- BACKGROUND: Substance dependence is associated with impaired decision-making and altered fronto-striatal-limbic activity. Both greater and lesser brain activity have been reported in drug users compared to controls during decision-making. Inconsistent results might be explained by group differences in the temporal profile of the functional magnetic resonance imaging (fMRI) response. While most previous studies model a canonical hemodynamic response, a finite impulse response (FIR) model measures fMRI signal at discrete time points without assuming a temporal profile. We compared brain activity during decision-making and feedback in substance users and controls using two models: a canonical hemodynamic response function (HRF) and a FIR model. METHODS: 37 substance-dependent individuals (SDI) and 43 controls performed event-related decision-making during fMRI scanning. Brain activity was compared across group using canonical HRF and FIR models. RESULTS: Compared to controls, SDI were impaired at decision-making. The canonical HRF model showed that SDI had significantly greater fronto-striatal-limbic activity during decisions and less activity during feedback than controls. The FIR model confirmed greater activity in SDI during decisions. However, lower activity in SDI during feedback corresponded to a lower post-stimulus undershoot of the hemodynamic response. CONCLUSIONS: Greater activity in fronto-striatal-limbic pathways in SDI compared to controls is consistent with prior work, further supporting the hypothesis that abnormalities in these circuits underlie impaired decision-making. We demonstrate for the first time using FIR analysis that lower activity during feedback may simply reflect the tail end of the hemodynamic response to decision, the post-stimulus undershoot, rather than an actual difference in feedback response.