Distractor filtering and task load in working memory training in healthy older adults.

Filtering efficiency (FE) has been suggested as a task-related process of working memory (WM) in older adults, but the interaction of distractors with WM when implemented as a training to improve WM capacity is unclear. To investigate the effect of manipulations of WM and/or FE load in a multicomponent model-based WM training in improving WM capacity. 205 healthy older adults (129 women; aged 64.0 ± 8.3 years) were randomised into three WM training groups with manipulations of WM and FE load (high WM; low FE load, high WM; high FE load and low WM; high FE load). All groups underwent three online cognitive testing sessions and twelve 40-min training sessions over three weeks using the SmartBrain smartphone application. WM capacity was measured with complex span tasks and FE using the Change Detection Task. Linear mixed-effect models adjusted for age, sex, education and pre-baseline performance showed increased WM capacity post-training, but no difference between groups. While both distractors and WM are needed to improve WM in the absence of distraction, manipulations of the FE and WM load do not influence improvements following training.

Tweaking synaptic plasticity: Deciphering the role of WWC1 in memory opens new therapeutic horizons.

WWC1 is a scaffolding protein in the evolutionarily conserved Hippo signaling network and is genetically linked to human memory and synaptic plasticity. In the archives of Science Signaling, Stepan et al. demonstrate the translational potential of modulating WWC1 through pharmacological inhibition of Hippo-pathway kinases to enhance cognition.

Role of GLR-1 in Age-Dependent Short-Term Memory Decline.

As the global elderly population grows, age-related cognitive decline is becoming an increasingly significant healthcare issue, often leading to various neuropsychiatric disorders. Among the many molecular players involved in memory, AMPA-type glutamate receptors are known to regulate learning and memory, but how their dynamics change with age and affect memory decline is not well understood. Here, we examined the in vivo properties of the AMPA-type glutamate receptor GLR-1 in the AVA interneuron of the Caenorhabditis elegans nervous system during physiological aging. We found that both total and membrane-bound GLR-1 receptor levels decrease with age in wild-type worms, regardless of their location along the axon. Using fluorescence recovery after photobleaching, we also demonstrated that a reduction in GLR-1 abundance correlates with decreased local, synaptic GLR-1 receptor dynamics. Importantly, we found that reduced GLR-1 levels strongly correlate with the age-related decline in short-term associative memory. Genetic manipulation of GLR-1 stability, by either deleting msi-1 or expressing a ubiquitination-defective GLR-1 (4KR) variant, prevented this age-related reduction in receptor abundance and improved the short-term memory performance in older animals, which reached performance levels similar to those of young animals. Overall, our data indicate that AMPA-type glutamate receptor abundance and dynamics are key factors in maintaining memory function and that changes in these parameters are linked to age-dependent short-term memory decline.

Differential methylation of linoleic acid pathway genes is associated with PTSD symptoms - a longitudinal study with Burundian soldiers returning from a war zone.

Soldiers may be exposed to traumatic stress during combat deployment and thus are at risk for developing posttraumatic stress disorder (PTSD). Genetic and epigenetic evidence suggests that PTSD is linked to forming stress-related memories. In the current study, we investigated post-deployment associations of PTSD symptoms with differential DNA methylation in a sample of Burundian soldiers returning from the African Union Mission in Somalia's war zone. We used a matched longitudinal study design to explore epigenetic changes associated with PTSD symptoms in N = 191 participants. PTSD symptoms and saliva samples were collected at 1-3 (t1) and 9-14 months (t2) after the return of the soldiers to their home base. Individuals with either worsening or improving PTSD symptoms were matched for age, stressful, traumatic and self-perpetrated events prior to the post-assessment, traumatic and violent experiences between the post- and the follow-up assessment, and violence experienced during childhood. A mixed model analysis was conducted to identify top nominally significantly differentially methylated genes, which were then used to perform a gene enrichment analysis. The linoleic acid metabolism pathway was significantly associated with post-deployment PTSD symptoms, after accounting for multiple comparisons. Linoleic acid has been linked to memory and immune related processes in previous research. Our findings suggest that differential methylation of linoleic acid pathway genes is associated with PTSD and thus may merit closer inspection as a possible mediator of resilience.

Neurofunctional underpinnings of individual differences in visual episodic memory performance.

Episodic memory, the ability to consciously recollect information and its context, varies substantially among individuals. While prior fMRI studies have identified certain brain regions linked to successful memory encoding at a group level, their role in explaining individual memory differences remains largely unexplored. Here, we analyze fMRI data of 1,498 adults participating in a picture encoding task in a single MRI scanner. We find that individual differences in responsivity of the hippocampus, orbitofrontal cortex, and posterior cingulate cortex account for individual variability in episodic memory performance. While these regions also emerge in our group-level analysis, other regions, predominantly within the lateral occipital cortex, are related to successful memory encoding but not to individual memory variation. Furthermore, our network-based approach reveals a link between the responsivity of nine functional connectivity networks and individual memory variability. Our work provides insights into the neurofunctional correlates of individual differences in visual episodic memory performance.

Sex-dependent differences in connectivity patterns are related to episodic memory recall.

Previous studies have shown that females typically outperform males on episodic memory tasks. In this study, we investigated if (1) there are differences between males and females in their connectome characteristics, (2) if these connectivity patterns are associated with memory performance, and (3) if these brain connectome characteristics contribute to the differences in episodic memory performance between sexes. In a sample of 655 healthy young subjects (n = 391 females; n = 264 males), we derived brain network characteristics from diffusion-weighted imaging (DWI) data using models of crossing fibers within each voxel of the brain and probabilistic tractography (graph strength, shortest path length, global efficiency, and weighted transitivity). Group differences were analysed with linear models and mediation analyses were used to explore how connectivity patterns might relate to sex-dependent differences in memory performance. Our results show significant sex-dependent differences in weighted transitivity (d = 0.42), with males showing higher values. Further, we observed a negative association between weighted transitivity and memory performance (r = -0.12). Finally, these distinct connectome characteristics partially mediated the observed differences in memory performance (effect size of the indirect effect r = 0.02). Our findings indicate a higher interconnectedness in females compared to males. Additionally, we demonstrate that the sex-dependent differences in episodic memory performance can be partially explained by the differences in this connectome measure. These results further underscore the importance of sex-dependent differences in brain connectivity and their impact on cognitive function.

Psychological well-being, mental distress, metabolic syndrome, and associated factors among people living in a refugee camp in Greece: a cross-sectional study.

Background: Forcibly displaced people face various challenges and are therefore at higher risk of being affected by mental and physiological distress. The present study aimed to determine levels of psychological well-being, PTSD symptom severity, metabolic syndrome, and associated factors among forcibly displaced people in Greece in response to WHO's call for evidence-based public health policies and programs for forcibly displaced people. Methods: We conducted a cross-sectional study among n = 150 (50% women) forcibly displaced people originating from Sub-Sahara Africa and Southwest Asia living in a Greek refugee camp. Self-report questionnaires were used to assess psychological well-being, symptoms of PTSD, depression, generalized anxiety disorder and insomnia, perceived stress, headache, and perceived fitness. Cardiovascular risk markers were assessed to determine metabolic syndrome, and cardiorespiratory fitness was measured with the Åstrand-Rhyming Test of Maximal Oxygen Uptake. Results: The prevalence of mental distress and physiological disorders was overall elevated. Only 53.0% of participants rated their psychological well-being as high. Altogether, 35.3% scored above the clinical cut-off for PTSD, 33.3% for depression, 27.9% for generalized anxiety disorder, and 33.8% for insomnia. One in four (28.8%) participants met criteria for metabolic syndrome. While the prevalence of moderate or severe insomnia symptoms and metabolic syndrome differed little from the global population, the risk of being affected by mental distress was markedly increased. In multivariable analysis, higher perceived fitness was associated with higher psychological well-being (OR = 1.35, p = 0.003) and a decreased likelihood for metabolic syndrome (OR = 0.80, p = 0.031). Participants with elevated psychiatric symptoms were less likely to report high psychological well-being (OR = 0.22, p = 0.003) and had increased odds for higher PTSD severity (OR = 3.27, p = 0.034). Increased stress perception was associated with higher PTSD symptoms (OR = 1.13, p = 0.002). Conclusion: There is an elevated risk for mental distress compared to the global population and an overall high mental and physiological burden among people living in a Greek refugee camp. The findings underpin the call for urgent action. Policies should aim to reduce post-migration stressors and address mental health and non-communicable diseases by various programs. Sport and exercise interventions may be a favorable add-on, given that perceived fitness is associated with both mental and physiological health benefits.

Epigenetics of traumatic stress: The association of NR3C1 methylation and posttraumatic stress disorder symptom changes in response to narrative exposure therapy.

Epigenetic processes allow plasticity in gene regulation in response to significant environmental events. Accumulating evidence suggests that effective psychotherapy is accompanied by epigenetic changes, rendering DNA methylation a potential biomarker of therapy success. Due to the central role of glucocorticoid dynamics in stress regulation and the alteration of aversive memories, glucocorticoid receptors are likely involved in the molecular processes that are required to successfully treat Posttraumatic Stress Disorder (PTSD). This study aimed to investigate the relationship between methylation at the glucocorticoid receptor gene (NR3C1) and PTSD treatment success of evidence-based psychotherapy. A sample of N = 153 conflict survivors from Northern Uganda (98 females and 55 males) with PTSD were treated with Narrative Exposure Therapy (NET). Diagnostic interviews and saliva sampling took place at pretreatment and 4 and 10 months after treatment completion. We investigated potential associations between PTSD symptom development and methylation changes at 38 CpG sites spanning NR3C1 over the three times of measurement using the repeated measures correlation. After accounting for multiple comparisons, DNA methylation at CpG site cg25535999 remained negatively associated with PTSD symptoms. These results were followed up by mixed models as well as structural equation modelling. These analyses revealed that treatment responders had a significant cg25535999 methylation increase after treatment with NET. Furthermore, lower methylation at cg25535999 pretreatment predicted a higher symptom improvement. Our results suggest different epigenetic profile dynamics at NR3C1 cg25535999 in therapy responders compared to non-responders and underscore the central role of glucocorticoid signaling in trauma-focused therapy.

(-)- Gossypol Inhibition of Musashi-Mediated Forgetting Improves Memory and Age-Dependent Memory Decline in Caenorhabditis elegans.

Musashi RNA-binding proteins (MSIs) retain a pivotal role in stem cell maintenance, tumorigenesis, and nervous system development. Recently, we showed in C. elegans that Musashi (MSI-1) actively promotes forgetting upon associative learning via a 3'UTR-dependent translational expression of the Arp2/3 actin branching complex. Here, we investigated the evolutionary conserved role of MSI proteins and the effect of their pharmacological inhibition on memory. Expression of human Musashi 1 (MSI1) and Musashi 2 (MSI2) under the endogenous Musashi promoter fully rescued the phenotype of msi-1(lf) worms. Furthermore, pharmacological inhibition of human MSI1 and MSI2 activity using (-)- gossypol resulted in improved memory retention, without causing locomotor, chemotactic, or learning deficits. No drug effect was observed in msi-1(lf) treated worms. Using Western blotting and confocal microscopy, we found no changes in MSI-1 protein abundance following (-)- gossypol treatment, suggesting that Musashi gene expression remains unaltered and that the compound exerts its inhibitory effect post-translationally. Additionally, (-)- gossypol suppressed the previously seen rescue of the msi-1(lf) phenotype in worms expressing human MSI1 specifically in the AVA neuron, indicating that (-)- gossypol can regulate the Musashi pathway in a memory-related neuronal circuit in worms. Finally, treating aged worms with (-)- gossypol reversed physiological age-dependent memory decline. Taken together, our findings indicate that pharmacological inhibition of Musashi might represent a promising approach for memory modulation.

The Iranian Corona Stress Study: Psychological Impacts of COVID-19 Pandemic in an Iranian Population.

Background: To assess the psychological consequences of changes during the coronavirus 2019 (COVID-19) pandemic in the Iranian population. Methods: We performed an anonymous online survey in the first 3 weeks of March 2020. Individuals older than 14 who could read Persian, and lived in Iran, were eligible for the study. The participants had to rate their stress levels and depressive symptoms (using a nine-item Patient Health Questionnaire PHQ-9) during the last 2 weeks and before the pandemic retrospectively. The changes in the psychological measurements and their association with the sociodemographic factors and burdens due to confinement were assessed. Results: Overall, among the 3,210 subjects who participated in our study, both the stress levels and average depression scores increased. However, about 23% of the subjects reported a decrease in their stress levels. The burden of childcare, restrictions in private life, and thoughts about the future were positively correlated with the changes in the stress levels and depression scores (|r| > 0.15). However, feeling relieved in the pandemic condition, and enjoying more family time were associated with less change in the stress and depression scores. Being religious (odds ratio [OR] [CI]: 1.5 [1.3-1-8]) and older age (OR [CI]: 2.9 [1.8-4.6] for >55 years old) were identified as the resilience factors, whereas being a student (OR [CI]: 2.1 [1.6;2.7]), seeking a job (OR [CI]: 2.6 [1.8;3.9]), and history of a psychiatric disorder (OR [CI]: 3.2 [2.6;4]) were identified as the risk factors for depression. Conclusions: The stress levels and depressive symptoms have increased during the COVID-19 pandemic and this increase is related to different social and personal burdens due to the confinement conditions.

The Impact of the COVID-19 Pandemic and Associated Control Measures on the Mental Health of the General Population : A Systematic Review and Dose-Response Meta-analysis.

BACKGROUND: To what extent the COVID-19 pandemic and its containment measures influenced mental health in the general population is still unclear. PURPOSE: To assess the trajectory of mental health symptoms during the first year of the pandemic and examine dose-response relations with characteristics of the pandemic and its containment. DATA SOURCES: Relevant articles were identified from the living evidence database of the COVID-19 Open Access Project, which indexes COVID-19-related publications from MEDLINE via PubMed, Embase via Ovid, and PsycInfo. Preprint publications were not considered. STUDY SELECTION: Longitudinal studies that reported data on the general population's mental health using validated scales and that were published before 31 March 2021 were eligible. DATA EXTRACTION: An international crowd of 109 trained reviewers screened references and extracted study characteristics, participant characteristics, and symptom scores at each timepoint. Data were also included for the following country-specific variables: days since the first case of SARS-CoV-2 infection, the stringency of governmental containment measures, and the cumulative numbers of cases and deaths. DATA SYNTHESIS: In a total of 43 studies (331 628 participants), changes in symptoms of psychological distress, sleep disturbances, and mental well-being varied substantially across studies. On average, depression and anxiety symptoms worsened in the first 2 months of the pandemic (standardized mean difference at 60 days, -0.39 [95% credible interval, -0.76 to -0.03]); thereafter, the trajectories were heterogeneous. There was a linear association of worsening depression and anxiety with increasing numbers of reported cases of SARS-CoV-2 infection and increasing stringency in governmental measures. Gender, age, country, deprivation, inequalities, risk of bias, and study design did not modify these associations. LIMITATIONS: The certainty of the evidence was low because of the high risk of bias in included studies and the large amount of heterogeneity. Stringency measures and surges in cases were strongly correlated and changed over time. The observed associations should not be interpreted as causal relationships. CONCLUSION: Although an initial increase in average symptoms of depression and anxiety and an association between higher numbers of reported cases and more stringent measures were found, changes in mental health symptoms varied substantially across studies after the first 2 months of the pandemic. This suggests that different populations responded differently to the psychological stress generated by the pandemic and its containment measures. PRIMARY FUNDING SOURCE: Swiss National Science Foundation. (PROSPERO: CRD42020180049).

Phosphorylation of MSI-1 is implicated in the regulation of associative memory in Caenorhabditis elegans.

The Musashi family of RNA-binding proteins controls several biological processes including stem cell maintenance, cell division and neural function. Previously, we demonstrated that the C. elegans Musashi ortholog, msi-1, regulates forgetting via translational repression of the Arp2/3 actin-branching complex. However, the mechanisms controlling MSI-1 activity during the regulation of forgetting are currently unknown. Here we investigated the effects of protein phosphorylation on MSI-1 activity. We showed that MSI-1 function is likely controlled by alterations of its activity rather than its expression levels. Furthermore, we found that MSI-1 is phosphorylated and using mass spectrometry we identified MSI-1 phosphorylation at three residues (T18, S19 and S34). CRISPR-based manipulations of MSI-1 phosphorylation sites revealed that phosphorylation is necessary for MSI-1 function in both short- and long-term aversive olfactory associative memory. Thus, our study provides insight into the mechanisms regulating memory-related MSI-1 activity and may facilitate the development of novel therapeutic approaches.

Human cerebellum and corticocerebellar connections involved in emotional memory enhancement.

Emotional information is better remembered than neutral information. Extensive evidence indicates that the amygdala and its interactions with other cerebral regions play an important role in the memory-enhancing effect of emotional arousal. While the cerebellum has been found to be involved in fear conditioning, its role in emotional enhancement of episodic memory is less clear. To address this issue, we used a whole-brain functional MRI approach in 1,418 healthy participants. First, we identified clusters significantly activated during enhanced memory encoding of negative and positive emotional pictures. In addition to the well-known emotional memory-related cerebral regions, we identified a cluster in the cerebellum. We then used dynamic causal modeling and identified several cerebellar connections with increased connection strength corresponding to enhanced emotional memory, including one to a cluster covering the amygdala and hippocampus, and bidirectional connections with a cluster covering the anterior cingulate cortex. The present findings indicate that the cerebellum is an integral part of a network involved in emotional enhancement of episodic memory.

Guilt is effectively induced by a written auto-biographical essay but not reduced by experimental pain.

Introduction: The aim of the present study was (1) to validate the method of guilt-induction by means of a written auto-biographical essay and (2) to test whether experimental pain is apt to alleviate the mental burden of guilt, a concept receiving support from both empirical research and clinical observation. Methods: Three independent groups of healthy male participants were recruited. Group allocation was not randomized but within group pain/sham administration was counterbalanced over the two test-days. Groups were tested in the following consecutive order: Group A: guilt induction, heat-pain/sham, N = 59; Group B: guilt induction, cold-pressure-pain/sham, N = 43; Group C: emotionally neutral induction, heat-pain/sham, N = 39. Guilt was induced on both test-days in group A and B before pain/sham administration. Visual analog scale (VAS) guilt ratings immediately after pain/sham stimulation served as the primary outcome. In a control group C the identical heat-pain experiment was performed like in group A but a neutral emotional state was induced. Results: A consistently strong overall effect of guilt-induction (heat-pain: p < 0.001, effect size r = 0.71; CPT-pain p < 0.001, r = 0.67) was found when compared to the control-condition (p = 0.25, r = 0.08). As expected, heat- and cold-pressure-stimuli were highly painful in all groups (p < 0.0001, r = 0.89). However, previous research supporting the hypothesis that pain is apt to reduce guilt was not replicated. Conclusion: Although guilt-induction was highly effective on both test-days no impact of pain on behavioral guilt-ratings in healthy individuals could be identified. Guilt induction per se did not depend on the order of testing. The result questions previous experimental work on the impact of pain on moral emotions.

The impact of the prolonged COVID-19 pandemic on stress resilience and mental health: A critical review across waves.

The global public health crisis caused by COVID-19 has lasted longer than many of us would have hoped and expected. With its high uncertainty and limited control, the COVID-19 pandemic has undoubtedly asked a lot from all of us. One important central question is: how resilient have we proved in face of the unprecedented and prolonged coronavirus pandemic? There is a vast and rapidly growing literature that has examined the impact of the pandemic on mental health both on the shorter (2020) and longer (2021) term. This not only concerns pandemic-related effects on resilience in the general population, but also how the pandemic has challenged stress resilience and mental health outcomes across more specific vulnerable population groups: patients with a psychiatric disorder, COVID-19 diagnosed patients, health care workers, children and adolescents, pregnant women, and elderly people. It is challenging to keep up to date with, and interpret, this rapidly increasing scientific literature. In this review, we provide a critical overview on how the COVID-19 pandemic has impacted mental health and how human stress resilience has been shaped by the pandemic on the shorter and longer term. The vast literature is dominated by a wealth of data which are, however, not always of the highest quality and heavily depend on online and self-report surveys. Nevertheless, it appears that we have proven surprisingly resilient over time, with fast recovery from COVID-19 measures. Still, vulnerable groups such as adolescents and health care personnel that have been severely impacted by the COVID-19 pandemic do exist. Large interindividual differences exist, and for future pandemics there is a clear need to comprehensively and integratively assess resilience from the start to provide personalized help and interventions tailored to the specific needs for vulnerable groups.

Effects of an exercise and sport intervention among refugees living in a Greek refugee camp on mental health, physical fitness and cardiovascular risk markers: study protocol for the SALEEM pragmatic randomized controlled trial.

BACKGROUND: Due to ongoing political and social conflicts, the number of international refugees has been increasing. Refugees are exposed to severe mental and physical strain, as well as traumatic experiences during their flight. Therefore, the risk of psychiatric disorders is markedly increased among international refugees. International organizations have criticized the lack of early interventions as a key problem, because untreated mental disorders are often difficult to cure at a later stage. Today, exercise and sport have been successfully employed to treat a wide range of psychiatric disorders. With patients with post-traumatic stress disorders (PTSD), very limited empirical evidence exists, and studies carried out with international refugees are nearly non-existent. METHODS: We intend to implement a pragmatic randomized controlled trial (RCT) with an exercise and sport intervention group (n = 68, 50% women) and a wait-list control group (n = 68, 50% women) in the Koutsochero refugee camp, located close to the city of Larissa (Greece). During the RCT, exercise and sport will be offered five times per week (60 min/session) for 10 weeks. Participants will be asked to participate in at least two sessions per week. The programme is developed according to the participants' needs and preferences and they will be able to choose between a range of activities. PTSD symptoms will serve as primary outcome, and several secondary outcomes will be assessed. Qualitative data collection methods will be used to gain a more in-depth appraisal of the participants' perception of the intervention programme. In the second year of study, the programme will be opened to all camp residents. A strategy will be developed how the programme can be continued after the end of the funding period, and how the programme can be scaled up beyond the borders of the Koutsochero camp. DISCUSSION: By moving towards the primary prevention of chronic physical conditions and psychiatric disorders, a relevant contribution can be done to enhance the quality and quantity of life of refugee camp residents in Greece. Our findings may also strengthen the evidence for exercise as medicine as a holistic care option in refugee camps, by helping camp residents to adopt and maintain a physically active lifestyle. TRIAL REGISTRATION: The study was registered prospectively on the 8 February 2021 with ISRCTN https://www.isrctn.com/ISRCTN16291983.

Cannabidiol enhances verbal episodic memory in healthy young participants: A randomized clinical trial.

Cannabis contains a multitude of different compounds. One of them, cannabidiol - a non-psychoactive substance - might counteract negative effects of Δ-9-Tetrahydrocannabinol on hippocampus-dependent memory impairment. The aim of the present study was to investigate the effect of vaping cannabidiol on verbal episodic memory in healthy young subjects. We used a double-blind, placebo-controlled, randomized crossover trial in 39 healthy young subjects. Participants received once a single dose of cannabidiol e-liquid (0.25 ml, 5% cannabidiol, 12.5 mg cannabidiol) and once placebo for vaping after learning 15 unrelated nouns. The primary outcome measure was the short delay verbal memory performance (number of correctly free recalled nouns) 20 min after learning. 34 participants (mean age: 22.26 [3.04]) completed all visits and entered analyses (17 received cannabidiol and 17 received placebo first). Cannabidiol enhanced verbal episodic memory performance (placebo: 7.03 [2.34]; cannabidiol 7.71 [2.48]; adjusted group difference 0.68, 95% CI 0.01 to 1.35; R2ß = .028, p = .048). Importantly, we did not detect medication effects on secondary outcome measures attention or working memory performance, suggesting that CBD has no negative impact on these basic cognitive functions. The results are in line with the idea that vaping cannabidiol interacts with the central endocannabinoid system and is capable to modulate memory processes, a phenomenon with possible therapeutic potential. Further studies are needed to investigate optimal dose-response and time-response relationships.

Investigation of a Model-Based Working Memory Training With and Without Distractor Inhibition and Its Comparative Efficacy: A Randomized Controlled Trial on Healthy Old Adults.

Background: Various working memory (WM) trainings have been tested, but differences in experimental designs, the lack of theoretical background, and the need of identifying task-related processes such as filtering efficiency limit conclusions about their comparative efficacy. Objectives: In this study, we compared the efficacy of a model-based WM training with (MB+) and without (MB) distractor inhibition on improving WM capacity to a dual n-back and active control condition. Methods: This randomized clinical trial included 123 healthy elderly adults (78 women, 45 men; aged 64.1 ± 8.3 years). All groups underwent 12 40-min training sessions over 3 weeks and four cognitive testing sessions. The first two sessions served as double baseline to account for practice effects. Primary outcome was WM capacity post-training measured by complex span tasks. Near and far transfer was assessed by simple span, n-back, visuospatial and verbal learning, processing speed, and reasoning tasks. Results: Due to preliminary termination (COVID-19), 93 subjects completed the post-training and 60 subjects the follow-up session. On a whole group level, practice effects occurred from prebaseline to baseline in WM capacity (b = 4.85, t (103) = 4.01, p < 0.001, r = 0.37). Linear mixed-effects models revealed a difference in WM capacity post-training between MB+ and MB (b = -9.62, t (82) = -2.52, p = 0.014, r = 0.27) and a trend difference between MB+ and dual n-back (b = -7.59, t (82) = -1.87, p = 0.065, r = 0.20) and control training (b = -7.08, t (82) = -1.86, p = 0.067, r = 0.20). Univariate analyses showed an increase between pre- and post-training for WM capacity within MB+ (t (22) = -3.34, p < 0.05) only. There was no difference between groups pre- and post-training regarding near and far transfer. Univariate analyses showed improved visuospatial learning within MB+ (t (21) = -3.8, p < 0.05), improved processing speed (t (23) = 2.19, p< 0.05) and n-back performance (t (23) = 2.12, p < 0.05) in MB, and improved n-back performance (t (25) = 3.83, p < 0.001) in the dual n-back training. Interpretation: A model-based WM training including filtering efficacy may be a promising approach to increase WM capacity and needs further investigation in randomized controlled studies.

Effectiveness of a smartphone-based, augmented reality exposure app to reduce fear of spiders in real-life: A randomized controlled trial.

Although in vivo exposure therapy is highly effective in the treatment of specific phobias, only a minority of patients seeks therapy. Exposure to virtual objects has been shown to be better tolerated, equally efficacious, but the technology has not been made widely accessible yet. We developed an augmented reality (AR) application (app) to reduce fear of spiders and performed a randomized controlled trial comparing the effects of our app (six 30-min sessions at home over a two-week period) with no intervention. Primary outcome was subjective fear, measured by a Subjective Units of Distress Scale (SUDS) in a Behavioural Approach Test (BAT) in a real-life spider situation at six weeks follow-up. Between Oct 7, 2019, and Dec 6, 2019, 66 individuals were enrolled and randomized. The intervention led to significantly lower subjective fear in the BAT compared to the control group (intervention group, baseline: 7.12 [SD 2.03] follow-up: 5.03 [SD 2.19] vs. control group, baseline: 7.06 [SD 2.34], follow-up 6.24 [SD 2.21]; adjusted group difference -1.24, 95 % CI -2.17 to -0.31; Cohen's d = 0.57, p = 0.010). The repeated use of the AR app reduces subjective fear in a real-life spider situation, providing a low-threshold and low-cost treatment for fear of spiders.