A behavioural and neurobiological assessment of effort-based decision-making in cannabis use disorder: An...

Low motivation for noncannabis rewards is a common clinical feature of cannabis use disorder (CUD), yet its underlying neurobiological mechanisms remain largely unknown. This study applied a sequential effort-based decision-making task during functional magnetic resonance imaging to quantify motivation and test for potential neurofunctional differences during prospective effort/reward encoding (Cue1), integration of effort and reward cues (Cue2), and choice behaviour in individuals with CUD (n = 21) and healthy controls (HCs) (n = 20). Behavioural in-scanner results demonstrated that participants in both groups made significantly fewer high-effort choices as effort levels increased on the task, yet they selected significantly more high-reward choices as reward magnitude increased. At the neural level, the CUD group showed decreased ventromedial prefrontal cortex activity, as well as reduced activity in the culmen, posterior cingulate, and superior temporal gyrus during the encoding of prospective effort and reward cues (Cue1) respectively, compared with controls. Conversely, the CUD group showed increased parietal lobule, superior temporal gyrus, fusiform gyrus, middle occipital gyrus, cingulate gyrus, and claustrum activity during the integration phase of the task (Cue2) relative to controls. Exploratory correlations revealed that bilateral ventral striatum activity during prospective effort cues was associated with the proportion of accepted high-effort and high-reward trials, predominantly driven by the CUD group. Altogether, these findings indicate fronto-striatal but also posterior cortical processing alterations during prospective signaling and during effort-reward information integration. By temporally disconnecting effort expenditure from reward magnitude, the current findings shed light on how these constructs independently and simultaneously influence dysregulated effortful goal-directed choice behaviour in CUD.