CELL TYPES IN ORBITOFRONTAL CORTEX AND THEIR CAUSAL INFLUENCE ON ECONOMIC CHOICE

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DESCRIPTION (provided by applicant): Economic choice (EC) is the behavior observed when individuals make choices solely based on subjective preferences - for example out of a restaurant menu. As a mental function, EC entails assigning values to the available options; a decision is then made by comparing these values. Several lines of evidence implicate the orbitofrontal cortex (OFC) as a neural substrate for EC. First, lesions or malfunction of the OFC (e.g., in frontotemporal dementia and drug addiction) typically disrupt EC behavior. Second, imaging studies in humans show enhanced OFC activation when subjects make choices compared to when choices are made for them. Third, individual neurons in the primate OFC encode the value subjects assign to different options when they choose between them. Taken together, these elements suggest that OFC plays a role in EC. However, a causal relationship between values encoded in the OFC and behavioral choices has not yet been established. To begin addressing this fundamental question, we will perform a secondary analysis of existing data (Aim 1) and we will conduct two pilot studies using electrical microstimulation and pharmacological inactivation (Aim 2). In our experiments monkeys choose between two juices offered in variable amounts. We previously found that neurons in the OFC encode the subjective values monkeys assign to different juices while choosing. More precisely, neuronal responses in the OFC encode 3 variables: offer value (the value of one of the two juices), chosen value (the value of the chosen juice) and taste (the chosen juice type, independently of the amount). In a computational sense, offer value responses (which are most prevalent immediately after the offer) seem to encode the values necessary to make a choice. Conversely, chosen value responses and taste responses seem to encode the result of the choice process. Thus our working hypothesis is that choices may be based on offer value responses. To test this hypothesis and establish a causal link between the encoding of offer values and choices, we will address three key questions. (1) Are variables offer value and chosen value encoded by distinct and perhaps anatomically clustered populations of cells? This question will be addressed with a secondary analysis of existing data. (2) Can choices be biased by "artificially" activating a population of neurons encoding the offer value? This question will be addressed using electrical microstimulation. Specifically, we will identify sites where neurons encode the offer value of a particular juice and inject small current as a monkey chooses between that juice and another juice. (3) Are choices disrupted by "silencing" this neuronal population? This question will be addressed using reversible pharmacological inactivation. Demonstrating a causal relationship between the encoding of value in OFC and choice behavior would represent an important breakthrough. Thus this research can potentially shape how we understand the neural mechanisms that underlie EC and that malfunction in mental illness. PUBLIC HEALTH RELEVANCE: When individual make choices - for example between different dishes on a restaurant menu - neurons in the orbitofrontal cortex (OFC) compute the subjective value of the different options. This research will test whether choices are indeed caused by values computed in the OFC.