An R21 for CEBRA: The blossoming field of functional neuroimaging studies has pointed to a network of neural structures that subserve the cognitive and behavioral processes of drug addiction, including nicotine. This neural network includes the orbitofrontal cortex, anterior cingulate, insular cortices, the amygdala, and the striatum (dorsal and ventral (nucleus accumbens) striatum). However, no work to date has addressed how damage to different components of this neural network in humans may impact the craving, subjective feeling of drug administration, and active seeking of drugs. Nor any study has asked which, if any, of these components is critically necessary for maintaining the addiction to drugs. This proposal will take advantage of our unique University of Iowa Department of Neurology Patient Registry to begin addressing some of these important issues in patients addicted to cigarette smoking. Our goal is to understand how focal lesions in brain areas hypothesized to be critical neural substrates for addiction affect cigarette smoking behavior, cue-induced craving and smoking urge, as well as the acute subjective effects of smoking. The studies we propose here seek to address 3 specific aims: (1) determining the real-life changes in smoking behavior, cigarette craving, and smoking satisfaction after the onset of brain damage; (2) determining in laboratory experiments the effects of focal brain lesions on (a) the emotional reactivity to smoking cues, (b) the subjective feeling of craving and urge to smoke, and (c) the subjective feeling of smoking a cigarette; and (3) establishing a Registry of neurological patients pre-morbidly known to abuse other substances, including alcohol, stimulants, and opiates, so that they will participate in future research on addiction to drugs. The proposal is promising because (1) it provides a novel perspective for looking at the neurobiological basis of addiction, which compliments and validates the ongoing work with functional neuroimaging techniques; (2) it may help us identify specific brain regions, which damage (or dysfunction) can effectively break the cycle of addiction. The proposed studies are feasible because of (1) our access to the patient population and resources necessary for the conduction of this type research; 2) the guidance of our investigations by an established theoretical framework, the somatic marker hypothesis, and by abundance of background evidence from functional neuroimaging studies. Thus, the proposed research is a beginning of a novel approach with potential for developing more effective therapies for breaking the vicious cycle of addiction.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21DA016708-02
Application #
6767769
Study Section
Special Emphasis Panel (ZDA1-TXL-Q (35))
Program Officer
Grant, Steven J
Project Start
2003-07-01
Project End
2006-06-30
Budget Start
2004-07-01
Budget End
2006-06-30
Support Year
2
Fiscal Year
2004
Total Cost
$147,500
Indirect Cost
Name
University of Iowa
Department
Neurology
Type
Schools of Medicine
DUNS #
062761671
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Brevers, Damien; Noël, Xavier; He, Qinghua et al. (2016) Increased ventral-striatal activity during monetary decision making is a marker of problem poker gambling severity. Addict Biol 21:688-99
Brevers, Damien; Noël, Xavier; Bechara, Antoine et al. (2015) Effect of casino-related sound, red light and pairs on decision-making during the Iowa gambling task. J Gambl Stud 31:409-21
Naqvi, Nasir H; Gaznick, Natassia; Tranel, Daniel et al. (2014) The insula: a critical neural substrate for craving and drug seeking under conflict and risk. Ann N Y Acad Sci 1316:53-70
Brevers, Damien; Bechara, Antoine; Cleeremans, Axel et al. (2014) Impaired decision-making under risk in individuals with alcohol dependence. Alcohol Clin Exp Res 38:1924-31
Brevers, Damien; Koritzky, Gilly; Bechara, Antoine et al. (2014) Cognitive processes underlying impaired decision-making under uncertainty in gambling disorder. Addict Behav 39:1533-6
Brevers, Damien; Noël, Xavier (2013) Pathological gambling and the loss of willpower: a neurocognitive perspective. Socioaffect Neurosci Psychol 3:21592
Xiao, Lin; Bechara, Antoine; Gong, Qiyong et al. (2013) Abnormal affective decision making revealed in adolescent binge drinkers using a functional magnetic resonance imaging study. Psychol Addict Behav 27:443-54
Tranel, Daniel; McNutt, Ashton; Bechara, Antoine (2012) Smoking cessation after brain damage does not lead to increased depression: implications for understanding the psychiatric complications of varenicline. Cogn Behav Neurol 25:16-24
Sobhani, Mona; Bechara, Antoine (2011) A somatic marker perspective of immoral and corrupt behavior. Soc Neurosci 6:640-52
Xue, Gui; Lu, Zhonglin; Levin, Irwin P et al. (2011) An fMRI study of risk-taking following wins and losses: implications for the gambler's fallacy. Hum Brain Mapp 32:271-81

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