Recovery of reward function in problematic substance users using a combination of robotics, electrophysiology, and TMS

Abstract

Background: Theoretical and empirical work suggest that addictive drugs potentiate dopaminergic reinforcement learning signals and disrupt the reward function of its neural targets, including the anterior midcingulate cortex (aMCC) and the basal ganglia. Here, we aim to use prefrontal 10-Hz TMS to enhance aMCC reward activity and reward learning by the basal ganglia in problematic substance users.

Methods: 22 problematic substance users were randomized into an Active and SHAM (coil flipped) TMS group. We recorded the reward positivity-an electrophysiological signal believed to index sensitivity of the aMCC to rewards-while participants engaged in 4 blocks (100 trials per block) of a reward-based choice task. A robotic arm positioned a TMS coil over a prefrontal cortex target, and 50 pulses were delivered at 10-Hz before every 10 trials of blocks 2-4 (1500 pulses, 400 trials). Participants then completed a decision-making task that is diagnostic of striatal dopamine dysfunction.

Results: The present study revealed three main findings. First, both groups failed to elicit a reward positivity during the first two task blocks. Second, applying robot-assisted TMS enhanced the amplitude of the reward positivity in the Active group, but not the SHAM group, across the last two task blocks. Third, the Active group performed relatively better at reward-based learning than the SHAM group.

Conclusion: These results demonstrate that 10-Hz TMS is successful in modulating the reward function of the aMCC and basal ganglia in problematic substance users, which may have utility in the treatment of reward-related neural dysfunction commonly associated with substance use disorders.

Keywords: Anterior midcingulate cortex; Cognitive control; Decision-making; Reward positivity; Substance use disorder; TMS.

Fig. 1.

Experimental Protocol. (A) Ri-TMS system (B) Block sequence (C) Single trial sequence. (D) ERPs associated with Reward (blue), No-reward (red), and reward positivity (black line-difference wave). Reward positivity occurs over frontal-central areas of the scalp about 250 to 350 ms post-feedback. Negative is plotted up by convention. The representative dataset of heathy adults is from Baker et al., 2020a.

Fig. 2.

Substance preference. (A) SHAM (white bars) or Active (dashed bars) TMS group according to their scores on the Global Continuum of Substance Risk (GCR) scale (Left panel) of the ASSIST. Red line denotes cut-offs scores established in previous validation studies of the ASSIST for substance dependence (score > 39.5) (Newcombe et al., 2005). Right panel: Substance preferences for SHAM (white bars) and Active (dashed bars) TMS groups as measured by the Specific Substance Involvement Score of the ASSIST. Red line denotes the bottom end of SSI midrange scores (score = 4; 11 for alcohol) for any substance.

Fig. 3.

Reward Positivity results. ERPs elicited by reward feedback (blue), no-reward feedback (red) and difference wave (black-reward positivity) averaged across all blocks for the SHAM group (A) and Active TMS Group (B). For purpose of comparison, topoplots denote the amplitude of the reward positivity at 300 msec for the SHAM and Active group averaged across TMS blocks. (C) Reward positivity amplitude across blocks for the SHAM (solid line, triangle) and Active (dashed line, circle) TMS group. Red box denotes the TMS blocks. Significant effects are shown as follows: *p < .05, **p < .01, ***p < .005, (two-tailed). Error bars denote standard error. Data are associated with channel Cz and negative is plotted up by convention.

Fig. 4.

Behavior results. (A) Top Panels. Ex-Gaussian parameters (Mu [left], sigma [middle], and tau [right]) associated with post-Reward and post-NoReward RTs for the SHAM (solid line, triangle) and Active (dashed line, circle) group. (B) Percentage of win-stay (blue lines) and lose-shift (red-lines) choice behavior across blocks for SHAM and Active TMS groups. (C) Performance on the Probabilistic Selection Task (PST). Accuracy (left panel) and RT (Right panel) data in the Test Phase of the PST for the SHAM and Active TMS Groups, separately for the Approach and Avoidance conditions. (D) An exploratory correlation analysis between the reward positivity amplitude and approach accuracy revealed a marginal correlation at Block 4 (r = −0.389, p = .07, two-tailed), but not any other block, indicating that the larger the reward positivity at the end of the task, the more accurate participants were at learning from positive feedback. Error bars denote standard error.