Irregular Autonomic Modulation Predicts Risky Drinking and Altered Ventromedial Prefrontal Cortex Response to Stress in Alcohol Use Disorder.

AIMS: Autonomic dysfunction has been associated with risky drinking and alcohol use disorder (AUD). Although autonomic nervous system (ANS) activity has been attributed to the ventromedial prefrontal cortex (VmPFC)-limbic-striatal regions, the specific role of ANS disruption in AUD and its association with these regions remain unclear. Using functional magnetic resonance imaging (fMRI) and concurrent electrocardiogram (ECG), the current study examined neural correlates of ANS activity in AUD and its role in AUD pathology. METHODS: Demographically matched 20 AUD patients and 20 social drinkers (SD) completed an fMRI task involving repeated exposure to stress, alcohol-cue and neutral-relaxing images in a block design. Based on the known VmPFC-limbic-striatal functions involved in emotions, reward and the ANS, we performed a regions of interest (ROI) analysis to examine the associations between ANS activity and neural responses in the VmPFC, amygdala, and ventral striatum. RESULTS: Across conditions, AUD patients showed significantly higher levels of overall heart rate (HR) and approximate entropy (ApEn) compared to SD (Ps < 0.05). In all participants, increased HR was associated with greater drinking volume (P < 0.05). In addition, higher ApEn levels were associated with greater drinking volume (P < 0.05) and decreased right VmPFC response to stress (P < 0.05). DISCUSSION: Our findings demonstrate ANS disruption in AUD indexed by high overall HR and ApEn. The association between ApEn and rVmPFC response suggests that ApEn may play a role in modulating drinking via interactions with neural regions of emotion regulation. These findings provide insight into patterns of ANS disruption and their relevance to AUD pathology.

Differential brain responses to alcohol-related and natural rewards are associated with alcohol use and problems: Evidence for reward dysregulation.

Multiple theoretical perspectives posit that drug use leads to biased valuation of drug-related reward, at the expense of naturally occurring rewarding activities (i.e., reward dysregulation). Recent research suggests that the comparative balance of drug-related and nondrug-related reward valuation is a powerful determinant of substance misuse and addiction. We examined differential neurophysiological responses-indexed with the P3 component of the event-related potential (ERP)-elicited by visual alcohol cues and cues depicting natural reward as a neurobiological indicator of problematic drinking. Nondependent, young adult drinkers (N = 143, aged 18-30 years) completed questionnaire measures assessing alcohol use and problems, and viewed alcohol cues (pictures of alcoholic beverages), high-arousing natural reward cues (erotica, adventure scenes), nonalcoholic beverage cues, and neutral scenes (e.g., household items) while ERPs were recorded. When examined separately, associations of P3-ERP reactivity to alcohol cues and natural reward cues with alcohol use and problems were weak. However, differential P3 response to the two types of cues (i.e., reward dysregulation P3) showed consistent and robust associations with all indices of alcohol use and problems and differentiated high-risk from lower-risk drinkers. The current results support the idea that the differential incentive-motivational value of alcohol, relative to naturally rewarding activities, is associated with increased risk for substance misuse and dependence, and highlight a novel neurophysiological indicator-the reward dysregulation P3-of this differential reward valuation.

Interactive Effects of Naturalistic Drinking Context and Alcohol Sensitivity on Neural Alcohol Cue-Reactivity Responses.

BACKGROUND: Considerable evidence indicates that a low level of subjective response to alcohol's acute effects (i.e., low sensitivity) is associated with enhanced risk for alcohol use disorder (AUD). Recent work suggests that the highest risk response profile consists of blunted sensitivity to alcohol's sedation-like effects, coupled with enhanced sensitivity to alcohol's stimulation-like effects (i.e., differential sensitivity). A largely separate body of work indicates that enhanced reactivity to alcohol-related cues is associated with increased AUD risk. AIMS: The current research examined the extent to which variability in alcohol response phenotypes is associated with enhanced P3 event-related potential (ERP) responses to alcohol-related pictures (ACR-P3), and whether this reactivity varies according to depicted drinking contexts. METHODS: Eighty young adults (aged 18 to 33 years) completed a self-report measure of alcohol sensitivity (the Alcohol Sensitivity Questionnaire) and viewed images depicting drinking in naturalistic contexts, alcohol and nonalcohol beverages in isolation (devoid of naturalistic drinking context), and neutral nonbeverage control images while ERPs were recorded. RESULTS: Results indicated that blunted sensitivity to alcohol's sedative-like effects was differentially associated with enhanced ACR-P3 but reduced P3 reactivity to nonalcohol cues. Variation in sensitivity to alcohol's stimulant-like effects was not associated with differential ACR-P3. Contrary to predictions, these effects were not potentiated by drinking contexts. CONCLUSIONS: The current results replicate and extend previous work linking low alcohol sensitivity with enhanced incentive salience for alcohol-related cues and suggest that cues depicting drinking contexts are less likely to differentiate high-risk from low-risk drinkers.

Brain correlates and functional connectivity linking stress, autonomic dysregulation, and alcohol motivation.

High stress is a key risk factor for alcohol use disorder (AUD) and often accompanied by physiological dysregulation including autonomic nervous system (ANS) disruptions. However, neural mechanisms underlying drinking behaviors associated with stress and ANS disruptions remain unclear. The current study aims to understand neural correlates of stress, ANS disruptions, and subsequent alcohol intake in social drinkers with risky drinking. Using functional magnetic resonance imaging (fMRI), we investigated brain and heart rate (HR) autonomic responses during brief exposure to stress, alcohol, and neutral cues utilizing a well-validated, individualized imagery paradigm in 48 social drinkers of which 26 reported high-risk drinking (HD) while 22 reported low-risk drinking (LD) patterns. Results indicated that HD individuals showed stress and ANS disruptions with increased basal HR, stress-induced craving, and decreased brain response to stress exposure in frontal-striatal regions including the ventromedial prefrontal cortex (VmPFC), anterior cingulate cortex, striatum, insula, and temporal gyrus. Furthermore, whole-brain correlation analysis indicated that greater basal HR was associated with hypoactive VmPFC, but hyperactive medulla oblongata (MOb) responses during stress, with an inverse association between activity in the VmPFC and Mob (whole-brain corrected (WBC), p < 0.05). Functional connectivity with the MOb as a seed to the whole brain indicated that HD versus LD had decreased functional connectivity between the VmPFC and MOb during stress (WBC, p < 0.05). In addition, those with more compromised functional connectivity between the VmPFC and MOb during stress consumed greater amount of alcohol beverage during an experimental alcohol taste test conducted on a separate day, as well as in their self-reported weekly alcohol intake. Together, these results indicate that stress-related, dysfunctional VmPFC control over brain regions of autonomic arousal contributes to greater alcohol motivation and may be a significant risk factor for hazardous alcohol use in non-dependent social drinkers. Findings also suggest that restoring VmPFC integrity in modulating autonomic arousal during stress may be critical for preventing the development of AUD.

Alcohol craving and withdrawal at treatment entry prospectively predict alcohol use outcomes during outpatient treatment.

OBJECTIVE: Chronic alcohol use increases risk of alcohol craving and withdrawal symptoms (AW) as well as abstinence-related distress symptoms, in those entering alcohol use disorder (AUD) treatment. Here, we examined whether AW and alcohol craving in AUD patients entering outpatient treatment prospectively predicts future heavy drinking days/week (HDD) and additional alcohol use outcomes during 8-weeks of outpatient treatment, and their relationship to abstinence symptoms of depression, anxiety and sleep difficulties. METHODS: Participants were 80 treatment-seeking adults with current DSM-5 AUD (39% female; 43% White; 20-60 years) who completed assessments of AW and alcohol craving and also alcohol abstinence symptoms of depression, anxiety, and sleep quality at treatment intake. Participants were prospectively followed using daily diaries for alcohol intake during 8-week of standardized weekly relapse prevention counseling to support recovery. RESULTS: After accounting for demographic and pre-treatment alcohol use, greater alcohol craving at treatment entry predicted higher HDD (p < .013) as well as greater drinking days (DD: p < .004), average drinks per drinking day/week (AvgD: p < .001) and relapse to heavy drinking (p < .05), while higher levels of pretreatment AW symptoms interacted with treatment week to predict greater HDD (p < .018). Abstinence symptoms of depression, anxiety, and sleep difficulties were associated with craving and AW but did not predict any drinking-related outcomes. CONCLUSIONS: These results provide evidence that increased alcohol craving and AW may serve as prognostic indicators of greater risk of heavy drinking in outpatient treatment. Findings suggest the need to evaluate craving and AW at outpatient treatment entry and develop targeted treatments to specifically address the effects of craving and AW on drinking outcomes in outpatient AUD treatment.

Neural correlates linking trauma and physical symptoms.

Trauma and chronic pain frequently co-occur, but the underlying neurological mechanisms are poorly understood. The current study investigated the neural correlates of stress and physical symptoms in trauma patients using functional magnetic resonance imaging (fMRI) and follow-up smartphone surveys. Participants were 10 patients diagnosed with Trauma- and Stressor-Related Disorders and 18 demographically-matched healthy controls who completed a fMRI stress provocation task in which they viewed stressful and neutral-relaxing images. Subsequently, participants completed daily smartphone surveys which prospectively monitored their stress and physical symptoms for 30 days. The trauma group experienced a significantly higher frequency of physical symptoms than controls during the follow-up period. During stress, trauma patients exhibited increased activity in the hippocampus, insula, and sensorimotor areas, but decreased activity in the ventromedial prefrontal cortex (vmPFC), lateral prefrontal cortex (LPFC), and dorsal striatum relative to controls. In all participants, higher physical symptom frequency was significantly associated with a hyperactive left hippocampal response to stress. The current study reports that trauma is characterized by greater physical symptoms and decreased prefrontal but increased limbic responses to stress. Our findings suggest that trauma may increase physical health symptoms by compromising hippocampal function, which could also increase vulnerability to stress- and pain-related disorders.

Acute effect of alcohol on working memory updating.

AIMS: To examine the acute effects of alcohol on working memory (WM) updating, including potential variation across the ascending limb (AL) and descending limb (DL) of the blood alcohol concentration (BAC) time-course. DESIGN: A two-session experiment in which participants were randomly assigned to one of three beverage conditions [alcohol (males: 0.80 g/kg; females: 0.72 g/kg), active placebo (0.04 g/kg) or non-alcohol control (tonic)] and one of two BAC limb testing conditions (AL and DL or DL-only) for the second session, yielding a 3 (beverage) × 2 (time-points tested) × 3 (time-point) mixed factorial design with repeated measures on the latter factor. One of the repeated assessments is 'missing by design' in the DL-only condition. SETTING: A psychology laboratory at the University of Missouri campus in Columbia, MO, USA. PARTICIPANTS: Two hundred thirty-one community-dwelling young adults (51% female; aged 21-34 years) recruited from Columbia, MO, USA, tested between 2011 and 2013. MEASUREMENTS: Latent WM updating performance as indexed by shared variance in accuracy on three WM updating tasks (letter memory, keep track, spatial 2-back) at three time-points. FINDINGS: Multi-group modeling of latent WM updating indicated that performance among participants who consumed placebo or control beverages improved during the second session at time-points corresponding to AL (∆ from baseline in latent mean ± standard error (SE) + 0.5 ± 0.01, P < 0.001) and DL (+ 0.08 ± 0.01, P < 0.001). Alcohol consumption did not impair WM updating (∆ from baseline in latent mean ± SE, at AL: + 0.01 ± 0.01, P = 0.56; at DL: + 0.05 ± 0.01, P < 0.001), but attenuated performance improvements (equality of latent means across beverage groups at AL or DL: Δχ2(1)  ≥ 7.53, P < 0.01). CONCLUSIONS: Acute alcohol-induced impairment in working memory updating may be limited, but dampening of practice effects by alcohol could interfere with the completion of novel, unpracticed tasks.

Inhibition tasks are not associated with a variety of behaviors in college students.

Executive functioning (EF) is defined as a set of top-down processes used in reasoning, forming goals, planning, concentrating, and inhibition. It is widely believed that these processes are critical to self-control and, therefore, that performance on behavioral task measures of EF should be associated with individual differences in everyday life outcomes. The purpose of the present study was to test this core assumption, focusing on the EF facet of inhibition. A sample of 463 undergraduates completed five laboratory inhibition tasks, along with three self-report measures of self-control and 28 self-report measures of life outcomes. Results showed that although most of the life outcome measures were associated with self-reported self-control, only one of the outcomes was associated with inhibition task performance at the latent-variable level, and this association was in the unexpected direction. Furthermore, few associations were found at the individual task level. These findings challenge the criterion validity of lab-based inhibition tasks. More generally, when considered alongside the known lack of convergent validity between inhibition tasks and self-report measures of self-control, the findings cast doubt on the task's construct validity as measures of self-control processes. Potential methodological and theoretical reasons for the poor performance of laboratory-based inhibition tasks are discussed.

Simulated self-organization of death by inherited mutations.

An agent-based computer simulation of death by inheritable mutations in a changing environment shows a maximal population, or avoids extinction, at some intermediate mutation rate of the individuals. Our results indicate that death seems needed to allow for evolution of the fittest, as required by a changing environment.

Polygenic liability for schizophrenia predicts shifting-specific executive function deficits and tobacco use in a moderate drinking community sample.

Individuals with schizophrenia have higher lifetime rates of substance use disorders than the general population, and research suggests high comorbidity rates may be partially explained by shared genetic influences related to common underlying etiology. Moreover, deficits in executive functions are thought to be central to the diagnosis of schizophrenia and are likewise associated with alcohol and tobacco use. The current study examined the associations between schizophrenia polygenic risk scores and tobacco and alcohol use and the mediation of these associations by executive function sub-domains. Results from the Psychiatric Genomics Consortium's meta-analysis of genome-wide association studies of schizophrenia were used to calculate polygenic risk scores in a sample of moderate drinkers. Schizophrenia risk scores were significantly associated with shifting-specific executive function deficits and tobacco use phenotypes. However, risk scores were not significantly associated with alcohol use and executive functions were not significantly associated with either tobacco or alcohol use. These findings extend previous research by suggesting that genetic risk for schizophrenia may be associated with specific sub-domains of executive function as well as smoking. The lack of a relation with alcohol use suggests genetic factors related to schizophrenia and executive functioning may not influence drinking in a non-disordered, social-drinking sample.

Associations between executive functioning, affect-regulation drinking motives, and alcohol use and problems.

Motivation to use alcohol to regulate positive and negative affect and deficits in cognitive control (i.e., executive functions [EFs]) have both been associated with increased alcohol involvement and alcohol-related consequences. Although dual-process models predict that affect-driven motivations and cognitive control should interact to determine alcohol involvement and alcohol-related consequences, this intersection has remained largely unexplored. The present study examined the extent to which effects of enhancement and coping drinking motives on alcohol use, heavy drinking, and alcohol-related consequences are moderated by individual differences in three theorized components of EF. We anticipated, in general, that drinking motives would more strongly predict alcohol use, heavy drinking, and alcohol-related consequences among individuals low versus high in cognitive control-EF. Participants (N = 801) completed a battery of nine EF tasks, as well as measures of drinking motives, alcohol use, heavy drinking, and alcohol-related negative consequences. A baseline structural model indicated that (a) both enhancement motives and coping motives predicted alcohol use and heavy drinking, (b) both enhancement and coping motives exerted their effects on alcohol-related consequences both directly and indirectly via alcohol use, and (c) shifting-specific abilities were modestly positively associated with heavy drinking. Most important for the aims of the study, latent variable interaction analyses failed to provide consistent evidence that better EF abilities attenuate the effects of drinking motives on alcohol use, heavy drinking, and alcohol-related consequences, as predicted. (PsycINFO Database Record

Validation of Brief Young Adult Alcohol Consequences Questionnaire (B-YAACQ): Portuguese version.

Extant literature suggests that Portuguese college students frequently drinking alcohol and experience a variety of alcohol-related negative consequences. However, to our knowledge, there is no validated measure to assess negative consequences of drinking alcohol for college students in Portugal. This article describes a validation of the Portuguese version of the Brief Young Adult Alcohol Consequences Questionnaire. Originally developed by Kahler, Strong, and Read (2005), this 24-item questionnaire is a widely used self-report measure with strong psychometric properties and validity for the evaluation of the negative consequences of drinking in college students. We collected data from 620 students at the University of Coimbra (Portugal). Participants completed (a) a background questionnaire, (b) the Alcohol Use Disorders Identification Test (AUDIT), (c) the Daily Drinking Questionnaire - Revised (DDQ-R), and (d) the Brief Young Adult Alcohol Consequences Questionnaire (B-YAACQ) translated into Portuguese as part of this study. Analyses showed that items fit a unidimensional Rasch model well with items infit statistics raging from .82 to 1.27, supporting using all items to create a total sum score of the Portuguese version of the B-YAACQ. The Portuguese version of the B-YAACQ showed adequate internal reliability (α = .87) and concurrent validity. Results support its use and integration in research on interventions targeted to reduce adverse effects associated with excessive drinking among Portuguese college students.

Validation of brief young adult alcohol consequences questionnaire (B-YAACQ): Portuguese version

Extant literature suggests that Portuguese college students frequently drinking alcohol and experience a variety of alcohol-related negative consequences. However, to our knowledge, there is no validated measure to assess negative consequences of drinking alcohol for college students in Portugal. This article describes a validation of the Portuguese version of the Brief Young Adult Alcohol Consequences Questionnaire. Originally developed by Kahler, Strong, and Read (2005), this 24-item questionnaire is a widely used self-report measure with strong psychometric properties and validity for the evaluation of the negative consequences of drinking in college students. We collected data from 620 students at the University of Coimbra (Portugal). Participants completed (a) a background questionnaire, (b) the Alcohol Use Disorders Identification Test (AUDIT), (c) the Daily Drinking Questionnaire - Revised (DDQ-R), and (d) the Brief Young Adult Alcohol Consequences Questionnaire (B-YAACQ) translated into Portuguese as part of this study. Analyses showed that items fit a unidimensional Rasch model well with items infit statistics raging from .82 to 1.27, supporting using all items to create a total sum score of the Portuguese version of the B-YAACQ. The Portuguese version of the B-YAACQ showed adequate internal reliability (α = .87) and concurrent validity. Results support its use and integration in research on interventions targeted to reduce adverse effects associated with excessive drinking among Portuguese college students (AU)

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Simulated self-organization of death by inherited mutations

An agent-based computer simulation of death by inheritable mutations in a changing environment shows a maximal population, or avoids extinction, at some intermediate mutation rate of the individuals. Our results indicate that death seems needed to allow for evolution of the fittest, as required by a changing environment.

Simulação computacional de agentes individuais que se reproduzem e morrem por acúmulo de mutações herdadas mostra um máximo da população ou evita extinção, para taxas de mutação intermediárias. Assim, as mortes parecem necessárias para a evolução dos mais adaptados a um ambiente mutante.

Computer simulations for biological aging and sexual reproduction

The sexual version of the Penna model of biological aging, simulated since 1996, is compared here with alternative forms of reproduction as well as with models not involving aging. In particular we want to check how sexual forms of life could have evolved and won over earlier asexual forms hundreds of million years ago. This computer model is based on the mutation-accumulation theory of aging, using bits-strings to represent the genome. Its population dynamics is studied by Monte Carlo methods