Problems with impulsivity are shared across a wide spectrum of psychiatric disorders, including substance use, eating, gambling, bipolar, attention deficit, antisocial and borderline personality disorders, and may explain the common co-occurrence of these disorders and their high rates of relapse. However, the putative relationship between impulsivity and relapse has not been demonstrated. An emerging neuroimaging literature suggests that impulsivity may be a result of neural disruptions that persist with abstinence. In previous studies with abstinent cocaine-addicted subjects, we have used single photon emission computed tomography (SPECT) to identify specific disruptions in the regional cerebral blood flow (rCBF) of the orbitofrontal cortex and rostral anterior cingulate. These brain areas are key in the regulation of impulse control. We have also observed deficits in several neurocognitive and self-assessment measures of impulsivity, and have successfully determined neural activation (using functional magnetic resonance imaging, or fMRI) during two tasks of impulsivity. We now propose to concurrently assess the neurocognitive and neural disruptions associated with impulsiveness in cocaine-addicted subjects, and examine the relationship between these alterations and prospective relapse. Two- to four-week abstinent, treatment-seeking cocaine dependent subjects and healthy controls will be studied. Two ecologically relevant neurocognitive constructs of impulsivity - disinhibition and decision-making - will be assessed. fMRI will be used to assess neural activity during a disinhibition task of response inhibition (the ability to rapidly inhibit a pre-potent response) and a decision-making task of response reversal [the ability to reverse (or shift) cognitive and behavioral strategies to suppress a course of action that is no longer appropriate]. Subjects will also be assessed for resting rCBF abnormalities with SPECT. Standardized and experimental neurocognitive tests, as well as self-assessment measures, will be used to assess disinhibition and decision- making. The tendency to relapse impulsively will be measured by the Impulsive Relapse Questionnaire, a novel measure of relapse style. Cocaine-addicted subjects will subsequently be followed for up to six months following residential treatment and assessed for time to substance use relapse. We hypothesize that both quantitative measures of impulsivity and the neural deficits associated with disinhibition and decision-making will significantly correlate with each other and predict time to substance use relapse. These studies will significantly strengthen our understanding of the neurobiologic and neurocognitive mechanisms related to impulsivity and relapse, and provide the framework for targeted interventions to prevent relapse in an identified population of impulsive, at-risk patients.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA023203-04
Application #
7800450
Study Section
Adult Psychopathology and Disorders of Aging Study Section (APDA)
Program Officer
Gordon, Harold
Project Start
2007-07-01
Project End
2012-04-30
Budget Start
2010-05-01
Budget End
2011-04-30
Support Year
4
Fiscal Year
2010
Total Cost
$299,334
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Psychiatry
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390
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Liu, Peiying; Lu, Hanzhang; Filbey, Francesca M et al. (2014) MRI assessment of cerebral oxygen metabolism in cocaine-addicted individuals: hypoactivity and dose dependence. NMR Biomed 27:726-32
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McHugh, Meredith J; Demers, Catherine H; Braud, Jacquelyn et al. (2013) Striatal-insula circuits in cocaine addiction: implications for impulsivity and relapse risk. Am J Drug Alcohol Abuse 39:424-32
Adinoff, Bryon; Braud, Jacquelyn; Devous, Michael D et al. (2012) Caudolateral orbitofrontal regional cerebral blood flow is decreased in abstinent cocaine-addicted subjects in two separate cohorts. Addict Biol 17:1001-12

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