Exploring the Effects of an Acute Dose of Antipsychotic Medication on Motivation-mediated BOLD Activity Using fMRI and a Perceptual Decision-making Task

Abstract

The left inferior frontal gyrus and the bilateral ventral striatum are thought to be involved in motivation-mediated decision-making. Antipsychotics may influence this relationship, and atypical antipsychotics improve secondary negative symptoms in schizophrenia, such as loss of motivation, although the acute effects of pharmacological medication on motivation are not fully understood. In this single-blinded, randomized controlled trial, 49 healthy volunteers were randomized into three groups to receive a single dose of haloperidol, aripiprazole or placebo. Between 4.0 and 5.6 h later, participant’s brain blood-oxygen-level dependent (BOLD) activity was recorded using functional magnetic resonance imaging (fMRI) while completing a perceptual decision-making fMRI task consisting of one neutral and one motivated condition. Response bias, reflecting the participant’s willingness to say that the target stimulus is present, was calculated using signal detection theory. Concurrent with widespread changes in BOLD signal in the motivated vs. neutral condition, a less conservative, mathematically optimal response bias was observed in the motivated condition across the whole sample. Within-group differences in BOLD signal in the left inferior frontal gyrus and bilateral ventral striatum were observed between conditions in the aripiprazole and haloperidol groups, but not in the placebo group. No robust between-group differences in brain activity in the left inferior frontal gyrus or the bilateral ventral striatum were found. Overall, we found no robust evidence for an effect of either aripiprazole or haloperidol on motivationally mediated behavior. An interesting pattern of correlations possibly related to pharmacologically induced alterations in the dopamine system was observed, although findings remain inconclusive and must be replicated in larger samples.