THE ROLE OF PREFRONTAL REGIONS IN ECONOMIC CHOICE AND CHOICE-GUIDED BEHAVIOR

ABSTRACT Economic choice behavior is specifically disrupted in neurological and 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. The past 20 years witnessed considerable progress. Economic choices are thought to involve two mental stages – subjective values are assigned to the available options and a decision is made by comparing values. Clinical data, lesion studies, functional imaging, and neurophysiology link these mental operations to the orbitofrontal cortex (OFC). In particular, previous work in my lab examined neuronal activity in the OFC of monkeys choosing between different juice flavors. We identified different groups of neurons encoding individual offer values, the binary choice outcome, and the chosen value. These variables capture both the input (offer value) and the output (chosen juice, chosen value) of the choice process, suggesting that the cell groups identified in OFC constitute the building blocks of a decision circuit. A series of empirical and computational results support this proposal. Importantly, current notions come primarily from experiments where subjects made simple binary choices, similar to that between steak and salmon a person might make when dining in a restaurant. However, real life decisions are often more complex. For example, in many circumstances, options are defined not by a single good (e.g., steak vs. salmon) but rather by a good bundle (e.g., steak and potatoes vs. salmon and rice). Furthermore, most restaurants offer many dishes – not just two. That is, choices often involve more than two options. Last but not least, choices depend on the internal state of the subject, which can vary. Thus, the same person dining in the same restaurant might choose different dishes on different nights. The overarching goal of this proposal is to assess how the decision circuit adapts or reconfigures itself to generate choices in different behavioral conditions. Neuronal recordings will focus on OFC. In Aim 1, we will examine choices between bundles. Each bundle will be constituted of 2 juice types (A+B vs. C+D design) that, if chosen, will be delivered sequentially. In Aim 2, we will examine choices between three options varying on three dimensions (juice type, quantity, probability). We will alternate binary and trinary choices and examine differences in neuronal activity. In Aim 3, we will assess how changes in the internal state of the subject shape decisions. We will examine choices under risk, where the internal state is defined by 3 parameters. Theoretical considerations suggest that changes in the relative value of the juices reflect changes in circuit connectivity. To test this and other predictions, we will record from large populations of neurons simultaneously, and we will use network inference analysis to estimate the effective connectivity of the circuit. Independent of the outcome of the experiments, fulfilling these Aims will significantly advance our understanding of the neuronal mechanisms underlying economic decisions. Our historic record and robust preliminary results indicate high likelihood of success.