Abstract Resting-state electroencephalography (rsEEG) yields robust indices of ageing, notably individual alpha peak frequency (iAPF), alpha power, and the aperiodic exponent. Whether these markers reflect stable traits or shift with cognitive exertion remains unresolved, with direct consequences for lifespan and clinical research. We parameterised periodic and aperiodic rsEEG activity before and after cognitive tasks in a lifespan cohort ( N = 390, aged 20–70), a five-year longitudinal follow-up ( N = 100), and an independent older-adult dataset completing a different task ( N = 71). Across datasets, cognitive exertion produced lifespan-wide iAPF slowing and increase in associated power. Notably, aperiodic shifts were age-dependent, with post-task steepening of the exponent in younger adults that progressively flattened with advancing age, resulting in a stronger effect of age on post-task exponents. Our results demonstrate that widely used spectral metrics exhibit acute state-dependency and post-task recordings offer a promising translational framework for indexing individual differences in healthy ageing and pathology. Trial registration Clinicaltrials.gov: NCT05155397
Electroencephalography (EEG) is commonly used in neuroscience to study cognitive and emotional processes, often showing functional lateralization. Alpha asymmetries are frequently interpreted as a reverse marker of functional asymmetries in cognitive activation. However, the role of motor activity versus cognitive demands in driving EEG asymmetries remains unclear. To explore this, we analyzed resting-state and task-based EEG asymmetry from 610 healthy adults (ages 20-70) from the Dortmund Vital Study (ClinicalTrials.gov: NCT05155397). Participants completed three tasks with increasing hand involvement and cognitive demands: Psychomotor Vigilance, Simon, and Stroop tasks. Timepoint (pre-stimulus vs. post-stimulus vs. resting-state) had the strongest impact, especially in the alpha and theta bands, with notable differences between resting-state and task-related asymmetries. Non-right-handers exhibited more dynamic shifts in asymmetry, while right-handers showed more stable lateralization patterns. Correlations between frequency bands, electrode pairs, and tasks revealed strong interhemispheric coupling in frontal and weaker coupling in central regions. Frontal post-stimulus asymmetry correlated more strongly than resting-state or pre-stimulus. Findings suggest that EEG asymmetry is a dynamic process influenced by cognitive and/or motor activity and perceptual processes mediated by frontoparietal circuits, with implications for interpreting EEG biomarkers in both research and clinical settings. This study offers reference standards in EEG asymmetry research.
White matter microstructure is a candidate neurobiological substrate underlying individual differences in fluid intelligence, potentially through differences in neural information transfer. Investigating the association between white matter microstructure and fluid intelligence requires precise modeling of these microstructural properties across the brain. Yet, it remains unclear whether MRI-derived markers of white matter microstructure generalize across tracts to support latent modeling approaches. Therefore, our primary objective was to derive measurement models for markers of white matter integrity (fractional anisotropy, FA), neurite density (intra-neurite volume fraction, INVF), and myelin content (magnetization transfer ratio, MTR) across 52 tracts (HCP-1065 atlas) grouped into ten functional clusters. We investigated data of N = 365 individuals (age range: 18−74) drawn from two independent samples (Dortmund Vital Study: 𝑁 = 150, Clinicaltrials.gov: NCT05155397; Mainz Network Study: 𝑁 = 215). Confirmatory factor analyses consistently favored hierarchical bifactor models, capturing both a general factor per marker and orthogonal hemisphere-specific factors, independent of participants’ age. The general factors FA and MTR of the favored measurement models were significantly associated with fluid intelligence, assessed with matrix reasoning tests, FA: 𝛽 = 0.26, 𝑝 < .001 and MTR: 𝛽 = 0.25, 𝑝 = .017. When controlling for age, the association of fluid intelligence with FA remained significant, 𝛽 = 0.14, 𝑝 < .043, while the association with MTR was no longer significant, 𝛽 = 0.11, 𝑝 = .328. These findings establish anatomically informed measurement models for white matter microstructure and provide a scalable framework for investigating the biological underpinnings of cognitive abilities.
White matter microstructure is a candidate neurobiological substrate underlying individual differences in fluid intelligence, potentially through differences in neural information transfer. Investigating the association between white matter microstructure and fluid intelligence requires precise modeling of these microstructural properties across the brain. Yet, it remains unclear whether MRI-derived markers of white matter microstructure generalize across tracts to support latent modeling approaches. Therefore, our primary objective was to derive measurement models for markers of white matter integrity (fractional anisotropy, FA), neurite density (intra-neurite volume fraction, INVF), and myelin content (magnetization transfer ratio, MTR) across 52 tracts (HCP-1065 atlas) grouped into 10 functional clusters. We investigated data of N = 365 individuals (age range: 18-74 years) drawn from two independent samples (Dortmund Vital Study: N = 150, Clinicaltrials.gov: NCT05155397; Mainz Network Study: N = 215). Confirmatory factor analyses consistently favored hierarchical bifactor models, capturing both a general factor per marker and orthogonal hemisphere-specific factors, independent of participants' age. The general factors FA and MTR of the favored measurement models were significantly associated with fluid intelligence, assessed with matrix reasoning tests, FA: β = 0.26, p < .001 and MTR: β = 0.25, p = .017. When controlling for age, the association of fluid intelligence with FA remained significant, β = 0.14, p < .043, while the association with MTR was no longer significant, β = 0.11, p = .328. These findings establish anatomically informed measurement models for white matter microstructure and provide a scalable framework for investigating the biological underpinnings of cognitive abilities.
Cognitive conflict is a ubiquitous aspect of our daily life, yet its underlying neural mechanisms remain debated. Competing theories propose that conflict processing is governed by either a domain-general system, multiple conflict-specific modules, or an architecture involving partially overlapping mechanisms. The aim of the current study was to clarify how these mechanisms operate at the neural level using a data-driven decoding approach. We analyzed electroencephalogram (EEG) data from 507 healthy participants (ages 20-70) from the Dortmund Vital Study (ClinicalTrials.gov NCT05155397) who completed three conflict tasks: a Change Detection task, a Simon task, and a Stroop task. Using multivariate decoding to distinguish conflict from non-conflict trials, we observed robust within-task decoding across all tasks. However, cross-task decoding revealed shared conflict representations only in specific task pairs. These findings support an account in which conflict processing relies on partially overlapping neural mechanisms rather than being fully domain-general or entirely task specific. We argue that conflict-related neural processes might be best conceptualized as a continuum of overlap and differentiation, with domain-generality and domain-specificity representing the endpoints of this spectrum.
Objective: To investigate whether EEG asymmetries are primarily driven by cognitive or motor processes, and to establish normative patterns across different task conditions. Methods: We analyzed resting-state and task-related EEG asymmetry data from 610 healthy adults aged 20 to 70, from the Dortmund Vital Study (ClinicalTrials.gov: NCT05155397). Participants completed three tasks with increasing cognitive and motor demands: Psychomotor Vigilance, Simon, and Stroop tasks. EEG asymmetries were examined during pre-stimulus, post-stimulus, and resting-state across multiple frequency bands. Results: Timepoint had the strongest impact on EEG asymmetry, particularly in alpha and theta bands, with significant differences between resting-state and task-related conditions. Age had minimal effect on asymmetry patterns. Non-right-handers displayed more dynamic shifts in asymmetry, while right-handers maintained more stable lateralization. Correlations of asymmetry indexes revealed strong interhemispheric coupling in frontal and weaker connectivity in central regions. Post-stimulus frontal asymmetries showed stronger correlations compared to resting-state and pre-stimulus, highlighting dynamic, task-specific lateralization. Conclusions: EEG asymmetry is not static but dynamically modulated by task engagement and stimulus novelty. Significance: This study highlights EEG asymmetry as a dynamic biomarker of brain function, offers standards in EEG-asymmetry research, and may serve as a reference for clinical and non-clinical studies.
Chronotype represents individual differences in circadian preferences that influence sleep-wake patterns, cognitive performance, and clinical outcomes across the lifespan. Given its growing relevance for clinical research and application, efficient and reliable chronotype assessment is essential. However, widely used tools like the Morningness-Eveningness-Questionnaire (MEQ) rely on composite scores, despite methodological concerns about multidimensionality and unequal item contributions. Addressing this limitation, the current study applied machine learning techniques to enhance theoretical understanding and empirical precision in chronotype assessment. Using the German MEQ in the Dortmund Vital Study (ClinicalTrials.gov NCT05155397), a prospective cohort study on healthy cognitive aging, we identified item-level predictive hierarchies and response patterns distinguishing morning, neutral, and evening types. Item 19 ("Which chronotype do you think you are?") demonstrated exceptional predictive utility, showing threefold greater importance than any other item. This metacognitive self-assessment appears to capture relatively accurate chronotype identification rooted in lived experience. Chronotype-specific analyses revealed distinct predictive patterns across types, each relying on different item combinations for optimal classification. Partial dependence analysis identified non-linear response patterns including sigmoid curves, threshold effects, and plateau regions. A six-item combination achieved robust overall classification, potentially reducing assessment burden by 70%. Overall, this research advances chronotype assessment by uncovering non-linear and heterogeneous classification mechanisms to circadian preference. The findings provide evidence-based foundations for developing abbreviated screening tools for primary care consultations, large-scale epidemiological studies, and clinical contexts. An open-access R tutorial ensures reproducibility and facilitates adaptation across diverse populations and assessment instruments, supporting widespread implementation in research and practice.
Background: Exhaustion and depersonalization are the core symptoms of the occupational burnout. However, burnout is not an all-or-nothing phenomenon, but can occur in a milder to moderate form in otherwise healthy employees. In the last two decades hair cortisol concentrations (HCC) were increasingly related to the cumulative effect of psychosocial stress at work. We analyzed data of the Dortmund Vital Study (Clinicaltrials.gov: NCT05155397) to explore the relationship of HCC and burnout symptoms. Moreover, we asked whether the HCC - burnout association was moderated by work ability, chronic stress, neuroticism, depressive symptoms, and stress-related immunological biomarkers such as T cell concentration, CD4/CD8 cell ratio, and proinflammatory cytokines TNF- alpha, IL-6, and IL-18. Methods: Burnout was assessed by the Oldenburg Burnout Inventory (OLBI), and the Maslach Burnout Inventory (MBI-D) in 196 working adults aged between 20 and 65 years (mean age 42.2 years). Several self-reported variables and biomarkers were collected. Results: The results showed an association between HCC and the burnout measures. A series of moderator analyses revealed that the association between HCC and burnout symptoms was substantial for low work ability, high chronic stress level, high neuroticism level, and mild to moderate depressive symptoms. Immunological markers moderated the HCC - burnout association for high concentrations of T cells, low CD4/CD8 ratio and low IL-6, IL-18 and TNF-alpha concentrations. These interactions were moderated by age showing the largest impact in middle-aged to older individuals. Conclusions: The present findings shed light on the complex interaction between burnout symptoms and work ability, chronic stress, personality, and the endocrinological and immunological responses across the working lifespan. These parameters should be considered when assessing the risk for developing burnout and validating the diagnosis of burnout. Trial registration: ClinicalTrials.gov NCT05155397; https://clinicaltrials.gov/ct2/show/NCT05155397.
Intelligence is associated with important life outcomes. Behavioral, genetic, structural, and functional brain correlates of intelligence have been studied for decades, but questions remain as to how genetics are related to trait expression and what intermediary role brain properties play. This study investigated these mediations in a representative sample of 434 individuals, comprising young and older adults. Polygenic scores (PGS) for intelligence were calculated. Resting-state EEG recordings were analyzed using graph theory quantifying functional connectivity across different frequencies. We tested whether global and local graph metrics like efficiency and clustering mediated the association between PGS and intelligence. PGS significantly predicted variance in intelligence and were related to frequency-specific graph metrics in areas predominantly located in parieto-frontal regions, which in turn were associated with intelligence. These findings, based on the first study linking PGS to intelligence using EEG-derived graph metrics, identify candidate pathways through which genetic variation may shape intelligence, providing a foundation for future hypothesis-driven investigations. Data for this study were collected as part of the Dortmund Vital Study ( https://www.researchprotocols.org/2022/3/e32352 ; ClinicalTrials.gov: NCT05155397).
Background: Recent findings showed serious consequences of latent T. gondii infection on the central nervous system, leading to psychiatric, immunological and cognitive impairments. However, little is known about the temporal dynamics of the latent T. gondii infection in respect to immunological and cognitive changes across the adult life span. The present study aims at evaluating the course of cognitive changes across the adult life span in relation to latent T. gondii infection and the interplay with proinflammatory cytokines leading to chronic inflammation as a potential origin of the cognitive decline in infected adults. Methods: In a double-blinded cross-sectional design, data of 218 seropositive and 475 seronegative adults aged between 20 and 88 years were compared regarding crucial cognitive domains: processing speed, working memory, immediate and delayed memory, sustained attention, and executive functions. In a subsample of up to 300 participants, concentrations of proinflammatory cytokines IL-6, IL-8, IL-18, and TNF-α were analyzed to evaluate their interaction with T. gondii, and to determine whether the cytokines interact in their effects on cognition across the lifespan. Results: The results showed an interaction between age and T. gondii status, with a decline in cognitive performance in infected, relative to non-infected, older individuals, and the reversed pattern in young to middle-aged adults. Specifically, this pattern was evident in working memory, immediate and delayed recall, as well as switching ability. Age was associated with increased levels of proinflammatory cytokines, and reduced concentration of T. gondii antibodies. IL-6, IL-8 and TNF-α levels were negatively associated with T. gondii antibody level and cognitive performance. Finally, T. gondii interacted with IL-6, IL-8 and TNF-α, predicting superior performance in immediate and delayed memory tasks in younger adults with high levels of T. gondii IgG antibodies and cytokines, whereas T. gondii IgG antibody and cytokine levels played less of a role for these functions in older age. Conclusion: The findings support a model of dynamically shifting effects of T. gondii and proinflammatory cytokines on the central nervous system and cognition with increasing age, suggesting positive effects of T. gondii infections in younger adults, and neuroinflammatory effects in older age presumably due to chronic inflammation. Given the high prevalence of latent toxoplasmosis in the general population and the growing population of older adults, these findings are of relevance for public health. Trial registration: Clinicaltrials.gov NCT05155397.
Latent, i.e., asymptomatic Toxoplasma gondii (T. gondii) infection might accelerate or modulate the aging process of cognitive and sensory functions involving pro-inflammatory immune responses. For evaluating a potential role of latent T. gondii infection in immunological aging, we determined T. gondii antibody levels and immunosenescence biomarkers in a cross-sectional sample of 584 volunteers aged 20-70 years from the Dortmund Vital Study (ClinicalTrials.gov Identifier NCT05155397) representing the regional population. One-hundred-sixty-one participants were seropositive, representing an overall 28% latent T. gondii seroprevalence, which did not significantly differ between males and females, but increased with age. Consequently, seropositive individuals were older than the seronegative participants. Latent T. gondii infection exhibited significant bivariate associations with the composite immune age index IMMAX pointing to accelerated immune aging in seropositive individuals. In addition, IMMAX increased with age and in males. However, associations of latent T. gondii infection with immunosenescence biomarkers disappeared when adjusting the analyses for sex and age. Moreover, the non-significant interaction between T. gondii status and age when predicting biomarker levels indicated that latent T. gondii infection did not modify the immunosenescence trend. Summarized, our results suggest that latent T. gondii infection is unlikely to modulate immune aging concerning cellular senescence in otherwise healthy working-age adults.
Cognitive aging is typically associated with a higher susceptibility to distraction by concurrent, but task-irrelevant stimuli. Here, we studied the cognitive sub-processes involved in a sample of 484 healthy adults aged 20-70 years from the Dortmund Vital Study (Clinicaltrials.gov NCT05155397). Participants judged the duration of tone stimuli of a random sequence of long and short tones, having either a regular (standard) pitch or rare (deviant) pitch. Deviance-related ERPs were explored, reflecting neuro-cognitive correlates of pre-attentive deviance detection (MMN), attention allocation toward (P3a) and processing of (P3b) the deviance, and re-orienting toward the task-relevant stimulus feature (RON). Accuracy was reduced for deviant long tones, possibly due to withdrawing attention from processing the time information, making long stimuli appear shorter. This effect increased with age, and cluster-based permutation tests on the correlation of ERPs and age as well as linear mixed modeling indicated a decrease in MMN, an increase in P3a with long tones, and decreases in P3b and RON. This suggests a greater attentional orienting to the deviant stimulus feature and a reduced re-orienting to the task-relevant feature with increasing age.
This dataset consists of 64-channels resting-state EEG recordings of 608 participants aged between 20 and 70 years, 61.8% female, as well as follow-up measurements after approximately 5 years of 208 participants, starting 2021. The EEG was measured for three minutes with eyes open and eyes closed before and after a 2-hour block of cognitive experimental tasks. The data set is part of the Dortmund Vital Study, a prospective study on the determinants of healthy cognitive aging. The dataset can be used for (1) analyzing cross-sectional resting-state EEG of healthy individuals across the adult life span; (2) generating normalization data sets for comparison of resting-state EEG data of patients with clinically relevant disorders; (3) studying effects of performing cognitive tasks on resting-state EEG and age; (4) exploring intra-individual changes in resting-state EEG and effects of task performance over a time period of about 5 years. The data are provided in Brain Imaging Data Structure (BIDS) format and are available on OpenNeuro.
An increased prevalence of mixed-handedness has been reported in several neurodevelopmental and psychiatric disorders. Unfortunately, there is high between-study variability in the definition of mixed-handedness, leading to a major methodological problem in clinical laterality research and endangering replicability and comparability of research findings. Adding to this challenge is the fact that sometimes researchers use the concepts of mixed-handedness and ambidexterity interchangeably. Therefore, having a consensus on how to determine mixed-handedness and how to distinguish it from ambidexterity is crucial for clinical laterality research. To this end, hand preference and hand performance data from more than 600 participants from the Dortmund Vital Study (Trial registration: ClinicalTrials.gov NCT05155397), a population-based study in Germany, was analyzed to ascertain an optimal classification to determine mixed-handedness and ambidexterity. Using a combination of latent class analyses, effect size determination, and comparisons with the existing literature, we establish that an LQ cut-off criterion of +/-60 for mixed-handedness is optimal for future clinical laterality studies. Moreover, we show that mixed-handedness and ambidexterity are not identical and that the terms should not be used interchangeably. We further highlight the need for a consensus on how to mathematically determine ambidexterity as results of existing categorization schemes largely differ.
Early life events can have long-lasting effects that may impact the quality of life into adulthood. The link between childhood adversities and adult mental and physical health is well documented, however, the underlying mechanisms remain poorly understood. Executive functions are assumed to be a key factor in successfully dealing with cognitive-emotional challenges thereby contributing to stress resilience and mental health across the life- span. Here, we examined whether cognitive control moderates the link between early life adversity and depression. Data was available from a sample of 424 participants aged 20-70 years (Clinicaltrials.gov: NCT05155397). They performed in the Stroop task and behavior as well as frontal theta power were recorded. Negative childhood experiences were assessed with the Childhood Trauma Questionnaire (CTQ), chronic stress was measured with the Trier Inventory for Chronic Stress (TICS) and depression symptoms with Beck's Depression Inventory (BDI). The CTQ predicted symptoms of chronic stress and depression. Regression models pointed to the TICS as a crucial mediator in the relationship between CTQ and BDI. However, parameters of cognitive control demonstrated a rather weak effect as moderators. These results indicate that chronic stress is an important mediator linking childhood trauma to depression but suggest only a limited role for cognitive control.
While several studies have shown associations between hearing disorders and congenital toxoplasmosis, the present study investigated the impact of chronic, latent Toxoplasma gondii (T. gondii) infection on hearing loss. We used a regression analysis to explore whether latent T. gondii infection modulates changes in hearing thresholds over an age range from 20 to 70 years. We analyzed audiometric data of 162 T. gondii IgG-positive and 430 T. gondii-negative participants, collected in the Dortmund Vital Study (DVS, ClinicalTrials.gov Identifier: NCT05155397), a prospective study on healthy cognitive aging. The regression analysis indicated that latent toxoplasmosis was associated with an accelerated development in hearing loss over the observed age range. Hearing loss was less frequent in IgG-positive than in IgG-negative participants up to the age of about 40 for a low (0.125–1 kHz)-frequency range. For high (2–8 kHz) frequencies, this pattern reversed for ages above 65 years. We discuss these findings on hearing function in the context of a recently proposed model, suggesting that latent toxoplasmosis can differentially affect brain functions across a lifespan.
Demographic change is leading to an increasing proportion of older employees in the labor market. At the same time, work activities are becoming more and more complex and require a high degree of flexibility, adaptability, and cognitive performance. Cognitive control mechanism, which is subject to age-related changes and is important in numerous everyday and work activities, plays a special role. Executive functions with its core functions updating, shifting, and inhibition comprises cognitive control mechanisms that serve to plan, coordinate, and achieve higher-level goals especially in inexperienced and conflicting actions. In this review, influences of age-related changes in cognitive control are demonstrated with reference to work and real-life activities, in which the selection of an information or response in the presence of competing but task-irrelevant stimuli or responses is particularly required. These activities comprise the understanding of spoken language under difficult listening conditions, dual-task walking, car driving in critical traffic situations, and coping with work interruptions. Mechanisms for compensating age-related limitations in cognitive control and their neurophysiological correlates are discussed with a focus on EEG measures. The examples illustrate how to access influences of age and cognitive control on and in everyday and work activities, focusing on its functional role for the work ability and well-being of older people.
Immunological aging type definition requires establishing reference intervals from the distribution of immunosenescence biomarkers conditional on age. For 1605 individuals (18–97 years), we determined the comprehensive immune age index IMMAX from flow-cytometry-based blood cell sub-populations and identified age-specific centiles by fitting generalized additive models for location, scale, and shape. The centiles were uncorrelated with age and facilitated the categorization of individuals as immunologically slow or fast aging types. Using its 50th percentile as a reference, we rescaled the IMMAX to equivalent years of life (EYOL) and computed the immunological age gap as the difference between EYOL and chronological age. Applied to preliminary baseline and follow-up measurements from 53 participants of the Dortmund Vital Study (Clinical-Trials.gov Identifier: NCT05155397), the averaged changes in the IMMAX and EYOL conformed to the 5-year follow-up period, whereas no significant changes occurred concerning IMMAX centiles and age gap. This suggested that the participants immunologically adapted to aging and kept their relative positions within the cohort. Sex was non-significant. Methodical comparisons indicated that future confirmatory analyses with the completed follow-up examinations could rely on percentile curves estimated by simple linear quantile regression, while the selection of the immunosenescence biomarker will greatly influence the outcome, with IMMAX representing the preferable choice.
The Path Integration (PI) task stands as a fundamental activity within spatial navigation, encompassing a multifaceted underlying process that requires extensive computation of both translational and directional information during navigation. This task is postulated to engage the entorhinal cortex (EC), a critical brain region. Although rodent studies have firmly linked the EC with the PI task, such a correlation has yet to be definitively established in humans. Individuals harboring high-risk genes associated with Alzheimer’s disease (AD) present a unique opportunity to explore PI task performance in humans because EC is the first targeted region during the pathological development of AD. Furthermore, the execution of the PI task is also susceptible to the influences of age and gender. In order to methodically probe the influences of various factors on PI performance, we conducted a PI task in a cohort characterized by high-risk AD-associated genes in a virtual island environment with surrounding landmarks. Our findings unveiled intricate interactions between these risk genes, age, and gender in shaping PI performance, an influence primarily mediated through distance and angle estimation. This study provides an illuminating perspective on the investigation into the functional role of the entorhinal cortex within the context of the PI task.