Prior cocaine use diminishes encoding of latent information by orbitofrontal, but not medial, prefrontal ensembles.

Maladaptive decision-making is a hallmark of substance use disorders (SUDs), though how drugs of abuse alter neural representations supporting adaptive behavior remains poorly understood. Past studies show that the orbitofrontal (OFC) and prelimbic (PL) cortices are important for decision-making, tracking both task-relevant and latent information. However, previous studies have focused on how drugs of abuse impact the firing rates of individual units. More work at the ensemble level is necessary to accurately characterize potential drug-induced changes. Using single-unit recordings in rats during a multidimensional decision-making task and then applying population- and ensemble-level analyses, we show that prior use of cocaine altered the strength and structure of task-relevant and latent representations in the OFC, changes relatable to suboptimal decision-making in this and perhaps other settings. These data expand our understanding of the neuropathological underpinnings of maladaptive decision-making in SUDs, potentially enabling enhanced future treatment strategies.