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.

Altered Dynamics of Canonical Feedback Inhibition Predicts Increased Burst Transmission in Chronic Epilepsy.

Inhibitory interneurons, organized into canonical feedforward and feedback motifs, play a key role in controlling normal and pathological neuronal activity. We demonstrate prominent quantitative changes in the dynamics of feedback inhibition in a rat model of chronic epilepsy (male Wistar rats). Systematic interneuron recordings revealed a large decrease in intrinsic excitability of basket cells and oriens-lacunosum moleculare interneurons in epileptic animals. Additionally, the temporal dynamics of interneuron recruitment by recurrent feedback excitation were strongly altered, resulting in a profound loss of initial feedback inhibition during synchronous CA1 pyramidal activity. Biophysically constrained models of the complete feedback circuit motifs of normal and epileptic animals revealed that, as a consequence of altered feedback inhibition, burst activity arising in CA3 is more strongly converted to a CA1 output. This suggests that altered dynamics of feedback inhibition promote the transmission of epileptiform bursts to hippocampal projection areas.SIGNIFICANCE STATEMENT We quantitatively characterized changes of the CA1 feedback inhibitory circuit in a model of chronic temporal lobe epilepsy. This study shows, for the first time, that dynamic recruitment of inhibition in feedback circuits is altered and establishes the cellular mechanisms for this change. Computational modeling revealed that the observed changes are likely to systematically alter CA1 input-output properties leading to (1) increased seizure propagation through CA1 and (2) altered computation of synchronous CA3 input.