Everyday behaviors are often driven by a complex interplay between external visual cues and internal desires, aversions, and idiosyncratic biases. For example, catching a baseball requires following its trajectory in flight but also suppressing a fear of getting hit by it. Ordering a meal at a restaurant depends on personal food preference but can also be biased by the sights (and smells) of other meals being served nearby. Despite recent progress in our understanding of how the brain interprets visual inputs to form perceptual decisions and how the brain uses outcome expectations to form value-based decisions, it remains unclear how the brain coordinates these processes. Our goal is to establish and characterize the central role played by the basal ganglia, an interconnected network of subcortical brain regions implicated in learning, valuation, and action selection, in coordinating visual and non-sensory factors to guide oculomotor behavior. Our four specific Aims address this topic by combining quantitative measures of behavior with electrophysiological techniques.
Aim 1 establishes an experimental and theoretical framework to quantitatively measure decision behavior based on both uncertain sensory information and reward-induced internal preferences.
Aim 2 uses single-neuron recordings to identify the neural computations in caudate, a primate input structure in the basal ganglia oculomotor pathway, in animals performing the novel task developed in Aim 1.
Aim 3 uses electrical microstimulation applied to sites in the caudate at different times within a trial of animals performing the task to test for a causal role in the decision process.
Aim 4 uses anti- and orthodromic stimulation techniques to examine the nature of the signals sent from prefrontal cortex to caudate and to determine the extent to which decision- and reward-related processing emerges in caudate or is sent there directly. The proposed project represents the first systematic examination of the caudate's role in complex decision-making involving uncertain visual stimuli and varying reward expectations. Upon completion, the new results will substantially advance our understanding of neural basis of complex visual decision-making, by providing much-needed insights into how and where in the brain visual cues are combined with non-sensory factors to guide our decisions. In the long-term, these insights will help build a more complete understanding of clinical impairments in goal-directed behavior, especially those involving the basal ganglia.

Public Health Relevance

The proposed work is basic research, designed to provide new insights into how a healthy nervous system combines incoming visual input with internal preferences to guide oculomotor behavior. Our focus on the basal ganglia is likely to provide health-related benefits in the long term, because this work will provide new insights into mechanisms that contribute to cognitive deficits in Parkinsonism, addiction and other disorders of these subcortical pathways.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY022411-02
Application #
8616760
Study Section
Special Emphasis Panel (SPC)
Program Officer
Steinmetz, Michael A
Project Start
2013-03-01
Project End
2017-02-28
Budget Start
2014-03-01
Budget End
2015-02-28
Support Year
2
Fiscal Year
2014
Total Cost
$392,000
Indirect Cost
$147,000
Name
University of Pennsylvania
Department
Neurosciences
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Fan, Yunshu; Gold, Joshua I; Ding, Long (2018) Ongoing, rational calibration of reward-driven perceptual biases. Elife 7:
Nakamura, Kae; Ding, Long (2017) Parsing Heterogeneous Striatal Activity. Front Neuroanat 11:43
Ding, Long (2015) Distinct dynamics of ramping activity in the frontal cortex and caudate nucleus in monkeys. J Neurophysiol 114:1850-61
Ding, Long; Perkel, David J (2014) Two tales of how expectation of reward modulates behavior. Curr Opin Neurobiol 29:142-7
Ding, Long; Gold, Joshua I (2013) The basal ganglia's contributions to perceptual decision making. Neuron 79:640-9