Distinct roles of the orbitofrontal cortex, ventral striatum, and dopamine neurons in counterfactual thinking of decision outcomes.

Individuals often assess past decisions by comparing what was gained with what would have been gained had they acted differently. Thoughts of past alternatives that counter what actually happened are called "counterfactuals." Recent theories emphasize the role of the prefrontal cortex in processing counterfactual outcomes in decision-making, although how subcortical regions contribute to this process remains to be elucidated. Here we report a clear distinction among the roles of the orbitofrontal cortex, ventral striatum and midbrain dopamine neurons in processing counterfactual outcomes in monkeys. Our findings suggest that actually gained and counterfactual outcome signals are both processed in the cortico-subcortical network constituted by these regions but in distinct manners and integrated only in the orbitofrontal cortex in a way to compare these outcomes. This study extends the prefrontal theory of counterfactual thinking and provides key insights regarding how the prefrontal cortex cooperates with subcortical regions to make decisions using counterfactual information.

Single-unit Recording in Awake Behaving Non-human Primates.

Non-human primates (NHPs) have been widely used as a species model in studies to understand higher brain functions in health and disease. These studies employ specifically designed behavioral tasks in which animal behavior is well-controlled, and record neuronal activity at high spatial and temporal resolutions while animals are performing the tasks. Here, we present a detailed procedure to conduct single-unit recording, which fulfils high spatial and temporal resolutions while macaque monkeys (i.e., widely used NHPs) perform behavioral tasks in a well-controlled manner. This procedure was used in our previous study to investigate the dynamics of neuronal activity during economic decision-making by the monkeys. Monkeys' behavior was quantitated by eye position tracking and button press/release detection. By inserting a microelectrode into the brain, with a grid system in reference to magnetic resonance imaging, we precisely recorded the brain regions. Our experimental system permits rigorous investigation of the link between neuronal activity and behavior.

Signal dynamics of midbrain dopamine neurons during economic decision-making in monkeys.

When we make economic choices, the brain first evaluates available options and then decides whether to choose them. Midbrain dopamine neurons are known to reinforce economic choices through their signal evoked by outcomes after decisions are made. However, although critical internal processing is executed while decisions are being made, little is known about the role of dopamine neurons during this period. We found that dopamine neurons exhibited dynamically changing signals related to the internal processing while rhesus monkeys were making decisions. These neurons encoded the value of an option immediately after it was offered and then gradually changed their activity to represent the animal's upcoming choice. Similar dynamics were observed in the orbitofrontal cortex, a center for economic decision-making, but the value-to-choice signal transition was completed earlier in dopamine neurons. Our findings suggest that dopamine neurons are a key component of the neural network that makes choices from values during ongoing decision-making processes.