Cognitive training and remediation interventions for substance use disorders: a Delphi consensus study.

AIMS: Substance use disorders (SUD) are associated with cognitive deficits that are not always addressed in current treatments, and this hampers recovery. Cognitive training and remediation interventions are well suited to fill the gap for managing cognitive deficits in SUD. We aimed to reach consensus on recommendations for developing and applying these interventions. DESIGN, SETTING AND PARTICIPANTS: We used a Delphi approach with two sequential phases: survey development and iterative surveying of experts. This was an on-line study. During survey development, we engaged a group of 15 experts from a working group of the International Society of Addiction Medicine (Steering Committee). During the surveying process, we engaged a larger pool of experts (n = 54) identified via recommendations from the Steering Committee and a systematic review. MEASUREMENTS: Survey with 67 items covering four key areas of intervention development: targets, intervention approaches, active ingredients and modes of delivery. FINDINGS: Across two iterative rounds (98% retention rate), the experts reached a consensus on 50 items including: (i) implicit biases, positive affect, arousal, executive functions and social processing as key targets of interventions; (ii) cognitive bias modification, contingency management, emotion regulation training and cognitive remediation as preferred approaches; (iii) practice, feedback, difficulty-titration, bias modification, goal-setting, strategy learning and meta-awareness as active ingredients; and (iv) both addiction treatment work-force and specialized neuropsychologists facilitating delivery, together with novel digital-based delivery modalities. CONCLUSIONS: Expert recommendations on cognitive training and remediation for substance use disorders highlight the relevance of targeting implicit biases, reward, emotion regulation and higher-order cognitive skills via well-validated intervention approaches qualified with mechanistic techniques and flexible delivery options.

The effect of N-acetylcysteine and working memory training on glutamate concentrations in the dACC and rACC in regular cocaine users - A randomized proof of concept study.

INTRODUCTION: Current treatments for cocaine use disorder (CUD) are not very effective and better treatments are needed. This study investigates the effectiveness of a combined intervention that targets the assumed underlying glutamate pathology in cocaine users. To this end, the combined effects of N-acetylcysteine (NAC) and working memory (WM) training on glutamate concentrations in the dorsal and rostral ACC were investigated in a randomized, double-blind placebo-controlled design. METHODS: In this study, 38 regular cocaine-using men were randomized to either 25-days with 2400 mg/day NAC and WM-training or 25 days with placebo with WM-training. Cocaine use, impulsivity, and glutamate concentrations in the dACC and rACC using proton Magnetic Resonance Spectroscopy were assessed at baseline and after treatment. RESULTS: Twenty-four participants completed the study, of which 9 received NAC and 15 received placebo. There were no baseline correlations of glutamate concentrations in the dACC or rACC with cocaine use measures or impulsivity. Additionally, there were no effects of NAC, WM-training, or the combination thereof on (changes in) glutamate concentrations in the dACC or rACC. DISCUSSION: This randomized proof of concept study could not confirm our hypotheses. Possible explanations are insufficient power and the possible absence of deviant baseline glutamate concentrations in the included participants. Future studies should consider larger samples and a non-using control group to confirm baseline deviations in glutamate in cocaine users.

Explicit and implicit attachment and the outcomes of acceptance and commitment therapy and cognitive behavioral therapy for depression.

BACKGROUND: Attachment theory predicts that patients who are not securely attached may benefit less from psychological treatment. However, evidence on the predictive role of attachment in the effectiveness of treatment for depression is limited. METHODS: Explicit attachment styles, levels of attachment anxiety and attachment avoidance, as well as implicit relational self-esteem and implicit relational anxiety were assessed in 67 patients with major depressive disorder (MDD) receiving Acceptance and Commitment Therapy (ACT) or Cognitive Behavioral Therapy (CBT). ANOVA and hierarchical regression analyses were performed to investigate the predictive power of explicit and implicit attachment measures on treatment outcome. RESULTS: Explicit attachment avoidance at pre-treatment significantly predicted reduction of depressive symptoms following treatment. Reductions in attachment anxiety and avoidance from pre- to post-treatment predicted better treatment outcomes. Neither one of the implicit measures, nor change in these measures from pre- tot post-treatment significantly predicted treatment outcome. CONCLUSIONS: Our findings show that attachment avoidance as well as reductions in avoidant and anxious attachment predict symptom reduction after psychological treatment for depression. Future research should use larger sample sizes to further examine the role of attachment orientation as moderator and mediator of treatment outcome. TRIAL REGISTRATION: clinicaltrials.gov; NCT01517503.

The effect of N-acetylcysteine and working memory training on neural mechanisms of working memory and cue reactivity in regular cocaine users.

The current study investigated the combined effects of N-acetylcysteine and working memory (WM) training on behavioral and neural mechanisms of cue reactivity and WM in cocaine users in a randomized, double-blind design. Twenty-four of 38 cocaine-using men completed a 25-day treatment with either 2400 mg/day NAC or placebo. Both groups performed WM-training. During pre- and post-test lab-visits, neural mechanisms of cue reactivity and WM, and cue-induced craving and WM performance were assessed. Additionally, exploratory whole brain analyses were performed. Overall, the hypotheses were not confirmed, possibly due to small sample size, low WM-training adherence and/or ongoing substance use.

Training Working Memory in Adolescents Using Serious Game Elements: Pilot Randomized Controlled Trial.

BACKGROUND: Working memory capacity has been found to be impaired in adolescents with various psychological problems, such as addictive behaviors. Training of working memory capacity can lead to significant behavioral improvements, but it is usually long and tedious, taxing participants' motivation to train. OBJECTIVE: This study aimed to evaluate whether adding game elements to the training could help improve adolescents' motivation to train while improving cognition. METHODS: A total of 84 high school students were allocated to a working memory capacity training, a gamified working memory capacity training, or a placebo condition. Working memory capacity, motivation to train, and drinking habits were assessed before and after training. RESULTS: Self-reported evaluations did not show a self-reported preference for the game, but participants in the gamified working memory capacity training condition did train significantly longer. The game successfully increased motivation to train, but this effect faded over time. Working memory capacity increased equally in all conditions but did not lead to significantly lower drinking, which may be due to low drinking levels at baseline. CONCLUSIONS: We recommend that future studies attempt to prolong this motivational effect, as it appeared to fade over time.

Reprint of The effect of N-acetylcysteine and working memory training on cocaine use, craving and inhibition in regular cocaine users: correspondence of lab assessments and Ecological Momentary Assessment.

INTRODUCTION: Effective treatment for cocaine use disorder should dampen hypersensitive cue-induced motivational processes and/or strengthen executive control. Using a randomized, double-blind, placebo-controlled intervention, the primary aim of this study was to investigate the effect of N-Acetylcysteine (NAC) and working memory (WM)-training to reduce cocaine use and craving and to improve inhibition assessed in the laboratory and during Ecological Momentary Assessment (EMA). The second aim was to examine correspondence between laboratory and EMA data. METHODS: Twenty-four of 38 cocaine-using men completed a 25-day intervention with 2400mg/day NAC or placebo and WM-training as well as two lab-visits assessing cocaine use, craving and inhibition (Stop Signal task). Additionally, cocaine use, craving and cognition (Stroop task) were assessed using EMA during treatment, with 26 participants completing 819 assessments. RESULTS: Cocaine problems according to the Drug Use Disorder Identification Test (DUDIT) decreased more after NAC than after placebo, and the proportion of cocaine-positive urines at lab-visit 2 was lower in the NAC group. No NAC effects were found on craving. For cocaine use and craving, results from the lab data were generally similar to EMA results. NAC also showed some effects on cognitive control: improved inhibition assessed with the Stop Signal task in the lab, and decreased classic Stroop performance during EMA. There were no significant effects of number of completed WM-training sessions. CONCLUSIONS: Overall this study revealed mixed findings regarding the treatment of cocaine use disorders with NAC and WM-training. The effect of NAC on inhibition should be further investigated.

Computer training of attention and inhibition for youngsters with obesity: A pilot study.

Obesity is a widespread problem that starts from an early age. Previous studies suggest that obese youngsters have an attentional bias and an automatic approach tendency towards high-calorie food and display difficulties inhibiting impulses, which may result in a higher intake of (high-calorie) food. An interesting idea for improvement of the current obesity treatment is adding a program that enables to train their difficulties. Subjects were 36 youngsters aged 9-15 years old from an inpatient treatment program for obesity, randomized over a training group and an active control group. The training consisted of six training sessions with cognitive tasks aimed at enhancing inhibition towards unhealthy food items (with a go/no-go task), as well as decreasing a food approach bias (using an approach/avoidance task) and a food attentional bias (using a dot-probe task). The current study evaluated the feasibility, acceptability and initial effectiveness of the training and explores if these characteristics helps obese youngsters to maintain weight-loss once they return home at the end of their inpatient treatment program. Results on the cognitive performances were investigated during two measurement sessions, spread over 5 weeks while weight evolution was followed over 13 weeks. Results showed that the training program was feasible and acceptable to the majority of participants and clinicians. Furthermore, the preliminary findings suggest that the training tasks used were ineffective in this group of obese children. Lessons learned and suggestions for future research are discussed.

The effect of N-acetylcysteine and working memory training on cocaine use, craving and inhibition in regular cocaine users: correspondence of lab assessments and Ecological Momentary Assessment.

INTRODUCTION: Effective treatment for cocaine use disorder should dampen hypersensitive cue-induced motivational processes and/or strengthen executive control. Using a randomized, double-blind, placebo-controlled intervention, the primary aim of this study was to investigate the effect of N-Acetylcysteine (NAC) and working memory (WM)-training to reduce cocaine use and craving and to improve inhibition assessed in the laboratory and during Ecological Momentary Assessment (EMA). The second aim was to examine correspondence between laboratory and EMA data. METHODS: Twenty-four of 38 cocaine-using men completed a 25-day intervention with 2400mg/day NAC or placebo and WM-training as well as two lab-visits assessing cocaine use, craving and inhibition (Stop Signal task). Additionally, cocaine use, craving and cognition (Stroop task) were assessed using EMA during treatment, with 26 participants completing 819 assessments. RESULTS: Cocaine problems according to the Drug Use Disorder Identification Test (DUDIT) decreased more after NAC than after placebo, and the proportion of cocaine-positive urines at lab-visit 2 was lower in the NAC group. No NAC effects were found on craving. For cocaine use and craving, results from the lab data were generally similar to EMA results. NAC also showed some effects on cognitive control: improved inhibition assessed with the Stop Signal task in the lab, and decreased classic Stroop performance during EMA. There were no significant effects of number of completed WM-training sessions. CONCLUSIONS: Overall this study revealed mixed findings regarding the treatment of cocaine use disorders with NAC and WM-training. The effect of NAC on inhibition should be further investigated.

Training Behavioral Control in Adolescents Using a Serious Game.

OBJECTIVE: Risk taking, such as heavy alcohol use, is commonplace among adolescents. Nevertheless, prolonged alcohol use at this age can lead to severe health problems. The goal of this study was to develop and evaluate a serious game training ("The Fling"), aimed at increasing behavioral control in adolescents and thereby helping them to improve control over their alcohol use. The game training was compared to a game placebo and a nongame training version in a randomized controlled trial. MATERIALS AND METHODS: A sample of 185 adolescents (mean age 14.9 years) in secondary education participated in the study. They performed four sessions of training, as well as a set of questionnaires and cognitive assessment tasks before and after the training. The basis for the training was the stop-signal paradigm, aimed at increasing behavioral control. RESULTS: The game variants were shown to motivate adolescents beyond the level of the nongame version. Behavioral control improved significantly over time, but this effect was also present in the game placebo, suggesting that the game activities alone may have had a beneficial effect on our measures of behavioral control. As baseline drinking levels were low, no significant training effects on drinking behavior were found. CONCLUSIONS: Although the current results are not yet conclusive as to whether "The Fling" is effective as a cognitive training, they do warrant further research in this direction. This study also shows that serious games may be uniquely suitable to bridge the gap between an evidence-based training paradigm and an attractive, motivating training environment.

Attentional Bias Modification With Serious Game Elements: Evaluating the Shots Game.

BACKGROUND: Young adults often experiment with heavy use of alcohol, which poses severe health risks and increases the chance of developing addiction problems. In clinical patients, cognitive retraining of automatic appetitive processes, such as selective attention toward alcohol (known as "cognitive bias modification of attention," or CBM-A), has been shown to be a promising add-on to treatment, helping to prevent relapse. OBJECTIVE: To prevent escalation of regular use into problematic use in youth, motivation appears to play a pivotal role. As CBM-A is often viewed as long and boring, this paper presents this training with the addition of serious game elements as a novel approach aimed at enhancing motivation to train. METHODS: A total of 96 heavy drinking undergraduate students carried out a regular CBM-A training, a gamified version (called "Shots"), or a placebo training version over 4 training sessions. Measures of motivation to change their behavior, motivation to train, drinking behavior, and attentional bias for alcohol were included before and after training. RESULTS: Alcohol attentional bias was reduced after training only in the regular training condition. Self-reported drinking behavior was not affected, but motivation to train decreased in all conditions, suggesting that the motivational features of the Shots game were not enough to fully counteract the tiresome nature of the training. Moreover, some of the motivational aspects decreased slightly more in the game condition, which may indicate potential detrimental effects of disappointing gamification. CONCLUSIONS: Gamification is not without its risks. When the motivational value of a training task with serious game elements is less than expected by the adolescent, effects detrimental to their motivation may occur. We therefore advise caution when using gamification, as well as underscore the importance of careful scientific evaluation.

Exploring Elements of Fun to Motivate Youth to Do Cognitive Bias Modification.

OBJECTIVE: Heavy drinking among young adults poses severe health risks, including development of later addiction problems. Cognitive retraining of automatic appetitive processes related to alcohol (so-called cognitive bias modification [CBM]) may help to prevent escalation of use. Although effective as a treatment in clinical patients, the use of CBM in youth proves more difficult, as motivation in this group is typically low, and the paradigms used are often viewed as boring and tedious. This article presents two separate studies that focused on three approaches that may enhance user experience and motivation to train: a serious game, a serious game in a social networking context, and a mobile application. MATERIALS AND METHODS: In the Game Study, 77 participants performed a regular CBM training, aimed at response matching, a gamified version, or a placebo version of that training. The gamified version was presented as a stand-alone game or in the context of a social network. In the Mobile Study, 64 participants completed a different CBM training, aimed at approach bias, either on a computer or on their mobile device. RESULTS: Although no training effects were found in the Game Study, adding (social) game elements did increase aspects of the user experience and motivation to train. The mobile training appeared to increase motivation to train in terms how often participants trained, but this effect disappeared after controlling for baseline motivation to train. CONCLUSIONS: Adding (social) game elements can increase motivation to train, and mobile training did not underperform compared with the regular training in this sample, which warrants more research into motivational elements for CBM training in younger audiences.

Executive Functions and Motivation as Moderators of the Relationship Between Automatic Associations and Alcohol Use in Problem Drinkers Seeking Online Help.

BACKGROUND: Dual process models posit that problem drinking is maintained by an imbalance between relatively strong automatic processes and weak controlled processes, a combination of executive functions and motivation. Few studies have examined how the interplay between automatic processes and executive functions is affected by motivation to change. This study examined this relationship in problem drinkers seeking online help to change their alcohol use. It was expected that executive functions (i.e., working memory, response inhibition) would moderate the relationship between automatic (valence and approach) associations and alcohol use and that this effect would be stronger in individuals with strong motivation to change. METHODS: A sample of 302 problem drinkers (mean age: 51.7 years) participated in this study as part of the baseline assessment before an Internet intervention. Participants completed an online version of the brief Implicit Association Test (valence and approach associations), the self-ordered pointing task (working memory), the Stroop task (response inhibition), the Readiness to Change Questionnaire (motivation to change), and the Timeline Follow-Back Questionnaire (alcohol use). Hierarchical moderated regression analysis was used to test the 4 hypothesized 3-way interactions. RESULTS: As expected, the interaction between valence associations and working memory only predicted alcohol use among individuals with strong motivation. This pattern was neither found for response inhibition nor for approach associations. CONCLUSIONS: Results provide partial support for the moderating role of motivation in the interplay between automatic processes and executive functions. Future studies should investigate this relationship in participants with the full range of motivation and alcohol use.

Weaknesses in executive functioning predict the initiating of adolescents' alcohol use.

Recently, it has been suggested that impairments in executive functioning might be risk factors for the onset of alcohol use rather than a result of heavy alcohol use. In the present study, we examined whether two aspects of executive functioning, working memory and response inhibition, predicted the first alcoholic drink and first binge drinking episode in young adolescents using discrete survival analyses. Adolescents were selected from several Dutch secondary schools including both mainstream and special education (externalizing behavioral problems). Participants were 534 adolescents between 12 and 14 years at baseline. Executive functioning and alcohol use were assessed four times over a period of two years. Working memory uniquely predicted the onset of first drink (p=.01) and first binge drinking episode (p=.04) while response inhibition only uniquely predicted the initiating of the first drink (p=.01). These results suggest that the association of executive functioning and alcohol consumption found in former studies cannot simply be interpreted as an effect of alcohol consumption, as weaknesses in executive functioning, found in alcohol naïve adolescents, predict the initiating of (binge) drinking. Though, prolonged and heavy alcohol use might further weaken already existing deficiencies.

Cognitive Bias Modification for adolescents with substance use problems--Can serious games help?

BACKGROUND AND OBJECTIVES: Excessive use of psychoactive substances and resulting disorders are a major societal problem, and the most prevalent mental disorder in young men. Recent reviews have concluded that Cognitive Bias Modification (CBM) shows promise as an intervention method in this field. As adolescence is a critical formative period, successful early intervention may be key in preventing later substance use disorders that are difficult to treat. One issue with adolescents, however, is that they often lack the motivation to change their behavior, and to engage in multisession cognitive training programs. The upcoming use of serious games for health may provide a solution to this motivational challenge. METHODS: As the use of game-elements in CBM is fairly new, there are very few published studies in this field. This review therefore focuses on currently available evidence from similar fields, such as cognitive training, as well as several ongoing CBM gamification projects, to illustrate the general principles. RESULTS: A number of steps in the gamification process are identified, starting with the original, evidence-based CBM task, towards full integration in a game. While more data is needed, some steps seem better suited for CBM gamification than others. Based on the current evidence, several recommendations are made. LIMITATIONS: As the field is still in its infancy, further research is needed before firm conclusions can be drawn. CONCLUSIONS: Gamified CBM may be a promising way to reach at risk youth, but the term "game" should be used with caution. Suggestions are made for future research.

Do online assessed self-report and behavioral measures of impulsivity-related constructs predict onset of substance use in adolescents?

INTRODUCTION: To prospectively predict the onset of use of alcohol, cigarettes and marijuana among Dutch adolescents, using behavioral and self-report measures of impulsivity-related facets. Specifically, we investigated whether behavioral measures of impulsivity predicted the onset of substance use above and beyond self-report measures of impulsivity and sensation seeking in an online sample. METHODS: Self-report and behavioral data from 284 adolescents (195 girls, mean age = 14.8 years, SD = 1.26) were collected at four time points over a period of two years, using an online survey system. Impulsivity-related facets were assessed at time point 1 with the Delay Discounting Task, the Balloon Analogue Risk Task and the Passive Avoidance Learning Task. We conducted logistic regression analysis to examine whether behavioral and self-report measures uniquely predicted onset of alcohol use, heavy episodic drinking, smoking and marijuana use. RESULTS: Onset of cigarette smoking was associated with behavioral assessment of impulsive decision making, but not after controlling for self-reported impulsivity and sensation seeking. Behavioral measures were sometimes associated with, but appeared not to prospectively predict, the onset of substance use in this online sample after controlling for self-report measures. CONCLUSIONS: Based on the present results, the added value of online behavioral assessment of impulsivity-related factors in the prediction of onset of substance use was not confirmed. We suggest that factors specific to each behavioral task underlie their lack of prediction and suggest that future research addresses limitations of current behavioral tasks to increase their validity in online testing.

Implicit motivational processes underlying smoking in american and dutch adolescents.

INTRODUCTION: Research demonstrates that cognitive biases toward drug-related stimuli are correlated with substance use. This study aimed to investigate differences in cognitive biases (i.e., approach bias, attentional bias, and memory associations) between smoking and non-smoking adolescents in the US and the Netherlands. Within the group of smokers, we examined the relative predictive value of the cognitive biases and impulsivity related constructs (including inhibition skills, working memory, and risk taking) on daily smoking and nicotine dependence. METHOD: A total of 125 American and Dutch adolescent smokers (n = 67) and non-smokers (n = 58) between 13 and 18 years old participated. Participants completed the smoking approach-avoidance task, the classical and emotional Stroop task, brief implicit associations task, balloon analog risk task, the self-ordering pointing task, and a questionnaire assessing level of nicotine dependence and smoking behavior. RESULTS: The analytical sample consisted of 56 Dutch adolescents (27 smokers and 29 non-smokers) and 37 American adolescents (19 smokers and 18 non-smokers). No differences in cognitive biases between smokers and non-smokers were found. Generally, Dutch adolescents demonstrated an avoidance bias toward both smoking and neutral stimuli whereas the American adolescents did not demonstrate a bias. Within the group of smokers, regression analyses showed that stronger attentional bias and weaker inhibition skills predicted greater nicotine dependence while weak working memory predicted more daily cigarette use. CONCLUSION: Attentional bias, inhibition skills, and working memory might be important factors explaining smoking in adolescence. Cultural differences in approach-avoidance bias should be considered in future research.