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bioRxiv · 10.1101/771915

Habenular and striatal activity during performance feedback are differentially linked with state-like and trait-like aspects of tobacco use disorder

Flannery, J. S.·Riedel, M. C.·Poudel, R.·Laird, A. R.·Ross, T. J.·Salmeron, B. J.·Stein, E. A.·Sutherland, M. T.
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Abstract

Although tobacco use disorder is linked with functional alterations in the striatum, anterior cingulate cortex (ACC), and insula, preclinical evidence also implicates the habenula as a contributor to negative reinforcement mechanisms maintaining nicotine use. The habenula is a small and understudied epithalamic nucleus involved in reward and aversive processing that is hypothesized to be hyperactive during nicotine withdrawal thereby contributing to anhedonia. In a pharmacologic fMRI study involving administration of nicotine and varenicline, two relatively efficacious cessation aids, we utilized a positive and negative performance feedback task previously shown to differentially activate the striatum and habenula. By administering these nicotinic drugs (vs. placebos) to both overnight abstinent smokers (n=24) and nonsmokers (n=20), we delineated feedback-related functional alterations both as a function of a chronic smoking history (trait: smokers vs. nonsmokers) and as a function of drug administration (state: nicotine, varenicline). We observed that smokers showed less ventral striatal responsivity to positive feedback, an alteration not mitigated by drug administration, but rather correlated with higher trait-level addiction severity among smokers and elevated self-reported negative affect across all participants. Conversely, nicotine administration reduced habenula activity following both positive and negative feedback among abstinent smokers, but not nonsmokers; greater habenula activity correlated with elevated abstinence-induced, state-level tobacco craving among smokers and elevated social anhedonia across all participants. These outcomes highlight a dissociation between neurobiological processes linked with the trait of dependence severity and with the state of acute nicotine withdrawal. Interventions simultaneously targeting both aspects may improve currently poor cessation outcomes.\n\nOne-sentence teaserIn a pharmacological fMRI study, e dissociate brain alterations in the habenula linked with nicotine withdrawal and striatal alterations linked with addiction.

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Flannery, J. S., Riedel, M. C., Poudel, R., Laird, A. R., Ross, T. J., Salmeron, B. J., Stein, E. A., Sutherland, M. T.. 2019-09-18. Habenular and striatal activity during performance feedback are differentially linked with state-like and trait-like aspects of tobacco use disorder. https://doi.org/10.1101/771915

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