Increased ventral striatal BOLD activity during non-drug reward anticipation in cannabis users

Abstract

Despite an increased understanding of the pharmacology and long-term cognitive effects of cannabis in humans, there has been no research to date examining its chronic effects upon reward processing in the brain. Motivational theories regarding long-term drug use posit contrasting predictions with respect to how drug users are likely to process non-drug incentives. The reward deficiency syndrome (RDS) of addiction posits that there are deficits in dopamine (DA) motivational circuitry for non-drug rewards, such that only drugs of abuse are capable of normalizing DA in the ventral striatum (VS). Alternatively, the opponent process theory (OPT) holds that in individuals prone to drug use, there exists some form of mesolimbic hyperactivity, in which there is a bias towards reward-centred behaviour concomitant with impulsivity. The current study examined BOLD responses during reward and loss anticipation and their outcome deliveries in 14 chronic cannabis users and 14 drug-naive controls during a monetary incentive delay (MID) task. Despite no significant behavioural differences between the two groups, cannabis users had significantly more right VS BOLD activity during reward anticipation. Correlation analyses demonstrated that this right VS BOLD response was significantly correlated with life-time use and reported life-time cannabis joints consumed. No correlations between cannabis abstinence and BOLD responses were observed. We also observed a number of group differences following outcome deliveries, most notably hypoactivity in the left insula cortex in response to loss and loss avoidance outcome notifications in the cannabis group. These results may suggest hypersensitivity during instrumental response anticipation for non-drug rewards and a hyposensitivity to loss outcomes in chronic cannabis users; the implications of which are discussed with respect to the potentially sensitizing effects of cannabis for other rewards.

Figure 1

Monetary Incentive Delay (MID) task structure. Participants were cued (2–8 sec) regarding a potential financial “win”, “loss” or “no-outcome” using one of three coloured squares. Participants were then required to respond to a target stimulus following cue presentation. The target stimulus was presented for 400ms, during which participants were required to respond, as quickly as possible, with a button press on a hand-held key pad. Following this, participants received feedback regarding their response (1500ms), before the presentation of an end fixation period (2–8 sec), during which they saw a centrally located crosshair.

Figure 2

a) Mean percentage accuracy (*p<0.05 “loss” versus “no-outcome”, **p<0.01 “win” versus “no-outcome”) and b) mean reaction time (milliseconds) (**p<0.01 “win” versus “no-outcome”) in the controls and cannabis users on the MID task (means and standard errors). Data were analyzed using two (group) x three (cue) univariate analyses

Figure 3

Activation t-test maps (combined) for the cannabis and control groups (p≥0.005) showing coronal sections during “win” cue anticipation across the whole brain.

Figure 4

a) Mean brain activity in the right VS (x = 20, y = 8, z = −4), b) graph showing cannabis and control groups significantly differed in right VS BOLD activity during “win” cue periods (*p<0.05 Independent t-tests) and c) correlation between right VS BOLD activity during the “win” cue period and the number of reported lifetime cannabis joints smoked (r=.6, p<0.05).

Figure 5

Post hoc analysis showing a) Mean brain activity in the right ventral putamen (x= 22, y =3, z= −5), b) graph showing cannabis users had a greater BOLD response to “loss” and “win” cues compared with “no-outcome” cues (^*p<0.05 Paired t-tests) in the right ventral putamen, c) graph showing cannabis users had a greater BOLD response in the right putamen (x= 19, y =10, z= −1) compared to controls during “win” cue presentation (*p<0.05 Independent t-tests) and d) correlation between right putamen BOLD activity during the “win” cue period and the number of reported life-time cannabis joints smoked (r=.7, p<0.01).

Figure 6

a) Mean brain activity in the right declive of vermis (x = 1, y = −77, z = −19), b) graph showing cannabis and control groups significantly differed in right declive of vermis BOLD activity during “loss” and “win” cue presentation (*p<0.05 Independent t-tests) and c) correlation between right declive of vermis BOLD activity during the “win” cue period and the number of reported life-time cannabis joints smoked (r=.7, p<0.01).