Reliability and validity of measures of attentional bias towards threat in unselected student samples: seek, but will you find?

Although attentional bias (AB) is considered a key characteristic of anxiety problems, the psychometric properties of most AB measures are either problematic or unknown. We conducted two experiments in which we addressed the reliability, convergent validity, and concurrent validity of different AB measures in unselected student samples. In Experiment 1 (N = 66), the visual probe task and the emotional flanker task yielded unreliable estimates of AB. Both the relevant and irrelevant feature visual search task yielded better reliability estimates, yet AB scores did not correlate significantly with each other nor with self-reported social anxiety. In Experiment 2 (N = 60), we retained only the visual search tasks. The relevant feature visual search task was again highly reliable, but it did not correlate significantly with anxiety measures. The irrelevant feature visual search task yielded only small reliability estimates, yet one of the scores was significantly correlated with implicit (but not self-reported or physiological) measures of social anxiety. Together, our results advocate the use of variants of visual search tasks to measure AB and they underline the importance of fundamental psychometric testing in AB research.

Knowledge about the predictive value of reward conditioned stimuli modulates their interference with cognitive processes.

Stimuli conditioned with a substance can generate drug-approach behaviors due to their acquired motivational properties. According to implicit theories of addiction, these stimuli can decrease cognitive control automatically. The present study (n = 49) examined whether reward-associated stimuli can interfere with cognitive processes in the absence of knowledge about stimulus-outcome contingencies. Conditioned stimuli (CS) were paired with high-reward (HR) or low-reward (LR) probabilities of monetary reward using a Pavlovian learning task. Participants were categorized as Aware or Unaware of contingencies using a Bayesian analysis. CS were then used as task-irrelevant distractors in modified flanker and N-back tasks. Results show HR CS can generate increased interference in the flanker task for participants Unaware of contingencies, contributing further evidence for the existence of implicit Pavlovian conditioning. For the N-back task, working memory performance was affected by HR CS, albeit only for Aware participants. These results suggest that CS can interfere implicitly with cognitive processes in a similar way to drug-related stimuli. Such an effect could occur in a stimulus-driven fashion, devoid of top-down goal-directedness. These findings have implications for the conceptualization and study of implicit processes in addiction and highlights the necessity to reconsider the measurement of such phenomena.

Cognitive Bias Modification for Behavior Change in Alcohol and Smoking Addiction: Bayesian Meta-Analysis of Individual Participant Data.

Cognitive Bias Modification (CBM) refers to a family of interventions targeting substance-related cognitive biases, which have been found to play a role in the maintenance of addictive behaviors. In this study, we conducted a Bayesian meta-analysis of individual patient data from studies investigating the effects of CBM as a behavior change intervention for the treatment of alcohol and tobacco use disorders, in individuals aware of the behavior change goal of the studies. Main outcomes included reduction in the targeted cognitive biases after the intervention and in substance use or relapse rate at the short-to-long term follow-up. Additional moderators, both at the study-level (type of addiction and CBM training) and at the participant-level (amount of completed training trials, severity of substance use), were progressively included in a series of hierarchical mixed-effects models. We included 14 studies involving 2435 participants. CBM appeared to have a small effect on cognitive bias (0.23, 95% credible interval = 0.06-0.41) and relapse rate (-0.27, 95% credible interval = -0.68 - 0.22), but not on reduction of substance use. Increased training practice showed a paradoxical moderation effect on relapse, with a relatively lower chance of relapse in the control condition with increased practice, compared to the training condition. All effects were associated with extremely wide 95% credible intervals, which indicate the absence of enough evidence in favor or against a reliable effect of CBM on cognitive bias and relapse rate in alcohol and tobacco use disorders. Besides the need for a larger body of evidence, research on the topic would benefit from a stronger adherence to the current methodological standards in randomized controlled trial design and the systematic investigation of shared protocols of CBM.

Annual Research Review: On the developmental neuropsychology of substance use disorders.

BACKGROUND: Adolescence represents a period of development during which critical biological, as well as social and cognitive, changes occur that are necessary for the transition into adulthood. A number of researchers have suggested that the pattern of normative brain changes that occurs during this period not only predisposes adolescents to engage in risk behaviours, such as experimentation with drugs, but that they additionally make the adolescent brain more vulnerable to the direct pharmacological impact of substances of abuse. The neural circuits that we examine in this review involve cortico-basal-ganglia/limbic networks implicated in the processing of rewards, emotion regulation, and the control of behaviour, emotion and cognition. FINDINGS AND CONCLUSIONS: We identify certain neurocognitive and personality/comorbidity-based risk factors for the onset of substance misuse during adolescence, and summarise the evidence suggesting that these risk factors may be further impacted by the direct effect of drugs on the underlying neural circuits implicated in substance misuse vulnerability.

Alcohol-related cues reduce cognitive control in social drinkers.

Alcohol-related stimuli attract social drinkers' attention (attentional bias). We devised a dual task to test whether attentional biases to alcohol-related stimuli are modulated by cognitive control mechanisms. Sixteen nondependent healthy social drinkers were required to respond to the direction of a central arrow (target) and to ignore adjacent congruent (low cognitive load) or incongruent (high cognitive load) distracting arrows (flankers) in the presence of alcohol-related, neutral or plain grey backgrounds. Percentages of correct responses to the target and reaction time of correct responses (latency) were recorded. The difference score of the flanker effect (latency incongruent-latency congruent) between trials when backgrounds were alcohol-related relative to when they were neutral was also computed. Latencies increased in the presence of the alcohol-related images relative to both the neutral and the grey displays, but only under high cognitive load. Response accuracy did not show this significant difference. The flanker effect difference score correlated positively with the participants' average weekly alcohol intake. The data suggest that the presence of alcohol-associated stimuli attenuates cognitive control processes in social drinkers, an effect that was associated with the participants' average weekly alcohol intake.

Differential brain responses for perception of pain during empathic response in binge drinkers compared to non-binge drinkers.

Individuals who engage in binge drinking behaviors may show evidence of impaired cognitive function and emotional dysregulation. Impaired empathy, characterized by a reduced ability to understand and respond appropriately to feelings of others, is increasingly recognized for its role in Alcohol Use Disorders (AUD). The present study examined a population of young adult social drinkers to compare individuals who show binge drinking behavior to those who do not on measures of empathic processing and associated neural responses. A secondary aim explored similarities and differences between binge drinkers living in the UK and France. Alcohol drinking history and impulsivity ratings were recorded from seventy-one participants [(37 UK (Binge drinkers N = 19); 34 France (Binge drinkers N = 17)], who then underwent a neuroimaging study. During functional magnetic resonance imaging, participants viewed images of bodily pain (vs. no-pain), while adopting the perspective of self (pain recipient) or other (observer of someone else experiencing pain). Anterior midcingulate cortex (aMCC) and insula activation distinguished pain from no-pain conditions. Binge drinkers showed stronger regional neural activation than non-binge drinkers within a cluster spanning fusiform gyrus and inferior temporal gyrus, encompassing the Fusiform Body Area. Binge drinkers compared to non-binge drinkers also took longer to respond when viewing pictures depicting pain, in particular when adopting the perspective of self. Relationships between changes in brain activation and behavioural responses in pain versus no pain conditions (self or other perspective) indicated that whereas non-binge drinkers engage areas supporting self to other distinction, binge drinkers do not. Our findings suggest that alcohol binge drinking is associated with different empathy-related behavioral and brain responses, consistent with the proposed importance of empathy in the development of AUD.

GABRB1 Single Nucleotide Polymorphism Associated with Altered Brain Responses (but not Performance) during Measures of Impulsivity and Reward Sensitivity in Human Adolescents.

Variations in genes encoding several GABAA receptors have been associated with human drug and alcohol abuse. Among these, a number of human studies have suggested an association between GABRB1, the gene encoding GABAA receptor ß1 subunits, with Alcohol dependence (AD), both on its own and comorbid with other substance dependence and psychiatric illnesses. In the present study, we hypothesized that the GABRB1 genetically-associated increased risk for developing alcoholism may be associated with impaired behavioral control and altered sensitivity to reward, as a consequence of altered brain function. Exploiting the IMAGEN database (Schumann et al., 2010), we explored in a human adolescent population whether possession of the minor (T) variant of the single nucleotide polymorphism (SNP) rs2044081 is associated with performance of tasks measuring aspects of impulsivity, and reward sensitivity that are implicated in drug and alcohol abuse. Allelic variation did not associate with altered performance in either a stop-signal task (SST), measuring one aspect of impulsivity, or a monetary incentive delay (MID) task assessing reward anticipation. However, increased functional magnetic resonance imaging (fMRI) blood-oxygen-level dependent (BOLD) response in the right hemisphere inferior frontal gyrus (IFG), left hemisphere caudate/insula and left hemisphere inferior temporal gyrus (ITG) during MID performance was higher in the minor (T) allelic group. In contrast, during SST performance, the BOLD response found in the right hemisphere supramarginal gyrus, right hemisphere lingual and left hemisphere inferior parietal gyrus indicated reduced responses in the minor genotype. We suggest that ß1-containing GABAA receptors may play a role in excitability of brain regions important in controlling reward-related behavior, which may contribute to susceptibility to addictive behavior.

Alcohol affects neuronal substrates of response inhibition but not of perceptual processing of stimuli signalling a stop response.

Alcohol impairs inhibitory control, including the ability to terminate an initiated action. While there is increasing knowledge about neural mechanisms involved in response inhibition, the level at which alcohol impairs such mechanisms remains poorly understood. Thirty-nine healthy social drinkers received either 0.4 g/kg or 0.8 g/kg of alcohol, or placebo, and performed two variants of a Visual Stop-signal task during acquisition of functional magnetic resonance imaging (fMRI) data. The two task variants differed only in their instructions: in the classic variant (VSST), participants inhibited their response to a "Go-stimulus" when it was followed by a "Stop-stimulus". In the control variant (VSST_C), participants responded to the "Go-stimulus" even if it was followed by a "Stop-stimulus". Comparison of successful Stop-trials (Sstop)>Go, and unsuccessful Stop-trials (Ustop)>Sstop between the three beverage groups enabled the identification of alcohol effects on functional neural circuits supporting inhibitory behaviour and error processing. Alcohol impaired inhibitory control as measured by the Stop-signal reaction time, but did not affect other aspects of VSST performance, nor performance on the VSST_C. The low alcohol dose evoked changes in neural activity within prefrontal, temporal, occipital and motor cortices. The high alcohol dose evoked changes in activity in areas affected by the low dose but importantly induced changes in activity within subcortical centres including the globus pallidus and thalamus. Alcohol did not affect neural correlates of perceptual processing of infrequent cues, as revealed by conjunction analyses of VSST and VSST_C tasks. Alcohol ingestion compromises the inhibitory control of action by modulating cortical regions supporting attentional, sensorimotor and action-planning processes. At higher doses the impact of alcohol also extends to affect subcortical nodes of fronto-basal ganglia- thalamo-cortical motor circuits. In contrast, alcohol appears to have little impact on the early visual processing of infrequent perceptual cues. These observations clarify clinically-important effects of alcohol on behaviour.

Acute alcohol effects on attentional bias are mediated by subcortical areas associated with arousal and salience attribution.

Acute alcohol ingestion increases attentional bias to alcohol-related stimuli; however, the underlying cognitive and brain mechanisms remain unknown. We combined functional magnetic resonance imaging (fMRI) with performance of a dual task that probed attentional distraction by alcohol-related stimuli during 'conflict' processing: the Concurrent Flanker/Alcohol-Attentional bias task (CFAAT). In this task, an Eriksen Flanker task is superimposed on task-unrelated background pictures with alcohol-associated or neutral content. Participants respond to the direction of a central 'target' arrow and ignore adjacent congruent (low cognitive load) or incongruent (high cognitive load) 'flanking' arrows. Using a between-subject design, 40 healthy moderate-to-heavy social drinkers received either no alcohol (placebo), 0.4 g/kg (low dose), or 0.8 g/kg (high dose) of alcohol, and underwent fMRI while performing the CFAAT. The low alcohol dose, relative to placebo, increased response latencies on trials with alcohol-associated backgrounds and, under low cognitive load, increased the activity evoked by these pictures within a medial hypothalamic region. Under high cognitive load, the low alcohol dose, relative to placebo, elicited greater activity within a more lateral hypothalamic region, and reduced activity within frontal motor areas. The high alcohol dose, relative to placebo, did not reliably affect response latencies or neural responses to background images, but reduced overall accuracy under high cognitive load. This effect correlated with changes in reactivity within medial and dorsal prefrontal cortices. These data suggest that alcohol at a low dose primes attentional bias to alcohol-associated stimuli, an effect mediated by activation of subcortical hypothalamic areas implicated in arousal and salience attribution.

Unique brain areas associated with abstinence control are damaged in multiply detoxified alcoholics.

BACKGROUND: The ability to abstain from drinking, despite incentives to imbibe, is essential to recovery from alcoholism. METHODS: We used an incentive conflict task to investigate ability to abstain from responding during presentations of incentive cues. Both alcoholic (n = 23) and healthy subjects (n = 22) were required to withhold responding during the simultaneous presentation of two visual stimuli in which the individual presentation allowed responding for monetary reward. Brain structures activated during performance of the task were studied using functional magnetic resonance imaging in healthy volunteers (n = 8), and changes in gray matter volume were studied in a separate group of patients (n = 29) compared with control subjects (n = 31) in regions of interest identified on functional magnetic resonance imaging. RESULTS: Abstinent alcoholic patients were severely impaired on the incentive conflict task. The impairment was greater in patients with experience of several versus a single detoxification. Healthy volunteers, during the same incentive conflict task, showed distinct patterns of brain activation (including gyrus rectus, ventromedial prefrontal cortex, and superior frontal gyrus). Reduction of gray matter volume in ventromedial prefrontal cortex and superior frontal gyrus of patients was more extensive in those with multiple detoxifications. CONCLUSIONS: Performance deficits in alcoholics are associated with withdrawal-induced impairments in prefrontal subfields, which are exacerbated following repeated episodes of detoxification. Detoxification thus compromises functional and structural integrity of prefrontal cortex and may thus impair the ability to control future drinking. Performance in the incentive conflict task is a sensitive biomarker for such deficits.