Many mental and neurological disorders - including frontotemporal dementia, obsessive-compulsive disorder and drug addiction - are broadly characterized by patients making poor choices. More specifically, deficits are observed when subjects make decisions based on subjective preferences - a behavior termed economic choice. Thus to better understand the origins of these disorders, and to pave the way for treatments, it is critical to understand the neuronal underpinnings of economic choice. This proposal builds on recent results showing that neurons in the primate orbitofrontal cortex (OFC) encode three variables intimately related to the decision. In the experiments, monkeys chose between different juices offered in variable amounts. Different groups of cells encoded the offer value (the value of one of the two juices, independent of the animal choice), the chosen value (the value of the chosen juice, independent of its identity) and the chosen juice (the identity of the chosen juice, independent of its value). In principle, these groups of cells could be sufficien to generate a decision. Furthermore, an established literature shows that OFC lesions selectively impair economic choices. We thus put forth the hypothesis that good-based decisions take place within the OFC. We will pursue three specific aims.
In Aim 1, we will assess whether and how the identity of individual neurons is maintained across behavioral contexts. Monkeys will choose between two juices (A and B) in a first trial block and between different juices (C and D) in a second trial block. Preliminary results indicate that a given cell typically encodes the same variable in the two blocks. At the same time, cells are re-assigned to the juices available in any given block.
In Aim 2, we will examine the neuronal origins of choice variability. We recently discovered several phenomena relating the decision made by the animal in any given trial with trial-by-trial fluctuations in the activity of individual neurons in OFC. Theoretical considerations indicate that these phenomena critically depend on how trial-by-trial fluctuations in the activity of different neurons are correlated with each other.
Under Aim 2, we will measure noise correlations in the OFC using high-density U-probes. In addition, we will assess whether different groups of cells are anatomically organized in clusters or mini-columns.
In Aim 3, we will examine the role of the amygdala (AMY). With the OFC, the AMY is the only area where lesions disrupt performance in reinforcer devaluation tasks. Previous work suggests that value-relevant information flows from the AMY to the OFC. However, the precise role of the AMY in economic decisions remains unclear. While lesion studies long implicated the OFC in choice behavior, the hypothesis that economic decisions take place within the OFC is highly innovative and potentially transformative. Throughout this proposal, experiments and computational work will proceed hand-in-hand. In our estimation, this research is the most advanced ever conducted to understand the neuronal mechanisms underlying economic decisions.

Public Health Relevance

Economic choice is a behavior specifically disrupted in drug addiction and disorders such as frontotemporal dementia, schizophrenia and major depression. This project will investigate the mechanisms through which economic decisions emerge from the activity of neurons in the orbitofrontal cortex and the amygdala. 1

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH104494-05
Application #
9654037
Study Section
Mechanisms of Sensory, Perceptual, and Cognitive Processes Study Section (SPC)
Program Officer
Rossi, Andrew
Project Start
2015-05-15
Project End
2020-02-28
Budget Start
2019-03-01
Budget End
2020-02-28
Support Year
5
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Washington University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Padoa-Schioppa, Camillo; Conen, Katherine E (2017) Orbitofrontal Cortex: A Neural Circuit for Economic Decisions. Neuron 96:736-754
Rustichini, Aldo; Conen, Katherine E; Cai, Xinying et al. (2017) Optimal coding and neuronal adaptation in economic decisions. Nat Commun 8:1208
Xie, Jue; Padoa-Schioppa, Camillo (2016) Neuronal remapping and circuit persistence in economic decisions. Nat Neurosci 19:855-61
Conen, Katherine E; Padoa-Schioppa, Camillo (2015) Neuronal variability in orbitofrontal cortex during economic decisions. J Neurophysiol 114:1367-81