Drug addiction is characterized by a transition from volitional drug use to drug use that is increasingly habitual and compulsive. Thus, behavior among addicted individuals, including drug-seeking behavior, may be partly controlled by motivational processes that occur below conscious awareness. A recent review indeed suggested that such impaired insight may be a hallmark of drug addiction. Using functional magnetic resonance imaging (fMRI), the current proposal seeks to inspect the neural correlates of this putative insight deficit. Specifically, this proposal will explore functioning of the anterior insula (AI) and anterior cingulate cortex (ACC), both posited to play key roles in insight and self-awareness, in cocaine addiction. To accomplish this aim, an event- related fMRI color word Stroop task, a classical neuropsychological conflict task, will be employed, which will be modified for the purposes of this proposal to test for insight into task-related errors. This modified fMRI Stroop task will be performed by three study groups: actively using cocaine addicted individuals (CUD+), treatment- seeking cocaine addicted individuals (CUD-), and healthy control subjects (HC). This fMRI insight-into-errors data will then be used to predict subsequent cocaine-related choice behavior. This latter study component will be accomplished through the use of the Preference for Image Viewing, Probabilistic (PIV-P) task, which examines choice for cocaine-related pictures compared with choice for other pleasant, unpleasant, or neutrally valenced pictures. This design will allow for testing of whether impaired insight and its neural underpinnings predict drug- seeking behavior. In addition, the CUD- individuals, who will be recruited from local treatment facilities, will complete this same PIV-P task bi-monthly during treatment-as-usual at these same facilities. This prospective design will allow for testing of the validity of 'incubated craving'(an escalating propensity for relapse during abstinence) in human addicted individuals as they progress through treatment (seven follow-up assessments are planned), and to further establish whether the fMRI insight data predict its time course. If successful, results of this proposal may help change the prevalent perception of drug addicted individuals as displaying treatment- resistant and oppositional """"""""denial."""""""" Instead, these results may identify drug addicted individuals as struggling with a neurally-based, and possibly treatment-amenable, insight deficit.

Public Health Relevance

Only 4.5% of the 21.1 million persons classified in 2006 as needing substance use treatment actually perceived a need for therapy, according to the latest report from the US Department of Health and Human Services. If successful, this study will have uncovered a previously unexplored impediment to treatment in addicted individuals. Longitudinal studies can then be used to predict longer-term treatment outcome (e.g., sustained abstinence after several years) among addicted individuals with compromised insight, perhaps ultimately culminating in the implementation of interventions to improve insight and thus improve treatment outcomes.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DA030017-02
Application #
8099693
Study Section
Special Emphasis Panel (ZRG1-F02A-J (20))
Program Officer
Bjork, James M
Project Start
2010-06-21
Project End
2013-06-20
Budget Start
2011-06-21
Budget End
2012-06-20
Support Year
2
Fiscal Year
2011
Total Cost
$52,221
Indirect Cost
Name
Brookhaven National Laboratory
Department
Type
DUNS #
027579460
City
Upton
State
NY
Country
United States
Zip Code
11973
Moeller, Scott J; Konova, Anna B; Tomasi, Dardo et al. (2016) Abnormal response to methylphenidate across multiple fMRI procedures in cocaine use disorder: feasibility study. Psychopharmacology (Berl) 233:2559-69
Konova, Anna B; Moeller, Scott J; Parvaz, Muhammad A et al. (2016) Converging effects of cocaine addiction and sex on neural responses to monetary rewards. Psychiatry Res 248:110-8
Parvaz, Muhammad A; Moeller, Scott J; Goldstein, Rita Z et al. (2015) Electrocortical evidence of increased post-reappraisal neural reactivity and its link to depressive symptoms. Soc Cogn Affect Neurosci 10:78-84
Moeller, Scott J; Konova, Anna B; Goldstein, Rita Z (2015) Multiple ambiguities in the measurement of drug craving. Addiction 110:205-6
Konova, Anna B; Moeller, Scott J; Tomasi, Dardo et al. (2015) Effects of chronic and acute stimulants on brain functional connectivity hubs. Brain Res 1628:147-56
Moeller, Scott J; Beebe-Wang, Nicasia; Schneider, Kristin E et al. (2015) Effects of an opioid (proenkephalin) polymorphism on neural response to errors in health and cocaine use disorder. Behav Brain Res 293:18-26
Moeller, Scott J; Honorio, Jean; Tomasi, Dardo et al. (2014) Methylphenidate enhances executive function and optimizes prefrontal function in both health and cocaine addiction. Cereb Cortex 24:643-53
Moeller, Scott J; Parvaz, Muhammad A; Shumay, Elena et al. (2014) Monoamine polygenic liability in health and cocaine dependence: imaging genetics study of aversive processing and associations with depression symptomatology. Drug Alcohol Depend 140:17-24
Moeller, Scott J; Froböse, Monja I; Konova, Anna B et al. (2014) Common and distinct neural correlates of inhibitory dysregulation: stroop fMRI study of cocaine addiction and intermittent explosive disorder. J Psychiatr Res 58:55-62
Moeller, Scott J; Konova, Anna B; Parvaz, Muhammad A et al. (2014) Functional, structural, and emotional correlates of impaired insight in cocaine addiction. JAMA Psychiatry 71:61-70

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