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Abstract Background In view of demographic change, rising retirement age, and a growing shortage of skilled workers, it is increasingly important to prevent widespread diseases such as type 2 diabetes or its risk factor metabolic syndrome. Since the workplace is an important setting for preventive measures and little is known about incident cases in the working population, the aim of this study was to identify vulnerable occupational groups for whom these interventions are particularly appropriate. Therefore, we investigated the 10-year incidence of type 2 diabetes and metabolic syndrome across occupational groups in Germany. Methods Employees of the population-based Gutenberg-Health-Study (GHS) were examined at baseline (2007–2012) and 10 years later. We calculated age- and sex-standardised incidence rates and standardised incidence ratios (SIR) with a 95% confidence interval (CI) for occupations, job complexity levels, and supervisory and managerial positions. 5954 persons at risk for type 2 diabetes and 5103 at risk for metabolic syndrome were observed. Results Between baseline and follow-up, 388 cases of type 2 diabetes and 1104 cases of metabolic syndrome occurred, and standardised incidences were 6.9% and 22.6%, respectively. The highest incidence of type 2 diabetes was observed in the occupational group “food production and processing” (20.7%) with a threefold increased incidence (SIR = 3.0, 95% CI 1.8–4.7) compared to the total working population of the GHS. Employees in “metal production, processing and construction” had the highest incidence of metabolic syndrome and a two times higher SIR (48.5%; SIR = 2.1, 95% CI 1.4–2.9). There was also a high incidence of both type 2 diabetes and metabolic syndrome in “cleaners” (16.5% and 34.8%) and “drivers and mobile plant operators” (14.8% and 41.2%). An increased incidence of type 2 diabetes and metabolic syndrome was observed with decreasing job complexity levels. Conclusions This study shows wide differences in the incidence of type 2 diabetes and metabolic syndrome between occupational groups and highlights the vulnerability of certain occupations. As the workplace is an important platform for interventions, the findings of this study could guide the development of more nuanced and effective workplace health initiatives to promote a healthier workforce for the future.

Abstract Age-related cognitive decline has become an increasingly relevant public health issue. However, risk and protective factors of cognitive decline have yet to be investigated prospectively taking into account genetic, lifestyle, physical and mental health factors. Population-based data from middle-aged (40 to 59 years; N = 2,764) and older individuals (60 to 80 years; N = 1,254) were drawn from a prospective community cohort study using the Tower of London (TOL) planning task. Assessments were repeated at a 5-year interval to investigate age-related changes in planning performance and to determine the impact of risk and protective factors. Planning performance improved in middle-aged, but declined in older participants over 5 years. SNPs affecting the dopamine system (COMT, DRD2) and APOE polymorphisms differentially predicted cognitive performance in older vs. middle-aged individuals. For older individuals, high alcohol consumption, antidepressant medication and living without a partner had additional negative predictive power on cognition. In contrast, undiagnosed hypertension, no obstructive lung disease, and fewer years of education predicted cognitive decline in the middle-aged group. The results inform screening for individuals particularly vulnerable to cognitive decline and interventions (e.g., focusing on lifestyle factors) to help maintain cognitive performance into old age.

Abstract Background Self-rated physical health (SRPH) is known as an important predictor of mortality. Previous studies mostly used baseline values of self-rated health to predict long-term mortality. The effect of change in self-rated physical health on mortality during the course of aging has rarely been researched. The present study aimed to determine SRPH over time in women and men of an aging population, assess whether and how change in SRPH affects mortality while adjusting for known determinants of mortality, and test effect modification by sex on the relation between course of SRPH and mortality. Methods Data of N = 12,423 respondents of the 5-year follow-up of the Gutenberg Health Study (GHS) with participation at the baseline assessment were analysed. All-cause mortality from 5-year follow-up onwards was defined as the primary outcome. SRPH was assessed by a single item. Cox proportional hazards models with adjustment for age, sex, socio-economic status and physical diseases were fitted to assess the predictive power of baseline score and course of SRPH. Additionally, effect modification by sex was assessed. Results During a median follow-up period of 7.3 years (quartiles 6.0-8.5 years), 618 (5%) participants died. Overall, 70.9% of the participants indicated good or very good SRPH at baseline (T1) and follow-up (T2), 6.9% rated their SRPH as not so good at T1 and T2, and 0.6% reported bad SRPH at T1 and T2. An improvement of SRPH was indicated by 9.6% and 12.0% indicated deterioration of their SRPH. Change in SRPH added substantial predictive information to the Cox proportional hazards models, when adjusting for relevant covariates. In men, deterioration and constantly bad SRPH were associated with the strongest increase in risk of mortality by 87%, resp. 228%. While improvements increased mortality risk in men (67%), women with an improved SRPH had a lower risk (57%). Conclusion A sizeable subgroup of aging participants reported deterioration of SRPH over five years. The association between change of SRPH and mortality is modified by sex. Deterioration of SRPH predicts mortality over baseline-assessment even when adjusted for relevant covariates. SRPH should be assessed regularly as part of an older individual’s health evaluation. Deterioration, constantly bad and improved SRPH should be taken seriously as unfavorable prognostic indicators, the latter only in men.

Background & Aims: Elevated liver stiffness has been associated with atrial fibrillation (AFib) in the general population. The mechanism underlying this association is unclear. Methods: Participants were recruited from the general population and prospectively enrolled with follow-up for 5 years. The fibrosis-4 (FIB-4) index was used as a surrogate marker for liver fibrosis. Proteomics analysis was performed using the 92-target Olink inflammation panel. Validation was performed using the NAFLD fibrosis score (NFS), aspartate aminotransferase to platelet index (APRI), and repeat confirmation proteomics. Results: A sample of 11,509 participants with a mean age of 54.0 ± 11.1 years, 51.3% women, and a median FIB-4 index of 0.85 (0.65/1.12), was used. The FIB-4 index was predictive for prevalent (FIB-4 index adjusted odds ratio (aOR) per SD: 1.100 with 95% CI 1.011-1.196; p = 0.026), but not incident AFib (log[FIB-4 index]) adjusted hazard ratio: 1.125 with 95% CI 0.943-1.342, p = 0.19). Elastic net regularized regression identified CCL20, DNER, and CXCL10 for prevalent AFib, and AXIN1, CXCL10, and Flt3L for the log(FIB-4 index) (per SD) as most important in common regulated proteins. The relationship between the FIB-4 index, the identified proteins, and AFib was relevant and reproduced at the 5-year follow-up for CXCL10 after adjusting for confounders (log[FIB-4 index] per SD - CXCL10 [per SD] adjusted β 0.160 with 95% CI 0.127-0.194, p

Abstract The relationship between noise annoyance and risk of cardiovascular disease (CVD) still needs to be fully elucidated. Thus, we examined the relationship between noise annoyance and CVD risk in a large population-based cohort study. Cross-sectional (N = 15,010, aged 35–74 years, baseline investigation period 2007–2012) and prospective data (5- and 10-year follow-up from 2012 to 2022) from the Gutenberg Health Study were used to examine the relationship between noise annoyance due to different sources and risk of prevalent and incident CVD comprising atrial fibrillation, coronary artery disease, myocardial infarction, stroke, chronic heart failure, peripheral artery disease, and venous thromboembolism. In cross-sectional analyses, noise annoyance was an independent risk factor for prevalent CVD, with the strongest associations seen for noise annoyance during sleep (e.g., neighborhood noise annoyance: odds ratio 1.20, 95% confidence interval 1.13–1.27, p

Abstract Even after successful extinction, conditioned fear can return. Strengthening the consolidation of the fear-inhibitory safety memory formed during extinction is one way to counteract return of fear. In a previous study, we found that post-extinction L-DOPA administration improved extinction memory retrieval 24 h later. Furthermore, spontaneous post-extinction reactivations of a neural activation pattern evoked in the ventromedial prefrontal cortex (vmPFC) during extinction predicted extinction memory retrieval, L-DOPA increased the number of these reactivations, and this mediated the effect of L-DOPA on extinction memory retrieval. Here, we conducted a preregistered replication study of this work in healthy male participants. We confirm that spontaneous post-extinction vmPFC reactivations predict extinction memory retrieval. This predictive effect, however, was only observed 90 min after extinction, and was not statistically significant at 45 min as in the discovery study. In contrast to our previous study, we find no evidence that L-DOPA administration significantly enhances retrieval and that this is mediated by enhancement of the number of vmPFC reactivations. However, additional non-preregistered analyses reveal a beneficial effect of L-DOPA on extinction retrieval when controlling for the trait-like stable baseline levels of salivary alpha-amylase enzymatic activity. Further, trait salivary alpha-amylase negatively predicts retrieval, and this effect is reduced by L-DOPA treatment. Importantly, the latter findings result from non-preregistered analyses and thus further investigation is needed.

Abstract The scientific interest in boredom is growing over the past decades. Boredom has not only been linked to symptoms of psychopathology, but also shows a remarkable effect on individual behavior under healthy conditions. Current characterizations of boredom in humans mostly rely on self-report assessments which proved to faithfully reflect boredom in a vast range of experimental environments. Two of the most commonly used and prominent self-report scales in order to assess boredom are the Multidimensional State Boredom Scale (MSBS) and the Boredom Proneness Scale (BPS). Here, we present the German translations of both questionnaires and their validation. We obtained and analyzed psychometric data from more than 800 healthy individuals. We find that the German MSBS and BPS show vast congruence with their originals in respect to item statistics, internal reliability and validity. In particular, we find remarkable associations of state boredom and trait boredom with indicators of mental burden. Testing the factor structure of both questionnaires, we find supporting evidence for a 5-factor model of the MSBS, whereas the BPS in line with its original shows an irregular, inconsistent factor structure. Thus, we validate the German versions of MSBS and BPS and set a starting point for further studies of boredom in German-speaking collectives.

Abstract Societies are exposed to major challenges at an increasing pace. This underscores the need for preventive measures such as resilience promotion that should be available in time and without access barriers. Our systematic review summarizes evidence on digital resilience interventions, which have the potential to meet these demands. We searched five databases for randomized-controlled trials in non-clinical adult populations. Primary outcomes were mental distress, positive mental health, and resilience factors. Multilevel meta-analyses were performed to compare intervention and control groups at post-intervention and follow-up assessments. We identified 101 studies comprising 20,010 participants. Meta-analyses showed small favorable effects on mental distress, SMD = –0.24, 95% CI [–0.31, –0.18], positive mental health, SMD = 0.27, 95% CI [0.13, 0.40], and resilience factors, SMD = 0.31, 95% CI [0.21, 0.41]. Among middle-aged samples, older age was associated with more beneficial effects at follow-up, and effects were smaller for active control groups. Effects were comparable to those of face-to-face interventions and underline the potential of digital resilience interventions to prepare for future challenges.

Abstract Boredom is a ubiquitous, aversive human experience typically elicited by low information and monotony. Boredom can occur either as a transient mental state that prompts individuals to adapt their behavior to avoid monotony or as a temporally stable trait, describing a chronic susceptibility to feeling bored. Increased trait boredom was found to correlate with various psychopathologies and indicators of mental burden. However, the role of state boredom in psychopathological conditions and its implications for psychiatric treatment remain elusive. Here, we address this issue by investigating state boredom and trait boredom in a cohort of psychiatric inpatients and a healthy control cohort. We find that in both groups, state boredom, even more than trait boredom, shows remarkable associations with psychopathology. In the inpatient group, state boredom is implicated broadly in multiple mental disorders and shows an association with treatment in closed psychiatric wards. Furthermore, through statistical modeling, we find that high-state boredom during inpatient therapy is predictive of a longer therapy duration. Thus, we show that state boredom constitutes an indicator of mild and severe psychopathology in different mental disorders, affecting the outcome of psychiatric patients. Potential therapeutic interventions are discussed, aiming to enhance information flow in the brain in order to alleviate boredom in clinical settings.

Abstract Biased population samples pose a prevalent problem in the social sciences. Therefore, we present two novel methods that are based on positive-unlabeled learning to mitigate bias. Both methods leverage auxiliary information from a representative data set and train machine learning classifiers to determine the sample weights. The first method, named maximum representative subsampling (MRS), uses a classifier to iteratively remove instances, by assigning a sample weight of 0, from the biased data set until it aligns with the representative one. The second method is a variant of MRS – Soft-MRS – that iteratively adapts sample weights instead of removing samples completely. To assess the effectiveness of our approach, we induced artificial bias in a public census data set and examined the corrected estimates. We compare the performance of our methods against existing techniques, evaluating the ability of sample weights created with Soft-MRS or MRS to minimize differences and improve downstream classification tasks. Lastly, we demonstrate the applicability of the proposed methods in a real-world study of resilience research, exploring the influence of resilience on voting behavior. Through our work, we address the issue of bias in social science, amongst others, and provide a versatile methodology for bias reduction based on machine learning. Based on our experiments, we recommend to use MRS for downstream classification tasks and Soft-MRS for downstream tasks where the relative bias of the dependent variable is relevant.

Abstract Resilience can be viewed as trajectory of stable good mental health or the quick recovery of mental health during or after stressor exposure. Resilience factors (RFs) are psychological resources that buffer the potentially negative effects of stress on mental health. A problem of resilience research is the large number of conceptually overlapping RFs complicating their understanding. The current study sheds light on the interrelations of RFs in the face of the COVID-19 pandemic as a use case for major disruptions. The non-preregistered prospective study assessed a sample of 1275 German-speaking people from February 2020 to March 2021 at seven timepoints. We measured coping, hardiness, control beliefs, optimism, self-efficacy, sense of coherence (SOC), sense of mastery, social support and dispositional resilience as RFs in February 2020, and mental health (i.e., psychopathological symptoms, COVID-19-related rumination, stress-related growth) at all timepoints. Analyses used partial correlation network models and latent growth mixture modeling (LGMM). Pre-pandemic RFs were strongly interrelated, with SOC being the most central node. The strongest associations emerged between coping using emotional support and social support, SOC and sense of mastery, and dispositional resilience and self-efficacy. SOC and active coping were negatively linked. When we examined RFs as predictors of mental health trajectories, SOC was the strongest predictor of psychopathological symptoms and rumination, while trajectories of stress-related growth were predicted by optimism. Subsequent network analyses, including individual intercepts and slopes from LGMM, showed that RFs had small to moderate associations with intercepts but were unrelated to slopes. Our findings provide evidence for SOC playing an important role in mental distress and suggest further examining SOC’s incremental validity. However, our results also propose that RFs might be more important for stable levels of mental health than for adaptation processes over time. The differential associations for negative and positive outcomes support the use of multidimensional outcomes in resilience research.

Persons with primary progressive aphasia (PPA) often experience limitations in their quality of life (QoL). Some studies have shown positive effects of speech and language therapy on QoL in persons with PPA. However, there is still a lack of evidence for disorder-specific approaches for this important therapeutic goal. The biographic-narrative approach (narraktiv) has been shown to significantly improve QoL in persons with post-stroke aphasia. In the planned study, the biographic-narrative approach will be adapted for persons with PPA (Cope PPA), and its efficacy will be investigated. First, a focus group interview with five persons with PPA will be conducted to identify the wishes and needs of participants. Based on the results, the narraktiv manual according to Corsten et al. (2015) will be revised. Second, an efficacy study will be conducted according to the new Cope PPA manual with 24 persons with PPA in a waiting group control design. The primary outcome, QoL, will be assessed using questionnaires (Stroke and Aphasia Quality of Life Scale-39) and semistructured interviews. Depressive symptoms, life satisfaction and cognitive/communicative functioning will also be assessed. If Cope PPA proves efficacy, this study may help to improve the treatment of persons with PPA.

Acute strokes can affect heart rate variability (HRV), the mechanisms how are not well understood. We included 42 acute stroke patients (2–7 days after ischemic stroke, mean age 66 years, 16 women). For analysis of HRV, 20 matched controls (mean age 60.7, 10 women) were recruited. HRV was assessed at rest, in a supine position and individual breathing rhythmus for 5 min. The coefficient of variation (VC), the root mean square of successive differences (RMSSD), the powers of low (LF, 0.04–0.14 Hz) and high (HF, 0.15–0.50 Hz) frequency bands were extracted. HRV parameters were z-transformed related to age- and sex-matched normal subjects. Z-values -1). No different connectivity could be found for the respective VC groups. Our results suggest that HRV alteration after acute stroke might be due to affecting resting-state brain networks.

Summary: Background: People with complex symptomatology but unclear diagnosis presenting to a centre for rare diseases (CRD) may present with mental (co-)morbidity. We hypothesised that combining an expert in somatic medicine with a mental health specialist working in tandem will improve the diagnostic outcome. Methods: Patients aged 12 years and older who presented to one of the 11 participating German CRDs with an unknown diagnosis were recruited into this prospective cohort trial with a two-phase cohort design. From October 1, 2018 to September 30, 2019, participants were allocated to standard care (SC, N = 684), and from October 1, 2019 to January 31, 2021 to innovative care (IC, N = 695). The cohorts consisted mainly of adult participants with only a minority of children included (N = 67). IC included the involvement of a mental health specialist in all aspects of care (e.g., assessing medical records, clinic visits, telehealth care, and case conferences). Clinicaltrials.gov identifier: NCT03563677. Findings: The proportion of patients with diagnoses established within 12 months after the first visit to the CRD explaining the entire symptomatology (primary outcome) was 19% (N = 131 of 672) in the SC and 42% (N = 286 of 686) in the IC cohort (OR adjusted for centre effects 3.45 [95% CrI: 1.99–5.65]). The difference was mainly due to a higher prevalence of mental disorders and non-rare somatic diseases in the IC cohort. The median time to explaining diagnoses was one month shorter with IC (95% CrI: 1–2), and significantly more patients could be referred to local regular care in the IC (27.5%; N = 181 of 659) compared to the SC (12.3%; N = 81 of 658) cohort (OR adjusted for centre effects 2.70 [95% CrI: 2.02–3.60]). At 12-month follow-up, patient satisfaction with care was significantly higher in the IC compared to the SC cohort, while quality of life was not different between cohorts. Interpretation: Our findings suggested that including a mental health specialist in the entire evaluation process of CRDs for undiagnosed adolescents and adults should become an integral part of the assessment of individuals with a suspected rare disease. Funding: The study was funded by the Global Innovation Fund from the Joint Federal Committee in Germany (Innovationsfonds des Gemeinsamen Bundesausschusses), grant number 01NVF17031.

BackgroundCross-sectional relationships between psychosocial resilience factors (RFs) and resilience, operationalized as the outcome of low mental health reactivity to stressor exposure (low “stressor reactivity” [SR]), were reported during the first wave of the COVID-19 pandemic in 2020. ObjectiveExtending these findings, we here examined prospective relationships and weekly dynamics between the same RFs and SR in a longitudinal sample during the aftermath of the first wave in several European countries. MethodsOver 5 weeks of app-based assessments, participants reported weekly stressor exposure, mental health problems, RFs, and demographic data in 1 of 6 different languages. As (partly) preregistered, hypotheses were tested cross-sectionally at baseline (N=558), and longitudinally (n=200), using mixed effects models and mediation analyses. ResultsRFs at baseline, including positive appraisal style (PAS), optimism (OPT), general self-efficacy (GSE), perceived good stress recovery (REC), and perceived social support (PSS), were negatively associated with SR scores, not only cross-sectionally (baseline SR scores; all P

BackgroundAn increasing number of mHealth interventions aim to contribute to mental healthcare of which interventions that foster cognitive reappraisal may be particularly effective.ObjectivesTo evaluate the efficacy of mHealth interventions enhancing cognitive reappraisal to improve mental health in adult populations.MethodsThe literature search (four databases) yielded 30 eligible randomized controlled trials (comprising 3,904 participants). We performed a multi-level meta-analysis to examine differences between intervention and comparator conditions at post-intervention assessment. Moderator analyses were conducted for potential moderator variables (e.g., type of comparators).ResultsMost interventions were CBT-based with other training components in addition to cognitive reappraisal. We found preliminary evidence for a small to medium effect favouring mHealth interventions to enhance cognitive reappraisal over comparators, M(SMD) = 0.34, p = .002. When analysing single symptoms, there was evidence for a small to medium effect of mHealth interventions on anxiety and depressive symptoms, but not for psychological distress and well-being. All analyses showed substantial heterogeneity. Moderator analyses revealed evidence for more favourable effects in studies with passive comparators. There was an overall high risk of bias in most of the studies.ConclusionsWe found preliminary evidence for a small to medium effect of mHealth interventions including a cognitive reappraisal component to improve mental health. However, most of the interventions were complex (i.e., reappraisal was provided alongside other components), which prevents us from examining reappraisal-specific effects beyond general mental health promotion in mHealth. Dismantling studies examining the effects of single intervention components are warranted to corroborate these promising results.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=142149, identifier [CRD42019142149].

Abstract The COVID-19 pandemic is a global stressor with inter-individually differing influences on mental health trajectories. Polygenic Risk Scores (PRSs) for psychiatric phenotypes are associated with individual mental health predispositions. Elevated hair cortisol concentrations (HCC) and high PRSs are related to negative mental health outcomes. We analyzed whether PRSs and HCC are related to different mental health trajectories during the first COVID lockdown in Germany. Among 523 participants selected from the longitudinal resilience assessment study (LORA), we previously reported three subgroups (acute dysfunction, delayed dysfunction, resilient) based on weekly mental health (GHQ-28) assessment during COVID lockdown. DNA from blood was collected at the baseline of the original LORA study (n = 364) and used to calculate the PRSs of 12 different psychopathological phenotypes. An explorative bifactor model with Schmid-Leiman transformation was calculated to extract a general genetic factor for psychiatric disorders. Hair samples were collected quarterly prior to the pandemic for determining HCC (n = 192). Bivariate logistic regressions were performed to test the associations of HCC and the PRS factors with the reported trajectories. The bifactor model revealed 1 general factor and 4 sub-factors. Results indicate a significant association between increased values on the general risk factor and the allocation to the acute dysfunction class. The same was found for elevated HCC and the exploratorily tested sub-factor “childhood-onset neurodevelopmental disorders”. Genetic risk and long-term cortisol secretion as a potential indicator of stress, indicated by PRSs and HCC, respectively, predicted different mental health trajectories. Results indicate a potential for future studies on risk prediction.

BackgroundDue to the SARS-CoV-2 pandemic, healthcare workers (HCWs) are experiencing tremendous levels of emotional and physical stress. Hospitals are trying to help personnel cope with work-related pressure. The aim of this study was to assess HCWs’ awareness and utilization of counseling and support services during the pandemic, HCWs’ unmet counseling and support needs, and the type and content of these services.MethodsA cross-sectional online survey was conducted from January to June 2021 through the German national research organization Network University Medicine (NUM). All participating hospitals (6 in total) were asked to inform their employees about the study.ResultsA total of 1,495 HCWs were included in the analysis. Of these, 42.8% (n = 637) were frontline HCWs (who had contact with COVID-19 patients), 23.1% (n = 344) were second-line HCWs (who only had contact with non-COVID-19 patients) and 34.1% (n = 508) had no contact with any patients. Participating hospitals offer various counseling and support services for their staff. The percentage of respondents who were unaware of available counseling and support services ranged from 5.0 to 42.0%. Depending on the type of counseling and support services, 23.0–53.6% of the respondents indicated that counseling and support services were provided but not used, while 1.7–11.6% indicated that, despite the need for them, such services were not available. HCWs’ overall satisfaction with the provided counseling and support services and their unmet support needs differed by patient contact: Frontline HCWs reported more unmet needs for counseling and support than second-line HCWs, while second-line HCWs reported more unmet needs than HCWs without patient contact.ConclusionThe results indicate that hospitals should make more efforts to inform HCWs about available counseling and support services. Hospitals could also create networks where HCWs could share information about the type and content of services and their experiences with various counseling and support services. These steps would enable hospitals to respond more quickly and effectively to the problems facing HCWs during pandemics.

BackgroundStress is among the leading causes for diseases. The assessment of subjectively perceived stress is essential for resilience research. While the Perceived Stress Scale (PSS) is a widely used questionnaire, a German short version of the scale is not yet available. In the current study, we developed such a short version using a machine learning approach for item reduction to facilitate the simultaneous optimization of multiple psychometric criteria.MethodWe recruited 1,437 participants from an online panel, who completed the German long version of the PSS along with measures of mental health and resilience. An ant-colony-optimization algorithm was used to select items, taking reliability, and construct validity into account. Findings on validity were visualized by psychological network models.ResultsWe replicated a bifactor structure for the long version of the PSS and derived a two-factor German short version of the PSS with four items, the PSS-2&2. Its factors helplessness and self-efficacy showed differential associations with mental health indicators and resilience-related factors, with helplessness being mainly linked to mental distress.ConclusionThe valid and economic short version of the PSS lends itself to be used in future resilience research. Our findings highlight the importance of the two-factor structure of the PSS short versions and challenge the validity of commonly used one-factor models. In cases where the general stress factor is of interest, researchers should use the longer versions of the PSS that allow for the interpretation of total scores, while the PSS-2&2 allows of an economic assessment of the PSS factors helplessness and self-efficacy.

BackgroundStress-related mental disorders are highly prevalent and pose a substantial burden on individuals and society. Improving strategies for the prevention and treatment of mental disorders requires a better understanding of their risk and resilience factors. This multicenter study aims to contribute to this endeavor by investigating psychological resilience in healthy but susceptible young adults over 9 months. Resilience is conceptualized in this study as the maintenance of mental health or quick recovery from mental health perturbations upon exposure to stressors, assessed longitudinally via frequent monitoring of stressors and mental health. ObjectiveThis study aims to investigate the factors predicting mental resilience and adaptive processes and mechanisms contributing to mental resilience and to provide a methodological and evidence-based framework for later intervention studies. MethodsIn a multicenter setting, across 5 research sites, a sample with a total target size of 250 young male and female adults was assessed longitudinally over 9 months. Participants were included if they reported at least 3 past stressful life events and an elevated level of (internalizing) mental health problems but were not presently affected by any mental disorder other than mild depression. At baseline, sociodemographic, psychological, neuropsychological, structural, and functional brain imaging; salivary cortisol and α-amylase levels; and cardiovascular data were acquired. In a 6-month longitudinal phase 1, stressor exposure, mental health problems, and perceived positive appraisal were monitored biweekly in a web-based environment, while ecological momentary assessments and ecological physiological assessments took place once per month for 1 week, using mobile phones and wristbands. In a subsequent 3-month longitudinal phase 2, web-based monitoring was reduced to once a month, and psychological resilience and risk factors were assessed again at the end of the 9-month period. In addition, samples for genetic, epigenetic, and microbiome analyses were collected at baseline and at months 3 and 6. As an approximation of resilience, an individual stressor reactivity score will be calculated. Using regularized regression methods, network modeling, ordinary differential equations, landmarking methods, and neural net–based methods for imputation and dimension reduction, we will identify the predictors and mechanisms of stressor reactivity and thus be able to identify resilience factors and mechanisms that facilitate adaptation to stressors. ResultsParticipant inclusion began in October 2020, and data acquisition was completed in June 2022. A total of 249 participants were assessed at baseline, 209 finished longitudinal phase 1, and 153 finished longitudinal phase 2. ConclusionsThe Dynamic Modelling of Resilience–Observational Study provides a methodological framework and data set to identify predictors and mechanisms of mental resilience, which are intended to serve as an empirical foundation for future intervention studies. International Registered Report Identifier (IRRID)DERR1-10.2196/39817

The structural and functional degradation of the corpus callosum (CC) has been shown to play an important role in the context of cognitive aging (Reuter-Lorenz and Stanczak, 2000). This is also reflected by findings of elongated interhemispheric transfer time (IHTT) in older adults (Riedel et al., 2022). At the same time, a protective effect of physical activity (PA) and cardiorespiratory fitness (CRF) on brain health including the CC is widely accepted (Hillman et al., 2008; Loprinzi et al., 2020). Based on this idea, the present study investigated the relationship between IHTT and PA/CRF in 107 healthy older adults (m: 64, f: 43) aged 67.69 ± 5.18. IHTT was calculated detecting event-related potentials (ERPs) using an established Dimond-Task. PA was evaluated using accelerometry resulting in estimates of overall bodily motion and time spent at higher intensity PA. CRF was estimated using graded exercise testing, approximating running speed at 4 mmol/l blood lactate concentration. The results showed a negative correlation between IHTTright→left and PA overall as well as in the male subgroup and between IHTTleft→right and CRF in women. This indicates a potential relationship between IHTT and PA/CRF. While the present investigation is only the first to hint at such a relationship taking into account the differential effects with regards to sex, mode of PA/CRF and IHTT direction, it is in line with previous findings and theoretical suggestions linking brain health to PA/CRF in the context of aging. Further research is needed in order to increase our understanding of the underlying mechanisms and of the influence of sex, PA intensity, degree of CRF and significance of IHTT direction.

Abstract Deep learning approaches can uncover complex patterns in data. In particular, variational autoencoders achieve this by a non-linear mapping of data into a low-dimensional latent space. Motivated by an application to psychological resilience in the Mainz Resilience Project, which features intermittent longitudinal measurements of stressors and mental health, we propose an approach for individualized, dynamic modeling in this latent space. Specifically, we utilize ordinary differential equations (ODEs) and develop a novel technique for obtaining person-specific ODE parameters even in settings with a rather small number of individuals and observations, incomplete data, and a differing number of observations per individual. This technique allows us to subsequently investigate individual reactions to stimuli, such as the mental health impact of stressors. A potentially large number of baseline characteristics can then be linked to this individual response by regularized regression, e.g., for identifying resilience factors. Thus, our new method provides a way of connecting different kinds of complex longitudinal and baseline measures via individualized, dynamic models. The promising results obtained in the exemplary resilience application indicate that our proposal for dynamic deep learning might also be more generally useful for other application domains.

Several practices contribute to low replication rates in neuroimaging; unreported analytical flexibility, publication biases, the lack of data sharing, the use of underpowered samples, and many more. In the current study, we tried to replicate emotional interference during motor response inhibition in a sample of N = 57 healthy students at a different study site. The failure to inhibit impulses in highly emotional situations is a characteristic of many mental disorders. Apart from this, exaggerated emotional responses can debilitate social and cognitive functioning in healthy participants. Functional magnetic resonance imaging was acquired while participants performed a combined stop signal and Simon task with neutral and negative, visual primes. Negative, visual primes led to prolonged reaction times and stopping latencies. FMRI data showed that negative, visual primes led to increased activation in the bilateral amygdala and enhanced visual processing. Consistent with other studies on emotional interference, we observed decreased activation in regions of the central-executive network and reduced deactivation in the ventromedial prefrontal cortex for negative trials. Replicating the results of our former studies (Kampa et al., 2018, 2020), we found an interaction effect in the right amygdala. Concurrent inhibition of motor responses thus seemed to downregulate the processing of negative stimuli in the right amygdala. We performed exploratory brain-behavior correlation analyses to test if increased right amygdala activation to negative primes was associated with a decrement in performance. We found no such relationship; however, because of the low statistical power, we cannot decide conclusively on the relationship between the right amygdala, and behavioral interference. We discuss potential solutions for overcoming the power problem associated with brain-behavior correlation analyses.

Abstract Background In individuals suffering from a rare disease the diagnostic process and the confirmation of a final diagnosis often extends over many years. Factors contributing to delayed diagnosis include health care professionals' limited knowledge of rare diseases and frequent (co-)occurrence of mental disorders that may complicate and delay the diagnostic process. The ZSE-DUO study aims to assess the benefits of a combination of a physician focusing on somatic aspects with a mental health expert working side by side as a tandem in the diagnostic process. Study design This multi-center, prospective controlled study has a two-phase cohort design. Methods Two cohorts of 682 patients each are sequentially recruited from 11 university-based German Centers for Rare Diseases (CRD): the standard care cohort (control, somatic expertise only) and the innovative care cohort (experimental, combined somatic and mental health expertise). Individuals aged 12 years and older presenting with symptoms and signs which are not explained by current diagnoses will be included. Data will be collected prior to the first visit to the CRD’s outpatient clinic (T0), at the first visit (T1) and 12 months thereafter (T2). Outcomes Primary outcome is the percentage of patients with one or more confirmed diagnoses covering the symptomatic spectrum presented. Sample size is calculated to detect a 10 percent increase from 30% in standard care to 40% in the innovative dual expert cohort. Secondary outcomes are (a) time to diagnosis/diagnoses explaining the symptomatology; (b) proportion of patients successfully referred from CRD to standard care; (c) costs of diagnosis including incremental cost effectiveness ratios; (d) predictive value of screening instruments administered at T0 to identify patients with mental disorders; (e) patients’ quality of life and evaluation of care; and f) physicians’ satisfaction with the innovative care approach. Conclusions This is the first multi-center study to investigate the effects of a mental health specialist working in tandem with a somatic expert physician in CRDs. If this innovative approach proves successful, it will be made available on a larger scale nationally and promoted internationally. In the best case, ZSE-DUO can significantly shorten the time to diagnosis for a suspected rare disease. Trial registration ClinicalTrials.gov; Identifier: NCT03563677; First posted: June 20, 2018, https://clinicaltrials.gov/ct2/show/NCT03563677 .

Abstract Boredom has been defined as an aversive mental state that is induced by the disability to engage in satisfying activity, most often experienced in monotonous environments. However, current understanding of the situational factors inducing boredom and driving subsequent behavior remains incomplete. Here, we introduce a two-alternative forced-choice task coupled with sensory stimulation of different degrees of monotony. We find that human subjects develop a bias in decision-making, avoiding the more monotonous alternative that is correlated with self-reported state boredom. This finding was replicated in independent laboratory and online experiments and proved to be specific for the induction of boredom rather than curiosity. Furthermore, using theoretical modeling we show that the entropy in the sequence of individually experienced stimuli, a measure of information gain, serves as a major determinant to predict choice behavior in the task. With this, we underline the relevance of boredom for driving behavioral responses that ensure a lasting stream of information to the brain.

Nature relies on highly distributed computation for the processing of information in nervous systems across the entire animal kingdom. Such distributed computation can be more easily understood if decomposed into the three elementary components of information processing, i.e. storage, transfer and modification, and rigorous information theoretic measures for these components exist. However, the distributed computation is often also linked to neural dynamics exhibiting distinct rhythms. Thus, it would be beneficial to associate the above components of information processing with distinct rhythmic processes where possible. Here we focus on the storage of information in neural dynamics and introduce a novel spectrally-resolved measure of active information storage (AIS). Drawing on intracortical recordings of neural activity in ferrets under anesthesia before and after loss of consciousness (LOC) we show that anesthesia- related modulation of AIS is highly specific to different frequency bands and that these frequency-specific effects differ across cortical layers and brain regions. We found that in the high/low gamma band the effects of anesthesia result in AIS modulation only in the supergranular layers, while in the alpha/beta band the strongest decrease in AIS can be seen at infragranular layers. Finally, we show that the increase of spectral power at multiple frequencies, in particular at alpha and delta bands in frontal areas, that is often observed during LOC ('anteriorization') also impacts local information processing-but in a frequency specific way: Increases in isoflurane concentration induced a decrease in AIS in the alpha frequencies, while they increased AIS in the delta frequency range < 2Hz. Thus, the analysis of spectrally-resolved AIS provides valuable additional insights into changes in cortical information processing under anaesthesia.

The ageing of an organism is associated with certain features of functional decline that can be assessed at the cellular level (e.g., reduced telomere length, loss of proteostasis, etc.), but also at the organismic level. Frailty is an independent syndrome that involves increased multidimensional age-related deficits, heightens vulnerability to stressors, and involves physical deficits in mainly the locomotor/muscular capacity, but also in physical appearance and cognition. For sporadic Alzheimer’s disease, age per se is one of the most relevant risk factors, but frailty has also been associated with this disease. Therefore, we aimed to answer the two following questions within a cross-sectional study: (1) do Alzheimer’s model mice show increased frailty, and (2) what changes of the microbiota occur concerning chronological age or frailty? Indeed, aged 5xFAD mice showed increased frailty compared to wild type littermates. In addition, 5xFAD mice had significantly lower quantities of Bacteroides spp. when only considering frailty, and lower levels of Bacteroidetes in terms of both frailty and chronological age compared to their wild type littermates. Thus, the quality of ageing—as assessed by frailty measures—should be taken into account to unravel potential changes in the gut microbial community in Alzheimer’s disease.

Abstract Background Mental burden due to the SARS-CoV-2 pandemic has been widely reported for the general public and specific risk groups like healthcare workers and different patient populations. We aimed to assess its impact on mental health during the early phase by comparing pandemic with prepandemic data and to identify potential risk and protective factors. Methods For this systematic review and meta-analyses, we systematically searched PubMed, PsycINFO, and Web of Science from January 1, 2019 to May 29, 2020, and screened reference lists of included studies. In addition, we searched PubMed and PsycINFO for prepandemic comparative data. Survey studies assessing mental burden by the SARS-CoV-2 pandemic in the general population, healthcare workers, or any patients (eg, COVID-19 patients), with a broad range of eligible mental health outcomes, and matching studies evaluating prepandemic comparative data in the same population (if available) were included. We used multilevel meta-analyses for main, subgroup, and sensitivity analyses, focusing on (perceived) stress, symptoms of anxiety and depression, and sleep-related symptoms as primary outcomes. Results Of 2429 records retrieved, 104 were included in the review (n = 208,261 participants), 43 in the meta-analysis (n = 71,613 participants). While symptoms of anxiety (standardized mean difference [SMD] 0.40; 95% CI 0.15–0.65) and depression (SMD 0.67; 95% CI 0.07–1.27) were increased in the general population during the early phase of the pandemic compared with prepandemic conditions, mental burden was not increased in patients as well as healthcare workers, irrespective of COVID-19 patient contact. Specific outcome measures (eg, Patient Health Questionnaire) and older comparative data (published ≥5 years ago) were associated with increased mental burden. Across the three population groups, existing mental disorders, female sex, and concerns about getting infected were repeatedly reported as risk factors, while older age, a good economic situation, and education were protective. Conclusions This meta-analysis paints a more differentiated picture of the mental health consequences in pandemic situations than previous reviews. High-quality, representative surveys, high granular longitudinal studies, and more research on protective factors are required to better understand the psychological impacts of the SARS-CoV-2 pandemic and to help design effective preventive measures and interventions that are tailored to the needs of specific population groups.

Abstract The SARS-CoV-2 pandemic is not only a threat to physical health but is also having severe impacts on mental health. Although increases in stress-related symptomatology and other adverse psycho-social outcomes, as well as their most important risk factors have been described, hardly anything is known about potential protective factors. Resilience refers to the maintenance of mental health despite adversity. To gain mechanistic insights about the relationship between described psycho-social resilience factors and resilience specifically in the current crisis, we assessed resilience factors, exposure to Corona crisis-specific and general stressors, as well as internalizing symptoms in a cross-sectional online survey conducted in 24 languages during the most intense phase of the lockdown in Europe (22 March to 19 April) in a convenience sample of N = 15,970 adults. Resilience, as an outcome, was conceptualized as good mental health despite stressor exposure and measured as the inverse residual between actual and predicted symptom total score. Preregistered hypotheses (osf.io/r6btn) were tested with multiple regression models and mediation analyses. Results confirmed our primary hypothesis that positive appraisal style (PAS) is positively associated with resilience (p

Psychiatric inpatient treatment, an important pillar of mental health care, is often of longer duration in Germany than in other countries. The COVID-19 pandemic called for infection prevention and control measures and thereby led to shifts in demand and inpatient capacities. The Germany-wide COVID Ψ Psychiatry Survey surveyed department heads of German psychiatric inpatient institutions. It assessed changes in utilization during the first two high incidence phases of the pandemic (spring 2020 and winter 2020/21) and also consequences for care, telemedicine experiences, hygiene measures, treatment of patients with mental illness and co-occuring SARS-CoV-2, and coercive measures in such patients. A total of n = 71 psychiatric departments (of 346 contacted) participated in the survey. The results showed a median decrease of inpatient treatment to 80% of 2019 levels and of day hospital treatment to 50% (first phase) and 70% (second phase). Reductions were mainly due to decreases in elective admissions, and emergency admissions remained unchanged or increased in 87% of departments. Utilization was reduced for affective, anxiety, personality, and addiction disorders but appeared roughly unaffected for psychotic disorders. A lack of integration of patients into their living environment, disease exacerbations, loss of contact, and suicide attempts were reported as problems resulting from reduced capacities and insufficient outpatient treatment alternatives. Almost all departments (96%) treated patients with severe mental illness and co-occurring SARS-CoV-2 infection. The majority established special wards and separate areas for (potentially) infectious patients. Telephone and video consultations were found to provide benefits in affective and anxiety disorders. Involuntary admissions of persons without mental illness because of infection protection law violations were reported by 6% of the hospitals. The survey showed high adaptability of psychiatric departments, which managed large capacity shifts and introduced new services for infectious patients, which include telemedicine services. However, the pandemic exacerbated some of the shortcomings of the German mental health system: Avoidable complications resulted from the lack of cooperation and integrated care sequences between in- and outpatient sectors and limited options for psychiatric hospitals to provide outpatient services. Preventive approaches to handle comparable pandemic situations in the future should focus on addressing these shortcomings.

Age-related cognitive decline has been attributed to degeneration of the corpus callosum (CC), which allows for interhemispheric integration and information processing [22,69]. Along with decreased structural integrity, altered functional properties of the CC may cause impaired cognitive performance in older adults, yet this aspect of age-related decline remains insufficiently researched [59]. In this context, potential sex-related differences have been proposed [31,58]. A promising parameter, which has been suggested to estimate functional properties of the CC is the interhemispheric transfer time (IHTT), which is ideally obtained from event-related potentials (ERP) evoked by lateralized stimuli [45]. To examine the possible functional consequences of aging with regards to the CC, the present study investigated the IHTT of 107 older (67.69 ± 5.18y) as well as of 23 younger participants (25.09 ± 2.59y). IHTT was obtained using an established letter matching task and targeting early N170 ERP components at posterior electrode sites. The results revealed significantly elongated IHTT in older compared to younger participants, but no significant sex differences. Furthermore, there was a significant positive correlation between IHTT and age, predominantly driven by the female participants. The present findings add support to the notion, that IHTT is subject to age-related elongation reflecting impaired interhemispheric transmission. Age-related decline in women appears to occur at a different age range compared to men.

Abstract Background Huntington’s disease (HD) is a rare, genetic neurodegenerative disorder often presenting with emotional, cognitive and behavioral abnormalities before manifestation of disease defining motor symptoms. Cognitive impairment is a frequent clinical feature caused by different dementia subtypes. Imaging cortical and subcortical glucose metabolism via 18F-FDG PET/CT can help to discriminate the underlying disease. Case presentation The patient is a 54-year old man presenting with progressive cognitive impairment and mild orofacial dyskinesia. 18F-FDG PET/CT of the brain revealed a severe bilateral hypometabolism in the striatum. Following imaging Huntington’s disease was suspected and a molecular genetic testing confirmed the diagnosis. Conclusions Huntington’s disease is a rare but important differential diagnosis of cognitive impairment, especially before motor symptoms are manifest. 18F-FDG PET is capable to show early striatal dysfunction in HD even when structural imaging is normal. We conclude that, in cases with negative family history the HD characteristic metabolic pattern can lead to the diagnosis when no other dementia-suspected changes are present.

Resilience has been defined as the maintenance or quick recovery of mental health during and after times of adversity. How to operationalize resilience and to determine the factors and processes that lead to good long-term mental health outcomes in stressor-exposed individuals is a matter of ongoing debate and of critical importance for the advancement of the field. One of the biggest challenges for implementing an outcome-based definition of resilience in longitudinal observational study designs lies in the fact that real-life adversity is usually unpredictable and that its substantial qualitative as well as temporal variability between subjects often precludes defining circumscribed time windows of inter-individually comparable stressor exposure relative to which the maintenance or recovery of mental health can be determined. To address this pertinent issue, we propose to frequently and regularly monitor stressor exposure (E) and mental health problems (P) throughout a study's observation period [Frequent Stressor and Mental Health Monitoring (FRESHMO)-paradigm]. On this basis, a subject's deviation at any single monitoring time point from the study sample's normative E–P relationship (the regression residual) can be used to calculate that subject's current mental health reactivity to stressor exposure (“stressor reactivity,” SR). The SR score takes into account the individual extent of experienced adversity and is comparable between and within subjects. Individual SR time courses across monitoring time points reflect intra-individual temporal variability in SR, where periods of under-reactivity (negative SR score) are associated with accumulation of fewer mental health problems than is normal for the sample. If FRESHMO is accompanied by regular measurement of potential resilience factors, temporal changes in resilience factors can be used to predict SR time courses. An increase in a resilience factor measurement explaining a lagged decrease in SR can then be considered to index a process of adaptation to stressor exposure that promotes a resilient outcome (an allostatic resilience process). This design principle allows resilience research to move beyond merely determining baseline predictors of resilience outcomes, which cannot inform about how individuals successfully adjust and adapt when confronted with adversity. Hence, FRESHMO plus regular resilience factor monitoring incorporates a dynamic-systems perspective into resilience research.

Background: Normal aging is associated with working memory decline. A decrease in working memory performance is associated with age-related changes in functional activation patterns in the dorsolateral prefrontal cortex (DLPFC). Cognitive training can improve cognitive performance in healthy older adults. We implemented a cognitive training study to assess determinants of generalization of training gains to untrained tasks, a key indicator for the effectiveness of cognitive training. We aimed to investigate the association of resting-state functional connectivity (FC) of DLPFC with working memory performance improvement and cognitive gains after the training.Method: A sample of 60 healthy older adults (mean age: 68 years) underwent a 4-week neuropsychological training, entailing a working memory task. Baseline resting-state functional MRI (rs-fMRI) images were acquired in order to investigate the FC of DLPFC. To evaluate training effects, participants underwent a neuropsychological assessment before and after the training. A second follow-up assessment was applied 12 weeks after the training. We used cognitive scores of digit span backward and visual block span backward tasks representing working memory function. The training group was divided into subjects who had and who did not have training gains, which was defined as a higher improvement in working memory tasks than the control group (N = 19).Results: A high FC of DLPFC of the right hemisphere was significantly associated with training gains and performance improvement in the visuospatial task. The maintenance of cognitive gains was restricted to the time period directly after the training. The training group showed performance improvement in the digit span backward task.Conclusion: Functional activation patterns of the DLPFC were associated with the degree of working memory training gains and visuospatial performance improvement. Although improvement through cognitive training and acquisition of training gains are possible in aging, they remain limited.

Motor inhibitory control implemented as response inhibition is an essential cognitive function required to dynamically adapt to rapidly changing environments. Despite over a decade of research on the neural mechanisms of response inhibition, it remains unclear, how exactly response inhibition is initiated and implemented. Using a multimodal MEG/fMRI approach in 59 subjects, our results reliably reveal that response inhibition is initiated by the right inferior frontal gyrus (rIFG) as a form of attention-independent top-down control that involves the modulation of beta-band activity. Furthermore, stopping performance was predicted by beta-band power, and beta-band connectivity was directed from rIFG to pre-supplementary motor area (pre-SMA), indicating rIFG’s dominance over pre-SMA. Thus, these results strongly support the hypothesis that rIFG initiates stopping, implemented by beta-band oscillations with potential to open up new ways of spatially localized oscillation-based interventions.

Introduction: Functional imaging studies have demonstrated the recruitment of additional neural resources as a possible mechanism to compensate for age and Alzheimer’s disease (AD)-related cerebral pathology, the efficacy of which is potentially modulated by underlying structural network connectivity. Additionally, structural network efficiency (SNE) is associated with intelligence across the lifespan, which is a known factor for resilience to cognitive decline. We hypothesized that SNE may be a surrogate of the physiological basis of resilience to cognitive decline in elderly persons without dementia and with age- and AD-related cerebral pathology.Methods: We included 85 cognitively normal elderly subjects or mild cognitive impairment (MCI) patients submitted to baseline diffusion imaging, liquor specimens, amyloid-PET and longitudinal cognitive assessments. SNE was calculated from baseline MRI scans using fiber tractography and graph theory. Mixed linear effects models were estimated to investigate the association of higher resilience to cognitive decline with higher SNE and the modulation of this association by increased cerebral amyloid, liquor tau or WMHV. Results: For the majority of cognitive outcome measures, higher SNE was associated with higher resilience to cognitive decline (p-values: 0.011–0.039). Additionally, subjects with higher SNE showed more resilience to cognitive decline at higher cerebral amyloid burden (p-values:

Information transfer, measured by transfer entropy, is a key component of distributed computation. It is therefore important to understand the pattern of information transfer in order to unravel the distributed computational algorithms of a system. Since in many natural systems distributed computation is thought to rely on rhythmic processes a frequency resolved measure of information transfer is highly desirable. Here, we present a novel algorithm, and its efficient implementation, to identify separately frequencies sending and receiving information in a network. Our approach relies on the invertible maximum overlap discrete wavelet transform (MODWT) for the creation of surrogate data in the computation of transfer entropy and entirely avoids filtering of the original signals. The approach thereby avoids well-known problems due to phase shifts or the ineffectiveness of filtering in the information theoretic setting. We also show that measuring frequency-resolved information transfer is a partial information decomposition problem that cannot be fully resolved to date and discuss the implications of this issue. Last, we evaluate the performance of our algorithm on simulated data and apply it to human magnetoencephalography (MEG) recordings and to local field potential recordings in the ferret. In human MEG we demonstrate top-down information flow in temporal cortex from very high frequencies (above 100Hz) to both similarly high frequencies and to frequencies around 20Hz, i.e. a complex spectral configuration of cortical information transmission that has not been described before. In the ferret we show that the prefrontal cortex sends information at low frequencies (4-8 Hz) to early visual cortex (V1), while V1 receives the information at high frequencies (> 125 Hz).

Cognition emerges from coordinated processing among distributed cortical brain regions, enabled through interconnected white matter networks. Cortical disconnection caused by age-related decline in white matter integrity (WMI) is likely to contribute to age-related cognitive decline. Physical activity (PA) has been suggested to have beneficial effects on white matter structure. However, its potential to counteract age-related decline in WMI is not yet well established. The present explorative study analyzed if PA was associated with WMI in cognitively healthy older adults and if this association was modulated by age. Forty-four cognitively healthy older individuals (aged 60–88 years) with diffusion-tensor imaging (DTI) and PA measurements were included from the AgeGain study. Voxelwise analysis using Tract-Based Spatial Statistics (TBSS) demonstrated that PA was associated with WMI in older adults. However, results emphasized that this association was restricted to high age. The association between PA and WMI was found in widespread white matter regions suggesting a global rather than a regional effect. Supplementary analyses demonstrated an association between the integrity of these regions and the performance in memory [verbal learning and memory test (VLMT)] and executive functioning (Tower of London).Results of the present explorative study support the assumption that PA is associated with WMI in older adults. However, results emphasize that this association is restricted to high age. Since cognitive decline in the elderly is typically most pronounced in later stages of aging, PA qualifies as a promising tool to foster resilience against age-related cognitive decline, via the preservation of the integrity of the brains WM.

Abstract Background Cognitively healthy older people can increase their performance in cognitive tasks through training. However, training effects are mostly limited to the trained task; thus, training effects only poorly transfer to untrained tasks or other contexts, which contributes to reduced adaptation abilities in aging. Stabilizing transfer capabilities in aging would increase the chance of persistent high performance in activities of daily living including longer independency, and prolonged active participation in social life. The trial AgeGain aims at elaborating the physiological brain mechanisms of transfer in aging and supposed major modulators of transfer capability, especially physical activity, cerebral vascular lesions, and amyloid burden. Methods This 4-year interventional, multicenter, phase 2a cognitive and physical training study will enroll 237 cognitively healthy older subjects in four recruiting centers. The primary endpoint of this trial is the prediction of transfer of cognitive training gains. Secondary endpoints are the structural connectivity of the corpus callosum, Default Mode Network activity, brain-derived neurotrophic factors, motor fitness, and maximal oxygen uptake. Discussion Cognitive transfer allows making use of cognitive training gains in everyday life. Thus, maintenance of transfer capability with aging increases the chance of persistent self-guidance and prolonged active participation in social life, which may support a good quality of life. The AgeGain study aims at identifying older people who will most benefit from cognitive training. It will increase the understanding of the neurobiological mechanisms of transfer in aging and will help in determining the impact of physical activity and sport as well as pathologic factors (such as cerebrovascular disease and amyloid load) on transfer capability. Trial registration German Clinical Trials Register (DRKS), ID: DRKS00013077. Registered on 19 November 2017.

Motivated by the recent replicability crisis we tested replicability of functional magnetic resonance imaging (fMRI) group activations in two independent samples. An identical behavioral and fMRI test battery for the longitudinal investigation of stress resilience mechanisms was developed for the Mainz Resilience Project (MARP) and conducted in a discovery (N = 54) and a replication sample (N = 103). The test battery consisted of a stress reactivity task, a reward sensitivity task, a fear conditioning and extinction paradigm, two volitional reappraisal tasks and an emotional interference inhibition task. Replicability of group activations was tested with the Jaccard index and the Intra Class Correlation (ICC). Overall, we observed good to excellent replicability of activations at the whole brain level. Only a minority of contrasts showed unsatisfactory replicability. Replicability at the level of individual regions of interest (ROIs) was generally lower. Tasks with stronger activation in the discovery sample showed better replicability.

Objective: Severe malnutrition in patients with anorexia nervosa (AN) as well as possible trait-related aberrations lead to pronounced structural brain changes whose reversibility after recovery is currently unclear. Previous diffusion tensor imaging (DTI) studies investigating white matter (WM) microstructure alterations in AN are inconsistent.Methods: In this so far largest DTI study in adults, we investigated 33 AN patients, 20 recovered (REC), and 33 healthy women. DTI data were processed using the “DTI and Fiber tools,” and the Computational Anatomy Toolbox. WM integrity, both in terms of fractional anisotropy (FA) and mean diffusivity (MD), was assessed.Results: We found a significant FA decrease in the corpus callosum (body) and an MD decrease in the posterior thalamic radiation in the AN group. The REC group displayed FA decrease in the corpus callosum in comparison to HC, whereas there were no MD differences between the REC and HC groups.Conclusion: Despite prolonged restoration of weight in the REC group, no significant regeneration of WM integrity in terms of FA could be observed. Transient changes in MD likely represent a reversible consequence of the acute state of starvation or result from dehydration. Reduction of FA either may be due to WM damage resulting from malnutrition or may be considered a pre-morbid marker.

Initial historical accounts as well as recent data suggest that emotion processing is dysfunctional in conversion disorder patients and that this alteration may be the pathomechanistic neurocognitive basis for symptoms in conversion disorder. However, to date evidence of direct interaction of altered negative emotion processing with motor control networks in conversion disorder is still lacking. To specifically study the neural correlates of emotion processing interacting with motor networks we used a task combining emotional and sensorimotor stimuli both separately as well as simultaneously during functional magnetic resonance imaging in a well characterized group of 13 conversion disorder patients with functional hemiparesis and 19 demographically matched healthy controls. We performed voxelwise statistical parametrical mapping for a priori regions of interest within emotion processing and motor control networks. Psychophysiological interaction (PPI) was used to test altered functional connectivity of emotion and motor control networks. Only during simultaneous emotional stimulation and passive movement of the affected hand patients displayed left amygdala hyperactivity. PPI revealed increased functional connectivity in patients between the left amygdala and the (pre-)supplemental motor area and the subthalamic nucleus, key regions within the motor control network. These findings suggest a novel mechanistic direct link between dysregulated emotion processing and motor control circuitry in conversion disorder. Keywords: Amygdala, Emotion processing, fMRI, Motor network, Psychogenic paresis, Conversion disorder

Abstract Loss of plasticity‐related gene 1 (PRG‐1), which regulates synaptic phospholipid signaling, leads to hyperexcitability via increased glutamate release altering excitation/inhibition (E/I) balance in cortical networks. A recently reported SNP in prg‐1 (R345T/mutPRG‐1) affects ~5 million European and US citizens in a monoallelic variant. Our studies show that this mutation leads to a loss‐of‐PRG‐1 function at the synapse due to its inability to control lysophosphatidic acid (LPA) levels via a cellular uptake mechanism which appears to depend on proper glycosylation altered by this SNP. PRG‐1+/− mice, which are animal correlates of human PRG‐1+/mut carriers, showed an altered cortical network function and stress‐related behavioral changes indicating altered resilience against psychiatric disorders. These could be reversed by modulation of phospholipid signaling via pharmacological inhibition of the LPA‐synthesizing molecule autotaxin. In line, EEG recordings in a human population‐based cohort revealed an E/I balance shift in monoallelic mutPRG‐1 carriers and an impaired sensory gating, which is regarded as an endophenotype of stress‐related mental disorders. Intervention into bioactive lipid signaling is thus a promising strategy to interfere with glutamate‐dependent symptoms in psychiatric diseases.

Smith and colleagues developed the Brief Resilience Scale (BRS) to assess the individual ability to recover from stress despite significant adversity. This study aimed to validate the German version of the BRS. We used data from a population-based (sample 1: n = 1.481) and a representative (sample 2: n = 1.128) sample of participants from the German general population (age ≥ 18) to assess reliability and validity. Confirmatory factor analyses (CFA) were conducted to compare one- and two-factorial models from previous studies with a method-factor model which especially accounts for the wording of the items. Reliability was analyzed. Convergent validity was measured by correlating BRS scores with mental health measures, coping, social support, and optimism. Reliability was good (α = .85, ω = .85 for both samples). The method-factor model showed excellent model fit (sample 1: χ2/df = 7.544; RMSEA = .07; CFI = .99; SRMR = .02; sample 2: χ2/df = 1.166; RMSEA = .01; CFI = 1.00; SRMR = .01) which was significantly better than the one-factor model (Δχ2(4) = 172.71, p < .001) or the two-factor model (Δχ2(3) = 31.16, p < .001). The BRS was positively correlated with well-being, social support, optimism, and the coping strategies active coping, positive reframing, acceptance, and humor. It was negatively correlated with somatic symptoms, anxiety and insomnia, social dysfunction, depression, and the coping strategies religion, denial, venting, substance use, and self-blame. To conclude, our results provide evidence for the reliability and validity of the German adaptation of the BRS as well as the unidimensional structure of the scale once method effects are accounted for.

Executive dysfunctions frequently occur in patients with Major Depressive Disorder and have been shown to improve during effective antidepressant treatment. However, the time course of improvement and its relationship to treatment outcome is unknown. The aim of the study was to assess the test performance and clinical outcome by repetitive assessments of executive test procedures during antidepressant treatment. Executive test performance was assessed in 209 -patients with Major Depressive Disorder (mean age 39.3 ± 11.4 years) and 84 healthy controls five times in biweekly intervals from baseline to week 8. Patients were treated by a defined treatment algorithm within the early medication change study (EMC trial; ClinicalTrials.gov NCT00974155), controls did not receive any intervention. Cognitive domains were processing speed, cognitive flexibility, phonemic and semantic verbal fluency. Intelligence was assessed at baseline. Depression severity was tested once a week by the Hamilton Depression Rating Scale (HAMD17). 130 patients (62%) showed executive dysfunctions in at least one of four tests at baseline. Linear mixed regression models revealed that the course of depression severity was associated to the course of cognitive flexibility (p = 0.004) and semantic verbal fluency (p = 0.020). Cognitive flexibility and semantic verbal fluency may be candidates easily to apply for therapy response prediction in clinical routine, which should be tested in further prospective studies.ClinicalTrials.gov NCT00974155 EudraCT: 2008-008280-96.

Recent studies have begun to carve out a specific role for the rostral part of the dorsal medial prefrontal cortex (dmPFC) and adjacent dorsal anterior cingulate cortex (dACC) in fear/anxiety. Within a novel general framework of dorsal mPFC/ACC areas subserving the appraisal of threat and concomitant expression of fear responses and ventral mPFC/ACC areas subserving fear regulation, the rostral dmPFC/dACC has been proposed to specifically mediate the conscious, negative appraisal of threat situations including, as an extreme variant, catastrophizing. An alternative explanation that has not been conclusively ruled out yet is that the area is involved in fear learning. We tested two different fear expression paradigms in separate fMRI studies (study 1: instructed fear, study 2: testing of Pavlovian conditioned fear) with independent groups of healthy adult subjects. In both paradigms the absence of reinforcement precluded conditioning. We demonstrate significant BOLD activation of an identical rostral dmPFC/dACC area. In the Pavlovian paradigm (study 2), the area only activated robustly once prior conditioning had finished. Thus, our data argue against a role of the area in fear learning. We further replicate a repeated observation of a dissociation between peripheral-physiological fear responding and rostral dmPFC/dACC activation, strongly suggesting the area does not directly generate fear responses but rather contributes to appraisal processes. Although we succeeded in preventing extinction of conditioned responding in either paradigm, the data do not allow us to definitively exclude an involvement of the area in fear extinction learning. We discuss the broader implications of this finding for our understanding of mPFC/ACC function in fear and in negative emotion more generally.