Running in the FAMILY: understanding and predicting the intergenerational transmission of mental illness.

Over 50% of children with a parent with severe mental illness will develop mental illness by early adulthood. However, intergenerational transmission of risk for mental illness in one's children is insufficiently considered in clinical practice, nor is it sufficiently utilised into diagnostics and care for children of ill parents. This leads to delays in diagnosing young offspring and missed opportunities for protective actions and resilience strengthening. Prior twin, family, and adoption studies suggest that the aetiology of mental illness is governed by a complex interplay of genetic and environmental factors, potentially mediated by changes in epigenetic programming and brain development. However, how these factors ultimately materialise into mental disorders remains unclear. Here, we present the FAMILY consortium, an interdisciplinary, multimodal (e.g., (epi)genetics, neuroimaging, environment, behaviour), multilevel (e.g., individual-level, family-level), and multisite study funded by a European Union Horizon-Staying-Healthy-2021 grant. FAMILY focuses on understanding and prediction of intergenerational transmission of mental illness, using genetically informed causal inference, multimodal normative prediction, and animal modelling. Moreover, FAMILY applies methods from social sciences to map social and ethical consequences of risk prediction to prepare clinical practice for future implementation. FAMILY aims to deliver: (i) new discoveries clarifying the aetiology of mental illness and the process of resilience, thereby providing new targets for prevention and intervention studies; (ii) a risk prediction model within a normative modelling framework to predict who is at risk for developing mental illness; and (iii) insight into social and ethical issues related to risk prediction to inform clinical guidelines.

No phenotypic or genotypic evidence for a link between sleep duration and brain atrophy.

Short sleep is held to cause poorer brain health, but is short sleep associated with higher rates of brain structural decline? Analysing 8,153 longitudinal MRIs from 3,893 healthy adults, we found no evidence for an association between sleep duration and brain atrophy. In contrast, cross-sectional analyses (51,295 observations) showed inverse U-shaped relationships, where a duration of 6.5 (95% confidence interval, (5.7, 7.3)) hours was associated with the thickest cortex and largest volumes relative to intracranial volume. This fits converging evidence from research on mortality, health and cognition that points to roughly seven hours being associated with good health. Genome-wide association analyses suggested that genes associated with longer sleep for below-average sleepers were linked to shorter sleep for above-average sleepers. Mendelian randomization did not yield evidence for causal impacts of sleep on brain structure. The combined results challenge the notion that habitual short sleep causes brain atrophy, suggesting that normal brains promote adequate sleep duration-which is shorter than current recommendations.

Lifestyle-related risk factors and their cumulative associations with hippocampal and total grey matter volume across the adult lifespan: A pooled analysis in the European Lifebrain consortium.

BACKGROUND: Lifestyle-related risk factors, such as obesity, physical inactivity, short sleep, smoking and alcohol use, have been associated with low hippocampal and total grey matter volumes (GMV). However, these risk factors have mostly been assessed as separate factors, leaving it unknown if variance explained by these factors is overlapping or additive. We investigated associations of five lifestyle-related factors separately and cumulatively with hippocampal and total GMV, pooled across eight European cohorts. METHODS: We included 3838 participants aged 18-90 years from eight cohorts of the European Lifebrain consortium. Using individual person data, we performed cross-sectional meta-analyses on associations of presence of lifestyle-related risk factors separately (overweight/obesity, physical inactivity, short sleep, smoking, high alcohol use) as well as a cumulative unhealthy lifestyle score (counting the number of present lifestyle-related risk factors) with FreeSurfer-derived hippocampal volume and total GMV. Lifestyle-related risk factors were defined according to public health guidelines. RESULTS: High alcohol use was associated with lower hippocampal volume (r = -0.10, p = 0.021), and overweight/obesity with lower total GMV (r = -0.09, p = 0.001). Other lifestyle-related risk factors were not significantly associated with hippocampal volume or GMV. The cumulative unhealthy lifestyle score was negatively associated with total GMV (r = -0.08, p = 0.001), but not hippocampal volume (r = -0.01, p = 0.625). CONCLUSIONS: This large pooled study confirmed the negative association of some lifestyle-related risk factors with hippocampal volume and GMV, although with small effect sizes. Lifestyle factors should not be seen in isolation as there is evidence that having multiple unhealthy lifestyle factors is associated with a linear reduction in overall brain volume.

Is Short Sleep Bad for the Brain? Brain Structure and Cognitive Function in Short Sleepers.

Many sleep less than recommended without experiencing daytime sleepiness. According to prevailing views, short sleep increases risk of lower brain health and cognitive function. Chronic mild sleep deprivation could cause undetected sleep debt, negatively affecting cognitive function and brain health. However, it is possible that some have less sleep need and are more resistant to negative effects of sleep loss. We investigated this using a cross-sectional and longitudinal sample of 47,029 participants of both sexes (20-89 years) from the Lifebrain consortium, Human Connectome project (HCP) and UK Biobank (UKB), with measures of self-reported sleep, including 51,295 MRIs of the brain and cognitive tests. A total of 740 participants who reported to sleep <6 h did not experience daytime sleepiness or sleep problems/disturbances interfering with falling or staying asleep. These short sleepers showed significantly larger regional brain volumes than both short sleepers with daytime sleepiness and sleep problems (n = 1742) and participants sleeping the recommended 7-8 h (n = 3886). However, both groups of short sleepers showed slightly lower general cognitive function (GCA), 0.16 and 0.19 SDs, respectively. Analyses using accelerometer-estimated sleep duration confirmed the findings, and the associations remained after controlling for body mass index, depression symptoms, income, and education. The results suggest that some people can cope with less sleep without obvious negative associations with brain morphometry and that sleepiness and sleep problems may be more related to brain structural differences than duration. However, the slightly lower performance on tests of general cognitive abilities warrants closer examination in natural settings.SIGNIFICANCE STATEMENT Short habitual sleep is prevalent, with unknown consequences for brain health and cognitive performance. Here, we show that daytime sleepiness and sleep problems are more strongly related to regional brain volumes than sleep duration. However, participants sleeping ≤6 h had slightly lower scores on tests of general cognitive function (GCA). This indicates that sleep need is individual and that sleep duration per se is very weakly if at all related brain health, while daytime sleepiness and sleep problems may show somewhat stronger associations. The association between habitual short sleep and lower scores on tests of general cognitive abilities must be further scrutinized in natural settings.

Stakeholder engagement in European brain research: Experiences of the Lifebrain consortium.

INTRODUCTION: Stakeholder engagement remains scarce in basic brain research. However, it can greatly improve the relevance of investigations and accelerate the translation of study findings to policy. The Lifebrain consortium investigated risk and protective factors influencing brain health using cognition, lifestyle and imaging data from European cohorts. Stakeholder activities of Lifebrain-organized in a separate work package-included organizing stakeholder events, investigating public perceptions of brain health and dissemination. Here, we describe the experiences of researchers and stakeholders regarding stakeholder engagement in the Lifebrain project. METHODS: Stakeholder engagement in Lifebrain was evaluated through surveys among researchers and stakeholders and stakeholders' feedback at stakeholder events through evaluation forms. Survey data were analysed using a simple content analysis approach, and results from evaluation forms were summarized after reviewing the frequency of responses. RESULTS: Consortium researchers and stakeholders experienced the engagement activities as meaningful and relevant. Researchers highlighted that it made the research and research processes more visible and contributed to new networks, optimized data collection on brain health perceptions and the production of papers and provided insights into stakeholder views. Stakeholders found research activities conducted in the stakeholder engagement work package to be within their field of interest and research results relevant to their work. Researchers identified barriers to stakeholder engagement, including lack of time, difficulties in identifying relevant stakeholders, and challenges in communicating complex scientific issues in lay language and maintaining relationships with stakeholders over time. Stakeholders identified barriers such as lack of budget, limited resources in their organization, time constraints and insufficient communication between researchers and stakeholders. CONCLUSION: Stakeholder engagement in basic brain research can greatly benefit researchers and stakeholders alike. Its success is conditional on dedicated human and financial resources, clear communication, transparent mutual expectations and clear roles and responsibilities. PUBLIC CONTRIBUTION: Patient organizations, research networks, policymakers and members of the general public were involved in engagement and research activities throughout the project duration.

Stability of associations between neuroticism and microstructural asymmetry of the cingulum during late childhood and adolescence: Insights from a longitudinal study with up to 11 waves.

Adolescence is characterized by significant brain development and marks a period of the life span with an increased incidence of mood disorders, especially in females. The risk of developing mood disorders is also higher in individuals scoring high on neuroticism, a personality trait characterized by a tendency to experience negative and anxious emotions. We previously found in a cross-sectional study that neuroticism is associated with microstructural left-right asymmetry of the fronto-limbic white matter involved in emotional processing, with opposite effects in female and male adolescents. We now have extended this work collecting longitudinal data in 76 typically developing children and adolescents aged 7-18 years, including repeated MRI sampling up to 11 times. This enabled us, for the first time, to address the critical question, whether the association between neuroticism and frontal-limbic white matter asymmetry changes or remains stable across late childhood and adolescence. Neuroticism was assessed up to four times and showed good intraindividual stability and did not significantly change with age. Conforming our cross-sectional results, females scoring high on neuroticism displayed increased left-right cingulum fractional anisotropy (FA), while males showed decreased left-right cingulum FA asymmetry. Despite ongoing age-related increases in FA in cingulum, the association between neuroticism and cingulum FA asymmetry was already expressed in females in late childhood and remained stable across adolescence. In males, the association appeared to become more prominent during adolescence. Future longitudinal studies need to cover an earlier age span to elucidate the time point at which the relationship between neuroticism and cingulum FA asymmetry arises.

Individual differences in brain aging: heterogeneity in cortico-hippocampal but not caudate atrophy rates.

It is well documented that some brain regions, such as association cortices, caudate, and hippocampus, are particularly prone to age-related atrophy, but it has been hypothesized that there are individual differences in atrophy profiles. Here, we document heterogeneity in regional-atrophy patterns using latent-profile analysis of 1,482 longitudinal magnetic resonance imaging observations. The results supported a 2-group solution reflecting differences in atrophy rates in cortical regions and hippocampus along with comparable caudate atrophy. The higher-atrophy group had the most marked atrophy in hippocampus and also lower episodic memory, and their normal caudate atrophy rate was accompanied by larger baseline volumes. Our findings support and refine models of heterogeneity in brain aging and suggest distinct mechanisms of atrophy in striatal versus hippocampal-cortical systems.

People's interest in brain health testing: Findings from an international, online cross-sectional survey.

Brain health entails mental wellbeing and cognitive health in the absence of brain disorders. The past decade has seen an explosion of tests, cognitive and biological, to predict various brain conditions, such as Alzheimer's Disease. In line with these current developments, we investigated people's willingness and reasons to-or not to-take a hypothetical brain health test to learn about risk of developing a brain disease, in a cross-sectional multilanguage online survey. The survey was part of the Global Brain Health Survey, open to the public from 4th June 2019 to 31st August 2020. Respondents were largely recruited via European brain councils and research organizations. 27,590 people responded aged 18 years or older and were predominantly women (71%), middle-aged or older (>40 years; 83%), and highly educated (69%). Responses were analyzed to explore the relationship between demographic variables and responses. Results: We found high public interest in brain health testing: over 91% would definitely or probably take a brain health test and 86% would do so even if it gave information about a disease that cannot be treated or prevented. The main reason for taking a test was the ability to respond if one was found to be at risk of brain disease, such as changing lifestyle, seeking counseling or starting treatment. Higher interest in brain health testing was found in men, respondents with lower education levels and those with poor self-reported cognitive health. Conclusion: High public interest in brain health and brain health testing in certain segments of society, coupled with an increase of commercial tests entering the market, is likely to put pressure on public health systems to inform the public about brain health testing in years to come.

Associations of depression and regional brain structure across the adult lifespan: Pooled analyses of six population-based and two clinical cohort studies in the European Lifebrain consortium.

OBJECTIVE: Major depressive disorder has been associated with lower prefrontal thickness and hippocampal volume, but it is unknown whether this association also holds for depressive symptoms in the general population. We investigated associations of depressive symptoms and depression status with brain structures across population-based and patient-control cohorts, and explored whether these associations are similar over the lifespan and across sexes. METHODS: We included 3,447 participants aged 18-89 years from six population-based and two clinical patient-control cohorts of the European Lifebrain consortium. Cross-sectional meta-analyses using individual person data were performed for associations of depressive symptoms and depression status with FreeSurfer-derived thickness of bilateral rostral anterior cingulate cortex (rACC) and medial orbitofrontal cortex (mOFC), and hippocampal and total grey matter volume (GMV), separately for population-based and clinical cohorts. RESULTS: Across patient-control cohorts, depressive symptoms and presence of mild-to-severe depression were associated with lower mOFC thickness (rsymptoms = -0.15/ rstatus = -0.22), rACC thickness (rsymptoms = -0.20/ rstatus = -0.25), hippocampal volume (rsymptoms = -0.13/ rstatus = 0.13) and total GMV (rsymptoms = -0.21/ rstatus = -0.25). Effect sizes were slightly larger for presence of moderate-to-severe depression. Associations were similar across age groups and sex. Across population-based cohorts, no associations between depression and brain structures were observed. CONCLUSIONS: Fitting with previous meta-analyses, depressive symptoms and depression status were associated with lower mOFC, rACC thickness, and hippocampal and total grey matter volume in clinical patient-control cohorts, although effect sizes were small. The absence of consistent associations in population-based cohorts with mostly mild depressive symptoms, suggests that significantly lower thickness and volume of the studied brain structures are only detectable in clinical populations with more severe depressive symptoms.

No Association Between Loneliness, Episodic Memory and Hippocampal Volume Change in Young and Healthy Older Adults: A Longitudinal European Multicenter Study.

Background: Loneliness is most prevalent during adolescence and late life and has been associated with mental health disorders as well as with cognitive decline during aging. Associations between longitudinal measures of loneliness and verbal episodic memory and brain structure should thus be investigated. Methods: We sought to determine associations between loneliness and verbal episodic memory as well as loneliness and hippocampal volume trajectories across three longitudinal cohorts within the Lifebrain Consortium, including children, adolescents (N = 69, age range 10-15 at baseline examination) and older adults (N = 1468 over 60). We also explored putative loneliness correlates of cortical thinning across the entire cortical mantle. Results: Loneliness was associated with worsening of verbal episodic memory in one cohort of older adults. Specifically, reporting medium to high levels of loneliness over time was related to significantly increased memory loss at follow-up examinations. The significance of the loneliness-memory change association was lost when eight participants were excluded after having developed dementia in any of the subsequent follow-up assessments. No significant structural brain correlates of loneliness were found, neither hippocampal volume change nor cortical thinning. Conclusion: In the present longitudinal European multicenter study, the association between loneliness and episodic memory was mainly driven by individuals exhibiting progressive cognitive decline, which reinforces previous findings associating loneliness with cognitive impairment and dementia.

White matter diffusivity and its correlations to state measures of psychopathology in male refugees with posttraumatic stress disorder.

Post-traumatic stress disorder (PTSD) is a heterogenous condition and the underlying neurobiology is still poorly understood. In this study, we tested the hypothesis that PTSD is associated with microstructural changes in white matter (WM) fibre tracts that connect regions involved in emotional processing, memory, attention, and language. Furthermore, we examined how different response patterns to individualized trauma-provoking stimuli related to underlying WM microstructure. Sixty-nine trauma-affected male refugees with PTSD (N = 38) or without PTSD (N = 31) underwent clinical assessments and diffusion-weighted magnetic resonance imaging (DWI) of the whole brain at 3 Tesla. Diffusion tensor metrics were computed from DWI data and used to characterize regional white-matter microstructure. An automated tract segmentation method was used to extract diffusion tensor metrics from subject-based reconstructions of tract segments (ROI), including uncinate fasciculus (UF), cingulum bundle (CB), superior longitudinal fasciculus (SLF) in three subdivisions (SLF I - III), and fibre bundles connecting orbito-frontal cortex to striatum (OF-ST). Outside the scanner we obtained measures of immediate (state) arousal, avoidance and dissociation symptoms assessed in response to auditory exposure to a personal traumatic memory. Using mean FA of the middle part of each ROI, mixed ANOVA revealed a significant interaction between group, ROI and hemisphere. Post-hoc comparisons showed that, relative to refugees without PTSD, refugees with PTSD had lower FA in right CB, left SLF-I, bilateral OF-ST and bilateral SLF-II. Mean FA scaled negatively with avoidance in right CB while mean FA in bilateral UF scaled positively with individual scores reflecting dissociation symptoms. The results support a pathophysiological model of PTSD that implicates limbic structures, prefrontal cortex and striatum. The results also emphasize the need to consider PTSD's multifaceted manifestations when searching for functional-structural relationships.

Education and Income Show Heterogeneous Relationships to Lifespan Brain and Cognitive Differences Across European and US Cohorts.

Higher socio-economic status (SES) has been proposed to have facilitating and protective effects on brain and cognition. We ask whether relationships between SES, brain volumes and cognitive ability differ across cohorts, by age and national origin. European and US cohorts covering the lifespan were studied (4-97 years, N = 500 000; 54 000 w/brain imaging). There was substantial heterogeneity across cohorts for all associations. Education was positively related to intracranial (ICV) and total gray matter (GM) volume. Income was related to ICV, but not GM. We did not observe reliable differences in associations as a function of age. SES was more strongly related to brain and cognition in US than European cohorts. Sample representativity varies, and this study cannot identify mechanisms underlying differences in associations across cohorts. Differences in neuroanatomical volumes partially explained SES-cognition relationships. SES was more strongly related to ICV than to GM, implying that SES-cognition relations in adulthood are less likely grounded in neuroprotective effects on GM volume in aging. The relatively stronger SES-ICV associations rather are compatible with SES-brain volume relationships being established early in life, as ICV stabilizes in childhood. The findings underscore that SES has no uniform association with, or impact on, brain and cognition.

Glucocorticoid treatment for non-cerebral diseases in children and adolescents is associated with differences in uncinate fasciculus microstructure.

BACKGROUND: Evidence suggests that fronto-limbic brain regions and connecting white matter fibre tracts in the left hemisphere are more sensitive to glucocorticoids than in the right hemisphere. It is unknown whether treatment with glucocorticoids in childhood is associated with microstructural differences of the uncinate fasciculus and cingulum bundle, which connect fronto-limbic brain regions. Here, we tested the hypothesis that prior glucocorticoid treatment would be associated with differences in fractional anisotropy (FA) of the left relative to right uncinate fasciculus and cingulum bundle. METHODS: We performed diffusion-weighted imaging in 28 children and adolescents aged 7-16 years previously treated with glucocorticoids for nephrotic syndrome or rheumatic disease and 28 healthy controls. RESULTS: Patients displayed significantly different asymmetry in the microstructure of uncinate fasciculus with higher left but similar right uncinate fasciculus FA and axial diffusivity compared to controls. No apparent differences were observed for the cingulum. Notably, higher cumulative glucocorticoid doses were significantly associated with higher uncinate fasciculus FA and axial diffusivity bilaterally. CONCLUSIONS: Our findings indicate that previous glucocorticoid treatment for non-cerebral diseases in children and adolescents is associated with long-term changes in the microstructure of the uncinate fasciculi, and that higher cumulative glucocorticoid doses have a proportional impact on the microstructure. IMPACT: It is unknown if treatment with glucocorticoids in childhood have long-term effects on fronto-limbic white matter microstructure. The study examined if children and adolescents previously treated with glucocorticoids for nephrotic syndrome or rheumatic disorder differed in fronto-limbic white matter microstructure compared to healthy controls. The nephrotic and rheumatic patients had higher left but similar right uncinate fasciculus FA and axial diffusivity. Higher bilateral uncinate fasciculus FA and axial diffusivity was associated with higher cumulative glucocorticoid doses. We revealed new evidence suggesting that previous glucocorticoid treatment for non-cerebral diseases in children and adolescents is associated with long-term changes in uncinate fasciculi microstructure.

Individual variations in 'brain age' relate to early-life factors more than to longitudinal brain change.

Brain age is a widely used index for quantifying individuals' brain health as deviation from a normative brain aging trajectory. Higher-than-expected brain age is thought partially to reflect above-average rate of brain aging. Here, we explicitly tested this assumption in two independent large test datasets (UK Biobank [main] and Lifebrain [replication]; longitudinal observations ≈ 2750 and 4200) by assessing the relationship between cross-sectional and longitudinal estimates of brain age. Brain age models were estimated in two different training datasets (n ≈ 38,000 [main] and 1800 individuals [replication]) based on brain structural features. The results showed no association between cross-sectional brain age and the rate of brain change measured longitudinally. Rather, brain age in adulthood was associated with the congenital factors of birth weight and polygenic scores of brain age, assumed to reflect a constant, lifelong influence on brain structure from early life. The results call for nuanced interpretations of cross-sectional indices of the aging brain and question their validity as markers of ongoing within-person changes of the aging brain. Longitudinal imaging data should be preferred whenever the goal is to understand individual change trajectories of brain and cognition in aging.

Scientists who study the brain and aging are keen to find an effective way to measure brain health, which could help identify people at risk for dementia or memory problems. One popular marker is 'brain age'. This measurement uses a brain scan to estimate a person's chronological age, then compares the estimated brain age to the person's actual age to determine whether their brain is aging faster or slower than expected for their age. However, since brain age relies on one brain scan taken at one point in time, it is not clear whether it really measures brain aging or if it might capture brain differences that have been present throughout the individual's life. Studies comparing individual brain scans over several years would be necessary to know for sure. Now, Vidal-Piñeiro et al. show that the brain-age measurement does not reflect faster brain aging. In the experiments, the researchers compared repeated brain scans of thousands of individuals over 40 years of age. The experiments showed that deviations from normative brain age detected in a single scan reflected early life differences more than changes in the brain over time. For example, people with older-looking brains were more likely to have had a low birth weight or to have a combination of genes associated with having an older looking brain. Vidal-Piñeiro et al. show that brain age mostly reflects a pre-existing brain condition rather than brain aging. The experiments also suggest that genetics and early brain development likely have a strong impact on brain health throughout life. Future studies trying to test or develop brain-aging measurements should use serial measurements to track brain changes over time.

Brain structure associations with phonemic and semantic fluency in typically-developing children.

Verbal fluency is the ability to retrieve lexical knowledge quickly and efficiently and develops during childhood and adolescence. Few studies have investigated associations between verbal fluency performance and brain structural variation in children. Here we examined associations of verbal fluency performance with structural measures of frontal and temporal language-related brain regions and their connections in 73 typically-developing children aged 7-13 years. Tract-based spatial statistics was used to extract fractional anisotropy (FA) from the superior longitudinal fasciculus/arcuate fasciculus (SLF/AF), and the white matter underlying frontal and temporal language-related regions. FreeSurfer was used to extract cortical thickness and surface area. Better semantic and phonemic fluency performance was associated with higher right SLF/AF FA, and phonemic fluency was also modestly associated with lower left SLF/AF FA. Explorative voxelwise analyses for semantic fluency suggested associations with FA in other fiber tracts, including corpus callosum and right inferior fronto-occipital fasciculus. Overall, our results suggest that verbal fluency performance in children may rely on right hemisphere structures, possibly involving both language and executive function networks, and less on solely left hemisphere structures as often is observed in adults. Longitudinal studies are needed to clarify whether these associations are mediated by maturational processes, stable characteristics and/or experience.

The Global Brain Health Survey: Development of a Multi-Language Survey of Public Views on Brain Health.

Background: Brain health is a multi-faceted concept used to describe brain physiology, cognitive function, mental health and well-being. Diseases of the brain account for one third of the global burden of disease and are becoming more prevalent as populations age. Diet, social interaction as well as physical and cognitive activity are lifestyle factors that can potentially influence facets of brain health. Yet, there is limited knowledge about the population's awareness of brain health and willingness to change lifestyle to maintain a healthy brain. This paper introduces the Global Brain Health Survey protocol, designed to assess people's perceptions of brain health and factors influencing brain health. Methods: The Global Brain Health Survey is an anonymous online questionnaire available in 14 languages to anyone above the age of 18 years. Questions focus on (1) willingness and motivation to maintain or improve brain health, (2) interest in learning more about individual brain health using standardized tests, and (3) interest in receiving individualized support to take care of own brain health. The survey questions were developed based on results from a qualitative interview study investigating brain health perceptions among participants in brain research studies. The survey includes 28 questions and takes 15-20 min to complete. Participants provide electronically informed consent prior to participation. The current survey wave was launched on June 4, 2019 and will close on August 31, 2020. We will provide descriptive statistics of samples distributions including analyses of differences as a function of age, gender, education, country of residence, and we will examine associations between items. The European Union funded Lifebrain project leads the survey in collaboration with national brain councils in Norway, Germany, and Belgium, Brain Foundations in the Netherlands and Sweden, the National University of Ostroh Academy and the Women's Brain Project. Discussion: Results from this survey will provide new insights in peoples' views on brain health, in particular, the extent to which the adoption of positive behaviors can be encouraged. The results will contribute to the development of policy recommendations for supporting population brain health, including measures tailored to individual needs, knowledge, motivations and life situations.

Maturational trajectories of white matter microstructure underlying the right presupplementary motor area reflect individual improvements in motor response cancellation in children and adolescents.

The ability to effectively suppress motor response tendencies is essential for focused and goal-directed behavior. Here, we tested the hypothesis that developmental improvement in the ability to cancel a motor response is reflected by maturational changes in the white matter underlying the right presupplementary motor area (preSMA) and posterior inferior frontal gyrus (IFG), two cortical key areas of the fronto-basal ganglia "stopping" network. Eighty-eight typically-developing children and adolescents, aged 7-19 years, were longitudinally assessed with the stop-signal task (SST) and diffusion tensor imaging (DTI) of the brain over a period of six years. Participants were examined from two to nine times with an average of 6.6 times, resulting in 576 SST-DTI datasets. We applied tract-based spatial statistics to extract mean fractional anisotropy (FA) from regions-of-interest in the white matter underlying the right IFG (IFGFA) and right preSMA (preSMAFA) at each time point. Motor response cancelation performance, estimated with the stop-signal reaction time (SSRT), improved with age. Initially well performing children plateaued around the age of 11 years, while initially poor performers caught up at the age of 13-14 years. White matter microstructure continued to mature across the investigated age range. Males generally displayed linear maturational trajectories, while females displayed more curvilinear trajectories that leveled off around 12-14 years of age. Maturational increases in right preSMAFA but not right IFGFA were associated with developmental improvements in SSRT. This association differed depending on the mean right preSMAFA across the individual maturational trajectory. Children with lower mean right preSMAFA exhibited poorer SSRT performance at younger ages but steeper developmental trajectories of SSRT improvement. Children with higher mean right preSMAFA exhibited flatter trajectories of SSRT improvement along with faster SSRT already at the first assessments. The results suggest that no further improvement in motor response cancellation is achieved once a certain level of maturity in the white matter underlying the right preSMA is reached. Similar dynamics may apply to other behavioral read-outs and brain structures and, thus, need to be considered in longitudinal MRI studies designed to map brain structural correlates of behavioral changes during development.

Are People Ready for Personalized Brain Health? Perspectives of Research Participants in the Lifebrain Consortium.

BACKGROUND AND OBJECTIVES: A healthy brain is central to physical and mental well-being. In this multi-site, qualitative study, we investigated views and attitudes of adult participants in brain research studies on the brain and personalized brain health as well as interest in maintaining a healthy brain. DESIGN AND METHODS: We conducted individual interviews with 44 adult participants in brain research cohorts of the Lifebrain consortium in Spain, Norway, Germany, and the United Kingdom. The interviews were audio recorded, transcribed, and coded using a cross-country codebook. The interview data were analyzed using qualitative content analysis. RESULTS: Most participants did not focus on their own brain health and expressed uncertainty regarding how to maintain it. Those actively focusing on brain health often picked one specific strategy like diet or memory training. The participants were interested in taking brain health tests to learn about their individual risk of developing brain diseases, and were willing to take measures to maintain their brain health if personalized follow-up was provided and the measures had proven impact. The participants were interested in more information on brain health. No differences in responses were identified between age groups, sex, or countries. DISCUSSION AND IMPLICATIONS: Concise, practical, personalized, and evidence-based information about the brain may promote brain health. Based on our findings, we have launched an ongoing global brain health survey to acquire more extensive, quantitative, and representative data on public perception of personalized brain health.