Abstract
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.
Highlights
A change in our understanding of drug addiction as a brain disorder was influenced by the notion that drug addiction was not a deficit of character, but rather the result of aberrant brain function caused by excessive drug use[1]
Task performance In keeping with the monetary incentive delay (MID)-task design to minimize behavioral differences, we did not find a main effect of familial risk or stimulants on performance measures (Table 1)
Risk associated with stimulant drug use encompasses both pre-existing factors related to the initiation of stimulant use and the effects of regular stimulant use
Summary
A change in our understanding of drug addiction as a brain disorder was influenced by the notion that drug addiction was not a deficit of character, but rather the result of aberrant brain function caused by excessive drug use[1]. Dysregulation of the mesolimbic dopamine reward system has been associated with both acute and chronic use of stimulant drugs[4,5], leading to changes in how drug users perceive and process reward. These changes hypothetically facilitate the development and maintenance of addiction[6,7]. The notion that drug use is the sole cause of aberrant reward processing in addicted individuals is disputable.
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