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Self-regulation of the Dopaminergic Reward Circuit in Cocaine Users with Mental Imagery and Neurofeedback

By Matthias Kirschner, Ronald Sladky, Amelie Haugg, Philipp Stäempfli, Elisabeth Jehli, Martina Hodel, Etna Engeli, Sarah Höesli, Markus R. Baumgartner, James Sulzer, Quentin J. M. Huys, Erich Seifritz, Boris B. Quednow, Frank Scharnowski, Marcus Herdener

Posted 14 May 2018
bioRxiv DOI: 10.1101/321166 (published DOI: 10.1016/j.ebiom.2018.10.052)

Background: Enhanced drug-related reward sensitivity accompanied by impaired sensitivity to non-drug related rewards in the mesolimbic dopamine system are thought to underlie the broad motivational deficits and dysfunctional decision-making frequently observed in cocaine use disorder (CUD). Effective approaches to modify this imbalance and reinstate non-drug reward responsiveness are urgently needed. Here we examine whether cocaine users (CU) can use mental imagery of non-drug rewards to self-regulate the ventral tegmental area and substantia nigra (VTA/SN). We expected that compulsive and obsessive thoughts about cocaine consumption would hamper the ability to self-regulate the VTA/SN. Finally, we tested if self-regulation of the VTA/SN can be improved with real-time fMRI (rtfMRI) neurofeedback (NFB). Methods: Twenty-two CU and 28 healthy controls (HC) were asked to voluntarily up-regulate VTA/SN activity with rewarding non-drug imagery alone, or combined with rtfMRI NFB of VTA/SN activity. Obsessive-compulsive drug use was measured with the Obsessive Compulsive Cocaine Use Scale (OCCUS). Results: CU were able to induce activity in the dopaminergic midbrain and other reward regions with reward imagery. The ability to self-regulate the VTA/SN was reduced in those with more severe obsessive-compulsive drug use. NFB enhanced the effect of non-drug imagery. Conclusion: CU can voluntary activate their reward system through non-drug related imagery and improve this ability with rtfMRI NFB. Combining reward imagery and rtFMRI NFB has great potential for modifying the maladapted reward sensitivity and reinstating non-drug reward responsiveness. This motivates further work to examine the therapeutic potential of cognitive neurostimulation in CUD.

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