Reduced brain connectivity underlying value-based choices and outcomes in stimulant use disorder

Abstract

BACKGROUND: Patients with stimulant use disorder (SUD) show impairments when making value-based choices that are associated with disruptions in neural processing across brain networks. Making optimal choices requires learning from outcomes to update knowledge and further optimise ongoing behaviour. The optimal functioning of neural systems that underpin the ability to make favourable choices is an essential component for life functioning, and successful recovery in patients with SUD. Therefore, we sought to investigate the neural processes that underpin value-based choices in SUD patients. We hypothesise that patients with SUD have reduced functional connectivity while making financial choices during a probabilistic reinforcement learning task. METHODS: We investigated connectivity associated with loss and reward value-based choices and their outcomes in patients with SUD and healthy control participants during a pharmacological magnetic resonance imaging study. Participants received a single dose of a dopamine receptor agonist, pramipexole, and a dopamine receptor antagonist, amisulpride, in a randomised, double-blind, placebo-controlled, balanced, crossover design. Functional task-related connectivity was analysed taking a whole brain connectomics approach to identify networks that are differentially modulated by dopaminergic receptor functioning. RESULTS: SUD patients showed widespread reductions in connectivity during both reward and loss value-based choices and outcomes, which were negatively correlated with the duration of stimulant drug use. Disturbances to functional brain connectivity in SUD patients during task performance were not modulated acutely by either amisulpride or pramipexole. CONCLUSIONS: Reductions in brain connectivity, particularly when making value-based choices and processing outcomes, may underlie learning impairments in SUD patients. Given that acute dopaminergic modulation did not improve brain connectivity impairments in SUD patients, it is likely that alternative treatments are needed.