Impaired Activation in Cognitive Control Regions Predicts Reversal Learning in Schizophrenia

Abstract

Reinforcement learning deficits have been associated with schizophrenia (SZ). However, the pathophysiology that gives rise to these abnormalities remains unclear. To address this question, SZ patients (N = 58) and controls (CN; N = 36) completed a probabilistic reversal-learning paradigm during functional magnetic resonance imaging scanning. During the task, participants choose between 2 stimuli. Initially, 1 stimulus was frequently rewarded (80%); the other was infrequently rewarded (20%). The reward contingencies reversed periodically because the participant learned the more rewarded stimulus. The results indicated that SZ patients achieved fewer reversals than CN, and demonstrated decreased winstayloseshift decision-making behavior. On loseshift compared to winstay trials, SZ patients showed reduced Blood Oxygen Level Dependent activation compared to CN in a network of brain regions widely associated with cognitive control, and striatal regions. Importantly, relationships between group membership and behavior were mediated by alterations in the activity of cognitive control regions, but not striatum. These findings indicate an important role for the cognitive control network in mediating the use and updating of value representations in SZ. Such results provide biological targets for further inquiry because researchers attempt to better characterize decision-making neural circuitry in SZ as a means to discover new pathways for interventions.

Volatility estimates increase choice switching and relate to prefrontal activity in schizophrenia

“…We present two core findings: First, medicated patients both overestimated their prior higher-level belief about the volatility of the environment and exhibited an increased influence of volatility estimates on lower-level learning of actionoutcome contingencies. This provides a computational explanation of the increased switching behavior seen in patients with schizophrenia, both in this and in previous studies (8,(11)(12)(13)(14)(15)(16). We replicate this finding in an independent cohort of unmedicated patients.…”

“…Replicating previous studies (8,(11)(12)(13)(14)(15)(16), patients were impaired in flexible decisionmaking driven by enhanced switching between choice options. Using computational modeling of hierarchical Bayesian learning, we demonstrate a possible underlying learning mechanism: an enhanced prior belief about the environment being volatile combined and a stronger influence of volatility on lower-level learning of action-outcome contingencies.…”

“…In such tasks, schizophrenia is characterized by increased switching between choice options (8,(11)(12)(13)(14)(15)(16). The underlying mechanisms of this instable behavior remain unknown but can be targeted by computational modeling (17).…”

Explaining Delusions: Reducing Uncertainty Through Basic and Computational Neuroscience

“…They exhibit increased switching and achieve fewer performance-dependent reversals, even when learning of initial stimulus-outcome associations appears intact. [91][92][93][94][95] This switching correlates with positive symptoms in both deterministic and probabilistic tasks. 93,96,97 In fact, patients with the highest positive symptom ratings exhibit the highest rates of switching, and they require fewer trials (i.e., less evidence) to alter responding after a reversal occurs.…”

“…103 Intriguingly, recent analyses of reversal learning point to patient subgroups among both unmedicated, drug-naive patients (in the earliest stages of the illness) and medicated patients in the chronic phase. [91][92][93][94][95] Unlike healthy controls and patients who successfully navigate the task, a subgroup with higher positive symptoms exhibited reduced prefrontal cortex activation and choice behavior inconsistent with a Hidden Markov Model (a computational estimation of beliefs about reversals and contingency stability updated trial-by-trial 93 ). Patients who switch excessively also have more positive symptoms.…”