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

Featured Paper of the Month – July 2020.

Developing brain-based biomarkers to assess drug dependence, including nicotine dependence, are essential to assess and improve the current, marginally effective, treatments. In humans, using brain-based resting state functional connectivity, we have previously identified a circuit between the dorsal anterior cingulate cortex(ACC) and the striatum whose connectivity decreased with increasing nicotine dependence severity. This circuit was unaffected by acute nicotine administration, suggesting a trait marker of nicotine addiction. However, whether this trait circuit dysregulation is predispositional or resultant from nicotine dependence remained unclear. Using a rat model of nicotine dependence in combination with longitudinal fMRI measurements, we recapitulated this ACC-striatum relationship in the rodent and determined that this circuit-dependence relationship was moderated by predispositional insular-frontal cortical functional connectivity. These data suggest that across species, the relationship between ACC-striatal functional connectivity and nicotine dependence severity is biased by baseline, pre-nicotine exposure individual differences in insular-based striatal-frontal circuits. Thus, pre-drug administration insular-ACC (regional components of the Salience Network, SN) functional circuits within a rodent homologue of the human SN, first observed cross-sectionally in humans and recapitulated herein, may drive nicotine-induced changes in ACC-striatal connectivity and its relationship with nicotine dependence severity.

Graphical Abstract
Figure 1

Publication Information

Keeley, Robin J; Hsu, Li-Ming; Brynildsen, Julia K; Lu, Hanbing; Yang, Yihong; Stein, Elliot A

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

In: Neuropsychopharmacology, vol. 45, no. 6, pp. 1042–1049, 2020, ISBN: 1740-634X.

Links

@article{Keeley:2020zj,
title = {Intrinsic differences in insular circuits moderate the negative association between nicotine dependence and cingulate-striatal connectivity strength},
author = {Robin J Keeley and Li-Ming Hsu and Julia K Brynildsen and Hanbing Lu and Yihong Yang and Elliot A Stein},
url = {https://pubmed.ncbi.nlm.nih.gov/32053829/},
doi = {10.1038/s41386-020-0635-x},
isbn = {1740-634X},
year = {2020},
date = {2020-01-01},
journal = {Neuropsychopharmacology},
volume = {45},
number = {6},
pages = {1042--1049},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

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  • https://pubmed.ncbi.nlm.nih.gov/32053829/
  • doi:10.1038/s41386-020-0635-x

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