Scott J Moeller1, Anna Zilverstand2, Anna B Konova3, Prantik Kundu4, Muhammad A Parvaz2, Rebecca Preston-Campbell5, Keren Bachi2, Nelly Alia-Klein2, Rita Z Goldstein2. 1. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Psychiatry, Stony Brook University School of Medicine, Stony Brook, New York. Electronic address: scott.moeller@stonybrookmedicine.edu. 2. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York. 3. Center for Neural Science, New York University, New York, New York. 4. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, New York. 5. Battelle Public Health Research & Translational Science, St. Louis, Missouri.
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.
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.
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