Attention-deficit hyperactivity disorder symptoms and brain morphology: Addressing potential selection bias with inverse probability weighting.

The goal of this study was to examine what happens to established associations between attention deficit hyperactivity disorder (ADHD) symptoms and cortical surface and thickness regions once we apply inverse probability of censoring weighting (IPCW) to address potential selection bias. Moreover, we illustrate how different factors that predict participation contribute to potential selection bias. Participants were 9- to 11-year-old children from the Generation R study (N = 2707). Cortical area and thickness were measured with magnetic resonance imaging (MRI) and ADHD symptoms with the Child Behavior Checklist. We examined how associations between ADHD symptoms and brain morphology change when we weight our sample back to either follow-up (ages 9-11), baseline (cohort at birth), or eligible (population of Rotterdam at time of recruitment). Weights were derived using IPCW or raking and missing predictors of participation used to estimate weights were imputed. Weighting analyses to baseline and eligible increased beta coefficients for the middle temporal gyrus surface area, as well as fusiform gyrus cortical thickness. Alternatively, the beta coefficient for the rostral anterior cingulate decreased. Removing one group of variables used for estimating weights resulted in the weighted regression coefficient moving closer to the unweighted regression coefficient. In addition, we found considerably different beta coefficients for most surface area regions and all thickness measures when we did not impute missing covariate data. Our findings highlight the importance of using inverse probability weighting (IPW) in the neuroimaging field, especially in the context of mental health-related research. We found that including all variables related to exposure-outcome in the IPW model and combining IPW with multiple imputations can help reduce bias. We encourage future psychiatric neuroimaging studies to define their target population, collect information on eligible but not included participants and use inverse probability of censoring weighting (IPCW) to reduce selection bias.

Social belonging: brain structure and function is linked to membership in sports teams, religious groups, and social clubs.

Human behavior across the life span is driven by the psychological need to belong, right from kindergarten to bingo nights. Being part of social groups constitutes a backbone for communal life and confers many benefits for the physical and mental health. Capitalizing on the neuroimaging and behavioral data from ∼40,000 participants from the UK Biobank population cohort, we used structural and functional analyses to explore how social participation is reflected in the human brain. Across 3 different types of social groups, structural analyses point toward the variance in ventromedial prefrontal cortex, fusiform gyrus, and anterior cingulate cortex as structural substrates tightly linked to social participation. Functional connectivity analyses not only emphasized the importance of default mode and limbic network but also showed differences for sports teams and religious groups as compared to social clubs. Taken together, our findings establish the structural and functional integrity of the default mode network as a neural signature of social belonging.

Subjective cognitive decline and cognitive change among diverse middle-aged and older Hispanic/Latino adults: Results from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA).

INTRODUCTION: The potential utility of subjective cognitive decline (SCD) as an early risk marker of Alzheimer's disease and related dementias is under consideration. We examined associations between SCD and cognitive change among middle-aged and older Hispanic/Latino adults living in the United States. METHODS: The short-form Everyday Cognition Scale (ECog-12) was assessed to generate global, executive function, and memory-related SCD scores. We used survey generalized regressions to model the change in learning, memory, verbal fluency, executive function, and global cognitive performance over 7 years as a function of SCD (at Visit 2). RESULTS: The mean age was 56.37 ± 8.10 years at Visit 1 (n = 6225). Higher ECog-12 was associated with greater decline in global cognitive performance (ECog-12 global: B = -0.17, standard error [SE] = 0.02; ECog-12 executive: B = -0.15, SE = 0.02; ECog-12 memory: B = -0.14, SE = 0.02, p's < 0.001). DISCUSSION: These results support the link between subjective reports of cognitive decline and objectively measured 7-year cognitive decline in community-dwelling, middle-aged, and older Hispanic/Latino adults. HIGHLIGHTS: We found that nearly two-thirds of diverse middle-aged and older Hispanics/Latinos reported cognitive concerns in a large and representative population study. Self-reported subjective experiences of cognitive decline reflect objective cognitive decline in US Hispanics/Latinos. The relationship is stronger among men compared to women. The relationship between subjective and objective changes to memory are stronger in those with cognitive concerns, and remain even in cognitively healthy individuals.

Home alone: A population neuroscience investigation of brain morphology substrates.

As a social species, ready exchange with peers is a pivotal asset - our "social capital". Yet, single-person households have come to pervade metropolitan cities worldwide, with unknown consequences in the long run. Here, we systematically explore the morphological manifestations associated with singular living in ∼40,000 UK Biobank participants. The uncovered population-level signature spotlights the highly associative default mode network, in addition to findings such as in the amygdala central, cortical and corticoamygdaloid nuclei groups, as well as the hippocampal fimbria and dentate gyrus. Both positive effects, equating to greater gray matter volume associated with living alone, and negative effects, which can be interpreted as greater gray matter associations with not living alone, were found across the cortex and subcortical structures Sex-stratified analyses revealed male-specific neural substrates, including somatomotor, saliency and visual systems, while female-specific neural substrates centered on the dorsomedial prefrontal cortex. In line with our demographic profiling results, the discovered neural pattern of living alone is potentially linked to alcohol and tobacco consumption, anxiety, sleep quality as well as daily TV watching. The persistent trend for solitary living will require new answers from public-health decision makers. SIGNIFICANCE STATEMENT: Living alone has profound consequences for mental and physical health. Despite this, there has been a rapid increase in single-person households worldwide, with the long-term consequences yet unknown. In the largest study of its kind, we investigate how the objective lack of everyday social interaction, through living alone, manifests in the brain. Our population neuroscience approach uncovered a gray matter signature that converged on the 'default network', alongside targeted subcortical, sex and demographic profiling analyses. The human urge for social relationships is highlighted by the evolving COVID-19 pandemic. Better understanding of how social isolation relates to the brain will influence health and social policy decision-making of pandemic planning, as well as social interventions in light of global shifts in houseful structures.

Variability in Brain Structure and Function Reflects Lack of Peer Support.

Humans are a highly social species. Complex interactions for mutual support range from helping neighbors to building social welfare institutions. During times of distress or crisis, sharing life experiences within one's social circle is critical for well-being. By translating pattern-learning algorithms to the UK Biobank imaging-genetics cohort (n = ~40 000 participants), we have delineated manifestations of regular social support in multimodal whole-brain measurements. In structural brain variation, we identified characteristic volumetric signatures in the salience and limbic networks for high- versus low-social support individuals. In patterns derived from functional coupling, we also located interindividual differences in social support in action-perception circuits related to binding sensory cues and initiating behavioral responses. In line with our demographic profiling analysis, the uncovered neural substrates have potential implications for loneliness, substance misuse, and resilience to stress.

Meaningful associations in the adolescent brain cognitive development study.

The Adolescent Brain Cognitive Development (ABCD) Study is the largest single-cohort prospective longitudinal study of neurodevelopment and children's health in the United States. A cohort of n = 11,880 children aged 9-10 years (and their parents/guardians) were recruited across 22 sites and are being followed with in-person visits on an annual basis for at least 10 years. The study approximates the US population on several key sociodemographic variables, including sex, race, ethnicity, household income, and parental education. Data collected include assessments of health, mental health, substance use, culture and environment and neurocognition, as well as geocoded exposures, structural and functional magnetic resonance imaging (MRI), and whole-genome genotyping. Here, we describe the ABCD Study aims and design, as well as issues surrounding estimation of meaningful associations using its data, including population inferences, hypothesis testing, power and precision, control of covariates, interpretation of associations, and recommended best practices for reproducible research, analytical procedures and reporting of results.

Loneliness is linked to specific subregional alterations in hippocampus-default network covariation.

Social interaction complexity makes humans unique. But in times of social deprivation, this strength risks exposure of important vulnerabilities. Human social neuroscience studies have placed a premium on the default network (DN). In contrast, hippocampus (HC) subfields have been intensely studied in rodents and monkeys. To bridge these two literatures, we here quantified how DN subregions systematically covary with specific HC subfields in the context of subjective social isolation (i.e., loneliness). By codecomposition using structural brain scans of ∼40,000 UK Biobank participants, loneliness was specially linked to midline subregions in the uncovered DN patterns. These association cortex patterns coincided with concomitant HC patterns implicating especially CA1 and molecular layer. These patterns also showed a strong affiliation with the fornix white matter tract and the nucleus accumbens. In addition, separable signatures of structural HC-DN covariation had distinct associations with the genetic predisposition for loneliness at the population level.NEW & NOTEWORTHY The hippocampus and default network have been implicated in rich social interaction. Yet, these allocortical and neocortical neural systems have been interrogated in mostly separate literatures. Here, we conjointly investigate the hippocampus and default network at a subregion level, by capitalizing structural brain scans from ∼40,000 participants. We thus reveal unique insights on the nature of the "lonely brain" by estimating the regimes of covariation between the hippocampus and default network at population scale.

Opportunities, risks and challenges in global mental health and population neuroscience: a case of Sino-German cooperation.

Large scale prospective cohorts have now been established across several countries, and continents, and among the aims include an assessment of the developmental trajectory of mental disorders. This level of international cooperation helps transfer research findings to new social contexts as well as enabling an assessment of which findings can be replicated, and which interventions are most effective, in different social and cultural settings. However, data sharing across different regional and national health care systems requires a careful consideration of different standards in ethical research, data protection and patient care, including respect for patients' rights, in cooperating jurisdictions. In our review, we discuss ethical, legal and practical challenges associated with such cooperation with a focus on research participants, specifically patient recruitment, by considering the instance of China and Germany. Our broader aim is to promote international cooperation by identifying key challenges that arise in international cooperation, and to facilitate an exchange in relation to legal and practical approaches.

Neurometabolic underpinning of the intergenerational transmission of prosociality.

Parent-child personality transmission can occur via biological gene-driven processes as well as through environmental factors such as shared environment and parenting style. We recently revealed a negative association between prosociality, a highly valued personality attribute in human society, and anterior cingulate cortex (ACC) γ-aminobutyric acid (GABA) levels in children at the age of 10 years. We thus hypothesized that prosociality would be intergenerationally transmitted, and that transmission would be underwritten by neurometabolic heritability. Here, we collected prosociality data from children aged 10 years and their parents in a large-scale population-based birth cohort study. We also measured ACC GABA+ and glutamate plus glutamine (Glx) levels in a follow-up assessment with a subsample of the participants (aged 11 years) using magnetic resonance spectroscopy. We analyzed the associations among children's and parents' prosociality and GABA+/Glx ratios. We also examined the effect of socioeconomic status (SES) and verbalized parental affection (VPA) on these associations. We found a significant positive parent-child association for prosociality (N â€‹= â€‹3026; children's mean age 10.2 years) and GABA+/Glx ratio (N â€‹= â€‹99; children's mean age 11.4 years). There was a significant negative association between GABA+/Glx ratio and prosociality in both children (N â€‹= â€‹208) and parents (N â€‹= â€‹128). Our model accounting for the effects of neurometabolic heritability on prosociality transmission fitted well. Moreover, in this model, a significant positive effect of VPA but not SES on children's prosociality was observed independently of the effect of neurometabolic transmission, while SES but not VPA was significantly associated with parental prosociality. Our results provide novel insights into the neurometabolic substrates of parent-child transmission of social behavior.

Smaller anterior subgenual cingulate volume mediates the effect of girls' early sexual maturation on negative psychobehavioral outcome.

Early-maturing girls are relatively likely to experience compromised psychobehavioral outcomes. Some studies have explored the association between puberty and brain morphology in adolescents, while the results were non-specific for females or the method was a region-of-interest analysis. To our knowledge, no large-scale study has comprehensively explored the effects of pubertal timing on whole-brain volumetric development or the neuroanatomical substrates of the association in girls between pubertal timing and psychobehavioral outcomes. We collected structural magnetic resonance imaging (MRI) data of a subsample (N â€‹= â€‹203, mean age 11.6 years) from a large-scale population-based birth cohort. Tanner stage, a scale of physical maturation in adolescents, was rated almost simultaneously with MRI scan. The Strengths and Difficulties Questionnaire total difficulties (SDQ-TD) scores were rated by primary parents some duration after MRI scan (mean age 12.1 years). In each sex group, we examined brain regions associated with Tanner stage using whole-brain analysis controlling for chronological age, followed by an exploration of brain regions also associated with the SDQ-TD scores. We also performed mediation analyses. In girls, Tanner stage was significantly negatively correlated with gray matter volumes (GMVs) in the anterior/middle cingulate cortex (ACC/MCC), of which the subgenual ACC (sgACC) showed a negative correlation between GMVs and SDQ-TD scores. Smaller GMVs in the sgACC mediated the association between higher Tanner stages and higher SDQ-TD scores. We found no significant results in boys. Our results from a minimally biased, large-scale sample provide new insights into neuroanatomical correlates of the effect of pubertal timing on developmental psychological difficulties emerging in adolescence.

Population-neuroscience study of the Tokyo TEEN Cohort (pn-TTC): Cohort longitudinal study to explore the neurobiological substrates of adolescent psychological and behavioral development.

AIM: Adolescence is a crucial stage of psychological development and is critically vulnerable to the onset of psychopathology. Our understanding of how the maturation of endocrine, epigenetics, and brain circuit may underlie psychological development in adolescence, however, has not been integrated. Here, we introduce our research project, the population-neuroscience study of the Tokyo TEEN Cohort (pn-TTC), a longitudinal study to explore the neurobiological substrates of development during adolescence. METHODS: Participants in the first wave of the pn-TTC (pn-TTC-1) study were recruited from those of the TTC study, a large-scale epidemiological survey in which 3171 parent-adolescent pairs were recruited from the general population. Participants underwent psychological, cognitive, sociological, and physical assessment. Moreover, adolescents and their parents underwent magnetic resonance imaging (MRI; structural MRI, resting-state functional MRI, and magnetic resonance spectroscopy), and adolescents provided saliva samples for hormone analysis and for DNA analysis including epigenetics. Furthermore, the second wave (pn-TTC-2) followed similar methods as in the first wave. RESULTS: A total of 301 parent-adolescent pairs participated in the pn-TTC-1 study. Moreover, 281 adolescents participated in the pn-TTC-2 study, 238 of whom were recruited from the pn-TTC-1 sample. The instruction for data request is available at: http://value.umin.jp/data-resource.html. CONCLUSION: The pn-TTC project is a large-scale and population-neuroscience-based survey with a plan of longitudinal biennial follow up. Through this approach we seek to elucidate adolescent developmental mechanisms according to biopsychosocial models. This current biomarker research project, using minimally biased samples recruited from the general population, has the potential to expand the new research field of population neuroscience.

A research framework for cognitive aging and Alzheimer's disease among diverse US Latinos: Design and implementation of the Hispanic Community Health Study/Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA).

Hispanics/Latinos are the largest ethnic/racial group in the United States and at high risk for Alzheimer's disease and related dementia (ADRD). Yet, ADRD among diverse Latinos is poorly understood and disparately understudied or unstudied compared to other ethnic/racial groups that leave the nation ill-prepared for major demographic shifts that lay ahead in coming decades. The primary purpose of this Perspectives article was to provide a new research framework for advancing Latino ADRD knowledge, encompassing the unique sociocultural, cardiometabolic, and genomic aspects of Latino health, aging, and ADRD. In addition, we describe some of the research challenges to progress in Latino ADRD research. Finally, we present the Study of Latinos - Investigation of Neurocognitive Aging (SOL-INCA) as an example of implementing this new framework for advancing Latino ADRD research.

Prevalence and correlates of mild cognitive impairment among diverse Hispanics/Latinos: Study of Latinos-Investigation of Neurocognitive Aging results.

INTRODUCTION: We estimated the prevalence and correlates of mild cognitive impairment (MCI) among middle-aged and older diverse Hispanics/Latinos. METHODS: Middle-aged and older diverse Hispanics/Latinos enrolled (n = 6377; 50-86 years) in this multisite prospective cohort study were evaluated for MCI using the National Institute on Aging-Alzheimer's Association diagnostic criteria. RESULTS: The overall MCI prevalence was 9.8%, which varied between Hispanic/Latino groups. Older age, high cardiovascular disease (CVD) risk, and elevated depressive symptoms were significant correlates of MCI prevalence. Apolipoprotein E4 (APOE) and APOE2 were not significantly associated with MCI. DISCUSSION: MCI prevalence varied among Hispanic/Latino backgrounds, but not as widely as reported in the previous studies. CVD risk and depressive symptoms were associated with increased MCI, whereas APOE4 was not, suggesting alternative etiologies for MCI among diverse Hispanics/Latinos. Our findings suggest that mitigating CVD risk factors may offer important pathways to understanding and reducing MCI and possibly dementia among diverse Hispanics/Latinos.

Automated quality assessment of structural magnetic resonance images in children: Comparison with visual inspection and surface-based reconstruction.

Motion-related artifacts are one of the major challenges associated with pediatric neuroimaging. Recent studies have shown a relationship between visual quality ratings of T1 images and cortical reconstruction measures. Automated algorithms offer more precision in quantifying movement-related artifacts compared to visual inspection. Thus, the goal of this study was to test three different automated quality assessment algorithms for structural MRI scans. The three algorithms included a Fourier-, integral-, and a gradient-based approach which were run on raw T1 -weighted imaging data collected from four different scanners. The four cohorts included a total of 6,662 MRI scans from two waves of the Generation R Study, the NIH NHGRI Study, and the GUSTO Study. Using receiver operating characteristics with visually inspected quality ratings of the T1 images, the area under the curve (AUC) for the gradient algorithm, which performed better than either the integral or Fourier approaches, was 0.95, 0.88, and 0.82 for the Generation R, NHGRI, and GUSTO studies, respectively. For scans of poor initial quality, repeating the scan often resulted in a better quality second image. Finally, we found that even minor differences in automated quality measurements were associated with FreeSurfer derived measures of cortical thickness and surface area, even in scans that were rated as good quality. Our findings suggest that the inclusion of automated quality assessment measures can augment visual inspection and may find use as a covariate in analyses or to identify thresholds to exclude poor quality data.

Population Neuroscience: Strategies to Promote Data Sharing While Protecting Privacy.

Population neuroscience aims to advance our understanding of how genetic and environmental factors influence brain development and brain health over the life span, by integrating genomics, epidemiology, and neuroscience at population scale. This big data approach depends on data sharing strategies at both the micro- and macro-level, as well as attention to effective data management and protection of participant privacy. At the micro-level, researchers participate in international consortia that support collaboration, standards, and data sharing. They also seek to link together cohort studies, administrative health databases, and measures of the physical, built, and social environment in creative ways. Large-scale, longitudinal, and multi-modal cohorts are being designed to support explorations of genetic and environmental impacts on the brain. At a macro-level, funding agency policies now require data across health research domains to be managed according to the FAIR (findable, accessible, interoperable, and re-useable) Data principles and made available to the research community in a timely manner to support reproducibility and re-use. Data repositories provide technical infrastructure for storing, accessing, and increasingly also analyzing rich population-level data. Federated and cloud-based approaches are being leveraged to improve the security, remote accessibility, and performance of repositories. Finally, legal frameworks are being developed to facilitate secure health data access, integration, and analysis, providing new opportunities for the field.

Sex and Gender in Population Neuroscience.

To understand psychiatric and neurological disorders and the structural and functional properties of the human brain, it is essential to consider the roles of sex and gender. In this chapter, I first define sex and gender and describe studies of sex differences in non-human animals. In humans, I describe the sex differences in behavioral and clinical phenotypes and neuroimaging-derived phenotypes, including whole-brain measures, regional subcortical and cortical measures, and structural and functional connectivity. Although structural whole-brain sex differences are large, regional effects (adjusting for whole-brain volumes) are typically much smaller and often fail to replicate. Nevertheless, while an individual neuroimaging feature may have a small effect size, aggregating them in a "maleness/femaleness" score or machine learning multivariate paradigm may prove to be predictive and informative of sex- and gender-related traits. Finally, I conclude by summarizing emerging investigations of gender norms and gender identity and provide methodological recommendations to incorporate sex and gender in population neuroscience research.

Responsible use of population neuroscience data: Towards standards of accountability and integrity.

This editorial focuses on the issue of data misuse which is increasingly evidenced in social media as well as some premiere scientific journals. This issue is of critical importance to open science projects in general, and ABCD in particular, given the broad array of biological, behavioral and environmental information collected on this American sample of 12.000 youth and parents. ABCD data are already widely used with over 1000 publications and twice as many citations per year as expected (relative citation index based on year, field and journal). However, the adverse consequences of misuse of data, and inaccurate interpretation of emergent findings from this precedent setting study may have profound impact on disadvantaged populations and perpetuate biases and societal injustices.

Hypertension, Cognitive Decline, and Mild Cognitive Impairment Among Diverse Hispanics/Latinos: Study of Latinos-Investigation of Neurocognitive Aging Results (SOL-INCA).

BACKGROUND: Hypertension can have deleterious effects on cognitive function; however, few studies have examined its effects on cognition among Hispanics/Latinos. OBJECTIVE: To assess associations between hypertension status with 1) change in cognitive performance, and 2) having mild cognitive impairment (MCI) among diverse Hispanics/Latinos. METHODS: This population-based, prospective cohort, multisite study included Hispanic/Latino adults aged 45 to 72 years in enrolled in the Hispanic Community Health Study/Study of Latinos at Visit 1 (2008-2011; mean age of 63.40±8.24 years), and the Study of Latinos-Investigation of Neurocognitive Aging at Visit 2 (2016-2018), with a mean follow-up duration of 7 years (n = 6,173). Hypertension status was assessed at both visits: normotension (no hypertension), incident hypertension (only at Visit 2), and persistent hypertension (at both visits). We examined change in cognitive performance and having MCI (only assessed at Visit 2) relative to hypertension status and adjusted for demographics and cardiovascular disease risk factors. RESULTS: Compared to normotension, persistent hypertension was associated with significantly increased decline in verbal fluency (ß= -0.08; CI = [-0.16;-0.01]; p < 0.05), and processing speed (ß= -0.11; CI = [-0.20;-0.02]; p < 0.05). Incident hypertension was not associated with significant change in cognitive performance. Both incident (OR = 1.70; CI = [1.16;2.50]; p < 0.01) and persistent hypertension (OR = 2.13; CI = [1.57;2.88]; p < 0.001) were associated with significantly higher odds ratios of having MCI. CONCLUSIONS: These findings indicate that persistent hypertension is associated with clinical impairment and domain-specific cognitive decline in middle-aged and older Hispanics/Latinos. It underscores the importance of monitoring blood pressure in routine healthcare visits beginning at midlife in this population to reduce the burden of cognitive decline.

Why weight? Analytic approaches for large-scale population neuroscience data.

Population-based neuroimaging studies that feature complex sampling designs enable researchers to generalize their results more widely. However, several theoretical and analytical questions pose challenges to researchers interested in these data. The following is a resource for researchers interested in using population-based neuroimaging data. We provide an overview of sampling designs and describe the differences between traditional model-based analyses and survey-oriented design-based analyses. To elucidate key concepts, we leverage data from the Adolescent Brain Cognitive Development℠ Study (ABCD Study®), a population-based sample of 11,878 9-10-year-olds in the United States. Analyses revealed modest sociodemographic discrepancies between the target population of 9-10-year-olds in the U.S. and both the recruited ABCD sample and the analytic sample with usable structural and functional imaging data. In evaluating the associations between socioeconomic resources (i.e., constructs that are tightly linked to recruitment biases) and several metrics of brain development, we show that model-based approaches over-estimated the associations of household income and under-estimated the associations of caregiver education with total cortical volume and surface area. Comparable results were found in models predicting neural function during two fMRI task paradigms. We conclude with recommendations for ABCD Study® users and users of population-based neuroimaging cohorts more broadly.

Tracing the development and lifespan change of population-level structural asymmetry in the cerebral cortex.

Cortical asymmetry is a ubiquitous feature of brain organization that is subtly altered in some neurodevelopmental disorders, yet we lack knowledge of how its development proceeds across life in health. Achieving consensus on the precise cortical asymmetries in humans is necessary to uncover the developmental timing of asymmetry and the extent to which it arises through genetic and later influences in childhood. Here, we delineate population-level asymmetry in cortical thickness and surface area vertex-wise in seven datasets and chart asymmetry trajectories longitudinally across life (4-89 years; observations = 3937; 70% longitudinal). We find replicable asymmetry interrelationships, heritability maps, and test asymmetry associations in large-scale data. Cortical asymmetry was robust across datasets. Whereas areal asymmetry is predominantly stable across life, thickness asymmetry grows in childhood and peaks in early adulthood. Areal asymmetry is low-moderately heritable (max h2SNP ~19%) and correlates phenotypically and genetically in specific regions, indicating coordinated development of asymmetries partly through genes. In contrast, thickness asymmetry is globally interrelated across the cortex in a pattern suggesting highly left-lateralized individuals tend towards left-lateralization also in population-level right-asymmetric regions (and vice versa), and exhibits low or absent heritability. We find less areal asymmetry in the most consistently lateralized region in humans associates with subtly lower cognitive ability, and confirm small handedness and sex effects. Results suggest areal asymmetry is developmentally stable and arises early in life through genetic but mainly subject-specific stochastic effects, whereas childhood developmental growth shapes thickness asymmetry and may lead to directional variability of global thickness lateralization in the population.