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Neuropsychopharmacology. 2020 Feb 13. doi: 10.1038/s41386-020-0635-x. [Epub ahead of print]

Intrinsic differences in insular circuits moderate the negative association between nicotine dependence and cingulate-striatal connectivity strength.

Author information

1
Neuroimaging Research Branch, National Institute on Drug Abuse, Intramural Research Program, 251 Bayview Blvd, Baltimore, MD, 21224, USA.
2
Department of Radiology and BRIC, University of North Carolina at Chapel Hill, 130 Mason Farm Rd, Chapel Hill, NC, 27599, USA.
3
Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA, 19104, USA.
4
Neuroimaging Research Branch, National Institute on Drug Abuse, Intramural Research Program, 251 Bayview Blvd, Baltimore, MD, 21224, USA. estein@nih.gov.

Abstract

The development of brain-based biomarkers to assess nicotine dependence severity and treatment efficacy are essential to improve the current marginally effective treatment outcomes. Cross-sectional resting state functional connectivity (rsFC) studies in humans identified a circuit between the dorsal anterior cingulate cortex and the ventral striatum that negatively correlated with increased nicotine dependence severity but was unaffected by acute nicotine administration, suggesting a trait marker of addiction. However, whether this trait circuit dysregulation is predispositional to or resultant from nicotine dependence is unclear. Using a rat model of nicotine dependence with longitudinal fMRI measurements, we assessed the relationship between ACC-striatal rsFC and nicotine dependence severity. Data-driven modularity-based parcellation of the rat medial prefrontal cortex (mPFC) combined with seed-based connectivity analysis with the striatum recapitulated the cingulate-striatum relationship observed in humans. Furthermore, the relationship between cingulate-striatal brain circuits and nicotine dependence severity as indexed by the intensity of precipitated withdrawal, was fully statistically moderated by a predispositional insular-frontal cortical functional circuit. These data suggest that the identified trans-species ACC-striatal circuit relationship with nicotine dependence severity is dysregulated following chronic nicotine administration-induced dependence and may be biased by individual differences in predispositional insula-based striatal-frontal circuits, highlighting the circuit's potential as a biomarker of dependence severity.

PMID:
32053829
DOI:
10.1038/s41386-020-0635-x

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