• Skip to primary navigation
  • Skip to main content
  • Skip to primary sidebar

NIDA IRP

National Institute on Drug Abuse - Intramural Research Program

  National Institute on Drug Abuse | NIH IRP | Treatment Info | Emergency Contacts
  • Home
  • News
    • Featured Paper of the Month
    • Reviews to Read
    • Hot off the Press
    • IRP News
    • Awards
    • Technology Development Initiative Paper of the Month
    • Seminar Series
    • Addiction Grand Rounds
  • About
    • About NIDA IRP
    • Contact Us
    • Directions and Map
    • Careers at NIDA IRP
    • Emergency Contacts
    • Employee Assistance Resources
  • Organization
    • Faculty
    • Office of the Scientific Director
    • Office of the Clinical Director
    • Office of Education and Career Development
    • Administrative Management Branch
    • Molecular Targets and Medications Discovery Branch
    • Cellular and Neurocomputational Systems Branch
    • Molecular Neuropsychiatry Research Branch
    • Neuroimaging Research Branch
    • Behavioral Neuroscience Research Branch
    • Integrative Neuroscience Research Branch
    • Translational Addiction Medicine Branch
    • Core Facilities
    • Community Outreach Group
  • Training Programs
    • Office of Education and Career Development
    • OECD Awards
    • Summer Internship Program
    • Postbaccalaureate Program
    • Graduate Partnership Program
    • Postdoctoral Program
    • NIDA Speakers Bureau
    • Clinical Electives Program
    • Clinical Mentoring Program
  • Study Volunteers

Intrinsic Insular-Frontal Networks Predict Future Nicotine Dependence Severity.

A portion of a figure from this studyFeatured Paper of the Month – October 2019.

Smoking remains a major public health burden, with approximately 20% of the world’s population engaging in regular smoking. Given the high relapse rate among smokers who enter treatments programs, early identification of vulnerable individuals, before the conversion from casual experimentation to regular smoking and addiction, is an important milestone to understand, prevent and potentially minimize nicotine dependence. Using a rodent model of nicotine dependence, we developed a quantitative predictor of subsequent nicotine dependence severity using graph theory-based analyses of fMRI BOLD resting state data collected at baseline, prior to any drug experience. Using an entirely data driven, hypothesis-free analytic strategy, we observed that connectivity between insular regions before drug exposure can predict dependence severity following subsequent nicotine exposure. This finding is in stark contrast to current biomarkers that have observed correlative relationships between brain connectivity and addiction-related behaviors observed after the onset and progression of a substance use disorder. The results of our preclinical model offer a novel finding of a predictive biomarker of addiction severity and provide a framework upon which intervention-based and mechanistic experiments can investigate the role of these brain modules in nicotine dependence, relapse and successful abstinence.

Publication Information

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

Intrinsic Insular-Frontal Networks Predict Future Nicotine Dependence Severity. Journal Article

In: J Neurosci, vol. 39, no. 25, pp. 5028–5037, 2019, ISSN: 1529-2401 (Electronic); 0270-6474 (Linking).

Abstract | Links

@article{Hsu:2019aa,
title = {Intrinsic Insular-Frontal Networks Predict Future Nicotine Dependence Severity.},
author = {Li-Ming Hsu and Robin J Keeley and Xia Liang and Julia K Brynildsen and Hanbing Lu and Yihong Yang and Elliot A Stein},
url = {https://www.ncbi.nlm.nih.gov/pubmed/30992371},
doi = {10.1523/JNEUROSCI.0140-19.2019},
issn = {1529-2401 (Electronic); 0270-6474 (Linking)},
year = {2019},
date = {2019-06-19},
journal = {J Neurosci},
volume = {39},
number = {25},
pages = {5028--5037},
address = {Neuroimaging Research Branch, National Institute on Drug Abuse, Intramural Research Program, Baltimore, Maryland 21224, and.},
abstract = {Although 60% of the US population have tried smoking cigarettes, only 16% smoke regularly. Identifying this susceptible subset of the population before the onset of nicotine dependence may encourage targeted early interventions to prevent regular smoking and/or minimize severity. While prospective neuroimaging in human populations can be challenging, preclinical neuroimaging models before chronic nicotine administration can help to develop translational biomarkers of disease risk. Chronic, intermittent nicotine (0, 1.2, or 4.8 mg/kg/d; N = 10-11/group) was administered to male Sprague Dawley rats for 14 d; dependence severity was quantified using precipitated withdrawal behaviors collected before, during, and following forced nicotine abstinence. Resting-state fMRI functional connectivity (FC) before drug administration was subjected to a graph theory analytical framework to form a predictive model of subsequent individual differences in nicotine dependence. Whole-brain modularity analysis identified five modules in the rat brain. A metric of intermodule connectivity, participation coefficient, of an identified insular-frontal cortical module predicted subsequent dependence severity, independent of nicotine dose. To better spatially isolate this effect, this module was subjected to a secondary exploratory modularity analysis, which segregated it into three submodules (frontal-motor, insular, and sensory). Higher FC among these three submodules and three of the five originally identified modules (striatal, frontal-executive, and sensory association) also predicted dependence severity. These data suggest that predispositional, intrinsic differences in circuit strength between insular-frontal-based brain networks before drug exposure may identify those at highest risk for the development of nicotine dependence.SIGNIFICANCE STATEMENT Developing biomarkers of individuals at high risk for addiction before the onset of this brain-based disease is essential for prevention, early intervention, and/or subsequent treatment decisions. Using a rodent model of nicotine dependence and a novel data-driven, network-based analysis of resting-state fMRI data collected before drug exposure, functional connections centered on an intrinsic insular-frontal module predicted the severity of nicotine dependence after drug exposure. The predictive capacity of baseline network measures was specific to inter-regional but not within-region connectivity. While insular and frontal regions have consistently been implicated in nicotine dependence, this is the first study to reveal that innate, individual differences in their circuit strength have the predictive capacity to identify those at greatest risk for and resilience to drug dependence.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

Close

Although 60% of the US population have tried smoking cigarettes, only 16% smoke regularly. Identifying this susceptible subset of the population before the onset of nicotine dependence may encourage targeted early interventions to prevent regular smoking and/or minimize severity. While prospective neuroimaging in human populations can be challenging, preclinical neuroimaging models before chronic nicotine administration can help to develop translational biomarkers of disease risk. Chronic, intermittent nicotine (0, 1.2, or 4.8 mg/kg/d; N = 10-11/group) was administered to male Sprague Dawley rats for 14 d; dependence severity was quantified using precipitated withdrawal behaviors collected before, during, and following forced nicotine abstinence. Resting-state fMRI functional connectivity (FC) before drug administration was subjected to a graph theory analytical framework to form a predictive model of subsequent individual differences in nicotine dependence. Whole-brain modularity analysis identified five modules in the rat brain. A metric of intermodule connectivity, participation coefficient, of an identified insular-frontal cortical module predicted subsequent dependence severity, independent of nicotine dose. To better spatially isolate this effect, this module was subjected to a secondary exploratory modularity analysis, which segregated it into three submodules (frontal-motor, insular, and sensory). Higher FC among these three submodules and three of the five originally identified modules (striatal, frontal-executive, and sensory association) also predicted dependence severity. These data suggest that predispositional, intrinsic differences in circuit strength between insular-frontal-based brain networks before drug exposure may identify those at highest risk for the development of nicotine dependence.SIGNIFICANCE STATEMENT Developing biomarkers of individuals at high risk for addiction before the onset of this brain-based disease is essential for prevention, early intervention, and/or subsequent treatment decisions. Using a rodent model of nicotine dependence and a novel data-driven, network-based analysis of resting-state fMRI data collected before drug exposure, functional connections centered on an intrinsic insular-frontal module predicted the severity of nicotine dependence after drug exposure. The predictive capacity of baseline network measures was specific to inter-regional but not within-region connectivity. While insular and frontal regions have consistently been implicated in nicotine dependence, this is the first study to reveal that innate, individual differences in their circuit strength have the predictive capacity to identify those at greatest risk for and resilience to drug dependence.

Close

  • https://www.ncbi.nlm.nih.gov/pubmed/30992371
  • doi:10.1523/JNEUROSCI.0140-19.2019

Close

Primary Sidebar

News

  • All News and Featured Publications
  • Featured Paper of the Month
  • Hot off the Press
  • Reviews to Read
  • IRP News
  • Awards
  • Technology Development Initiative Paper of the Month
  • Seminar Series
Home / News Main / Featured Paper of the Month / Intrinsic Insular-Frontal Networks Predict Future Nicotine Dependence Severity.
  • National Institute on Drug Abuse
  • NIH Intramural Research Program
  • National Institutes of Health
  • Health and Human Services
  • USA.GOV
  • Emergency Contacts
  • Employee Assistance
  • Treatment Information
  • Contact Us
  • Careers at NIDA IRP
  • Accessibility
  • Privacy
  • HHS Vulnerability Disclosure
  • Freedom of Information Act
  • Document Viewing Tools
  • Offsite Links
  • National Institute on Drug Abuse
  • NIH Intramural Research Program
  • National Institutes of Health
  • Health and Human Services
  • USA.GOV
  • Emergency Contacts
  • Employee Assistance
  • Treatment Information
  • Contact Us
  • Careers at NIDA IRP
  • Accessibility
  • Privacy
  • HHS Vulnerability Disclosure
  • Freedom of Information Act
  • Document Viewing Tools
  • Offsite Links

  • Home
  • News
    ▼
    • Featured Paper of the Month
    • Reviews to Read
    • Hot off the Press
    • IRP News
    • Awards
    • Technology Development Initiative Paper of the Month
    • Seminar Series
    • Addiction Grand Rounds
  • About
    ▼
    • About NIDA IRP
    • Contact Us
    • Directions and Map
    • Careers at NIDA IRP
    • Emergency Contacts
    • Employee Assistance Resources
  • Organization
    ▼
    • Faculty
    • Office of the Scientific Director
    • Office of the Clinical Director
    • Office of Education and Career Development
    • Administrative Management Branch
    • Molecular Targets and Medications Discovery Branch
    • Cellular and Neurocomputational Systems Branch
    • Molecular Neuropsychiatry Research Branch
    • Neuroimaging Research Branch
    • Behavioral Neuroscience Research Branch
    • Integrative Neuroscience Research Branch
    • Translational Addiction Medicine Branch
    • Core Facilities
    • Community Outreach Group
  • Training Programs
    ▼
    • Office of Education and Career Development
    • OECD Awards
    • Summer Internship Program
    • Postbaccalaureate Program
    • Graduate Partnership Program
    • Postdoctoral Program
    • NIDA Speakers Bureau
    • Clinical Electives Program
    • Clinical Mentoring Program
  • Study Volunteers