A network of neural structures crucial for the cognitive and behavioral processes of drug addiction, including nicotine, includes the orbitofrontal cortex, anterior cingulate, insular cortices, the amygdala, and the striatum. However, no work has addressed how damage to different components of this neural network in humans may impact the maintenance of addiction to drugs. Under the tenure of an R21 awarded through CEBRA (Cutting- Edge Basic Research Awards), we began addressing this important issue in patients addicted to cigarette smoking and who had suffered a stroke that included any of these areas. It was found that although lesions of the ventromedial prefrontal cortex (VMPFC) were associated with a marked impairment of cue-induced urge in the laboratory, they were not associated with an increased likelihood of quitting smoking. In fact, lesions of the insular cortex were associated with an ability to quit smoking easily, immediately, without relapses and without a lasting urge to smoke. Although preliminary, these results suggest that, while VMPFC lesions may disrupt cue-induced urges, they do not disrupt smoking addiction. However, the insula, which also plays a key role in urges, seems most critical for maintaining smoking addiction and driving smoking behavior. The results also suggest that the insula functions in psychological processes that may contribute to the difficulty of quitting smoking. Encouraged by these intriguing, but preliminary, results, our primary aims are to (1) expand and confirm these findings in a larger sample, using more precise anatomical analyses to characterize the size and placement of lesions;(2) examine whether there are gender differences in terms of the ease to quit smoking after a lesion;and (3) conduct prospective studies on smokers who suffer strokes and monitor their smoking behavior for several years after the lesion onset. The proposed research is a beginning of a novel approach with potential for developing more effective therapies for breaking the vicious cycle of addiction. Specifically, one therapeutic approach called up by the proposed research would be to directly modulate the function of the insula.

Public Health Relevance

A prune-sized region deep in the brain called the insula is intimately involved in smoking addiction, and damage to this structure can completely erase the body's urge to smoke. Obviously brain damage is not a treatment option for nicotine addiction, but if confirmed, these results may offer leads for therapies to help smokers kick the habit, or for monitoring smokers'progress while using existing therapies.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
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Risk, Prevention and Intervention for Addictions Study Section (RPIA)
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Grant, Steven J
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University of Southern California
Schools of Arts and Sciences
Los Angeles
United States
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Wood, Samantha M W; Schembre, Susan M; He, Qinghua et al. (2016) Emotional eating and routine restraint scores are associated with activity in brain regions involved in urge and self-control. Physiol Behav 165:405-12
He, Qinghua; Chen, Chuansheng; Dong, Qi et al. (2015) Gray and white matter structures in the midcingulate cortex region contribute to body mass index in Chinese young adults. Brain Struct Funct 220:319-29
Koritzky, Gilly; Rice, Chantelle; Dieterle, Camille et al. (2015) The Biggest Loser Thinks Long-Term: Recency as a Predictor of Success in Weight Management. Front Psychol 6:1864
Koritzky, Gilly; Dieterle, Camille; Rice, Chantelle et al. (2014) Decision-making, sensitivity to reward and attrition in weight management. Obesity (Silver Spring) 22:1904-9
Turel, Ofir; He, Qinghua; Xue, Gui et al. (2014) Examination of neural systems sub-serving facebook ""addiction"". Psychol Rep 115:675-95
Gaznick, Natassia; Tranel, Daniel; McNutt, Ashton et al. (2014) Basal ganglia plus insula damage yields stronger disruption of smoking addiction than basal ganglia damage alone. Nicotine Tob Res 16:445-53
He, Qinghua; Xiao, Lin; Xue, Gui et al. (2014) Poor ability to resist tempting calorie rich food is linked to altered balance between neural systems involved in urge and self-control. Nutr J 13:92
Levens, Sara M; Larsen, Jeff T; Bruss, Joel et al. (2014) What might have been? The role of the ventromedial prefrontal cortex and lateral orbitofrontal cortex in counterfactual emotions and choice. Neuropsychologia 54:77-86
Yan, Wan-Sen; Li, Yong-Hui; Xiao, Lin et al. (2014) Working memory and affective decision-making in addiction: a neurocognitive comparison between heroin addicts, pathological gamblers and healthy controls. Drug Alcohol Depend 134:194-200
Gaznick, Natassia; Bechara, Antoine; Tranel, Daniel (2014) Hemispheric side of damage influences sex-related differences in smoking cessation in neurological patients. J Clin Exp Neuropsychol 36:551-8

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