Joshua C. Gray

Interrelationships among Individual Differences in Alcohol Demand, Impulsivity, and Alcohol Misuse

An Alcohol Purchase Task (APT) is a novel behavioral economic measure for characterizing the incentive value of alcohol to an individual (i.e., alcohol demand). Individual differences in alcohol demand have been associated with a number of alcohol-related outcomes and the current investigation sought to extend these previous findings in a number of ways. The goals of the study were: (a) to examine the relationship between alcohol demand and alcohol misuse in a large sample of community adults; (b) to examine sex differences in alcohol demand; and, (c) to examine the relationship between alcohol demand and impulsive personality traits, both in general and as moderating variables. Participants (N = 720; 39% female) were adult smokers who reported drinking in the last year and were recruited from the community at large. All four behavioral economic indices of demand from the APT were significantly associated with alcohol misuse, with Omax and intensity uniquely associated in combined analyses. Males exhibited significantly higher demand, but these differences were largely eliminated after adjusting for drinks per week and other covariates. Trait levels of urgency, sensation-seeking and lack of premeditation were significantly associated with intensity and urgency was associated with Omax, but no moderating relationships were present. The significant relationships between aspects of impulsivity and the demand indices may signify a common process underlying disinhibition and demand for alcohol. These findings further support the relationship between indices of alcohol demand and alcohol misuse and a link between demand and impulsivity. Methodological considerations and future directions are discussed.

The neuroeconomics of alcohol demand: An initial investigation of the neural correlates of alcohol cost-benefit decision making in heavy drinking men

Neuroeconomics integrates concepts and methods from psychology, economics, and cognitive neuroscience to understand how the brain makes decisions. In economics, demand refers to the relationship between a commodity’s consumption and its cost, and, in behavioral studies, high alcohol demand has been consistently associated with greater alcohol misuse. Relatively little is known about how the brain processes demand decision making, and the current study is an initial investigation of the neural correlates of alcohol demand among heavy drinkers. Using an event-related functional magnetic resonance imaging (fMRI) paradigm, participants (N=24) selected how much they would drink under varying levels of price. These choices determined access to alcohol during a subsequent bar laboratory self-administration period. During decisions to drink in general, greater activity was present in multiple distinct subunits of the prefrontal and parietal cortices. In contrast, during decisions to drink that were demonstrably affected by the cost of alcohol, significantly greater activation was evident in frontostriatal regions, suggesting an active interplay between cognitive deliberation and subjective reward value. These choices were also characterized by significant deactivation in default mode network regions, suggesting suppression resulting from greater cognitive load. Across choice types, the anterior insula was notably recruited in diverse roles, further implicating the importance of interoceptive processing in decision-making behavior. These findings reveal the neural signatures subserving alcohol cost–benefit decision making, providing a foundation for future clinical applications of this paradigm and extending this approach to understanding the neural correlates of demand for other addictive commodities.

Protective prevention effects on the association of poverty with brain development

Importance This study was designed to determine whether a preventive intervention focused on enhancing supportive parenting could ameliorate the association between exposure to poverty and brain development in low socioeconomic status African American individuals from the rural South. Objective To determine whether participation in an efficacious prevention program designed to enhance supportive parenting for rural African American children will ameliorate the association between living in poverty and reduced hippocampal and amygdalar volumes in adulthood. Design, Setting, and Participants In the rural southeastern United States, African American parents and their 11-year-old children were assigned randomly to the Strong African American Families randomized prevention trial or to a control condition. Parents provided data used to calculate income-to-needs ratios when children were aged 11 to 13 years and 16 to 18 years. When the participants were aged 25 years, hippocampal and amygdalar volumes were measured using magnetic resonance imaging. Exposures Household poverty was measured by income-to-needs ratios. Main Outcomes and Measures Young adults’ whole hippocampal, dentate gyrus, and CA3 hippocampal subfields as well as amygdalar volumes were assessed using magnetic resonance imaging. Results Of the 667 participants in the Strong African American Families randomized prevention trial, 119 right-handed African American individuals aged 25 years living in rural areas were recruited. Years lived in poverty across ages 11 to 18 years forecasted diminished left dentate gyrus (simple slope, −14.20; standard error, 5.22; P = .008) and CA3 (simple slope, −6.42; standard error, 2.42; P = .009) hippocampal subfields and left amygdalar (simple slope, −34.62; standard error, 12.74; P = .008) volumes among young adults in the control condition (mean [SD] time, 2.04 [1.88] years) but not among those who participated in the Strong African American Families program (mean [SD] time, 2.61 [1.77] years). Conclusions and Relevance In this study, we described how participation in a randomized clinical trial designed to enhance supportive parenting ameliorated the association of years lived in poverty with left dentate gyrus and CA3 hippocampal subfields and left amygdalar volumes. These findings are consistent with a possible role for supportive parenting and suggest a strategy for narrowing social disparities.

Genetic basis of delay discounting in frequent gamblers: examination of a priori candidates and exploration of a panel of dopamine-related loci

Delay discounting is a behavioral economic index of impulsivity that reflects preferences for small immediate rewards relative to larger delayed rewards. It has been consistently linked to pathological gambling and other forms of addictive behavior, and has been proposed to be a behavioral characteristic that may link genetic variation and risk of developing addictive disorders (i.e., an endophenotype). Studies to date have revealed significant associations with polymorphisms associated with dopamine neurotransmission. The current study examined associations between delay discounting and both previously linked variants and a novel panel of dopamine‐related variants in a sample of frequent gamblers.

Impulsive delayed reward discounting as a genetically-influenced target for drug abuse prevention: a critical evaluation

This review evaluates the viability of delayed reward discounting (DRD), an index of how much an individual devalues a future reward based on its delay in time, for genetically-informed drug abuse prevention. A review of the literature suggests that impulsive DRD is robustly associated with drug addiction and meets most of the criteria for being an endophenotype, albeit with mixed findings for specific molecular genetic influences. Several modes of experimental manipulation have been demonstrated to reduce DRD acutely. These include behavioral strategies, such as mindfulness, reward bundling, and episodic future thinking; pharmacological interventions, including noradrenergic agonists, adrenergic agonists, and multiple monoamine agonists; and neuromodulatory interventions, such as transcranial magnetic stimulation and transcranial direct current stimulation. However, the generalization of these interventions to positive clinical outcomes remains unclear and no studies to date have examined interventions on DRD in the context of prevention. Collectively, these findings suggest it would be premature to target DRD for genetically-informed prevention. Indeed, given the evidence of environmental contributions to impulsive DRD, whether genetically-informed secondary prevention would ever be warranted is debatable. Progress in identifying polymorphisms associated with DRD profiles could further clarify the underlying biological systems for pharmacological and neuromodulatory interventions, and, as a qualitatively different risk factor from existing prevention programs, impulsive DRD is worthy of investigation at a more general level as a novel and promising drug abuse prevention target.

Genome-wide association study of delay discounting in 23,217 adult research participants of European ancestry

Delay discounting (DD), the tendency to discount the value of delayed versus current rewards, is elevated in a constellation of diseases and behavioral conditions. We performed a genome-wide association study of DD using 23,127 research participants of European ancestry. The most significantly associated single-nucleotide polymorphism was rs6528024 (P = 2.40 × 10−8), which is located in an intron of the gene GPM6B. We also showed that 12% of the variance in DD was accounted for by genotype and that the genetic signature of DD overlapped with attention-deficit/hyperactivity disorder, schizophrenia, major depression, smoking, personality, cognition and body weight.A genome-wide association study of delay discounting (DD) on 23,127 subjects found that genotype accounted for 12% of variance in DD; the DD genetic signature overlapped with ADHD, schizophrenia, depression, smoking, personality, cognition and weight.

Genome-wide association study of alcohol use disorder identification test (AUDIT) scores in 20 328 research participants of European ancestry.

Genetic factors contribute to the risk for developing alcohol use disorder (AUD). In collaboration with the genetics company 23andMe, Inc., we performed a genome‐wide association study of the alcohol use disorder identification test (AUDIT), an instrument designed to screen for alcohol misuse over the past year. Our final sample consisted of 20 328 research participants of European ancestry (55.3% females; mean age = 53.8, SD = 16.1) who reported ever using alcohol. Our results showed that the ‘chip‐heritability’ of AUDIT score, when treated as a continuous phenotype, was 12%. No loci reached genome‐wide significance. The gene ADH1C, which has been previously implicated in AUD, was among our most significant associations (4.4 × 10−7; rs141973904). We also detected a suggestive association on chromosome 1 (2.1 × 10−7; rs182344113) near the gene KCNJ9, which has been implicated in mouse models of high ethanol drinking. Using linkage disequilibrium score regression, we identified positive genetic correlations between AUDIT score, high alcohol consumption and cigarette smoking. We also observed an unexpected positive genetic correlation between AUDIT and educational attainment and additional unexpected negative correlations with body mass index/obesity and attention‐deficit/hyperactivity disorder. We conclude that conducting a genetic study using responses to an online questionnaire in a population not ascertained for AUD may represent a cost‐effective strategy for elucidating aspects of the etiology of AUD.

Item-Based Analysis of Delayed Reward Discounting Decision Making

Delayed reward discounting (DRD) is a behavioral economic index of time preference, referring to how much an individual devalues a reward based on its delay in time, and has been linked to a wide array of health behaviors. It is commonly assessed using a task that asks participants to make dichotomous choices between two monetary rewards, one available immediately and the other after a delay. This study sought to shorten an extended iterative DRD assessment to increase its versatility and efficiency. Data were drawn from two young adult samples, an exploratory sample (N=130) and a confirmatory sample (N=247). In the exploratory sample, eight items were identified as predicting the majority of the variance in the full task area under the curve (AUC) (R(2)=.821; p<.001). In the confirmatory sample, the same eight items similarly predicted the majority of variance in the full task AUC (R(2)=.844, p<.001). These results provide initial support for the validity of a brief 8-item assessment of DRD. Priorities for further validation and potential applications are discussed.

Delay and Probability Discounting as Candidate Markers for Dementia: An Initial Investigation

The present study investigated delay discounting and probability discounting-behavioral economic indices of impulsivity and risk proneness, respectively-in 39 healthy older adults and 25 older adults with mild cognitive impairment (MCI). Relative to the healthy group, it was hypothesized that older adults with MCI would display greater levels of impulsivity, risk proneness, and response inconsistency. The MCI group was found to display a unique delay discounting profile characterized by increasing impulsivity with decreasing reward magnitude, such that cognitively impaired older adults were significantly more impulsive than healthy controls at the small reward magnitude. The two groups exhibited similar levels of probability discounting, though older adults with MCI were significantly less consistent in their risk preferences. The present findings shed light onto decision-making in pre-dementia disease stages and suggest that discounting performance holds potential to complement early diagnostic instruments, likely due to pathophysiological processes in relevant brain regions.

Clarifying the neural basis for incentive salience of tobacco cues in smokers.

In functional magnetic resonance imaging (fMRI) studies, smoking cues have been found to elicit increases in brain activity in regions associated with processing rewarding and emotional stimuli. However, most smoking cue studies to date have reported effects relative to neutral control stimuli with no incentive properties, making it unclear whether the observed activation pertains to value in general or the value of cigarettes in particular. The current fMRI study sought to clarify the neural activity reflecting tobacco-specific incentive value versus domain-general incentive value by examining smoking cues, neutral cues, and a third set of cues, monetary cues, which served as an active control condition. Participants were 42 male daily smokers. Compared to neutral cues, significantly greater activation was found in the left ventral striatum in response to tobacco and money cues. Monetary cues also elicited significantly increased activation in the right inferior frontal gyrus and cuneus compared to the other two cue types. Overall, the results suggest that the salience of monetary cues was the highest and, as a result, might have reduced the incentive salience of tobacco cues.