to change drastically across the 4 conditions, but the measured correlates of perceptual processing speed should not. Aim 3: To test the hypothesis that an overall increase in the level of activation in FEF alters the timing and accuracy of a subject's choices, but not the observed perceptual processing speed. Subthreshold microstimulation current will be injected into the FEF at different points in time during task performance. The question is whether the evoked activity is interpreted as a purely motor signal or if it has a direct impact on the subject's perceptual processing capacity. Intellectual merit: The proposed experiments track how a subject's perceptual performance unfolds in time, and open up an entirely new avenue for investigating how choices are made. It will be possible (1) to determine the specific contributions of various cognitive factors such as attention, motivation, motor preparation, and perceptual processing speed to a subject's measured psychophysical performance, (2) to investigate how neuronal activity is related to each of these factors during a choice task, and (3) to reveal how the time course of this neuronal activity correlates with the time course of a subject's choice accuracy. Broader impacts: (1) Teaching. The results of this study will be incorporated into courses taught by the PIs. (2) Education. Undergraduate students with a minor in neuroscience will be hosted for research academic credit in the PIs' laboratories. A graduate student and a postdoctoral fellow will develop combined electrophysiological and computational skills. (3) Scientific understanding. The results are expected to be widely discussed and disseminated. (4) Enhancement of infrastructure for research. Cutting-edge equipment will be acquired for use in this and future projects. (5) Benefits to society. The novel task design has the potential to be adapted to human subjects and become a powerful diagnostic tool for elucidating how specific neural circuits or brain 'modules' are compromised by a given mental disorder.

R01DA030750

2010-09-30

2015-06-30