Orbitofrontal cortex control of striatum leads economic decision-making

Economic decision-making, the process of evaluating options to determine the best course of action, is crucial for survival and well-being. This process involves integrating information about predicted outcomes with the subjective value of each option. While several brain regions, such as the OFC, medial prefrontal cortex, DMS, and mediodorsal thalamus, have been implicated in value-based decision-making, the interactions between these regions remain poorly understood. Most previous research has focused on non-human primates, limiting the ability to precisely manipulate and record neural activity in multiple defined populations. This study addresses this gap by adapting an economic decision-making task for rats, allowing for more precise manipulations and recordings of neural activity across brain regions while rats perform the task.

Previous studies have suggested a role for the OFC in economic decision-making. Electrical microstimulation of the OFC can bias choice behavior, supporting its involvement in value-based decisions. However, lesions and inactivation studies have yielded conflicting results, highlighting the need for a more detailed investigation. Studies have also identified representations of subjective value in other regions, such as the medial prefrontal cortex, DMS, and mediodorsal thalamus, further emphasizing the complexity of this process and the potential for interactions between multiple brain regions in mediating economic choices. This study expands on these prior studies by focusing on the interactions between the OFC and DMS in rats using advanced techniques for manipulating and recording neural activity.

The researchers developed an economic decision-making task for rats. Rats were presented with two visual cues, each predicting a reward of a specific type and quantity of flavored water. The size of the visual cue indicated the reward amount. Rats were trained to associate cues with rewards and make choices to maximize reward. After training, optogenetic inactivation was used to investigate the role of different brain regions in this task. AAVs encoding the inhibitory opsins SwiChR++ and eNpHR3.0-NRN were bilaterally injected into the OFC, DMS, mediodorsal thalamus, or prelimbic cortex. Optical fibers were implanted to allow for light-induced inhibition of neural activity during the cue evaluation period. The impact of inhibition on choice behavior was assessed by analyzing choice probability, latency to choose, and preference scores. Wireless extracellular electrophysiological recordings were conducted in the OFC and DMS of freely moving rats to investigate the temporal dynamics of neural activity during decision-making. Linear support vector machines (SVMs) were used to decode choice direction from neural activity data. Finally, the researchers examined the axonal projections from the OFC and specifically inhibited the direct projection to the DMS using optogenetics to investigate the role of this specific pathway in economic decision-making.

Optogenetic inhibition of the OFC or DMS impaired economic decision-making, as evidenced by flatter psychometric curves and slower latencies for easy choices. Inhibition of the OFC also disrupted juice preferences, while DMS inhibition only affected choices based on reward volume. In contrast, inhibition of the prelimbic cortex or mediodorsal thalamus had no effect on decision-making. Electrophysiological recordings revealed that a large proportion of task-modulated single units were identified in both the OFC and DMS, with activity dominated by spatial features of the task. Choice-related activity emerged earlier in the OFC than in the DMS, and this temporal relationship was strongly correlated with choice accuracy. Specifically inhibiting the OFC projection to the DMS selectively impaired decision-making related to reward volume, demonstrating the importance of this pathway for economic decisions. This effect was specific to the choice task and not observed in a control task without the choice component, indicating that the impairments are related to decision-making itself and not sensory, motor, or motivational deficits.

The findings demonstrate that both the OFC and DMS are critical for economic decision-making in rats, with the OFC playing a leading role by relaying choice information to the DMS. The temporal precedence of OFC activity suggests that it provides a crucial initial representation of choice options, influencing subsequent processing in the DMS which is involved in generating goal-directed actions. The results support the hypothesis that the OFC acts as a cognitive map, integrating various sources of information to resolve motivational conflict and guide decisions. The use of optogenetics in this study allowed the researchers to demonstrate a causal relationship between specific neural circuits and behavior, providing a more definitive answer to the roles of these brain areas in economic decision-making than previous lesion studies could offer. These results offer insights into the neural mechanisms of economic decision-making and highlight the importance of interactions between cortical and striatal regions.

This study provides compelling evidence for a critical role of the OFC-DMS pathway in economic decision-making. The OFC's role in representing choice options and its temporal precedence over DMS activity, along with the specific impairment caused by inhibiting the OFC-DMS projection, strongly suggests a hierarchical processing system where the OFC guides the DMS in making value-based choices. Further research could investigate the specific neural computations performed by these areas and explore the extent to which these findings generalize across species.

The study primarily focused on the ventrolateral OFC, and future research should examine the roles of other OFC subregions. The use of optogenetic inhibition might have had some off-target effects, although control experiments suggest these were minimal. The task used was relatively simple, and the generalizability of these findings to more complex decision-making scenarios requires further investigation.