Investigating Neural Processing of Risk and Reward in Stimulant Users using Structural and Functional Magnetic Resonance Imaging

Abstract

Despite the negative consequences, stimulant users often struggle to quit, which has been attributed to altered risk-taking and/or impulsivity. While the growing evidence suggests structural and functional alterations in stimulant users (e.g., cortical deficits and striatal hypersensitivity), the precise neurobehavioural mechanisms underlying risk and impulsivity are poorly understood. To complicate matters, polydrug use is highly prevalent, making it difficult to distinguish neuroadaptations attributed to a particular stimulant alone. In this thesis, we aimed to investigate neural processing of risk and reward in abstinent methamphetamine users (MAP) and current smokers (NIC). In Study I, grey matter (GM) volume was compared with control subjects using voxel-based morphometry, and effect of drug use parameters (e.g., years of use and cumulative amount) were also explored. In Study II, we used a modified version of the monetary incentive delay task (MIDT) in conjunction with functional MRI to compare neural activation between stimulant users and controls. While both MAP and NIC exhibited smaller volume in the anterior cingulate cortex (ACC) and enlarged striatal volume, relative to controls, a different neuroanatomical profile was observed in the prefrontal cortex (PFC), i.e., MAP exhibited GM deficits while NIC showed larger volume. Among MAP, a correlation with years of use was observed in the striatum (negative) and PFC (positive); no correlation was detected with smoking parameters in NIC. Furthermore, we observed distinct risk-related activation patterns between MAP and NIC, i.e., MAP exhibited attenuated PFC activation during risk processing, but increased activation in response to loss prospect; while NIC exhibited hyperactivation to risk in the amygdala, and attenuated activation to loss prospect in the ACC and insula. In addition, during reward prospect, MAP showed hyperactivation in the striatum, while NIC exhibited attenuated PFC activation, relative to controls. Consistent with previous literature, our preliminary findings support structural alterations in both MAP and NIC but implicate distinctive neurophysiological changes in MAP. Considered together with neurotoxicity findings in animal studies, these findings seem to support the notion that long-term methamphetamine abuse alters the brain. However, due to high smoking prevalence among MAP, the overlapping alterations may also be attributed to long-term smoking.