Neural mechanisms of risky decision-making and reward response in adolescent onset cannabis use disorder

Abstract

Background: Neural mechanisms of decision-making and reward response in adolescent cannabis use disorder (CUD) are underexplored.

Methods: Three groups of male adolescents were studied: CUD in full remission (n=15); controls with psychopathology without substance use disorder history (n=23); and healthy controls (n=18). We investigated neural processing of decision-making and reward under conditions of varying risk and uncertainty with the Decision-Reward Uncertainty Task while participants were scanned using functional magnetic resonance imaging.

Results: Abstinent adolescents with CUD compared to controls with psychopathology showed hyperactivation in one cluster that spanned left superior parietal lobule/left lateral occipital cortex/precuneus while making risky decisions that involved uncertainty, and hypoactivation in left orbitofrontal cortex to rewarded outcomes compared to no-reward after making risky decisions. Post hoc region of interest analyses revealed that both control groups significantly differed from the CUD group (but not from each other) during both the decision-making and reward outcome phase of the Decision-Reward Uncertainty Task. In the CUD group, orbitofrontal activations to reward significantly and negatively correlated with total number of individual drug classes the CUD patients experimented with prior to treatment. CUD duration significantly and negatively correlated with orbitofrontal activations to no-reward.

Conclusions: The adolescent CUD group demonstrated distinctly different activation patterns during risky decision-making and reward processing (after risky decision-making) compared to both the controls with psychopathology and healthy control groups. These findings suggest that neural differences in risky decision-making and reward processes are present in adolescent addiction, persist after remission from first CUD treatment, and may contribute to vulnerability for adolescent addiction.

Keywords: Adolescence; Behavioral risk; Cannabis use disorder; Decision-making; Orbitofrontal cortex; Reward response.

Figure 1

Geometric shape cues, button press response(s), and probabilities of reward for each risk condition for the Decision-Reward Uncertainty Task. No risk cues (left button press on right hand for a star, or right button press on right hand for a square) signaled that the known behavioral response would be rewarded with 100% certainty. Reward risk cues (right button press for a trapezoid, or left button press for a circle) signaled that the known behavioral response would be rewarded with 50% probability. However, the behavioral risk cue (a triangle) signaled that the behavioral response was unknown; either one of the two possible responses (right or left button press) would guarantee a reward, while the other would not. Every trial began with the decision-making phase (in blue), where the cue was presented for 250 milliseconds, followed by a fixed 3 second delay that accompanied a fixation cross. Then participants were prompted with a question mark (“?”) for 1 second in which to make a button press to execute their decision. This was followed by a 1–7 second jittered delay, where the fixation cross was presented. Then the trial outcome phase (in red) was presented for 1 second. The stimuli were either behavioral risk or reward risk, rewarded: “$$”; no risk rewarded: “$”; or no reward for behavioral, reward, or no risk trials, “X” when an incorrect button was pressed. The outcome of each trial was determined by both a correct right or left button response and a probabilistically determined reward. An updated tally of cumulative earnings was displayed in the lower portion of the screen. Finally, the fixation cross was presented again during a 2–8 second jittered inter-trial interval and another decision-making phase began. Participants completed 150 trials on average, split evenly among six 6-minute runs. Optimal performance could yield up to an additional $15 (e.g., $0.15 per correct response for one dollar sign; $0.30 for two dollar signs) in addition to study compensation. Analyses modeled activation during the decision phase and outcome phase separately.

Figure 2. The Decision-Making Phase

2A) The whole-brain voxelwise analyses contrasting the activation between risky decisions involving uncertainty (the behavioral risk versus the reward risk and no risk condition) revealed greater activations in the cluster involving regions of the left superior parietal lobule, left lateral occipital cortex, and left and right precuneus in the CUD group compared with the controls with psychopathology. Figure-2B. Superior parietal lobule (SPL) mean percent BOLD signal change (and standard error bars) to behavioral risk > baseline (i.e., the jittered fixation between trials) in the three groups. Region of interest analyses demonstrated that the CUD group significantly differed from controls with psychopathology and healthy controls (F_1,56=8.70, p=.0005); post-hoc analyses showed CUD behavioral risk activation (purple column) was higher compared to controls with psychopathology (light blue column) and healthy controls (green column). Post-hoc pairwise comparisons were made with LS Means Differences Tukey’s HSD, *p<.05.

Figure 3

Figure-3A. The Reward Outcome Phase Whole-brain analysis of behavioral and reward risk rewarded > behavioral and reward risk no-reward. Decreased left OFC activations were seen in the CUD group compared to controls with psychopathology. Figure-3B. Region of interest measures showing mean left OFC percent signal change (and standard error bars) to reward minus no-reward after making a risky decision in the three groups. OFC activation was lower in the CUD group (purple column) compared to controls with psychopathology and healthy controls (F_2,53=4.8, p<.01); post-hoc analyses showed that CUD activations (purple column) were lower compared to controls with psychopathology (light blue column) and healthy controls (green column). Post-hoc pairwise comparisons were made with LS Means Differences Tukey’s HSD, *p<.05.

Figure 4

Figures-4A & 4B The total number of individual drug classes experimented with prior to CUD treatment was associated with lower left OFC BOLD response to reward (r_s=−.60, p<.02) and reward minus no-reward (r_s =−.63, p=.01).

Figure 5

Figure-5A. Mean percent signal change and standard error bars to behavioral and reward risk trials rewarded (reward) and behavioral and reward risk trials not rewarded (no-reward) shown for each group. Percent signal change was extracted from the left OFC cluster found in the whole-brain analysis to illustrate left OFC response of each of the groups to reward and no-reward. The left OFC showed a significant interaction between both control groups and condition (reward versus no-reward) (F_2,53 =4.8, p=0.01). Figure-5B. CUD duration significantly and negatively correlated with left OFC response to no-reward covarying for the participant’s current age (Partial correlation= −0.7620, p<.009). This suggests that the longer participants had a CUD diagnosis, the more the CUD participant’s response to no-reward appeared similar to both control groups.