Effects of computerized working memory training on neuroplasticity in healthy individuals: A combined neuroimaging and neurotransmitter study.

Working memory (WM) is an essential cognitive function that underpins various higher-order cognitive processes. Improving WM capacity through targeted training interventions has emergered as a potential approach for enhancing cognitive abilities. The present study employed an 8-week regimen of computerized WM training (WMT) to investigate its effect on neuroplasticity in healthy individuals, utilizing neuroimaging data gathered both before and after the training. The key metrics assessed included the amplitude of low-frequency fluctuations (ALFF), voxel-based morphometry (VBM), and the spatial distribution correlations of neurotransmitter. The results indicated that post-training, compared to baseline, there was a reduction in ALFF in the medial superior frontal gyrus and an elevation in ALFF in the left middle occipital gyrus within the training group. In comparison to the control group, the training group also exhibited decreased ALFF in the anterior cingulate cortex, angular gyrus, and superior parietal lobule, along with increased ALFF in the postcentral gyrus post-training. VBM analysis revealed a significant increase in gray matter volume (GMV) in the right dorsal superior frontal gyrus after the training period, compared to the initial baseline measurement. Furthermore, the training group showed GMV increases in the dorsal superior frontal gyrus, Rolandic operculum, precentral gyrus, and postcentral gyrus when compared to the control group. In addition, significant associations were identifed between neuroimaging measurements (AFLL and VBM) and the spatial patterns of neurotransmitters such as serotonin (5-HT), dopamine (DA), and N-methyl-D-aspartate (NMDA), providing insights into the underlying neurochemical processes. These findings clarify the neuroplastic changes caused by WMT, offering a deeper understanding of brain plasticity and highlighting the potential advantages of cognitive training interventions.

Prenatal affective cognitive training to reduce the risk of postpartum depression (PACT): study protocol for a randomized controlled trial.

BACKGROUND: Postpartum depression (PPD) affects 30-50% of women with a history of previous depression or bipolar disorder and 8% of women with no history of depression. Negative cognitive biases in the perception of infant cues and difficulties with emotion regulation are replicated risk factors. Current interventions focus on detecting and treating rather than preventing PPD. The aim of this randomized controlled intervention trial is therefore to investigate the potential prophylactic effects of prenatal affective cognitive training for pregnant women at heightened risk of PPD. METHODS: The study will enrol a total of 292 pregnant women: 146 at high risk and 146 at low risk of PPD. Participants undergo comprehensive assessments of affective cognitive processing, clinical depressive symptoms, and complete questionnaires at baseline. Based on the responses, pregnant women will be categorized as either at high or low risk of PPD. High-risk participants will be randomized to either prenatal affective cognitive training (PACT) or care as usual (CAU) immediately after the baseline testing. The PACT intervention is based on emerging evidence for efficacy of affective cognitive training approaches in depression, including cognitive bias modification, attention bias modification, mindfulness-inspired emotion regulation exercises, and working memory training. Participants randomised to PACT will complete five individual computerised and virtual reality-based training sessions over 5 weeks. The primary outcome is the difference between intervention arms in the incidence of PPD, assessed with an interview 6 months after birth. We will also assess the severity of depressive symptoms, rated weekly online during the first 6 weeks postpartum. DISCUSSION: The results will have implications for future early prophylactic interventions for pregnant women at heightened risk of PPD. If the PACT intervention reduces the incidence of PPD, it can become a feasible, non-invasive prophylactic strategy during pregnancy, with positive mental health implications for these women and their children. TRIAL REGISTRATION: ClinicalTrials.gov NCT06046456 registered 21-09-2023, updated 08-07-2024.

Does working memory training improve emotion regulation and reduce internalizing symptoms? A pair of three-level meta-analyses.

BACKGROUND: Emotional dysfunction is a core feature of many mental disorders. Working memory training (WM-T) is promising to improve emotion regulation and reduce internalizing symptoms (anxiety and depressive symptoms), but the results are mixed. Therefore, we conducted meta-analyses to clarify these mixed results. METHODS: We searched Web of Science, PubMed, ScienceDirect, and EBSCO to identify relevant studies and screened the references. The effect size was calculated using Hedges' g. Three-level, random-effects models were run using metafor in R. RESULTS: The current study included 44 articles, of which 29 were involved with emotion regulation, and 30 were involved with internalizing symptoms. The results showed that WM-T could yield emotional benefits, but the benefits were confined to enhancing explicit emotional regulation capacity and reducing anxiety symptoms. For the meta-analysis regarding the effect of WM-T on emotion regulation, there was no significant moderator. For the meta-analysis regarding the effect of WM-T on internalizing symptoms, the emotional valence of the material and control group were statistically significant moderators. CONCLUSION: WM-T could yield certain emotional effects, but only to improve explicit emotion regulation capacity and reduce anxiety symptoms. In addition, some measures could enhance the effect, such as targeting specific populations, increasing the number of training sessions (≥15) or duration (>450 minutes), using negative material, and using n-back training tasks.

Cerebral blood flow and structural connectivity after working memory or physical training in paediatric cancer survivors - Exploratory findings.

Paediatric cancer survivors often suffer from cognitive long-term difficulties. Consequently, strengthening cognition is of major clinical relevance. This study investigated cerebral changes in relation to cognition in non-brain tumour paediatric cancer survivors after working memory or physical training compared to a control group. Thirty-four children (≥one-year post-treatment) either underwent eight weeks of working memory training (n = 10), physical training (n = 11), or a waiting period (n = 13). Cognition and MRI, including arterial spin labelling and diffusion tensor imaging, were assessed at three time points (baseline, post-training, and three-month follow-up). Results show lower cerebral blood flow immediately after working memory training (z = -2.073, p = .038) and higher structural connectivity at the three-month follow-up (z = -2.240, p = .025). No cerebral changes occurred after physical training. Short-term changes in cerebral blood flow correlated with short-term changes in cognitive flexibility (r = -.667, p = .049), while long-term changes in structural connectivity correlated with long-term changes in working memory (r = .786, p = .021). Despite the caution given when interpreting data from small samples, this study suggests a link between working memory training and neurophysiological changes. Further research is needed to validate these findings.

Is Training Working Memory in Children with Learning Disabilities a Viable Solution? A Systematic Review.

Background: Working memory (WM) is one of the most influential cognitive functions in encoding, registering, and retrieving information. It influences the learning process in children. Its role becomes essential, especially in a child with a learning disability (LD). Researchers worldwide are giving much prominence to WM, especially in devising cognitive retraining strategies for better cognitive functioning and academic attainment in these children. This current study aims to explore globally used instruments to measure this construct and review effective WM training models in the cognitive rehabilitation of children with LD. This study used a systematic review, availing the elaborate "Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA)" guidelines. Summary: The databases of Google Scholar, PubMed, and Web of Science were searched thoroughly, and those studies, which met the inclusion criteria, were considered for this review. Out of 770 studies found with keywords, only six met the inclusion criteria and were selected for a detailed analysis. The outcome of the current review provides trustworthy evidence of poor performance, especially in tasks involving verbal and executive WM in children with all types of learning disabilities (LD) and difficulties. The studies reviewed support the hypothesis that WM can improve with training and significantly improve children's academic attainment. Key Message: Further this review recommends that research and efforts must go into devising these cognitive training techniques. Children have high cerebral plasticity; hence, using cognitive training (emphasizing WM training and other cognitive functions) with them would enhance their cognitive functioning and capacity, improving their academic performance.

Aberrant cognitive empathy in individuals with elevated social anxiety and regulation with emotional working memory training.

Social anxiety may disrupt the empathic process, and well-regulated empathy is critical for navigating the social world. Two studies aimed to further understand empathy in the context of social anxiety. Study 1 compared individuals with elevated or normative social anxiety on a measure assessing cognitive and affective empathy for positive and negative emotions conveyed by other people ("targets"), completed under social threat. Relative to individuals with normative social anxiety, individuals with elevated social anxiety had greater cognitive empathy and no differences in affective empathy, regardless of emotion type. As greater cognitive empathy can be maladaptive, Study 2 tested whether this could be down-regulated. Individuals with elevated social anxiety underwent emotional working memory training (eWMT) for negative emotional information, or control training (CT). Effects on an empathy measure completed under social threat were assessed. Cognitive empathy for negative emotions decreased following eWMT but not CT, and this was only evident for those with higher pre-training working memory capacity. Cognitive empathy for positive emotions and affective empathy were not affected. Overall, social anxiety is associated with aberrant elevated cognitive empathy for negative and positive emotions, and the deviation in cognitive empathy for negative emotions can be regulated with eWMT for certain individuals.Trial registration: Australian New Zealand Clinical Trials Registry identifier: ACTRN12618001196235..

The effects of working memory training on attention deficit, adaptive and non-adaptive cognitive emotion regulation of Chinese children with Attention Deficit/Hyperactivity Disorder (ADHD).

BACKGROUND: Attention Deficit/Hyperactivity Disorder (ADHD) poses cognitive and emotional challenges for Chinese children. This study addresses the potential benefits of Working Memory Training for ADHD-affected children. Understanding its impact on Attention, cognitive regulation, and emotional responses is crucial for tailored interventions in the Chinese context. The Trial Registration Number (TRN) for this study is [TRN-2023-123,456], and it was officially registered on July 15, 2023, by Changchun Normal University. OBJECTIVES: This study investigated how Working Memory training influences Attention, adaptive cognitive regulation, and non-adaptive cognitive emotion regulation in Chinese children with ADHD. It also assessed changes in attentional focus, improvements in adaptive cognitive regulation, and alterations in non-adaptive cognitive emotion regulation strategies. METHODOLOGY: This quasi-experimental study aimed to assess the impact of working memory training on Chinese children with ADHD. Using pretest-posttest measures, 120 female students underwent Cogmed software training, targeting attention deficits and cognitive emotion regulation. Three reliable instruments measured outcomes. The procedure involved informed consent, questionnaires, 25 training sessions, and a two-month follow-up. Statistical analyses, including repeated measures ANOVA, assessed training effects. RESULTS: ANOVA revealed a significant impact of Working memory training on attention deficit. Repeated measures ANOVA for cognitive emotion regulation indicated positive changes in adaptive and non-adaptive strategies over time, with sustained improvements in self-blame, rumination, catastrophizing, and blaming others. Bonferroni follow-up tests showed significant differences between pre-test, post-test, and follow-up, favoring the post-test and follow-up tests. CONCLUSIONS: In summary, this research sheds light on the positive impact of memory training on Attention and cognitive emotion regulation in children with ADHD. The study underscores the potential of working memory interventions, particularly software-focused approaches, in enhancing attention levels and improving cognitive emotion regulation. The findings align with existing literature emphasizing the role of working memory deficits in ADHD. IMPLICATIONS: Practically, incorporating memory training interventions into educational settings emerges as a viable strategy to support children with ADHD. This includes integrating memory training programs into both classroom activities and home-based interventions. Additionally, sustained implementation and long-term follow-up assessments are crucial for maximizing the effectiveness of memory training interventions. Tailoring interventions to specific ADHD subtypes and seamlessly integrating memory training activities into daily routines offer practical and personalized solutions for managing ADHD symptoms in diverse settings.

The effect of working memory training on test anxiety symptoms and attentional control in adolescents.

OBJECTIVE: The percentage of adolescents with test anxiety is increasing rapidly. Working memory (WM) training has been demonstrated to reduce anxiety levels and enhance attentional control in individuals. Therefore, we investigated whether adaptive dual n-back WM training could lower test anxiety level and improve attentional control in adolescents. METHODS: Forty adolescents were allocated to either adaptive dual n-back WM training (n = 21) or non-adaptive dual 1-back WM training (n = 19) for 10 days. The Test Anxiety Scale was applied to measure individuals' test anxiety symptoms. The Attentional Control Scale (ACS), the flanker task, and the Go/Nogo task were used to measure attentional control. RESULTS: Compared with the control group, the training group reported significantly relief of test anxiety symptoms; however, there were no significant differences between the two groups in pre-to-post changes in ACS scores or performance on the flanker task and Go/Nogo task. CONCLUSION: In sum, adaptive dual n-back WM training effectively reduced adolescents' level of test anxiety but did not improve their attentional control.

Exploring Working Memory Capacity and Efficiency Processes to Understand Working Memory Training Outcomes in Primary School Children.

Despite the abundance of research evaluating working memory training outcomes in children, few studies have examined the underlying cognitive mechanisms. This study aimed to contribute understanding by exploring whether working memory capacity (maximum span) and/or efficiency (basic and cognitive processing speeds), two proposed cognitive mechanisms, are associated with children's working memory performance immediately and 6-months post-intervention. We used data from a previous trial in primary school children (7-11 years) who completed working memory training (n = 52) or an active control (n = 36), comprising 10 sessions (each 20-minutes) in class over two weeks. Children completed five working memory measures at baseline, immediately and 6-months post-intervention: two Backwards Span and two Following Instructions measures (same paradigms as training activities), and one n-back measure (different paradigm). Maximum span, basic and cognitive processing speeds, and performance were calculated for each measure. Associations between change in maximum span, processing speeds and change in performance on the working memory measures from baseline to immediately and 6-months post-intervention did not differ between groups (all p < .05). Maximum span, processing speeds and performance on working memory measures did not differ between groups. Findings provide little evidence that the studied capacity or efficiency processes contribute to understanding working memory training outcomes in primary school children. Furthermore, working memory training did not have benefits for children's working capacity, efficiency or performance up to 6-months post-intervention. It is of interest for future studies to explore cognitive mechanisms, including strategy use, maximum span and information processing, in datasets where training effects are observed.

Can Emotional Working Memory Training Improve Cognitive Behavioral Therapy Outcomes for Social Anxiety Disorder: A Pilot Study.

Social anxiety disorder (SAD) models highlight maladaptive attention as a maintaining factor of SAD, potentially negatively impacting how individuals with SAD engage with cognitive behavioral therapy (CBT) content in a therapist's presence. Emotional working memory training (eWMT) has been shown to improve affective attentional control. This pilot study assessed the proposed methodology for a randomized controlled trial (RCT) to determine whether eWMT, by improving attentional control prior to internet-based CBT (iCBT), results in better CBT outcomes. The RCT would be considered feasible if the pilot study achieved rates ≥80% for eligible participants recruited, study measures completion, intervention completion, and participant retention. Results from 10 randomized participants showed rates ≥80% for recruitment of eligible participants and iCBT intervention completion. Completion of study measures, eWMT and Placebo training interventions, and participant retention were <80%. Results highlight the need to consider strategies to improve the methodology prior to the RCT.

Working Memory Training Responsiveness in Parkinson's Disease Is Not Determined by Cortical Thickness or White Matter Lesions.

Patients with Parkinson's disease are highly vulnerable for cognitive decline. Thus, early intervention by means of working memory training (WMT) may be effective for the preservation of cognition. However, the influence of structural brain properties, i.e., cortical thickness and volume of white matter lesions on training responsiveness have not been studied. Here, behavioral and neuroimaging data of 46 patients with Parkinson's disease, 21 of whom engaged in home-based, computerized adaptive WMT, was analyzed. While cortical thickness and white matter lesions volume were associated with cognitive performance at baseline, these structural brain properties do not seem to determine WMT responsiveness.

Treatment Response Following Adaptive PASAT Training for Depression Vulnerability: a Systematic Review and Meta-Analysis.

In recent years, cognitive control training (CCT) has gained momentum as an intervention to remediate cognitive impairments and decrease depressive symptoms. One promising operationalization to train cognitive control is the adaptive Paced Auditory Serial Addition Task (aPASAT). In this systematic review and meta-analysis of aPASAT training, the efficacy of the intervention and potential moderators were examined. The PsycINFO, MEDLINE, Embase, Web of Science and Cochrane Library electronic databases were searched for studies examining aPASAT training for depressive symptomatology or rumination. Nineteen studies (n = 1255) were included, comprising of depressed patients, remitted depressed patients, at-risk, and healthy participants. We found small significant effects directly after training for both depressive symptomatology and rumination, with similar effect sizes at follow-up. Subgroup analyses suggest a significantly higher mean effect of aPASAT training in non-healthy populations for rumination immediately following training, but not for depressive symptomatology. The amount of training sessions did not moderate effects of CCT. aPASAT has a small but significant effect on depressive symptoms, with direct effects immediately after training, as well as sustained long-term effects. It is currently unclear how many sessions are required for sustained effects due to heterogeneity in training dosage and absence of sufficient trials. Our results suggest that aPASAT training may be most effective for at-risk, remitted- and clinically depressed populations. The effect sizes resulting from this meta-analysis could be used to adequately power future research, which could investigate a dose-response relationship and examine potential treatment gains when combining CCT with other antidepressant interventions.

Discourse-based verbal working memory training and transfer effects for individuals with an amnestic type of mild cognitive impairment.

PURPOSE: The purpose of the study was to investigate the treatment efficacy of a discourse-based working memory (WM) protocol for individuals with the amnestic type of mild cognitive impairment (MCI). METHOD: The current study employed a randomised, single-blind design. Fourteen individuals with MCI participated in the study (n = 7 treatment group and n = 7 control group). The treatment protocol consisted of 10 sessions two times per week, and treatment was individually administered only to the treatment group. A Wilcoxon signed-rank test was performed to verify pre-post comparisons within each group. Mann-Whitney nonparametric tests were conducted to confirm the differences between the treatment and control groups for the post-treatment scores. RESULT: The treatment group demonstrated a significant increase in story-retelling outcomes for both the treated stories and untreated novel stories compared to the control group. Furthermore, the treatment group presented transfer effects for WM span measures and controlled word association tasks. CONCLUSION: The results indicated that a discourse-based WM treatment protocol is efficacious for the amnestic type of mild cognitive impairment with the effects transferred to frontal lobe functions, as measured by WM tasks and semantic word fluency measures. Further studies are needed to track the trajectory of performance across sessions.

Working memory training for reward processing in university students with subsyndromal depression: The influence of baseline severity of depression.

Previous studies have tentatively suggested that working memory training (WMT) has the potential to improve reward processing, but it is not known how long this improvement lasts, whether there is a lag effect, or whether it is reflected in neurophysiological indicators. In this study, 40 university students with subsyndromal depression were randomly assigned to a training group or a control group and completed a 20-day working memory training task and a simple memory task, respectively. All participants completed the Temporal Experience of Pleasure Scale (TEPS) and a doors task with electroencephalogram (EEG) signals recorded simultaneously on a pre- and post-test and a 3-month follow-up. The reward-related positivity (RewP) amplitude, theta power, and their differences between conditions (i.e., ΔRewP and Δtheta power, respectively) in the doors task were the primary outcomes, and the score on TEPS was the secondary outcome. The results indicated no group-related effects were demonstrated in primary and secondary outcomes at post-test and 3-month follow-up. Furthermore, the differences in the pre- and post-test in Δtheta power were moderated by the baseline severity of depression. This was primarily driven by the fact that the change values in the control group increased with the severity of depression, while the change values in the training group had high homogeneity. Our findings did not provide support for the effect of WMT on reward processing across the whole sample, but without intervention, there would be high heterogeneity in the change in the cognitive control ability to loss feedback, which is detrimental to individuals with high depression severity.

Working Memory Training in Norwegian Children with Cerebral Palsy (CP) Show Minimal Evidence of Near and No Far Transfer Effects.

In children with cerebral palsy (CP), learning disabilities are well documented, and impairments in executive functions, such as attention, inhibition, shifting and working memory, represent significant burdens on patients, their families and the society. The aim of this study was to evaluate whether Cogmed RM working memory training could improve working memory in children with CP and investigate whether increased working memory capacity would generalize to other cognitive functions. Twenty-eight children completed the training and the results were compared to a waitlist control group (n = 32). The results yielded three main findings. First, children with CP improved with practice on trained working memory tasks. Second, the intervention group showed minimal near transfer effects to non-trained working memory tasks. Third, no effects on cognitive and behavioral far transfer measures were found.

Improvement in self-reported cognitive functioning but not in rumination following online working memory training in a two-year follow-up study of remitted major depressive disorder.

Self-reported subjective cognitive difficulties (subjective deficits) and rumination are central residual cognitive symptoms following major depressive disorder (MDD). These are risk factors for more a severe course of illness, and despite the considerable relapse risk of MDD, few interventions target the remitted phase, a high-risk period for developing new episodes. Online distribution of interventions could help close this gap. Computerized working memory training (CWMT) shows promising results, but findings are inconclusive regarding which symptoms improve following this intervention, and its long-term effects. This study reports results from a longitudinal open-label two-year follow-up pilot-study of self-reported cognitive residual symptoms following 25 sessions (40 min), five times a week of a digitally delivered CWMT intervention. Ten of 29 patients remitted from MDD completed two-year follow-up assessment. Significant large improvements in self-reported cognitive functioning on the behavior rating inventory of executive function-adult version appeared after two-years (d = 0.98), but no significant improvements were found in rumination (d < 0.308) measured by the ruminative responses scale. The former showed moderate non-significant associations to improvement in CWMT both post-intervention (r = 0.575) and at two-year follow-up (r = 0.308). Strengths in the study included a comprehensive intervention and long follow-up time. Limitations were small sample and no control group. No significant differences between completers and drop-outs were found, however, attrition effects cannot be ruled out and demand characteristics could influence findings. Results suggested lasting improvements in self-reported cognitive functioning following online CWMT. Controlled studies with larger samples should replicate these promising preliminary findings.

Working memory training in children with neurodevelopmental disorders and intellectual disabilities, the role of coaching: A double-blind randomised controlled trial.

BACKGROUND: Working memory training (WMT) can offer therapeutic benefits to patients with neurodevelopmental disorders (NDD) and mild to borderline intellectual disability (MBID). However, consistent evidence for treatment benefits of WMT over placebo training is missing. So far, participants in double-blind research designs did receive non-specific coaching, whereas active coaching based on individual training results might increase the efficacy of WMT. Furthermore, the intensity and duration of WMT is often too stressful for these children. This study therefore investigated whether a less intensive but more prolonged WMT, with active personalised coaching and feedback, would reduce behavioural symptoms and improve neurocognitive functioning and academic achievements in children with NDD and MBID. METHOD: A double-blind randomised controlled trial in children (aged 10;0-13;11) with MBID (60 < IQ < 85) and ADHD and/or ASD evaluated the effects of a less intensive but prolonged version of the original Cogmed WMT (30 min a day, 4 days a week, 8 weeks in total). Eighteen participants received active, personalised coaching and feedback, based on their actual individual performance during training. Twenty-two received general non-personalised coaching for the same amount of time. Executive functioning, academic achievements and several behavioural measurements were administered, before and after training, with a 6-months follow-up. RESULTS: We observed a significant effect of time on both primary and secondary outcome measures, indicating that all children improved in working memory performance and other neurocognitive and academic outcomes. The interaction between time and group was not significant. DISCUSSION: This study was unable to document superior effects of active personalised coaching and feedback compared with general non-personalised coaching and no feedback in an adaptive WMT in children with MBID and NDD. The objectively documented changes over time suggest that for these vulnerable children, a regular, structured and structural contact with a coach and adapted exercises is enough to develop therapy fidelity, boost motivation and improve neurodevelopmental task performance. Further research is needed to examine which possible subgroups within this heterogenic group of children profit more from WMT compared with other subgroups.

Experimental investigation of training schedule on home-based working memory training in healthy older adults.

Introduction: The efficacy of working memory training (WMT) for cognitive enhancement in healthy older adults has been extensively investigated. Typically, WMT results in improved performance on the training task, but limited or no transfer of improvement to other cognitive tasks. Accordingly, there is a need to identify optimal intervention parameters to maximize training and transfer task effects of WMT. The current study aimed to investigate the effect of training schedule on training and transfer task performance of WMT in healthy older adults. A secondary aim was to examine the feasibility of participants performing the intervention online at home, unsupervised, and using their personal devices. Methods: Participants (N = 71; mean age: 66 years) completed sixteen WMT or active-control sessions over eight (distributed) or four (intensive) weeks. Adaptive verbal and spatial n-back tasks were used as the WMT tasks. We tested near transfer effects to a digit-span task and far transfer effects to an abstract relational reasoning task. Results: Participants successfully performed the cognitively demanding intervention using their own devices, online at home, and with minimal contact with the researcher. We observed a significant improvement in WMT task performance in the WMT group relative to active-controls, but no evidence of near or far transfer. Similar training effects were observed irrespective of the intensity of the training schedule. Discussion: Our results suggest that comparable benefits could be observed when using less intensive schedules that may be more easily accommodated into everyday life.

Approach-Bias Retraining and Other Training Interventions as Add-On in the Treatment of AUD Patients.

In the past two decades, a variety of cognitive training interventions have been developed to help people overcome their addictive behaviors. Conceptually, it is important to distinguish between programs in which reactions to addiction-relevant cues are trained (varieties of cognitive bias modification, CBM) and programs in which general abilities are trained such as working memory or mindfulness. CBM was first developed to study the hypothesized causal role in mental disorders: by directly manipulating the bias, it was investigated to what extent this influenced disorder-relevant behavior. In these proof-of-principle studies, the bias was temporarily modified in volunteers, either temporarily increased or decreased, with corresponding effects on behavior (e.g., beer consumption), in case the bias was successfully manipulated. In subsequent clinical randomized controlled trials (RCTs), training (away from the substance vs. sham training) was added to clinical treatment. These studies have demonstrated that CBM, as added to treatment, reduces relapse with a small effect of about 10% (similar effect size as for medication, with the strongest evidence for approach-bias modification). This has not been found for general ability training (e.g., working memory training), although effects on other psychological functions have been found (e.g., impulsivity). Mindfulness also has been found to help people overcome addictions, and different from CBM, also as stand-alone intervention. Research on (neuro-)cognitive mechanisms underlying approach-bias modification has pointed to a new perspective in which automatic inferences rather than associations are influenced by training, which has led to the development of a new variety of training: ABC training.