Neuroscience-informed classification of prevention interventions in substance use disorders: An RDoC-based approach.

Neuroscience has contributed to uncover the mechanisms underpinning substance use disorders (SUD). The next frontier is to leverage these mechanisms as active targets to create more effective interventions for SUD treatment and prevention. Recent large-scale cohort studies from early childhood are generating multiple levels of neuroscience-based information with the potential to inform the development and refinement of future preventive strategies. However, there are still no available well-recognized frameworks to guide the integration of these multi-level datasets into prevention interventions. The Research Domain Criteria (RDoC) provides a neuroscience-based multi-system framework that is well suited to facilitate translation of neurobiological mechanisms into behavioral domains amenable to preventative interventions. We propose a novel RDoC-based framework for prevention science and adapted the framework for the existing preventive interventions. From a systematic review of randomized controlled trials using a person-centered drug/alcohol preventive approach for adolescents, we identified 22 unique preventive interventions. By teasing apart these 22 interventions into the RDoC domains, we proposed distinct neurocognitive trajectories which have been recognized as precursors or risk factors for SUDs, to be targeted, engaged and modified for effective addiction prevention.

Which intellectual activities are related to cognitive reserve? Introduction and testing a three-dimensional model.

BACKGROUND: A common belief among people and some researchers is that keeping yourself mentally active may decrease the risk of dementia. Over the past years, despite widespread efforts to identify proxies for protecting cognitive reserve against age-related changes, it is still not clear what type of intellectual activity would be beneficial for cognitive reserve. To fill this gap, we propose a three-dimensional model of intellectual activity. According to this conceptual model, intellectual activities could be distinguished based on their locations in a three-dimensions space, including; (1) Activation: active vs. passive, (2) Novelty: novel vs. familiar, and (3) Productivity: productive vs. receptive. We assumed that the activities that are categorized as more active, novel, and productive could be considered as a cognitive reserve proxy. METHODS: To test this hypothesis, a sample of 237 participants older than 50 years (Mage = 58.76 ± 6.66; 63.7% women) was recruited to take part in the study. Episodic, semantic and working memory were assessed with computerized battery tests (Sepidar) and a self-report questionnaire was used to assess intellectual activities. Activities were categorized in terms of; (1) passive, familiar, and receptive activities (radio/watching TV), (2) active, familiar, and receptive activities (solving crosswords), (3) active, novel, and receptive activities (reading), and (4) active, novel, and productive activities (writing). RESULTS: The results indicated that writing moderates the effect of age on episodic and semantic memory. Reading only moderates the effect of age on semantic memory, and radio/watching TV and solving crosswords do not play a role in moderation analysis. CONCLUSIONS: Our finding suggests that intellectual activities have different moderating effects on the relationships between age and memory performance. Individuals with high levels of participation in novel and productive activities over the life course are less likely to clinically demonstrate cognitive impairments. Our results support the potential benefit of the three-dimensional model to provide a better insight into the complex role of intellectual activities in cognitive reserve, particularly for older adults. Further research is needed to evaluate the efficacy and the benefits of the model.

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.

How do cannabis users mentally travel in time? Evidence from an fMRI study of episodic future thinking.

RATIONALE: Episodic future thinking (EFT) is a cognitive function that allows individuals to imagine novel experiences that may happen in the future. Prior studies show that EFT is impaired in different groups of substance users. However, there is no evidence regarding the neurobiological mechanisms of EFT in cannabis users. OBJECTIVES: We aimed to compare brain activations of regular cannabis users and non-using controls during an EFT fMRI task. Exploratory analyses were also conducted to investigate the association between EFT and cannabis use variables (e.g., duration of use, age onset, frequency of use). METHODS: Twenty current cannabis users and 22 drug-naïve controls underwent an fMRI scanning session while completing a task involving envisioning future-related events and retrieval of past memories as a control condition. The EFT fMRI task was adapted from the autobiographical interview and composed of 20 auditory cue sentences (10 cues for past and 10 cues for future events). Participants were asked to recall a past or generate a future event, in response to the cues, and then rate their vividness after each response. RESULTS: We found that cannabis users compared to non-user controls had lower activation within the cerebellum, medial and superior temporal gyrus, lateral occipital cortex, and occipital fusiform gyrus while envisioning future events. Cannabis users rated the vividness of past events significantly lower than non-users (P < 0.005). There were marginal group differences for rating the vividness of future events (P = 0.052). Significant correlations were also found between the medial and superior temporal gyrus activities and behavioral measures of EFT and episodic memory. CONCLUSIONS: Cannabis users, compared to drug-naïve controls, have lower brain activation in EFT relevant regions. Thus, any attempts to improve aberrant EFT performance in cannabis users may benefit from EFT training.

Baseline executive functions and receiving cognitive rehabilitation can predict treatment response in people with opioid use disorder.

BACKGROUND: Impaired cognitive functions, particularly executive function, predicts poor treatment success in people with substance use disorders. The current study investigated the effect of receiving adjunct cognitive rehabilitation and baseline executive function (EF) measures on treatment response among people with opioid use disorder (OUD). METHOD: The analysis sample consisted of 113 participants with OUD who were discharged from a compulsory court-mandated methadone maintenance treatment (MMT) and followed for 3 months. We used the Backward digit span/Auditory verbal learning, Stroop, and Trail making tests to assess the three measures of EF, including working memory, inhibition, and shifting, respectively. Treatment response was operationalized as (1) treatment retention and (2) the number of positive urine tests for morphine during 3-month follow-up periods. The study used Cox's proportional hazards model and linear mixed model to identify predictive factors. RESULTS: Lower Stroop interference scores predicted increased length of stay in treatment (χ2 = 33.15, P < 0.001). The linear mixed model showed that scores on auditory verbal learning test and group intervention predicted the number of positive urine tests during a 3-month follow-up. CONCLUSION: Working memory and inhibitory control, as well as receiving cognitive rehabilitation, could be potentially considered as predictors of treatment response for newly MMT admitted patients with OUD. Assessment of EF before treatment initiation may inform treatment providers about patient's cognitive deficits that may interfere with therapeutic interventions.

Neurocognitive Empowerment for Addiction Treatment (NEAT): study protocol for a randomized controlled trial.

BACKGROUND: Neurocognitive deficits (NCDs) and associated meta-cognition difficulties associated with chronic substance use often delay the learning and change process necessary for addiction recovery and relapse prevention. However, very few cognitive remediation programs have been developed to target NCDs and meta-cognition for substance users. The study described herein aims to investigate the efficacy of a multi-component neurocognitive rehabilitation and awareness program termed "Neurocognitive Empowerment for Addiction Treatment" (NEAT). NEAT is a fully manualized, cartoon-based intervention involving psychoeducation, cognitive practice, and compensatory strategies relevant across 10 major cognitive domains, including aspects of attention, memory, executive functions, and decision-making. METHOD/DESIGN: In a single-blind randomized controlled trial (RCT), 80 female opioid and/or methamphetamine users will be recruited from an addiction recovery program providing an alternative to incarceration for women with substance use-related offenses. Eight groups of 9-12 participants will be randomized into NEAT or treatment-as-usual (TAU). NEAT involves 14 90-min sessions, delivered twice weekly. The primary outcome is change in self-reported drug craving from before to after intervention using Obsessive Compulsive Drug Use Scale. Secondary and exploratory outcomes include additional psychological, neurocognitive, and structural and functional neuroimaging measures. Clinical measures will be performed at five time points (pre- and post-intervention, 3-, 6-, and 12-month follow-up); neuroimaging measures will be completed at pre- and post-intervention. DISCUSSION: The present RCT is the first study to examine the efficacy of an adjunctive neurocognitive rehabilitation and awareness program for addiction. Results from this study will provide initial information concerning potential clinical efficacy of the treatment, as well as delineate neural mechanisms potentially targeted by this novel intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT03922646 . Registered on 22 April 2019.

Neuroscience-Informed Psychoeducation for Recovery: A Program to Promote Metacognition in People With Substance Use Disorders.

INTRODUCTION: A brief neuroscience-informed psychoeducation program (Neuroscience-Informed Psychoeducation for Recovery [NIPER]) was developed to promote awareness (metacognition) in the main cognitive domains affected by drug and alcohol use to increase willingness to invest time and effort in the brain and cognition recovery process. The primary aim of this pilot study was to determine the feasibility and acceptability of the NIPER program and its potential effectiveness in increasing metacognition, psychological wellbeing, and willingness for the brain and cognition recovery programs among patients with Substance Use Disorders (SUDs). METHODS: A total of 56 patients with SUDs were recruited from four outpatient treatment centers in Tehran City, Iran. They participated in four 90-min weekly sessions delivered adjunct to their routine treatment. The program's effectiveness was measured in terms of metacognition and psychological wellbeing at baseline and the end of the program. The rate of adherence and participation and willingness to continue with brain and cognition recovery programs were measured as feasibility outcomes. RESULTS: A total of 51 participants completed the study. Compared to the baseline assessments, patients reported more problems in dimensions of attention, memory, inhibitory control, decision making, motor/speech, interoception, insight, and a higher level of psychological wellbeing (t=4.66; P<0.001). In terms of feasibility outcomes, the adherence and participation rates were found above 85%. Most participants expressed their high willingness to continue the brain and cognition recovery programs (86.2%) and would introduce NIPER to their peers (98%). CONCLUSION: Considering the pilot results in terms of feasibility and preliminary effectiveness of NIPER in the clinical context of addiction treatment, we think that NIPER is a potentially beneficial intervention to be offered to people with SUD. It would increase their awareness and engage them in the brain and cognition recovery process. However, the clinical efficacy of the intervention should be tested in future randomized clinical trials.

How People Emotionally Respond to the News on COVID-19: An Online Survey.

INTRODUCTION: During the Coronavirus Disease 2019 (COVID-19) outbreak, news media has played an important role in informing people to satisfy their curiosity about this stressful condition. Regular exposure to such stressful news may elicit different emotions in people and engage them in using strategies to control their emotions. In the present study, we aimed at exploring the most common negative emotion(s) experienced by individuals, as well as the most frequent Emotion Regulation (ER) strategies used facing the COVID-19-related news. We also examined whether the variable of personal relevance can moderate these emotional responses. METHODS: 617 individuals living in Tehran who regularly read the news about the COVID-19 from the early stages of spread completed an online survey. After excluding the participants with high scores from the Beck Depression Inventory (>18), data obtained from 443 participants were analyzed in terms of the experienced negative emotions and ER strategies. RESULTS: Anxiety (55.8%) was the most common negative emotion reported by participants facing COVID-19-related news and problem-solving was the most frequent strategy used to control negative emotions. Both groups with high and low personal relevance indicated a similar pattern in experiencing high and low arousal emotions, as well as using ER strategies, and no significant differences were found (X2=0.006, p=0.51; X2=0.14, p=0.39, respectively). We also found that participants with high scores in the resilience scale used an integrative rather than a single approach of the ER strategies (rbp=0.15, p=0.01). CONCLUSION: We found that during the COVID-19 outbreak, news media may have important role in triggering anxiety in people who regularly read the relevant news, and problem-solving was the most frequent strategy among them. Being directly involved with COVID-19 in personal life did not make any differences in the way that individuals emotionally respond to the news. While using an integrative approach in regulating emotion was found in more resilient individuals.

The effects of different proxies of cognitive reserve on episodic memory performance: aging study in Iran.

OBJECTIVE: The main aim of the present study is to investigate the association between different measures of cognitive reserve including bilingualism, mental activities, type of education (continuous versus distributed), age, educational level, and episodic memory in a healthy aging sample. METHODS: Four hundred and fifteen participants aged between 50 and 83 years participated in this cross-sectional study and were assessed with the Psychology Experimental Building Language Test battery tapping episodic memory. Demographic variables were collected from a questionnaire designed by the research team. RESULTS: Compared to participants with continuous type of education, those with distributed type performed better in tests of episodic memory, while no differences were found between bilingual and monolingual participants. We additionally found that age negatively predicts episodic memory, whereas playing mind teasers and educational level have positive relationships with episodic memory. CONCLUSIONS: Our results indicate that higher cognitive reserve, as measured by distributed educational training, higher level of education, and doing regular mental activities, is associated with better performance on episodic memory tasks in older adults. These results were discussed in connection with successful aging and protection against memory decline with aging.

Efficacy of Neurocognitive Rehabilitation After Coronary Artery Bypass Graft Surgery in Improving Quality of Life: An Interventional Trial.

INTRODUCTION: Cognitive deficits are frequent after coronary artery bypass graft (CABG) surgery and consequently could lead to a decrease in quality of life. This is the first study that has been conducted with the aim of examining the efficacy of a computerized cognitive rehabilitation therapy (CCRT) in improving quality of life in patients after CABG surgery. METHODS: In this study, an interventional trial with pre-, post-, and follow-up assessments in active (CCRT), active control and control groups was conducted. Seventy-five patients after CABG surgery were selected and assigned to the groups (n = 25 for each group). CCRT consists of four modules of attention, working memory, response inhibition and processing speed training with graded schedule in 20-min sessions three times per week within 8 weeks. Cognitive functions (attention and working memory) were assessed by the tests of continuous performance, Flanker, useful field of view and digit span at three time points: pre- and post-intervention (T0 and T1) and 6-month follow-up (T2). Quality of life was assessed by the SF-36 questionnaire at the same time points. The CCRT group received the cognitive rehabilitation for 2 months, active control group received a sham version of CCRT in an equal time duration and control group did not receive any cognitive intervention. RESULTS: Repeated measures analysis of variance (ANOVA) revealed a time by group interaction on cognitive functions, with CCRT producing a significant improvement at T1 (p < 0.01) and these improvements were maintained at T2. Moreover, in CCRT and active control groups, quality of life (QoL) improved at T1 and these improvements remained stable throughout follow-up (T2). However, improvement of QoL in CCRT group was greater than improvement of QoL in the other two groups at T1. Pearson's correlation analysis shows a positive correlation between QoL improvement and sustained attention and working memory enhancement (p < 0.05). CONCLUSION: Cognitive rehabilitation can lead to a significant improvement in the cognitive functions that have been trained in patients receiving CABG. Interestingly enough, cognitive rehabilitation can also improve quality of life in patients after CABG surgery and this improvement is maintained for at least 6 months.

Cognitive rehabilitation for individuals with opioid use disorder: A randomized controlled trial.

Aim: To examine the efficacy of cognitive rehabilitation treatment (CRT) for people with opioid use disorder who were recruited into a methadone maintenance treatment (MMT) programme. Method: 120 male subjects were randomly assigned to (1) MMT plus CRT in two months or (2) MMT plus a control intervention. Subjects were assessed at the beginning, mid-point and post-intervention as well as at 1-, 3- and 6-month follow-up time points. Results: Analysis with repeated measure ANOVA showed that the CRT group performed significantly better in tests of learning, switching, processing speed, working memory and memory span. Moreover, the CRT group had significantly lower opiate use over the control group during 3-months follow-up. Analysis including only those with a history of methamphetamine use showed that the CRT group had significantly lower amphetamine use. No group differences were observed for treatment retention. Conclusions: Our findings provide evidence that adding CRT as an adjunct intervention to MMT can improve cognitive performance as well as abstinence from both opiates and stimulants.

A Roadmap for Integrating Neuroscience Into Addiction Treatment: A Consensus of the Neuroscience Interest Group of the International Society of Addiction Medicine.

Although there is general consensus that altered brain structure and function underpins addictive disorders, clinicians working in addiction treatment rarely incorporate neuroscience-informed approaches into their practice. We recently launched the Neuroscience Interest Group within the International Society of Addiction Medicine (ISAM-NIG) to promote initiatives to bridge this gap. This article summarizes the ISAM-NIG key priorities and strategies to achieve implementation of addiction neuroscience knowledge and tools for the assessment and treatment of substance use disorders. We cover two assessment areas: cognitive assessment and neuroimaging, and two interventional areas: cognitive training/remediation and neuromodulation, where we identify key challenges and proposed solutions. We reason that incorporating cognitive assessment into clinical settings requires the identification of constructs that predict meaningful clinical outcomes. Other requirements are the development of measures that are easily-administered, reliable, and ecologically-valid. Translation of neuroimaging techniques requires the development of diagnostic and prognostic biomarkers and testing the cost-effectiveness of these biomarkers in individualized prediction algorithms for relapse prevention and treatment selection. Integration of cognitive assessments with neuroimaging can provide multilevel targets including neural, cognitive, and behavioral outcomes for neuroscience-informed interventions. Application of neuroscience-informed interventions including cognitive training/remediation and neuromodulation requires clear pathways to design treatments based on multilevel targets, additional evidence from randomized trials and subsequent clinical implementation, including evaluation of cost-effectiveness. We propose to address these challenges by promoting international collaboration between researchers and clinicians, developing harmonized protocols and data management systems, and prioritizing multi-site research that focuses on improving clinical outcomes.

Neuroscience-informed psychoeducation for addiction medicine: A neurocognitive perspective.

Psychoeducation (PE) is defined as an intervention with systematic, structured, and didactic knowledge transfer for an illness and its treatment, integrating emotional and motivational aspects to enable patients to cope with the illness and to improve its treatment adherence and efficacy. PE is considered an important component of treatment in both medical and psychiatric disorders, especially for mental health disorders associated with lack of insight, such as alcohol and substance use disorders (ASUDs). New advancements in neuroscience have shed light on how various aspects of ASUDs may relate to neural processes. However, the actual impact of neuroscience in the real-life clinical practice of addiction medicine is minimal. In this chapter, we provide a perspective on how PE in addiction medicine can be informed by neuroscience in two dimensions: content (knowledge we transfer in PE) and structure (methods we use to deliver PE). The content of conventional PE targets knowledge about etiology of illness, treatment process, adverse effects of prescribed medications, coping strategies, family education, and life skill training. Adding neuroscience evidence to the content of PE could be helpful in communicating not only the impact of drug use but also the beneficial impact of various treatments (i.e., on brain function), thus enhancing motivation for compliance and further destigmatizing their symptoms. PE can also be optimized in its "structure" by implicitly and explicitly engaging different neurocognitive processes, including salience/attention, memory, and self-awareness. There are many interactions between these two dimensions, structure and content, in the delivery of neuroscience-informed psychoeducation (NIPE). We explore these interactions in the development of a cartoon-based NIPE to promote brain recovery during addiction treatment as a part of the brain awareness for addiction recovery initiative.

Perspectives on neurocognitive rehabilitation as an adjunct treatment for addictive disorders: From cognitive improvement to relapse prevention.

Addiction, as a brain disorder, can be defined with two distinct but interacting components: drug dependency and neurocognitive deficits. Most of the therapeutic interventions in addiction medicine, including pharmacological or psychosocial therapies, that are in clinical use have been mainly focused on directly addressing addictive behaviors, especially drug use and urges to use drugs. In the field of addiction treatment, it is often presumed that drug users' neurocognitive deficits will reverse following abstinence. However, in many cases, neurocognitive deficits are not fully ameliorated following sustained abstinence, and neurocognitive function may further deteriorate in early abstinence. It can be argued that many cognitive functions, such as sustained attention and executive control, are essential for full recovery and long-term abstinence from addiction. Recent advances in cognitive neuroscience have provided scientific foundations for neurocognitive rehabilitation as a means of facilitating recovery from drug addiction. Neurocognitive rehabilitation for drug addicted individuals could be implemented as part of addiction treatment, with highly flexible delivery methods including traditional "paper and pencil" testing, or computer-based technology via laptops, web-based, or smartphones in inpatient and outpatient settings. Despite this promise, there has been limited research into the potential efficacy of neurocognitive rehabilitation as a treatment for drug addiction. Further, many questions including the optimum treatment length, session duration, and necessary treatment adherence for treatment efficacy remain to be addressed. In this chapter, we first introduce cognitive rehabilitation as one of the potential areas to bridge the gap between cognitive neuroscience and addiction medicine, followed by an overview of current challenges and future directions.

NEuro COgnitive REhabilitation for Disease of Addiction (NECOREDA) Program: From Development to Trial.

Despite extensive evidence for cognitive deficits associated with drug use and multiple publications supporting the efficacy of cognitive rehabilitation treatment (CRT) services for drug addictions, there are a few well-structured tools and organized programs to improve cognitive abilities in substance users. Most published studies on cognitive rehabilitation for drug dependent patients used rehabilitation tools, which have been previously designed for other types of brain injuries such as schizophrenia or traumatic brain injuries and not specifically designed for drug dependent patients. These studies also suffer from small sample size, lack of follow-up period assessments and or comprehensive treatment outcome measures. To address these limitations, we decided to develop and investigate the efficacy of a paper and pencil cognitive rehabilitation package called NECOREDA (Neurocognitive Rehabilitation for Disease of Addiction) to improve neurocognitive deficits associated with drug dependence particularly caused by stimulants (e.g. amphetamine type stimulants and cocaine) and opiates. To evaluate the feasibility of NECOREDA program, we conducted a pilot study with 10 opiate and methamphetamine dependent patients for 3 months in outpatient setting. NECOREDA was revised based on qualitative comments received from clients and treatment providers. Final version of NECOREDA is composed of brain training exercises called "Brain Gym" and psychoeducational modules called "Brain Treasures" which is implemented in 16 training sessions interleaved with 16 review and practice sessions. NECOREDA will be evaluated as an add-on intervention to methadone maintenance treatment in a randomized clinical trial among opiate dependent patients starting from August 2015. We discuss methodological features of NECOREDA development and evaluation in this article.

Influence of traffic-related noise and air pollution on self-reported fatigue.

A growing body of evidence suggests that exposure to environmental pollutions is related to health problems. It is, however, questionable whether this condition affects working performance in occupational settings. The aim of this study is to determine the predictive value of age as well as traffic related air and noise pollutions for fatigue. 246 traffic officers participated in this study. Air pollution data were obtained from the local Air Quality Control Company. A sound level meter was used for measuring ambient noise. Fatigue was evaluated by the MFI-20 questionnaire. The general and physical scales showed the highest, while the reduced activity scale showed the lowest level of fatigue. Age had an independent direct effect on reduced activity and physical fatigue. The average of daytime equivalent noise level was between 71.63 and 88.51 dB(A). In the case of high noise exposure, older officers feel more fatigue than younger ones. Exposure to PM10 and O3 resulted in general and physical fatigue. Complex Interactions between SO2, CO and NO2 were found. Exposure to noise and some components of air pollution, especially O3 and PM10, increases fatigue. The authorities should adopt and rigorously implement environmental protection policies in order to protect people.