Effects of familial risk and stimulant drug use on the anticipation of monetary reward: an fMRI study

The association between stimulant drug use and aberrant reward processing is well-documented in the literature, but the nature of these abnormalities remains elusive. The present study aims to disentangle the separate and interacting effects of stimulant drug use and pre-existing familial risk on abnormal reward processing associated with stimulant drug addiction. We used the Monetary Incentive Delay task, a well-validated measure of reward processing, during fMRI scanning in four distinct groups: individuals with familial risk who were either stimulant drug-dependent (N = 41) or had never used stimulant drugs (N = 46); and individuals without familial risk who were either using stimulant drugs (N = 25) or not (N = 48). We first examined task-related whole-brain activation followed by a psychophysiological interaction analysis to further explore brain functional connectivity. For analyses, we used a univariate model with two fixed factors (familial risk and stimulant drug use). Our results showed increased task-related activation in the putamen and motor cortex of stimulant-using participants. We also found altered task-related functional connectivity between the putamen and frontal regions in participants with a familial risk (irrespective of whether they were using stimulant drugs or not). Additionally, we identified an interaction between stimulant drug use and familial risk in task-related functional connectivity between the putamen and motor-related cortical regions in potentially at-risk individuals. Our findings suggest that abnormal task-related activation in motor brain systems is associated with regular stimulant drug use, whereas abnormal task-related functional connectivity in frontostriatal brain systems, in individuals with familial risk, may indicate pre-existing neural vulnerability for developing addiction.