Neural Correlates of Drug-Biased Choice in Currently Using and Abstinent Individuals With Cocaine Use Disorder

Abstract

Background: The choice for drugs over alternative reinforcers is a translational hallmark feature of drug addiction. The neural basis of such drug-biased choice is not well understood, particularly in individuals with protracted drug abstinence who cannot ethically participate in studies that offer drug-using opportunities.

Methods: We developed a functional magnetic resonance imaging drug-choice task to examine the choice for viewing drug-related images, rather than for actually consuming a drug. Actively using (n = 18) and abstaining (n = 19) individuals with a history of cocaine use disorder (CUD: dependence or abuse) and matched healthy control subjects (n = 26) participated.

Results: Individuals with CUD, especially those actively using cocaine outside the laboratory, made more choices than control subjects to view images depicting cocaine (especially when directly compared against images depicting an alternative appetitive reinforcer [food]). Functional magnetic resonance imaging data revealed that in individuals with CUD, the act of making drug-related choices engaged brain regions implicated in choice difficulty or ambivalence (i.e., dorsal anterior cingulate cortex, which was higher in all individuals with CUD than control subjects). Drug-related choices in CUD also engaged brain regions implicated in reward (e.g., midbrain/ventral tegmental area, which was most activated in active users, although this region was not hypothesized a priori).

Conclusions: These results help clarify the neural mechanisms underlying drug-biased choice in human addiction, which, beyond mechanisms involved in value assignment or reward, may critically involve mechanisms that contribute to resolving difficult decisions. Future studies are needed to validate these behavioral and neural abnormalities as markers of drug seeking and relapse in treatment contexts.

Keywords: Abstinence; Choice behavior; Decision making; Drug addiction; Value; fMRI.

Conflict of interest statement

Disclosure/Conflict of Interest

The authors report no biomedical financial interests or potential conflicts of interest.

Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Task schematic and individual data on cocaine versus food choices. (A) On each trial, participants viewed an image belonging to one of three global categories: food, threat, or cocaine (food and cocaine are depicted here) and made a choice (with strength of preference associated with that choice: Strong No, No, Yes, Strong Yes, coded 1–4) about whether they prefer to view the current image over a neutral image (wicker basket). Participants chose while only viewing the food, cocaine, or threat image – that is, the basket did not appear on the screen in each trial; a constant neutral stimulus could have artificially inflated the appeal of the alternative image, where the resulting behavior may not have provided an accurate depiction of an individual’s absolute preference.

Figure 2

Behavioral data. (A–B) Trial-by-trial analyses, spotlighting the hypothesized interaction between Image and Diagnosis, and the interaction between Image and baseline craving (‘Crave’), respectively (see Table 2 for complete information). (A) Individuals with active cocaine use disorder (CUD) had greater choice preference than the other groups specifically for cocaine images. The y-axis has values 1 (Strong No), 2 (No), 3, (Yes), and 4 (Strong Yes). The dashed line in (A) reflects decision indifference between the respective picture category and the neutral wicker basket, with values above signifying preference for the trial image and values below signifying preference for the neutral reference image. (B) Across all CUD, craving was more positively associated with choice preference during cocaine trials than during other trials. (C) Subject-level data, showing that across the entire task individuals with active CUD had greater (less negative) choice preference ratings for cocaine relative to food, and thus appeared to have the greatest ambivalence about their cocaine-related choices (with corroborating evidence when examining cocaine>food choice certainty scores; see Supplement). Asterisks mark significant group differences at p<0.05.

Figure 3

Whole-brain group differences during cocaine relative to food (cocaine>food) decisions. Individuals with cocaine use disorder (CUD) displayed higher cocaine>food activation than controls in the (A) dorsal anterior cingulate cortex (dACC) extending to the (B) supplementary motor area (SMA). Individuals with active CUD, relative to abstinent CUD and controls, displayed greater cocaine>food activation in the (C) midbrain/ventral tegmental area. In the same model, across all participants, (D) greater cocaine>food activation in the orbitofrontal cortex (OFC) negatively correlated with behavioral cocaine>food choice preference. For display purposes, activations are thresholded at 2.75 ≤ T ≤ 4.5.

Figure 4

Trial-by-trial parametric modulation by choice preference (linear ordering of preferences). There was a negative trial-by-trial correlation with choice preference across all task conditions in the (A) midcingulate and (B) temporal cortex, effects that did not differ by group but rather emerged in all participants. For display purposes, activations are thresholded at 2.75 ≤ T ≤ 4.5.