Individuals are at greatest risk for developing an alcohol use disorder (AUD) during late adolescence (Kandel and Logan, 1984;Brown et al., 2008), possibly due to the relative impulsiveness of late adolescents/young adults. Kandel and Logan (1984) have suggested that the decline in heavy alcohol use that typically occurs in the mid-twenties may reflect a maturational or developmental process, as the development of frontal structures implicated in self-regulation and impulse control is complete in humans around the early- to-mid twenties (Giedd, 2004;Hooper et al., 2004;Rubia et al., 2006;Eshel et al., 2007). Although there is general acceptance of the idea that frontal circuits are still maturing in late adolescents no work to date has specifically investigated changes in the function of frontal circuits engaged during Now versus Later decision making, a quantifiable measure of impulsiveness. The proposed studies will compare late adolescents (ages 18-23) and adults (ages 25-40) using functional MRI approaches to identify differences in the brain areas engaged during Now versus Later decision-making. In addition, we will determine whether heavy alcohol use is associated with abnormalities in normally observed age-related differences in these neural circuits. Our central hypothesis is that immaturity in frontal circuits and relatively increased signaling in striato-limbic structures promote impulsive decision making in late adolescents. We will test our central hypothesis via the following Specific Aims: 1) Indentify functional differences in frontostriatal circuits associated with Now/Later decision making in late adolescents versus adults. 2) Determine whether the impulsive decision-making observed in heavy drinking adults is associated with signs of functional immaturity in frontal circuits. To achieve the goals of this research plan, a previously validated delay-discounting task (Mitchell et al., 2005;Boettiger et al., 2007) will be used to measure Now/Later decision making behavior in late adolescents and adults in the context of functional MRI. We will seek to determine whether age-dependent differences in the function of brain structures of interest correlate with age-dependent differences in decision-making. These studies will be conducted in both moderate and heavy drinking populations to determine how alcohol use impacts age- related changes in brain structures engaged in Now/Later decision making. This research stands to significantly improve our understanding of the neural underpinnings of changes in decision-making from late adolescence to adulthood, which may bear on why late adolescents are at an increased risk for developing alcohol use disorders. Greater knowledge of the mechanisms underlying risk for developing alcohol use disorders may allow for the development of better treatments or interventions.

Public Health Relevance

This research project seeks to understand the neurobiological bases for the decline in the tendency to choose smaller, sooner rewards (""""""""Now"""""""") over larger, later rewards (""""""""Later"""""""") from late adolescence to early adulthood, a tendency that also characterizes individuals with alcohol use disorders. Studying developmental changes in the function of frontal structures that regulate Now/Later decision-making may provide insight into why late adolescents are at increased risk for developing alcohol use disorders, which may in turn aid in the development of new prevention and treatment approaches for this vulnerable age group.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Predoctoral Individual National Research Service Award (F31)
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Health Services Research Review Subcommittee (AA)
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Matochik, John A
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University of North Carolina Chapel Hill
Schools of Arts and Sciences
Chapel Hill
United States
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Elton, Amanda; Smith, Christopher T; Parrish, Michael H et al. (2017) Neural Systems Underlying Individual Differences in Intertemporal Decision-making. J Cogn Neurosci 29:467-479
Elton, Amanda; Smith, Christopher T; Parrish, Michael H et al. (2017) COMT Val158Met Polymorphism Exerts Sex-Dependent Effects on fMRI Measures of Brain Function. Front Hum Neurosci 11:578
Smith, Christopher T; Wallace, Deanna L; Dang, Linh C et al. (2016) Modulation of impulsivity and reward sensitivity in intertemporal choice by striatal and midbrain dopamine synthesis in healthy adults. J Neurophysiol 115:1146-56
Smith, Christopher T; Steel, Eleanor A; Parrish, Michael H et al. (2015) Intertemporal Choice Behavior in Emerging Adults and Adults: Effects of Age Interact with Alcohol Use and Family History Status. Front Hum Neurosci 9:627
Swift-Scanlan, Theresa; Smith, Christopher T; Bardowell, Sabrina A et al. (2014) Comprehensive interrogation of CpG island methylation in the gene encoding COMT, a key estrogen and catecholamine regulator. BMC Med Genomics 7:5
Smith, Christopher T; Sierra, Yecenia; Oppler, Scott H et al. (2014) Ovarian cycle effects on immediate reward selection bias in humans: a role for estradiol. J Neurosci 34:5468-76
Smith, Christopher T; Swift-Scanlan, Theresa; Boettiger, Charlotte A (2014) Genetic polymorphisms regulating dopamine signaling in the frontal cortex interact to affect target detection under high working memory load. J Cogn Neurosci 26:395-407
Smith, Christopher T; Boettiger, Charlotte A (2012) Age modulates the effect of COMT genotype on delay discounting behavior. Psychopharmacology (Berl) 222:609-17