Introducing COSMOS: a Web Platform for Multimodal Game-Based Psychological Assessment Geared Towards Open Science Practice

We have established the COgnitive Science Metrics Online Survey (COSMOS) platform that contains a digital psychometrics toolset in the guise of applied games measuring a wide range of cognitive functions. Here, we are outlining this online research endeavor designed for automatized psychometric data collection and scalable assessment: once set up, the low costs and expenditure associated with individual psychometric testing allow substantially increased study cohorts and thus contribute to enhancing study outcome reliability. We are leveraging gamification of the data acquisition method to make the tests suitable for online administration. By putting a strong focus on entertainment and individually tailored feedback, we aim to maximize subjects’ incentives for repeated and continued participation. The objective of measuring repeatedly is obtaining more revealing multitrial average scores and measures from various operationalizations of the same psychological construct instead of relying on single-shot measurements. COSMOS is set up to acquire an automatically and continuously growing dataset that can be used to answer a wide variety of research questions. Following the principles of the open science movement, this data set will also be made accessible to other publicly funded researchers, given that all precautions for individual data protection are fulfilled. We have developed a secure hosting platform and a series of digital gamified testing instruments that can measure theory of mind, attention, working memory, episodic long- and short-term memory, spatial memory, reaction times, eye-hand coordination, impulsivity, humor appreciation, altruism, fairness, strategic thinking, decision-making, and risk-taking behavior. Furthermore, some of the game-based testing instruments also offer the possibility of using classical questionnaire items. A subset of these gamified tests is already implemented in the COSMOS platform, publicly accessible and currently undergoing evaluation and calibration as normative data is being collected. In summary, our approach can be used to accomplish a detailed and reliable psychometric characterization of thousands of individuals to supply various studies with large-scale neurocognitive phenotypes. Our game-based online testing strategy can also guide recruitment for studies as they allow very efficient screening and sample composition. Finally, this setup also allows to evaluate potential cognitive training effects and whether improvements are merely task specific or if generalization effects occur in or even across cognitive domains

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; R; 2β; = .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

Psychiatry in the Digital Age: A Blessing or a Curse?

Social distancing and the shortage of healthcare professionals during the COVID-19 pandemic, the impact of population aging on the healthcare system, as well as the rapid pace of digital innovation are catalyzing the development and implementation of new technologies and digital services in psychiatry. Is this transformation a blessing or a curse for psychiatry? To answer this question, we conducted a literature review covering a broad range of new technologies and eHealth services, including telepsychiatry; computer-, internet-, and app-based cognitive behavioral therapy; virtual reality; digital applied games; a digital medicine system; omics; neuroimaging; machine learning; precision psychiatry; clinical decision support; electronic health records; physician charting; digital language translators; and online mental health resources for patients. We found that eHealth services provide effective, scalable, and cost-efficient options for the treatment of people with limited or no access to mental health care. This review highlights innovative technologies spearheading the way to more effective and safer treatments. We identified artificially intelligent tools that relieve physicians from routine tasks, allowing them to focus on collaborative doctor-patient relationships. The transformation of traditional clinics into digital ones is outlined, and the challenges associated with the successful deployment of digitalization in psychiatry are highlighted

The prion gene is associated with human long-term memory

Human cognitive processes are highly variable across individuals and are influenced by both genetic and environmental factors. Although genetic variations affect short-term memory in humans, it is unknown whether genetic variability has also an impact on long-term memory. Because prion-like conformational changes may be involved in the induction of long-lasting synaptic plasticity, we examined the impact of single-nucleotide polymorphisms (SNPs) of the prion protein gene (PRNP) on long-term memory in healthy young humans. SNPs in the genomic region of PRNP were associated with better long-term memory performance in two independent populations with different educational background. Among the examined PRNP SNPs, the common Met129Val polymorphism yielded the highest effect size. Twenty-four hours after a word list-learning task, carriers of either the 129MM or the 129MV genotype recalled 17% more information than 129VV carriers, but short-term memory was unaffected. These results suggest a role for the prion protein in the formation of long-term memory in human

Recognition memory performance can be estimated based on brain activation networks

Recognition memory is an essential ability for functioning in everyday life. Establishing robust brain networks linked to recognition memory performance can help to understand the neural basis of recognition memory itself and the interindividual differences in recognition memory performance.; We analysed behavioural and whole-brain fMRI data from 1'410 healthy young adults during the testing phase of a picture-recognition task. Using independent component analysis (ICA), we decomposed the fMRI contrast for previously seen vs. new (old-new) pictures into networks of brain activity. This was done in two independent samples (training sample: N = 645, replication sample: N = 665). Next, we investigated the relationship between the identified brain networks and interindividual differences in recognition memory performance by conducting a prediction analysis. We estimated the prediction accuracy in a third independent sample (test sample: N = 100).; We identified 12 robust and replicable brain networks using two independent samples. Based on the activity of those networks we could successfully estimate interindividual differences in recognition memory performance with high accuracy in a third independent sample (r = 0.5, p = 1.29 × 10; -07; ).; Given the robustness of the ICA decomposition as well as the high prediction estimate, the identified brain networks may be considered as potential biomarkers of recognition memory performance in healthy young adults and can be further investigated in the context of health and disease

Evolutionary conserved role of neural cell adhesion molecule-1 in memory.

Vukojevic V, Mastrandreas P, Arnold A, et al. Evolutionary conserved role of neural cell adhesion molecule-1 in memory. Translational psychiatry. 2020;10(1): 217.The neural cell adhesion molecule 1 (NCAM-1) has been implicated in several brain-related biological processes, including neuronal migration, axonal branching, fasciculation, and synaptogenesis, with a pivotal role in synaptic plasticity. Here, we investigated the evolutionary conserved role of NCAM-1 in learning and memory. First, we investigated sustained changes in ncam-1 expression following aversive olfactory conditioning in C. elegans using molecular genetic methods. Furthermore, we examined the link between epigenetic signatures of the NCAM1 gene and memory in two human samples of healthy individuals (N=568 and N=319) and in two samples of traumatized individuals (N=350 and N=463). We found that olfactory conditioning in C. elegans induced ncam-1 expression and that loss of ncam-1 function selectively impaired associative long-term memory, without causing acquisition, sensory, or short-term memory deficits. Reintroduction of the C. elegans or human NCAM1 fully rescued memory impairment, suggesting a conserved role of NCAM1 for memory. In parallel, DNA methylation of the NCAM1 promoter in two independent healthy Swiss cohorts was associated with memory performance. In two independent Sub-Saharan populations of conflict zone survivors who had faced severe trauma, DNA methylation at an alternative promoter of the NCAM1 gene was associated with traumatic memories. Our results support a role of NCAM1 in associative memory in nematodes and humans, and might, ultimately, be helpful in elucidating diagnostic markers or suggest novel therapy targets for memory-related disorders, like PTSD

Effectiveness of a stand-alone, smartphone-based virtual reality exposure app to reduce fear of heights in real-life: a randomized trial

Smartphone-based virtual reality (VR) applications (apps) might help to counter low utilization rates of available treatments for fear of heights. Demonstration of effectiveness in real-life situations of such apps is crucial, but lacking so far. Objective of this study was to develop a stand-alone, smartphone-based VR exposure app-Easy Heights-and to test its effectiveness in a real-life situation. We performed a single-blind, parallel group, randomized controlled trial. We recruited 70 participants with fear of heights, aged 18-60 years. Primary outcome was performance in a real-life Behavioral Avoidance Test (BAT) on a lookout tower after a single 1-h app use (phase 1) and after additional repeated (6 × 30 min) app use at home (phase 2). After phase 2, but not phase 1, participants in the Easy Heights condition showed significantly higher BAT scores compared to participants in the control condition (Cohen's d = 1.3, p = 0.0001). Repeated use of our stand-alone, smartphone-based VR exposure app reduces avoidance behavior and fear, providing a low-threshold treatment for fear of heights

ER-mitochondria contacts and cholesterol metabolism are disrupted by disease-associated tau protein

Abnormal tau protein impairs mitochondrial function, including transport, dynamics, and bioenergetics. Mitochondria interact with the endoplasmic reticulum (ER) via mitochondria-associated ER membranes (MAMs), which coordinate and modulate many cellular functions, including mitochondrial cholesterol metabolism. Here, we show that abnormal tau loosens the association between the ER and mitochondria in vivo and in vitro. Especially, ER-mitochondria interactions via vesicle-associated membrane protein-associated protein (VAPB)-protein tyrosine phosphatase-interacting protein 51 (PTPIP51) are decreased in the presence of abnormal tau. Disruption of MAMs in cells with abnormal tau alters the levels of mitochondrial cholesterol and pregnenolone, indicating that conversion of cholesterol into pregnenolone is impaired. Opposite effects are observed in the absence of tau. Besides, targeted metabolomics reveals overall alterations in cholesterol-related metabolites by tau. The inhibition of GSK3β decreases abnormal tau hyperphosphorylation and increases VAPB-PTPIP51 interactions, restoring mitochondrial cholesterol and pregnenolone levels. This study is the first to highlight a link between tau-induced impairments in the ER-mitochondria interaction and cholesterol metabolism

SPHN - The Swiss Aging Citizen Reference (SACR)

In Switzerland by 2045, we expect 2.7 Mio citizens aged 65+ of whom 1.0 Mio. aged 80+. A priority and focus of personalized health research is therefore aging biology to extend healthy life expectancy. Novel molecular and imaging features will emerge as candidate targets for risk prediction and screening of chronic diseases. It is of utmost importance to test the clinical and public health utility of candidate biomarkers evolving from this research in citizen reference cohorts. We will build a Swiss Aging Citizen Reference (SACR), a testable and scalable reference cohort offering interoperable, searchable, and accessible data. 1000 participants from existing Swiss citizen cohorts will be combined and analyzed for DNA methylation and MRI brain imaging. SACR will serve as a testbed for clinical and public health utility of candidate biomarkers. As for a proof-of-concept study, we will conduct an agnostic search for structural and functional brain features associated with epigenetic aging acceleration to examine the potential of epigenetic age acceleration as the intermediate aging biomarker and to better understand the aging mechanism in brain

Better Memory and Neural Efficiency in Young Apolipoprotein E ε4 Carriers

The apolipoprotein E (APOE) ε4 allele is the major genetic risk factor for Alzheimer's disease, but an APOE effect on memory performance and memory-related neurophysiology in young, healthy subjects is unknown. We found an association of APOE ε4 with better episodic memory compared with APOE ε2 and ε3 in 340 young, healthy persons. Neuroimaging was performed in a subset of 34 memory-matched individuals to study genetic effects on memory-related brain activity independently of differential performance. E4 carriers decreased brain activity over 3 learning runs, whereas ε2 and ε3 carriers increased activity. This smaller neural investment of ε4 carriers into learning reappeared during retrieval: ε4 carriers exhibited reduced retrieval-related activity with equal retrieval performance. APOE isoforms had no differential effects on cognitive measures other than memory, brain volumes, and brain activity related to working memory. We suggest that APOE ε4 is associated with good episodic memory and an economic use of memory-related neural resources in young, healthy human