Aberrant reward prediction errors in young adult at-risk alcohol users.

Previous studies suggest that individuals with substance use disorder have abnormally large responses to unexpected outcomes (reward prediction errors [RPEs]). However, there is much less information on RPE in individuals at risk of alcohol misuse, prior to neurobiological adaptations that might result from sustained alcohol use. Here, participants (mean age 23.77 years, range 18-32 years) performed the electrophysiological monetary incentive delay task. This task involved responding to a target stimulus following reward incentive cues to win, or avoid losing, the cued reward while brain activity was recorded under 64-channel EEG. The Alcohol Use Disorders Identification Test (AUDIT) was used to quantify at-risk alcohol use, with high (n = 22, mean AUDIT score: 13.82) and low (n = 22, mean AUDIT score: 5.77) alcohol use groups. Trial-by-trial RPEs were estimated using a Rescorla-Wagner reinforcement model based on behavioral data. A single-trial analysis revealed that the feedback-related negativity (FRN) and feedback P3 (fb-P3) event-related potential components were significantly modulated by RPEs. There was increased RPE-related fb-P3 amplitude for those in the high alcohol use group. Next, the mean amplitude of ERPs elicited by positive and negative RPEs were compared between groups. We found that high alcohol use participants had attenuated FRN amplitude in contrast with low alcohol use participants for both positive and negative RPEs but enhanced fb-P3 for both positive and negative RPE. These results, with differences in RPE in an at-risk group, suggest that RPE a potential vulnerability marker for alcohol use disorder.

Inhibitory-control event-related potentials correlate with individual differences in alcohol use.

Impulsivity is a multidimensional construct that is related to different aspects of alcohol use, abuse, and dependence. Inhibitory control, one facet of impulsivity, can be assayed using the stop-signal task (SST) and quantified behaviorally via the stop-signal reaction time (SSRT) and electrophysiologically using event-related potentials (ERPs). Research on the relationship between alcohol use and SSRTs, and between alcohol use and inhibitory-control ERPs, is mixed. Here, adult alcohol users (n = 79), with a wide range of scores on the Alcohol Use Disorders Identification Test (AUDIT), completed the SST under electroencephalography (EEG) (70% of participants had AUDIT total scores greater than or equal to 8). Other measures, including demographic, self-report, and task-based measures of impulsivity, personality, and psychological factors, were also recorded. A machine-learning method with penalized linear regression was used to correlate individual differences in alcohol use with impulsivity measures. Four separate models were tested, with out-of-sample validation used to quantify performance. ERPs alone statistically predicted alcohol use (cross-validated r = 0.28), with both early and late ERP components contributing to the model (larger N2, but smaller P3, amplitude). Behavioral data from a wide range of impulsivity measures were also associated with alcohol use (r = 0.37). SSRT was a relatively weak statistical predictor, whereas the Stroop interference effect was relatively strong. The addition of nonimpulsivity behavioral measures did not improve the correlation (r = 0.34) and was similar when ERPs were combined with non-ERP data (r = 0.29). These findings show that inhibitory control ERPs are robustly correlated individual differences in alcohol use.

Neural circuitry underlying sustained attention in healthy adolescents and in ADHD symptomatology.

Moment-to-moment reaction time variability on tasks of attention, often quantified by intra-individual response variability (IRV), provides a good indication of the degree to which an individual is vulnerable to lapses in sustained attention. Increased IRV is a hallmark of several disorders of attention, including Attention-Deficit/Hyperactivity Disorder (ADHD). Here, task-based fMRI was used to provide the first examination of how average brain activation and functional connectivity patterns in adolescents are related to individual differences in sustained attention as measured by IRV. We computed IRV in a large sample of adolescents (n = 758) across 'Go' trials of a Stop Signal Task (SST). A data-driven, multi-step analysis approach was used to identify networks associated with low IRV (i.e., good sustained attention) and high IRV (i.e., poorer sustained attention). Low IRV was associated with greater functional segregation (i.e., stronger negative connectivity) amongst an array of brain networks, particularly between cerebellum and motor, cerebellum and prefrontal, and occipital and motor networks. In contrast, high IRV was associated with stronger positive connectivity within the motor network bilaterally and between motor and parietal, prefrontal, and limbic networks. Consistent with these observations, a separate sample of adolescents exhibiting elevated ADHD symptoms had increased fMRI activation and stronger positive connectivity within the same motor network denoting poorer sustained attention, compared to a matched asymptomatic control sample. With respect to the functional connectivity signature of low IRV, there were no statistically significant differences in networks denoting good sustained attention between the ADHD symptom group and asymptomatic control group. We propose that sustained attentional processes are facilitated by an array of neural networks working together, and provide an empirical account of how the functional role of the cerebellum extends to cognition in adolescents. This work highlights the involvement of motor cortex in the integrity of sustained attention, and suggests that atypically strong connectivity within motor networks characterizes poor attentional capacity in both typically developing and ADHD symptomatic adolescents.

A Combination of Impulsivity Subdomains Predict Alcohol Intoxication Frequency.

BACKGROUND: Impulsivity, broadly characterized as the tendency to act prematurely without foresight, is linked to alcohol misuse in college students. However, impulsivity is a multidimensional construct and different subdomains likely underlie different patterns of alcohol misuse. Here, we quantified the association between alcohol intoxication frequency and alcohol consumption frequency and choice, action, cognitive, and trait domains of impulsivity. METHODS: University student drinkers (n = 106) completed a battery of demographic and alcohol-related items, as well as self-report and task-based measures indexing different facets of impulsivity. Two orthogonal latent factors, intoxication frequency and alcohol consumption frequency, were generated. Their validity was demonstrated with respect to adverse consequences of alcohol use. Machine learning with penalized regression and feature selection was then utilized to predict intoxication and alcohol consumption frequency using all impulsivity subdomains. Out-of-sample validation was used to quantify model performance. RESULTS: Impulsivity measures alone were significant predictors of intoxication frequency, but not consumption frequency. Propensity for increased intoxication frequency was characterized by increased trait impulsivity, including the Disinhibition subscale of the Sensation Seeking Scale, Attentional and Non-planning subscales of the Barratt Impulsiveness Scale, increased task-based cognitive impulsivity (response time variability), and increased choice impulsivity (steeper delay discounting on a delay discounting questionnaire). A model combining impulsivity domains with other risk factors (gender; nicotine, cannabis, and other drug use; executive functioning; and learning processes) was also significant but did not outperform the model comprising of impulsivity alone. CONCLUSIONS: Intoxication frequency, but not consumption frequency, was characterized by a number of impulsivity subdomains.

Individual differences in learning from probabilistic reward and punishment predicts smoking status.

INTRODUCTION: The ability to update reward and punishment contingencies is a fundamental aspect of effective decision-making, requiring the ability to successfully adapt to the changing demands of one's environment. In the case of nicotine addiction, research has predominantly focused on reward- and punishment-based learning processes among current smokers relative to non-smokers, whereas less is known about these processes in former smokers. METHODS: In a total sample of 105 students, we used the Probabilistic Selection Task to examine differences in reinforcement learning among 41 current smokers, 29 ex-smokers, and 35 non-smokers. The PST was comprised of a training and test phase that allowed for the comparison of learning from positive versus negative feedback. RESULTS: The test phase of the Probabilistic Selection Task significantly predicted smoking status. Current and non-smokers were classified with moderate accuracy, whereas ex-smokers were typically misclassified as smokers. Lower rates of learning from rewards were associated with an increased likelihood of being a smoker or an ex-smoker compared with being a non-smoker. Higher rates of learning from punishment were associated with an increased likelihood of being a smoker relative to non-smoker. However, learning from punishment did not predict ex-smoker status. CONCLUSIONS: Current smokers and ex-smokers were less likely to learn from rewards, supporting the hypothesis that deficient reward processing is a feature of chronic addiction. In addition, current smokers were more sensitive to punishment than ex-smokers, contradicting some recent findings.

The potential of neuroimaging for identifying predictors of adolescent alcohol use initiation and misuse.

BACKGROUND AND AIMS: Dysfunction in brain regions underlying impulse control, reward processing and executive function have been associated previously with adolescent alcohol misuse. However, identifying pre-existing neurobiological risk factors, as distinct from changes arising from early alcohol-use, is difficult. Here, we outline how neuroimaging data can identify the neural predictors of adolescent alcohol-use initiation and misuse by using prospective longitudinal studies to follow initially alcohol-naive individuals over time and by neuroimaging adolescents with inherited risk factors for alcohol misuse. METHOD: A comprehensive narrative of the literature regarding neuroimaging studies published between 2010 and 2016 focusing on predictors of adolescent alcohol use initiation and misuse. FINDINGS: Prospective, longitudinal neuroimaging studies have identified pre-existing differences between adolescents who remained alcohol-naive and those who transitioned subsequently to alcohol use. Both functional and structural grey matter differences were observed in temporal and frontal regions, including reduced brain activity in the superior frontal gyrus and temporal lobe, and thinner temporal cortices of future alcohol users. Interactions between brain function and genetic predispositions have been identified, including significant association found between the Ras protein-specific guanine nucleotide releasing factor 2 (RASGRF2) gene and reward-related striatal functioning. CONCLUSIONS: Neuroimaging predictors of alcohol use have shown modest utility to date. Future research should use out-of-sample performance as a quantitative measure of a predictor's utility. Neuroimaging data should be combined across multiple modalities, including structural information such as volumetrics and cortical thickness, in conjunction with white-matter tractography. A number of relevant neurocognitive systems should be assayed; particularly, inhibitory control, reward processing and executive functioning. Combining a rich magnetic resonance imaging data set could permit the generation of neuroimaging risk scores, which could potentially yield targeted interventions.

Flexible emotion-based decision-making behavior varies in current and former smokers.

INTRODUCTION: Suboptimal decision-making is a feature in the initiation and maintenance of substance use, often manifested in choosing for short-term benefits rather than long-term gain, and the failure to display cognitive flexibility, respectively. Studies of nicotine users typically focus on characterizing those who are already addicted; less is known about decision-making in former smokers. METHODS: Non- (n=21), former daily- (n=23) and current daily smokers (n=24), completed the contingency-shifting variant Iowa Gambling Task (csIGT), in which the reward and punishment contingencies of the decks are systematically varied after 100 trials of the 'standard' IGT. Scores on the standard blocks of the csIGT provided an index of emotion-based decision-making, while the contingency-shifting blocks assessed flexible decision-making. Subjective ratings were also recorded at 20-trial intervals. RESULTS: Both current and former smokers showed significantly impaired performance relative to non-smokers when making decisions during the standard blocks of the csIGT. Both former and non-smokers' awareness of the reward/punishment contingencies was significantly higher than those of current smokers at the end of the standard IGT. Both former and non-smokers had significantly better performance on the contingency shifting blocks, relative to current smokers. CONCLUSIONS: The findings indicate that both current and former smokers display a suboptimal pattern of decision-making than non-smokers during the standard IGT. However, with respect to the ability to change behavior following reversed contingencies, former smokers are more similar to non-smokers than to current smokers. Former smokers were also more aware of the contingencies than current smokers.

Sweet's syndrome presenting as acute hand infection.

BACKGROUND: Sweet's syndrome, originally described as an acute febrile neutrophilic dermatosis, belongs to a class of skin lesions that histologically have intense epidermal and/or dermal inflammatory infiltrate of neutrophils without evidence of infection or vasculitis. Skin lesions of Sweet's syndrome most commonly present on the face, trunk, upper extremities, and hands. The presenting lesions are often confused with infections because of their clinical appearance. METHODS: A retrospective search of the electronic medical record was performed to identify patients with Sweet's syndrome from 1996 to the present. These records were then reviewed to identify those patients who had Sweet's syndrome that involved the hands. RESULTS: A total of 103 patients with Sweet's syndrome have been seen and treated at Scott and White Memorial Hospital since 1996. Of these, 49 patients had lesions on the hands. The presentation, treatment, and outcomes of several of these patients are presented. CONCLUSIONS: As physicians responsible for the treatment of hand lesions, it is important to consider the diagnosis of Sweet's syndrome because these wounds are unresponsive to antibiotics, do not benefit from débridement, and instead, require treatment with steroids.