The basal ganglia (BG) pathway has been hypothesized to contribute in several important ways to decision- making, including accumulating evidence, controlling decision termination and commitment, transforming abstract decisions to appropriate motor responses, and providing the machinery for evaluating and adjusting the decision performance. However, many of these functions have been proposed in computational modeling studies but have yet to be examined in detail in the brain, leaving important knowledge gaps that seriously impede our ability to understand normal BG function in healthy brains and to diagnose and treat clinical disorders that affect BG function. Our long-term goal is to conduct experiments that allow us to understand the exact nature of the BG pathway's causal contributions to decision-making. Our original project examined the causal roles of the caudate nucleus, an input structure in the BG, in incorporating reward and visual evidence to make saccade decisions. Here we propose to examine the causal roles of two other BG structures, the substantia nigra pars reticulata (SNr, the output structure in the oculomotor BG) and subthalamic nucleus (STN, a BG nucleus with high clinical importance), in decision-making. Guided by predictions of several prominent theoretical models, we combine computational, behavioral, and neurophysiological techniques to examine how SNr (Aim 1) and STN (Aim 2) neurons contribute to decision deliberation and commitment given uncertain visual input alone, and in the context of flexible decisions that must also take into account changes in reward expectation (Aim 3). Results from the proposed project will provide the first direct experimental evidence for how these specific, clinically relevant nuclei contribute to decision-making. These findings will be particularly useful for constraining and informing theories about the neural implementation of decision-making in the primate brain. These findings will also serve as a foundation for investigating the cognitive impairments associated with BG dysfunction.

Public Health Relevance

The proposed work is basic research, designed to provide new insights into how a healthy nervous system implements computations necessary for guiding oculomotor behavior. Our focus on the basal ganglia pathway is likely to provide health-related benefits in the long term, because this work will likely provide new insights into mechanisms that contribute to cognitive deficits in Parkinsonism, addiction and other disorders of the subcortical pathway.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Mechanisms of Sensory, Perceptual, and Cognitive Processes Study Section (SPC)
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Flanders, Martha C
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University of Pennsylvania
Schools of Medicine
United States
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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