Saturday, May 17, 2025
5/17/2025
Neuronal Mechanisms of Good-Based Economic Decisions - ABSTRACT Economic choice behavior is specifically disrupted in mental disorders such as frontotemporal dementia, major depression and drug addiction. To shed light on these diseases and to pave the way for treatments, it is critical to understand the neural underpinnings of this behavior. In this respect, the past 15 years witnessed very significant progress. Evidence from clinical data, lesion studies, functional imaging and neurophysiology links economic choice to the orbitofrontal cortex (OFC). In particular, work in my lab examined the activity of OFC neurons in monkeys choosing between different juices. We thus identified three populations of cells intimately related to choices: offer value cells encoding individual offer values, chosen juice cells encoding the binary choice outcome, and chosen value cells. In a recent breakthrough, we used electrical stimulation to show that offer values encoded in OFC are causal to choices. Together with work from other labs, our results lay the foundations for a satisfactory understanding of economic choices. However, at least three major questions remain open. (1) It is unclear where in the brain and how value comparisons (i.e., decisions) take place. (2) It is unclear where and how offer values are first computed (or “constructed”). (3) It is unclear whether offer values represented in other brain regions – such as the amygdala – are also causal to choices. The overarching goal of this proposal is to address these fundamental questions. All the experiments will be conducted in non- human primates. Using a combination of behavioral manipulation, neuronal recordings, electrical stimulation and computational techniques, we will pursue two Specific Aims. Under Aim 1, two experiments will examine whether neurons in the OFC participate in value comparison. The cell groups identified in this area represent both the input (offer value) and the output (chosen juice, chosen value) of the decision process, suggesting that they constitute the building blocks of a decision circuit. Exp.1 will assess whether the three cell groups are stable across choice conditions. In parallel, Exp.2 will use electrical stimulation to assess whether neuronal activity in OFC is necessary for value comparison. Under Aim 2, we will examine whether and how three brain regions interconnected with OFC – gustatory cortex (GC), inferotemporal cortex (IT) and basolateral amygdala (BLA) – are involved in the choice process. A working hypothesis is that GC and/or IT might participate in the construction of offer values. Two experiments will test this hypothesis by recording neuronal activity from these two areas. Work conducted in the previous cycle found that neurons in BLA encode the same variables represented in OFC, with some differences. In the last experiment, we will use electrical stimulation to assess (a) whether offer values encoded in BLA are causal to choices and (b) whether BLA participates in the decision process. Fulfilling these Aims will significantly advance our understanding of the neural circuits that underlie economic choices and that malfunction in mental illness. Our track record and substantial preliminary results indicate a high likelihood of success.
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