EEGManyPipelines: A Large-scale, Grassroots Multi-analyst Study of Electroencephalography Analysis Practices in the Wild.

The ongoing reproducibility crisis in psychology and cognitive neuroscience has sparked increasing calls to re-evaluate and reshape scientific culture and practices. Heeding those calls, we have recently launched the EEGManyPipelines project as a means to assess the robustness of EEG research in naturalistic conditions and experiment with an alternative model of conducting scientific research. One hundred sixty-eight analyst teams, encompassing 396 individual researchers from 37 countries, independently analyzed the same unpublished, representative EEG data set to test the same set of predefined hypotheses and then provided their analysis pipelines and reported outcomes. Here, we lay out how large-scale scientific projects can be set up in a grassroots, community-driven manner without a central organizing laboratory. We explain our recruitment strategy, our guidance for analysts, the eventual outputs of this project, and how it might have a lasting impact on the field.

Regression to the mean in latent change score models: an example involving breastfeeding and intelligence.

BACKGROUND: Latent change score models are often used to study change over time in observational data. However, latent change score models may be susceptible to regression to the mean. Earlier observational studies have identified a positive association between breastfeeding and child intelligence, even when adjusting for maternal intelligence. METHOD: In the present study, we investigate regression to the mean in the case of breastfeeding and intelligence of children. We used latent change score modeling to analyze intergenerational change in intelligence, both from mothers to children and backward from children to mothers, in the 1979 National Longitudinal Survey of Youth (NLSY79) dataset (N = 6283). RESULTS: When analyzing change from mothers to children, breastfeeding was found to have a positive association with intergenerational change in intelligence, whereas when analyzing backward change from children to mothers, a negative association was found. CONCLUSIONS: These discrepant findings highlight a hidden flexibility in the analytical space and call into question the reliability of earlier studies of breastfeeding and intelligence using observational data.

ENIGMA-Sleep: Challenges, opportunities, and the road map.

Neuroimaging and genetics studies have advanced our understanding of the neurobiology of sleep and its disorders. However, individual studies usually have limitations to identifying consistent and reproducible effects, including modest sample sizes, heterogeneous clinical characteristics and varied methodologies. These issues call for a large-scale multi-centre effort in sleep research, in order to increase the number of samples, and harmonize the methods of data collection, preprocessing and analysis using pre-registered well-established protocols. The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) consortium provides a powerful collaborative framework for combining datasets across individual sites. Recently, we have launched the ENIGMA-Sleep working group with the collaboration of several institutes from 15 countries to perform large-scale worldwide neuroimaging and genetics studies for better understanding the neurobiology of impaired sleep quality in population-based healthy individuals, the neural consequences of sleep deprivation, pathophysiology of sleep disorders, as well as neural correlates of sleep disturbances across various neuropsychiatric disorders. In this introductory review, we describe the details of our currently available datasets and our ongoing projects in the ENIGMA-Sleep group, and discuss both the potential challenges and opportunities of a collaborative initiative in sleep medicine.

Effects of late-night short-sleep on in-home polysomnography: relation to adult age and sex.

Bedtime is frequently delayed by many factors in life, and a homeostatic response to the delay may compensate partly for increased time awake and shortened sleep. Because sleep becomes shorter with age and women complain of disturbed sleep more often than men, age and sex differences in the homeostatic response to a delayed bedtime may modify the homeostatic response. The purpose of the present study was to investigate the effect of late-night short-sleep (3 h with awakening at about 07:00 hours) on in-home recorded sleep in men and women in two age groups (20-30 and 65-75 years). Results (N = 59) showed that late-night short-sleep was associated with an increase in percentage of N3 sleep and a decrease in percentage of rapid eye movement sleep, as well as decreases in several measures of sleep discontinuity and rapid eye movement density. Men showed a smaller decrease in percentage of rapid eye movement sleep than women in response to late-night short-sleep, as did older individuals of both sexes compared with younger. Older men showed a weaker percentage of N3 sleep in response to late-night short-sleep than younger men. In general, men showed a greater percentage of rapid eye movement sleep and a lower percentage of N3 sleep than women, and older individuals showed a lower percentage of N3 sleep than younger. In particular, older men showed very low levels of percentage of N3 sleep. We conclude that older males show less of a homeostatic response to late-night short-sleep. This may be an indication of impaired capacity for recovery in older men. Future studies should investigate if this pattern can be linked to gender-associated differences in morbidity and mortality.

Intrinsic functional connectivity of insular cortex and symptoms of sickness during acute experimental inflammation.

Task-based fMRI has been used to study the effects of experimental inflammation on the human brain, but it remains unknown whether intrinsic connectivity in the brain at rest changes during a sickness response. Here, we investigated the effect of experimental inflammation on connectivity between areas relevant for monitoring of bodily states, motivation, and subjective symptoms of sickness. In a double-blind randomized controlled experiment, 52 healthy volunteers were injected with 0.6ng/kg LPS (lipopolysaccharide) or placebo, and participated in a resting state fMRI experiment after approximately 2h 45min. Resting state fMRI data were available from 48 participants, of which 28 received LPS and 20 received placebo. Bilateral anterior and bilateral posterior insula sections were used as seed regions and connectivity with bilateral orbitofrontal and cingulate (anterior and middle) cortices was investigated. Back pain, headache and global sickness increased significantly after as compared to before LPS, while a non-significant trend was shown for increased nausea. Compared to placebo, LPS was followed by increased connectivity between left anterior insula and left midcingulate cortex. This connectivity was significantly correlated to increase in back pain after LPS and tended to be related to increased global sickness, but was not related to increased headache or nausea. LPS did not affect the connectivity from other insular seeds. In conclusion, the finding of increased functional connectivity between left anterior insula and middle cingulate cortex suggests a potential neurophysiological mechanism that can be further tested to understand the subjective feeling of malaise and discomfort during a sickness response.

[Registration and reporting of results from clinical trials in Nordic countries - there is scope for improvement]. / Registrering och rapportering av kliniska studier kan bli bättre.

Reporting of results from clinical trials is necessary for reliable evidence in clinical decision making, and is mandated as an ethical and regulatory obligation. We have recently followed up reporting of clinical trials in the Nordic countries sponsored by medical universities and university hospitals. Of 2113 studies registered on the EU Clinical Trials Registry (EUCTR) or on clinicaltrials.gov and completed 2016-2019, about half reported results in any form after 24 months and more than one in five did not report results at all. For trials registered on clinicaltrials.gov, about half were prospectively registered. These results are consistent with results from follow-up of registered trials in other contexts and demonstrate that there is scope for improvement in registration and reporting of clinical trials. We urge public sector trial sponsors to enhance their support to trialists in order to ensure that trials are reported in a timely manner.

Breastfeeding, cognitive ability, and residual confounding: A comment on studies by Pereyra-Elìas et al.

Recent studies found positive effects of breastfeeding on the child's cognitive ability and educational outcomes even when adjusting for maternal cognitive ability in addition to a large number of other potential confounders. The authors claimed an important role of breastfeeding for the child's cognitive scores. However, it is well known that error in the measurement of confounders can leave room for residual confounding. In the present reanalyses, we found incongruent effects indicating simultaneous increasing and decreasing effects of breastfeeding on the child's cognitive ability and educational outcomes. We conclude that findings in the reanalyses may have been due to residual confounding due to error in the measurement of maternal cognitive ability. Consequently, it appears premature to assume a genuine increasing effect of breastfeeding on the child's cognitive ability and educational outcomes and claims in this regard may be challenged.

A formal model accounting for measurement reliability shows attenuated effect of higher education on intelligence in longitudinal data.

The effect of higher education on intelligence has been examined using longitudinal data. Typically, these studies reveal a positive effect, approximately 1 IQ point per year of higher education, particularly when pre-education intelligence is considered as a covariate in the analyses. However, such covariate adjustment is known to yield positively biased results if the covariate has measurement errors and is correlated with the predictor. Simultaneously, a negative bias may emerge if the intelligence measure after higher education has non-classical measurement errors as in data from the 1970 British Cohort Study that were used in a previous study of the effect of higher education. In response, we have devised an estimation method that used iterated simulations to account for both classical measurement errors in the covariate and non-classical errors in the dependent variable. Upon applying this method in a reanalysis of the data from the 1970 British Cohort Study, we find that the estimated effect of higher education diminishes to 0.4 IQ points per year. Additionally, our findings suggest that the impact of higher education is somewhat more pronounced in the initial 2 years of higher education, aligning with the notion of diminishing marginal cognitive benefits.

Altered empathy processing in frontotemporal dementia A task-based fMRI study.

A lack of empathy, and particularly its affective components, is a core symptom of behavioural variant frontotemporal dementia (bvFTD). Visual exposure to images of a needle pricking a hand (pain condition) and Q-tips touching a hand (control condition) is an established functional magnetic resonance imaging (fMRI) paradigm used to investigate empathy for pain (EFP; pain condition minus control condition). EFP has been associated with increased blood oxygen level dependent (BOLD) signal in regions known to become atrophic in the early stages in bvFTD, including the anterior insula and the anterior cingulate. We therefore hypothesized that patients with bvFTD would display altered empathy processing in the EFP paradigm. Here we examined empathy processing using the EFP paradigm in 28 patients with bvFTD and 28 sex and age matched controls. Participants underwent structural MRI, task-based and resting-state fMRI. The Interpersonal Reactivity Index (IRI) was used as a measure of different facets of empathic function outside the scanner. The EFP paradigm was analysed at a whole brain level and using two regions-of-interest approaches, one based on a metanalysis of affective perceptual empathy versus cognitive evaluative empathy and one based on the controls activation pattern. In controls, EFP was linked to an expected increase of BOLD signal that displayed an overlap with the pattern of atrophy in the bvFTD patients (insula and anterior cingulate). Additional regions with increased signal were the supramarginal gyrus and the occipital cortex. These latter regions were the only ones that displayed increased BOLD signal in bvFTD patients. BOLD signal increase under the affective perceptual empathy but not the cognitive evaluative empathy region of interest was significantly greater in controls than in bvFTD patients. The controls rating on their empathic concern subscale of the IRI was significantly correlated with the BOLD signal in the EFP paradigm, as were an informants ratings of the patients empathic concern subscale. This correlation was not observed on other subscales of the IRI or when using the patient's self-ratings. Finally, controls and patients showed different connectivity patterns in empathy related networks during resting-state fMRI, mainly in nodes overlapping the ventral attention network. Our results indicate that reduced neural activity in regions typically affected by pathology in bvFTD is associated with reduced empathy processing, and a predictor of patients capacity to experience affective empathy.

Selenite induces posttranscriptional blockade of HLA-E expression and sensitizes tumor cells to CD94/NKG2A-positive NK cells.

CD94/NKG2A is an inhibitory receptor that controls the activity of a large proportion of human NK cells following interactions with the nonclassical HLA class Ib molecule HLA-E expressed on target cells. In this study, we show that selenite (SeO(3)(2-)), an inorganic selenium compound, induces an almost complete loss of cell surface expression of HLA-E on tumor cells of various origins. Selenite abrogated the HLA-E expression at a posttranscriptional level, since selenite exposure led to a dose-dependent decrease in cellular HLA-E protein expression whereas the mRNA levels remained intact. The loss of HLA-E expression following selenite treatment was associated with decreased levels of intracellular free thiols in the tumor cells, suggesting that the reduced HLA-E protein synthesis was caused by oxidative stress. Indeed, HLA-E expression and the level of free thiols remained intact following treatment with selenomethionine, a selenium compound that does not generate oxidative stress. Loss of HLA-E expression, but not of total HLA class I expression, on tumor cells resulted in increased susceptibility to CD94/NK group 2A-positive NK cells. Our results suggest that selenite may be used to potentiate the anti-tumor cytotoxicity in settings of NK cell-based immunotherapies.

[Same data - different conclusions: Analytical flexibility in medical research can be considerable]. / Olika slutsatser från samma data.

Analysis of research data entails many choices. As a result, a space of different analytical strategies is open to researchers. Different justifiable analyses may not give similar results. The method of multiple analysts is a way to study the analytical flexibility and behaviour of researchers under naturalistic conditions, as part of the field known as metascience. Analytical flexibility and risks of bias can be counteracted by open data sharing, pre-registration of analysis plans, and registration of clinical trials in trial registers. These measures are particularly important for retrospective studies where analytical flexibility can be greatest, although pre-registration is less useful in this context. Synthetic datasets can be an alternative to pre-registration when used to decide what analyses should be conducted on real datasets by independent parties. All these strategies help build trustworthiness in scientific reports, and improve the reliability of research findings.

Distorted meta-analytic findings on peer influence: A reanalysis.

In a recent meta-analysis, Giletta et al. (2021) [1] found a positive effect of peers' behavior at time 1 on target youths' behavior at time 2 while adjusting for target youths' behavior at time 1 and claimed to have quantified peer influence. However, it is established that controlled cross-lagged effects could be due to correlations with measurement errors and reversion in the direction of the mean rather than due to true decreasing or increasing effects. Here, in a reanalysis of the same meta-analytic data as used by Giletta et al., we found that peer influence, as operationalized by Giletta et al., may have been distorted (i.e. spurious). We do not claim that peer influence does not exist, but it may be hard, maybe not even possible, to prove by analyses of observational data that it does exist. Difficulties to prove causal effects by analyses of observational data is common for all areas of research and not specific for research on peer influence.

Dangers of including outcome at baseline as a covariate in latent change score models: Results from simulations and empirical re-analyses.

Latent change score modeling is a type of structural equation modeling used for estimating change over time. Often change is regressed on the initial value of the outcome variable. However, similarly to other regression analyses, this procedure may be susceptible to regression to the mean. The present study employed simulations as well as re-analyses of previously published data, claimed to indicate reciprocal promoting effects of vocabulary and matrix reasoning on each other's longitudinal development. Both in simulations and empirical re-analyses, when adjusting for initial value on the outcome, latent change score modeling tended to indicate an effect of a predictor on the change in an outcome even when no change had taken place. Furthermore, analyses tended to indicate a paradoxical effect on change both forward and backward in time. We conclude that results from latent change score modeling are susceptible to regression to the mean when adjusting for the initial value on the outcome. Researchers are recommended not to regress change on the initial value included in the calculation of the change score when employing latent change score modeling but, instead, to define this parameter as a covariance.

Unmasking artifactual links: A reanalysis reveals No direct causal relationship between self-esteem and quality of social relations.

A meta-analysis conducted by Harris and Orth (2020) found positive prospective cross-lagged effects between quality of social relations and self-esteem in included longitudinal studies. Harris and Orth concluded that the link between self-esteem and quality of social relations is reciprocal and characterized by a positive feedback loop. However, meta-analytic effects were estimated while controlling for a prior measurement of the outcome and such effects are known to be susceptible to artifactual (i.e. spurious) effects due to correlations with measurement errors and reversion to mediocrity. We reanalyzed the same data and found paradoxical effects indicating, simultaneously, both increasing and decreasing effects between self-esteem and social relations. These findings suggest that prospective effects between self-esteem and quality of social relations are artifactual rather than due to a true reciprocal effect. Thus, these findings have important theoretical implications and challenge both the risk regulation model, which posits that self-esteem has a causal effect on quality of social relations, and the sociometer theory, which claims that quality of relations is the cause and self-esteem the effect. The present results prompt further investigation into the underlying mechanisms driving these artifactual associations. Additionally, the study highlights the importance of considering methodological limitations in future meta-analyses to improve the accuracy of causal inferences.

Replacing academic journals.

Replacing traditional journals with a more modern solution is not a new idea. Here, we propose ways to overcome the social dilemma underlying the decades of inaction. Any solution needs to not only resolve the current problems but also be capable of preventing takeover by corporations: it needs to replace traditional journals with a decentralized, resilient, evolvable network that is interconnected by open standards and open-source norms under the governance of the scholarly community. It needs to replace the monopolies connected to journals with a genuine, functioning and well-regulated market. In this new market, substitutable service providers compete and innovate according to the conditions of the scholarly community, avoiding sustained vendor lock-in. Therefore, a standards body needs to form under the governance of the scholarly community to allow the development of open scholarly infrastructures servicing the entire research workflow. We propose a redirection of money from legacy publishers to the new network by funding bodies broadening their minimal infrastructure requirements at recipient institutions to include modern infrastructure components replacing and complementing journal functionalities. Such updated eligibility criteria by funding agencies would help realign the financial incentives for recipient institutions with public and scholarly interest.

Questioning the vulnerability model: Prospective associations between low self-esteem and subsequent depression ratings may be spurious.

BACKGROUND: According to the vulnerability model, low self-esteem makes people more depressed. Support for the vulnerability model comes almost exclusively from analyses using cross-lagged panel models, showing a negative effect of initial self-esteem on subsequent depression ratings when adjusting for initial depression. However, it is well known that such adjusted effects are susceptible to regression toward the mean. METHODS: Data from four waves of measurements in five different samples (total N = 2703) were analyzed with two different cross-lagged panel models, two different random intercept cross-lagged panel models, and two different latent change score models, predicting change forwards as well as backwards in time. RESULTS: High initial self-esteem predicted both decreased and increased depression ratings between measurements and an increase in self-esteem between measurements predicted a concurrent decrease in depression ratings. LIMITATIONS: Only data from two western countries, Switzerland and USA, were analyzed. Whether the main finding, that a prospective effect of self-esteem on subsequent depression ratings might be spurious, applies to other countries and cultures remains an open question. CONCLUSIONS: Due to the incongruent results, any causal effect of self-esteem on depression ratings, and thus the vulnerability model as such, cannot be corroborated by the data and models analyzed here. Instead, we propose, tentatively, that prospective associations between self-esteem and depression ratings may be spurious due to a combination of reasons, including regression toward the mean. The indication that depression might not be affected by measures to improve individuals' self-esteem is of clinical relevance.

Exhaustion disorder: scoping review of research on a recently introduced stress-related diagnosis.

BACKGROUND: Symptoms related to chronic stress are prevalent and entail high societal costs, yet there is a lack of international consensus regarding diagnostics and treatment. A new stress-related diagnosis, exhaustion disorder, was introduced into the Swedish version of ICD-10 in 2005. Since then, use of the diagnosis has increased rapidly. AIMS: To create the first comprehensive synthesis of research on exhaustion disorder to report on the current state of knowledge. Preregistration: Open Science Framework (http://www.w3.org/1999/xlink">osf.io), doi 10.17605/OSF.IO/VFDKW. METHOD: A PRISMA-guided scoping review of all empirical studies of exhaustion disorder was conducted. Searches were run in the MEDLINE, PsycInfo and Web of Science databases. Data were systematically charted and thematically categorised based on primary area of investigation. RESULTS: Eighty-nine included studies were sorted into six themes relating to lived experience of exhaustion disorder (n = 9), symptom presentation and course (n = 13), cognitive functioning (n = 10), biological measures (n = 24), symptom measurement scales (n = 4) and treatment (n = 29). Several studies indicated that individuals with exhaustion disorder experience a range of psychiatric and somatic symptoms beyond fatigue, but robust findings within most thematic categories were scarce. The limited number of studies, lack of replication of findings and methodological limitations (e.g. small samples and scarcity of specified primary outcomes) preclude firm conclusions about the diagnostic construct. CONCLUSIONS: More research is needed to build a solid knowledge base for exhaustion disorder. International collaboration regarding the conceptualisation of chronic stress and fatigue is warranted to accelerate the growth of evidence.

Microscopy-BIDS: An Extension to the Brain Imaging Data Structure for Microscopy Data.

The Brain Imaging Data Structure (BIDS) is a specification for organizing, sharing, and archiving neuroimaging data and metadata in a reusable way. First developed for magnetic resonance imaging (MRI) datasets, the community-led specification evolved rapidly to include other modalities such as magnetoencephalography, positron emission tomography, and quantitative MRI (qMRI). In this work, we present an extension to BIDS for microscopy imaging data, along with example datasets. Microscopy-BIDS supports common imaging methods, including 2D/3D, ex/in vivo, micro-CT, and optical and electron microscopy. Microscopy-BIDS also includes comprehensible metadata definitions for hardware, image acquisition, and sample properties. This extension will facilitate future harmonization efforts in the context of multi-modal, multi-scale imaging such as the characterization of tissue microstructure with qMRI.

Learning in a simple biological system: a pilot study of classical conditioning of human macrophages in vitro.

Recent advances in cell biology and gene regulation suggest mechanisms whereby associative learning could be performed by single cells. Therefore, we explored a model of classical conditioning in human macrophages in vitro. In macrophage cultures, bacterial lipopolysaccharide (LPS; unconditioned stimulus) was paired once with streptomycin (conditioned stimulus). Secretion of interleukin-6 (IL-6) was used as response measure. At evocation, conditioning was not observed. Levels of IL-6 were higher only in those cultures that had been exposed to LPS in the learning phase (p's < .05), regardless whether they received the conditioned stimulus or not at evocation.However, habituation was evident, with a 62% loss of the IL-6 response after three LPS presentations (p < .001). If further experiments confirm that simple learning can occur in immune cells, this may have bearings not only on immune regulation, but also on the brain response to molecular signals detected in the periphery. Importantly, whether capacities for simple learning in single cells extend beyond habituation, and how this would be demonstrated, remain open questions.

The new accounting for expected adjusted effect test (AEAE test) has higher positive predictive value than a zero-order significance test.

OBJECTIVE: The present simulation study aimed to assess positive predictive value (PPV) and negative predictive value (NPV) for our newly introduced Accounting for Expected Adjusted Effect test (AEAE test) and compare it to PPV and NPV for a traditional zero-order significance test. RESULTS: The AEAE test exhibited greater PPV compared to a traditional zero-order significance test, especially with a strong true adjusted effect, low prior probability, high degree of confounding, large sample size, high reliability in the measurement of predictor X and outcome Y, and low reliability in the measurement of confounder Z. The zero-order significance test, on the other hand, exhibited higher NPV, except for some combinations of high degree of confounding and large sample size, or low reliability in the measurement of Z and high reliability in the measurement of X/Y, in which case the zero-order significance test can be completely uninformative. Taken together, the findings demonstrate desirable statistical properties for the AEAE test compared to a traditional zero-order significance test.