Alcohol-dependent individuals frequently have deficits in self-control, as measured by their excessive discounting of delayed rewards. The dual neurobehavioral decision systems model suggests that these deficits may result from a disruption in the regulatory balance between two interacting neurobiological systems. These systems are the executive system (prefrontal cortex and parietal cortex) which is responsible for valuing delayed rewards (i.e., long-term goals), and the impulsive system (limbic and paralimbic areas) which is associated with immediate rewards (i.e., instant gratification). Our recent research has demonstrated that working memory (WM) training repairs self-control, putatively by restoring regulatory balance between these systems. There is, however, still much to learn about repairing self-control.
In Aim 1, we will further explore the effects WM training on a range of WM, self-control, and clinically relevant (e.g., craving) measures. Additionally, the neural mechanisms of WM training will be explored though functional neuroimaging techniques. We will examine the dose-effect function of WM training by systematically varying the number of WM training sessions across several groups of alcohol-dependent individuals. The duration of these improvements in self-control will be tested by conducting follow-up assessments one month, three months, and six months after training.
In Aim 2 we plan to capitalize on the neurobiological knowledge gained in Aim 1 to test the effects of two variants of real time fMRI neuro-feedback on our suite of WM, self-control, and clinically significant measures. This novel exploration of neuro-feedback effects on neurocognitive and clinically significant measures will include a direct comparison of feedback techniques based on a specific brain region and across a distributed neural network. Long-term changes in neural function and/or our neurocognitive measures will be explored during a one-month follow-up visit. Successfully achieving our aims could allow us to both refine our current techniques (i.e., WM training), and possibly begin the process of developing novel techniques (i.e., neuro-feedback) for the repair of self-control in alcohol-dependent individuals. This application will contribute to personalized medicine approaches in alcohol dependence, where treatment is defined by documented self-control deficits. Furthermore, the functional neuroimaging data collected across both aims should provide unique insights into both patterns of neural disruption seen in alcohol dependence and any treatment associated changes in neural function.

Public Health Relevance

The proposed project will provide new information about the repair of alcohol-dependent individuals'self- control via working memory training and neurofeedback (real-time fMRI). By examining the brain regions that underlie impaired self-control before, during, and after intervention, we expect to provide novel insights into the neurobiology of self-control repair. We believe that a greater understanding of these neural mechanisms could lead to new and refined treatments for the pathologic decision-making seen in alcohol dependence.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Research Project (R01)
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Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
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Matochik, John A
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Virginia Polytechnic Institute and State University
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Bickel, Warren K; Snider, Sarah E; Quisenberry, Amanda J et al. (2016) Competing neurobehavioral decision systems theory of cocaine addiction: From mechanisms to therapeutic opportunities. Prog Brain Res 223:269-93
Bickel, Warren K; Moody, Lara; Higgins, Stephen T (2016) Some current dimensions of the behavioral economics of health-related behavior change. Prev Med 92:16-23
Snider, Sarah E; Quisenberry, Amanda J; Bickel, Warren K (2016) Order in the absence of an effect: Identifying rate-dependent relationships. Behav Processes 127:18-24
Bickel, Warren K; Mellis, Alexandra M; Snider, Sarah E et al. (2016) Novel Therapeutics for Addiction: Behavioral and Neuroeconomic Approaches. Curr Treat Options Psychiatry 3:277-292
Bickel, W K; Quisenberry, A J; Snider, S E (2016) Does impulsivity change rate dependently following stimulant administration? A translational selective review and re-analysis. Psychopharmacology (Berl) 233:1-18
Sheffer, Christine E; Mackillop, James; Fernandez, Arislenia et al. (2016) Initial examination of priming tasks to decrease delay discounting. Behav Processes 128:144-52
Bickel, Warren K; Quisenberry, Amanda J; Moody, Lara et al. (2015) Therapeutic Opportunities for Self-Control Repair in Addiction and Related Disorders: Change and the Limits of Change in Trans-Disease Processes. Clin Psychol Sci 3:140-153
Wilson, A George; Franck, Christopher T; Mueller, E Terry et al. (2015) Predictors of delay discounting among smokers: education level and a Utility Measure of Cigarette Reinforcement Efficacy are better predictors than demographics, smoking characteristics, executive functioning, impulsivity, or time perception. Addict Behav 45:124-33
Quisenberry, Amanda J; Eddy, Celia R; Patterson, David L et al. (2015) Regret Expression and Social Learning Increases Delay to Sexual Gratification. PLoS One 10:e0135977
Bickel, Warren K (2015) Discounting of delayed rewards as an endophenotype. Biol Psychiatry 77:846-7

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