Training-Dependent Gradients of Timescales of Neural Dynamics in the Primate Prefrontal Cortex and Their Contributions to Working Memory.

Cortical neurons exhibit multiple timescales related to dynamics of spontaneous fluctuations (intrinsic timescales) and response to task events (seasonal timescales) in addition to selectivity to task-relevant signals. These timescales increase systematically across the cortical hierarchy, for example, from parietal to prefrontal and cingulate cortex, pointing to their role in cortical computations. It is currently unknown whether these timescales are inherent properties of neurons and/or depend on training in a specific task and if the latter, how their modulations contribute to task performance. To address these questions, we analyzed single-cell recordings within five subregions of the prefrontal cortex (PFC) of male macaques before and after training on a working-memory task. We found fine-grained but opposite gradients of intrinsic and seasonal timescales that mainly appeared after training. Intrinsic timescales decreased whereas seasonal timescales increased from posterior to anterior subregions within both dorsal and ventral PFC. Moreover, training was accompanied by increases in proportions of neurons that exhibited intrinsic and seasonal timescales. These effects were comparable to the emergence of response selectivity due to training. Finally, task selectivity accompanied opposite neural dynamics such that neurons with task-relevant selectivity exhibited longer intrinsic and shorter seasonal timescales. Notably, neurons with longer intrinsic and shorter seasonal timescales exhibited superior population-level coding, but these advantages extended to the delay period mainly after training. Together, our results provide evidence for plastic, fine-grained gradients of timescales within PFC that can influence both single-cell and population coding, pointing to the importance of these timescales in understanding cognition.

Multiple timescales of neural dynamics and integration of task-relevant signals across cortex.

A long-lasting challenge in neuroscience has been to find a set of principles that could be used to organize the brain into distinct areas with specific functions. Recent studies have proposed the orderly progression in the time constants of neural dynamics as an organizational principle of cortical computations. However, relationships between these timescales and their dependence on response properties of individual neurons are unknown, making it impossible to determine how mechanisms underlying such a computational principle are related to other aspects of neural processing. Here, we developed a comprehensive method to simultaneously estimate multiple timescales in neuronal dynamics and integration of task-relevant signals along with selectivity to those signals. By applying our method to neural and behavioral data during a dynamic decision-making task, we found that most neurons exhibited multiple timescales in their response, which consistently increased from parietal to prefrontal and cingulate cortex. While predicting rates of behavioral adjustments, these timescales were not correlated across individual neurons in any cortical area, resulting in independent parallel hierarchies of timescales. Additionally, none of these timescales depended on selectivity to task-relevant signals. Our results not only suggest the existence of multiple canonical mechanisms for increasing timescales of neural dynamics across cortex but also point to additional mechanisms that allow decorrelation of these timescales to enable more flexibility.

Salience-Driven Value Construction for Adaptive Choice under Risk.

Decisions we face in real life are inherently risky and can result in one of many possible outcomes. However, most of what we know about choice under risk is based on studies that use options with only two possible outcomes (simple gambles), so it remains unclear how the brain constructs reward values for more complex risky options faced in real life. To address this question, we combined experimental and modeling approaches to examine choice between pairs of simple gambles and pairs of three-outcome gambles in male and female human subjects. We found that subjects evaluated individual outcomes of three-outcome gambles by multiplying functions of reward magnitude and probability. To construct the overall value of each gamble, however, most subjects differentially weighted possible outcomes based on either reward magnitude or probability. These results reveal a novel dissociation between how reward information is processed when evaluating complex gambles: valuation of each outcome is based on a combination of reward information whereas weighting of possible outcomes mainly relies on a single piece of reward information. We show that differential weighting of possible outcomes could enable subjects to make decisions more easily and quickly. Together, our findings reveal a plausible mechanism for how salience, in terms of possible reward magnitude or probability, can influence the construction of subjective values for complex gambles. They also point to separable neural mechanisms for how reward value controls choice and attention to allow for more adaptive decision making under risk.SIGNIFICANCE STATEMENT Real-life decisions are inherently risky and can result in one of many possible outcomes, but how does the brain integrate information from all these outcomes to make decisions? To address this question, we examined choice between pairs of gambles with multiple outcomes using various computational models. We found that subjects evaluated individual outcomes by multiplying functions of reward magnitude and probability. To construct the overall value of each gamble, however, they differentially weighted possible outcomes based on either reward magnitude or probability. By doing so, they were able to make decisions more easily and quickly. Our findings illustrate how salience, in terms of possible reward magnitude or probability, can influence the construction of subjective values for more adaptive choice.

Combinations of low-level and high-level neural processes account for distinct patterns of context-dependent choice.

Context effects have been explained by either low-level neural adjustments or high-level cognitive processes but not their combination. It is currently unclear how these processes interact to shape individuals' responses to context. Here, we used a large cohort of human subjects in experiments involving choice between two or three gambles in order to study the dependence of context effects on neural adaptation and individuals' risk attitudes. Our experiments did not provide any evidence that neural adaptation on long timescales (~100 trials) contributes to context effects. Using post-hoc analyses we identified two groups of subjects with distinct patterns of responses to decoys, both of which depended on individuals' risk aversion. Subjects in the first group exhibited strong, consistent decoy effects and became more risk averse due to decoy presentation. In contrast, subjects in the second group did not show consistent decoy effects and became more risk seeking. The degree of change in risk aversion due to decoy presentation was positively correlated with the original degrees of risk aversion. To explain these results and reveal underlying neural mechanisms, we developed new models incorporating both low- and high-level processes and used these models to fit individuals' choice behavior. We found that observed distinct patterns of decoy effects can be explained by a combination of adjustments in neural representations and competitive weighting of reward attributes, both of which depend on risk aversion but in opposite directions. Altogether, our results demonstrate how a combination of low- and high-level processes shapes choice behavior in more naturalistic settings, modulates overall risk preference, and explains distinct behavioral phenotypes.

Training-dependent gradients of timescales of neural dynamics in the primate prefrontal cortex and their contributions to working memory.

Cortical neurons exhibit multiple timescales related to dynamics of spontaneous fluctuations (intrinsic timescales) and response to task events (seasonal timescales) in addition to selectivity to task-relevant signals. These timescales increase systematically across the cortical hierarchy, e.g., from parietal to prefrontal and cingulate cortex, pointing to their role in cortical computations. It is currently unknown whether these timescales depend on training in a specific task and/or are an inherent property of neurons, and whether more fine-grained hierarchies of timescales exist within specific cortical regions. To address these questions, we analyzed single-cell recordings within five subregions of the prefrontal cortex (PFC) of male macaques before and after training on a working-memory task. We found fine-grained but opposite gradients of intrinsic and seasonal timescales that mainly appeared after training. Intrinsic timescales decreased whereas seasonal timescales increased from posterior to anterior subregions within both dorsal and ventral PFC. Moreover, training was accompanied by increases in proportions of neurons that exhibited intrinsic and seasonal timescales. These effects were comparable to the emergence of response selectivity due to training. Finally, task selectivity accompanied opposite neural dynamics such that neurons with task-relevant selectivity exhibited longer intrinsic and shorter seasonal timescales. Notably, neurons with longer intrinsic and shorter seasonal timescales exhibited superior population-level coding, but these advantages extended to the delay period mainly after training. Together, our results provide evidence for plastic, fine-grained gradients of timescales within PFC that can influence both single-cell and population coding, pointing to the importance of these timescales in understanding cognition. Significance statement: Recent studies have demonstrated that neural responses exhibit dynamics with different timescales that follow a certain order or hierarchy across cortical areas. While the hierarchy of timescales is consistent across different tasks, it is unknown if these timescales emerge only after training or if they represent inherent properties of neurons. To answer this question, we estimated multiple timescales in neural response across five subregions of the monkeys' lateral prefrontal cortex before and after training on a working-memory task. Our results provide evidence for fine-grained gradients related to certain neural dynamics. Moreover, we show that these timescales depend on and can be modulated by training in a cognitive task, and contribute to encoding of task-relevant information at single-cell and population levels.

Entropy-based metrics for predicting choice behavior based on local response to reward.

For decades, behavioral scientists have used the matching law to quantify how animals distribute their choices between multiple options in response to reinforcement they receive. More recently, many reinforcement learning (RL) models have been developed to explain choice by integrating reward feedback over time. Despite reasonable success of RL models in capturing choice on a trial-by-trial basis, these models cannot capture variability in matching behavior. To address this, we developed metrics based on information theory and applied them to choice data from dynamic learning tasks in mice and monkeys. We found that a single entropy-based metric can explain 50% and 41% of variance in matching in mice and monkeys, respectively. We then used limitations of existing RL models in capturing entropy-based metrics to construct more accurate models of choice. Together, our entropy-based metrics provide a model-free tool to predict adaptive choice behavior and reveal underlying neural mechanisms.