Showing papers by "Tonya White published in 2017"

Best practices in data analysis and sharing in neuroimaging using MRI.

Abstract: Given concerns about the reproducibility of scientific findings, neuroimaging must define best practices for data analysis, results reporting, and algorithm and data sharing to promote transparency, reliability and collaboration. We describe insights from developing a set of recommendations on behalf of the Organization for Human Brain Mapping and identify barriers that impede these practices, including how the discipline must change to fully exploit the potential of the world's neuroimaging data.

Enhancing studies of the connectome in autism using the autism brain imaging data exchange II

Abstract: The second iteration of the Autism Brain Imaging Data Exchange (ABIDE II) aims to enhance the scope of brain connectomics research in Autism Spectrum Disorder (ASD). Consistent with the initial ABIDE effort (ABIDE I), that released 1112 datasets in 2012, this new multisite open-data resource is an aggregate of resting state functional magnetic resonance imaging (MRI) and corresponding structural MRI and phenotypic datasets. ABIDE II includes datasets from an additional 487 individuals with ASD and 557 controls previously collected across 16 international institutions. The combination of ABIDE I and ABIDE II provides investigators with 2156 unique cross-sectional datasets allowing selection of samples for discovery and/or replication. This sample size can also facilitate the identification of neurobiological subgroups, as well as preliminary examinations of sex differences in ASD. Additionally, ABIDE II includes a range of psychiatric variables to inform our understanding of the neural correlates of co-occurring psychopathology; 284 diffusion imaging datasets are also included. It is anticipated that these enhancements will contribute to unraveling key sources of ASD heterogeneity.

Novel genetic loci associated with hippocampal volume

Abstract: The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer’s disease (rg=−0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.

Incidental Findings on Brain Imaging in the General Pediatric Population

Abstract: Brain MRI in 3966 children from the population-based Generation R Study (mean age, 10.1 years) revealed incidental findings in 25.6%. Most findings did not require neurosurgical intervention, but 7 children (0.18%) had suspected primary brain tumors.

Gestational vitamin D deficiency and autism spectrum disorder

Abstract: Background There is growing interest in linking vitamin D deficiency with autism spectrum disorders (ASDs). The association between vitamin D deficiency during gestation, a critical period in neurodevelopment, and ASD is not well understood. Aims To determine the association between gestational vitamin D status and ASD. Method Based on a birth cohort (n=4334), we examined the association between 25-hydroxyvitamin D (25OHD), assessed from both maternal mid-gestation sera and neonatal sera, and ASD (defined by clinical records; n=68 cases). Results Individuals in the 25OHD-deficient group at mid-gestation had more than twofold increased risk of ASD (odds ratio (OR)=2.42, 95% confidence interval (CI) 1.09 to 5.07, P=0.03) compared with the sufficient group. The findings persisted in analyses including children of European ethnicity only. Conclusions Mid-gestational vitamin D deficiency was associated with an increased risk of ASD. Because gestational vitamin D deficiency is readily preventable with safe, inexpensive and readily available supplementation, this risk factor warrants closer scrutiny.

Insensitive parenting may accelerate the development of the amygdala-medial prefrontal cortex circuit

Abstract: This study examined whether the association between age and amygdala-medial prefrontal cortex (mPFC) connectivity in typically developing 6- to 10-year-old children is correlated with parental care. Resting-state functional magnetic resonance imaging scans were acquired from 124 children of the Generation R Study who at 4 years old had been observed interacting with their parents to assess maternal and paternal sensitivity. Amygdala functional connectivity was assessed using a general linear model with the amygdalae time series as explanatory variables. Higher level analyses assessing Sensitivity × Age as well as exploratory Sensitivity × Age × Gender interaction effects were performed restricted to voxels in the mPFC. We found significant Sensitivity × Age interaction effects on amygdala-mPFC connectivity. Age was related to stronger amygdala-mPFC connectivity in children with a lower combined parental sensitivity score (b = 0.11, p =.004, b = 0.06, p =.06, right and left amygdala, respectively), but not in children with a higher parental sensitivity score, (b = -0.07, p =.12, b = -0.06, p =.12, right and left amygdala, respectively). A similar effect was found for maternal sensitivity, with stronger amygdala-mPFC connectivity in children with less sensitive mothers. Exploratory (parental, maternal, paternal) Sensitivity × Age × Gender interaction analyses suggested that this effect was especially pronounced in girls. Amygdala-mPFC resting-state functional connectivity has been shown to increase from age 10.5 years onward, implying that the positive association between age and amygdala-mPFC connectivity in 6- to 10-year-old children of less sensitive parents represents accelerated development of the amygdala-mPFC circuit.

The developmental course of sleep disturbances across childhood relates to brain morphology at age 7: The generation r study

Abstract: textObjectives: Little is known about the impact of sleep disturbances on the structural properties of the developing brain. This study explored associations between childhood sleep disturbances and brain morphology at 7 years. Methods: Mothers from the Generation R cohort reported sleep disturbances in 720 children at ages 2 months, 1.5, 2, 3, and 6 years. T1-weighted Magnetic Resonance Imaging (MRI) images were used to assess brain structure at 7 years. Associations of sleep disturbances at each age and of sleep disturbance trajectories with brain volumes (total brain volume, cortical and subcortical grey matter, white matter) were tested with linear regressions. To assess regional differences, sleep disturbance trajectories were tested as determinants for cortical thickness in whole-brain analyses. Results: Sleep disturbances followed a declining trend from toddlerhood onwards. Infant sleep was not associated with brain morphology at age 7. Per SD sleep disturbances (one frequent symptom or two less frequent symptoms) at 2 and 3 years of age, children had-6.3 (-11.7 to-0.8) cm3 and-6.4 (-11.7 to-1.7) cm3 smaller grey matter volumes, respectively. Sleep disturbances at age 6 years were associated with global brain morphology (grey matter:-7.3 (-12.1 to-2.6), p value = .01). Consistently, trajectory analyses showed that more adverse developmental course of childhood sleep disturbances are associated with smaller grey matter volumes and thinner dorsolateral prefrontal cortex. Conclusion: Sleep disturbances from age 2 years onwards are associated with smaller grey matter volumes. Thinner prefrontal cortex in children with adverse sleep disturbance trajectories may reflect effects of sleep disturbances on brain maturation.

Cognitive functioning in children with internalising, externalising and dysregulation problems: a population-based study.

Abstract: Psychiatric symptoms in childhood are closely related to neurocognitive deficits. However, it is unclear whether internalising and externalising symptoms are associated with general or distinct cognitive problems. We examined the relation between different types of psychiatric symptoms and neurocognitive functioning in a population-based sample of 1177 school-aged children. Internalising and externalising behaviour was studied both continuously and categorically. For continuous, variable-centred analyses, broadband scores of internalising and externalising symptoms were used. However, these measures are strongly correlated, which may prevent identification of distinct cognitive patterns. To distinguish groups of children with relatively homogeneous symptom patterns, a latent profile analysis of symptoms at age 6 yielded four exclusive groups of children: a class of children with predominantly internalising symptoms, a class with externalising symptoms, a class with co-occurring internalising and externalising symptoms, that resembles the CBCL dysregulation profile and a class with no problems. Five domains of neurocognitive ability were tested: attention/executive functioning, language, memory and learning, sensorimotor functioning, and visuospatial processing. Consistently, these two different modelling approaches demonstrated that children with internalising and externalising symptoms show distinct cognitive profiles. Children with more externalising symptoms performed lower in the attention/executive functioning domain, while children with more internalising symptoms showed impairment in verbal fluency and memory. In the most severely affected class of children with internalising and externalising symptoms, we found specific impairment in the sensorimotor domain. This study illustrates the specific interrelation of internalising and externalising symptoms and cognition in young children.

GWAS Meta-Analysis of Neuroticism (N=449,484) Identifies Novel Genetic Loci and Pathways

Abstract: Neuroticism is an important risk factor for psychiatric traits including depression, anxiety, and schizophrenia. Previous genome-wide association studies (GWAS) reported 16 genomic loci. Here we report the largest neuroticism GWAS meta-analysis to date (N=449,484), and identify 136 independent genome-wide significant loci (124 novel), implicating 599 genes. Extensive functional follow-up analyses show enrichment in several brain regions and involvement of specific cell-types, including dopaminergic neuroblasts (P=3E-8), medium spiny neurons (P=4E-8) and serotonergic neurons (P=1E-7). Gene-set analyses implicate three specific pathways: neurogenesis (P=4.4E-9), behavioural response to cocaine processes (P=1.84E-7), and axon part (P=5.26E-8). We show that neuroticism9s genetic signal partly originates in two genetically distinguishable subclusters (depressed affect and worry, the former being genetically strongly related to depression, rg=0.84), suggesting distinct causal mechanisms for subtypes of individuals. These results vastly enhance our neurobiological understanding of neuroticism, and provide specific leads for functional follow-up experiments.

The association of gender, age, and intelligence with neuropsychological functioning in young typically developing children: The Generation R study.

Abstract: Although early childhood is a period of rapid neurocognitive development, few studies have assessed neuropsychological functioning in various cognitive domains in young typically developing children. Also, results regarding its association with gender and intelligence are mixed. In 853 typically developing children aged 6 to 10 years old, the association of gender, age, and intelligence with neuropsychological functioning in the domains of attention, executive functioning, language, memory, sensorimotor functioning, and visuospatial processing was explored. Clear positive associations with age were observed. In addition, gender differences were found and showed that girls generally outperformed boys, with the exception of visuospatial tasks. Furthermore, IQ was positively associated with neuropsychological functioning, which was strongest in visuospatial tasks. Performance in different neuropsychological domains was associated with age, gender, and intelligence in young typically developing children, and these factors should be taken into account when assessing neuropsychological functioning in clinical or research settings.

Infant muscle tone and childhood autistic traits: A longitudinal study in the general population.

Abstract: In a longitudinal population-based study of 2,905 children, we investigated if infants' neuromotor development was associated with autistic traits in childhood. Overall motor development and muscle tone were examined by trained research assistants with an adapted version of Touwen's Neurodevelopmental Examination between ages 2 and 5 months. Tone was assessed in several positions and items were scored as normal, low, or high tone. Parents rated their children's autistic traits with the Social Responsiveness Scale (SRS) and the Pervasive Developmental Problems (PDP) subscale of the Child Behavior Checklist at 6 years. We defined clinical PDP if scores were >98th percentile of the norm population. Diagnosis of autism spectrum disorder (ASD) was clinically confirmed in 30 children. We observed a modest association between overall neuromotor development in infants and autistic traits. Low muscle tone in infancy predicted autistic traits measured by SRS (adjusted beta = 0.05, 95% CI for B: 0.00-0.02, P = 0.01), and PDP (adjusted beta = 0.08, 95% CI for B: 0.04-0.10, P < 0.001). Similar results emerged for the association of low muscle tone and clinical PDP (adjusted OR = 1.36, 95% CI: 1.08-1.72, P = 0.01) at age 6 years. Results remained unchanged if adjusted for child intelligence. There was no association between high muscle tone and SRS or PDP. Exclusion of children with ASD diagnosis did not change the association. This large study showed a prospective association of infant muscle tone with autistic traits in childhood. Our findings suggest that early detection of low muscle tone might be a gateway to improve early diagnosis of ASD. Autism Res 2017, 10: 757-768. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

GWAS meta-analysis (N=279,930) identifies new genes and functional links to intelligence

Abstract: Intelligence is highly heritable and a major determinant of human health and well-being. Recent genome-wide meta-analyses have identified 24 genomic loci linked to intelligence, but much about its genetic underpinnings remains to be discovered. Here, we present the largest genetic association study of intelligence to date (N=279,930), identifying 206 genomic loci (191 novel) and implicating 1,041 genes (963 novel) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and identify 89 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain and specifically in striatal medium spiny neurons and cortical and hippocampal pyramidal neurons. Gene-set analyses implicate pathways related to neurogenesis, neuron differentiation and synaptic structure. We confirm previous strong genetic correlations with several neuropsychiatric disorders, and Mendelian Randomization results suggest protective effects of intelligence for Alzheimer9s dementia and ADHD, and bidirectional causation with strong pleiotropy for schizophrenia. These results are a major step forward in understanding the neurobiology of intelligence as well as genetically associated neuropsychiatric traits.

Prenatal exposure to selective serotonin reuptake inhibitors and non-verbal cognitive functioning in childhood:

Abstract: Selective serotonin reuptake Inhibitors (SSRIs) are frequently used during pregnancy. Evidence about the long-term consequences of prenatal SSRI exposure on child neurodevelopment is controversial. We prospectively investigated whether prenatal SSRI exposure was associated with childhood non-verbal cognition in a population-based study, and contrasted it to exposure to depressive symptoms (without SSRIs). We included 71 children prenatally exposed to SSRIs, 385 children prenatally exposed to maternal depressive symptoms and 5427 unexposed children. Child executive functioning was assessed by maternal report at 4 years ( n=4020). Non-verbal intelligence was measured at 5 years ( n=5001) and children were tested with a neuropsychological battery at 7 years ( n=1194). Prenatal SSRI exposure was not related to maternal reported executive function at 4 years, nor was it related with observed non-verbal intelligence at age 5 or neuropsychological function at 7 years. Exposure to untreated maternal depressive symptoms was related to maternal reported shifting problems and emotional control problems at 4 years. No associations between exposure to depressive symptoms and observed non-verbal IQ at 5 years or neuropsychological function at 7 years were found. This population-based study suggests that neither SSRI use nor untreated depressive symptoms during pregnancy had a major impact on child non-verbal cognition.

Neonatal critical illness and development: white matter and hippocampus alterations in school-age neonatal extracorporeal membrane oxygenation survivors

Abstract: Aim To examine the neurobiology of long-term neuropsychological deficits after neonatal extracorporeal membrane oxygenation (ECMO). Method This cross-sectional study assessed white matter integrity and hippocampal volume of ECMO survivors (8–15y) and healthy children (8–17y) using diffusion tensor imaging (DTI) and structural magnetic resonance imaging (MRI) respectively. Neuropsychological outcome was evaluated in ECMO survivors. Included clinical predictors of white matter integrity: age start ECMO, ECMO duration, highest oxygenation index before ECMO, highest mean airway pressure, and mechanical ventilation duration. Results ECMO survivors (n=23) had lower global fractional anisotropy than healthy children (n=54) (patients=0.368; comparison group=0.381; p=0.018), but similar global mean diffusivity (p=0.410). ECMO survivors had lower fractional anisotropy in the left cingulum bundle (ECMO survivors=0.345; comparison group=0.399; p<0.001) and higher mean diffusivity in a region of the left parahippocampal cingulum (patients=0.916; comparison group=0.871; p<0.001). Higher global mean diffusivity predicted worse verbal memory in ECMO survivors (n=17) (β=–0.74, p=0.008). ECMO survivors (n=23) had smaller bilateral hippocampal volume than healthy children (n=43) (left, p<0.001; right, p<0.001) and this was related to worse verbal memory (left, β=0.65, p=0.018; right, β=0.71, p=0.006). Interpretation Neonatal ECMO survivors are at risk for long-term brain alterations, which may partly explain long-term neuropsychological impairments. Neuroimaging may contribute to better risk stratification of long-term impairments.

Associations of maternal folic acid supplementation and folate concentrations during pregnancy with foetal and child head growth: the Generation R Study.

Abstract: Folic acid supplementation during pregnancy has been associated with a reduced risk of common neurodevelopmental delays in the offspring. However, it is unclear whether low folate status has effects on the developing brain. We evaluated the associations of maternal folic acid supplementation and folate concentrations during pregnancy with repeatedly measured prenatal and postnatal head circumference in the offspring. Within a population-based prospective cohort, we measured maternal plasma folate concentrations at approximately 13 weeks of gestation (90 % range 10.5–17.2) and assessed folic acid supplementation by questionnaire (2001–2005). Up to 11 repeated measures of head circumference were obtained during foetal life (20 and 30 weeks of gestation) and childhood (between birth and age 6 years) in 5866 children (2002–2012). In unadjusted models, foetal head growth was 0.006 SD (95 % CI 0.003; 0.009, P < 0.001) faster per week per 1-SD higher maternal folate concentration. After adjustment for confounders, this association was attenuated to 0.004 SD per week (95 % CI 0.000; 0.007, P = 0.02; estimated absolute difference at birth of 2.7 mm). The association was independent of overall foetal growth. No associations were found between maternal folate concentrations and child postnatal head growth. Preconceptional start of folic acid supplementation was associated with larger prenatal head size, but not with prenatal or postnatal head growth. Our results suggest an independent, modest association between maternal folate concentrations in early pregnancy and foetal head growth. More research is needed to identify whether specific brain regions are affected and whether effects of folate on foetal head growth influence children’s long-term functioning.

Neurobiologic Correlates of Attention and Memory Deficits Following Critical Illness in Early Life.

Abstract: Objectives:Survivors of critical illness in early life are at risk of long-term–memory and attention impairments. However, their neurobiologic substrates remain largely unknown.Design:A prospective follow-up study.Setting:Erasmus MC-Sophia Children’s Hospital, Rotterdam, the Netherlands.Patients:Thi

Altered functional resting-state hypothalamic connectivity and abnormal pituitary morphology in children with Prader-Willi syndrome

Abstract: Prader-Willi syndrome (PWS) is a complex neurodevelopmental disorder, characterized by endocrine problems and hyperphagia, indicating hypothalamic-pituitary dysfunction. However, few studies have explored the underlying neurobiology of the hypothalamus and its functional connectivity with other brain regions. Thus, the aim of this study was to examine the anatomical differences of the hypothalamus, mammillary bodies, and pituitary gland as well as resting state functional connectivity of the hypothalamus in children with PWS. Twenty-seven children with PWS (13 DEL, 14 mUPD) and 28 typically developing children were included. Manual segmentations by a blinded investigator were performed to determine the volumes of the hypothalamus, mammillary bodies, and pituitary gland. In addition, brain-wide functional connectivity analysis was performed using the obtained masks of the hypothalamus. Children with PWS showed altered resting state functional connectivity between hypothalamus and right and left lateral occipital complex, compared to healthy controls. In addition, children with PWS had on average a 50% smaller pituitary volume, an irregular shape of the pituitary, and a longer pituitary stalk. Pituitary volume did not increase in volume during puberty in PWS. No volumetric differences in the hypothalamus and mammillary bodies were found. In all subjects, the posterior pituitary bright spot was observed. We report altered functional hypothalamic connectivity with lateral occipital complexes in both hemispheres, which are implicated in response to food and reward system, and absence of connectivity might therefore at least partially contribute to the preoccupation with food in PWS.

White matter microstructure in children with autistic traits

Abstract: Autism spectrum disorder (ASD) is thought to arise from aberrant development of connections in the brain. Previous studies have identified differences in white matter microstructure in children with ASD, offering support to such hypotheses. While ASD is thought to represent the severe end of a spectrum of traits, there are no studies evaluating white matter microstructure in relation to autistic traits in children from the general population. In a population-based sample of 604 6-to-10 year-old children, we assessed the relation between a continuous measure of autistic traits and white matter microstructure, using both probabilistic tractography and Tract-Based Spatial Statistics (TBSS). Using the TBSS approach, a cluster in the left superior longitudinal fasciculus (SLF) was identified where autistic traits negatively associated with fractional anisotropy (FA). In addition, two clusters of lower axial diffusion were identified; one in the corpus callosum and another in the corticospinal tract. Part of the findings remained when excluding children with ASD and were paralleled with similar, trend-level differences in 19 children with ASD, compared to matched controls. This study showed localized associations between autistic traits on a continuum and white matter microstructure, which could indicate a continuum of the neurobiology along the spectrum of autistic symptoms.

Aberrant White Matter Microstructure in Children and Adolescents With the Subtype of Prader-Willi Syndrome at High Risk for Psychosis.

Abstract: Prader-Willi Syndrome (PWS) is a complex neurogenetic disorder caused by loss of the paternal 15q11.2-q13 locus, due to deletion (DEL), maternal uniparental disomy (mUPD), or imprinting center defects. Individuals with mUPD have up to 60% risk of developing psychosis in early adulthood. Given the increasing evidence for white matter abnormalities in psychotic disorders, we investigated white matter microstructure in children and adolescents with PWS, with a particular emphasis on the DEL and mUPD subtypes. Magnetic resonance diffusion weighted images were acquired in 35 directions at 3T and analyzed using fractional anisotropy (FA), mean, axial, and radial diffusivity (MD, AD, RD) values obtained by tract-based spatial statistics (TBSS) in 28 children and adolescents with PWS and 61 controls. In addition, we employed a recently developed white matter pothole approach, which does not require local FA differences to be spatially co-localized across subjects. After accounting for age and gender, individuals with PWS had significantly lower global FA and higher MD, compared with controls. Individuals with mUPD had lower FA in multiple regions including the corpus callosum, cingulate, and superior longitudinal fasciculus and larger potholes, compared with DEL and controls. The observed differences in individuals with mUPD are similar to the white matter abnormalities in individuals with psychotic disorders. Conversely, the subtle white matter abnormalities in individuals with DEL are consistent with their substantially lower risk of psychosis. Future studies to investigate the specific neurobiological mechanism underlying the differential psychosis risk between the DEL and mUPD subtypes of PWS are highly warranted.

Genetic Architecture of Subcortical Brain Structures in Over 40,000 Individuals Worldwide

Abstract: Subcortical brain structures are integral to motion, consciousness, emotions, and learning. We identified common genetic variation related to the volumes of nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen, and thalamus, using genome-wide association analyses in over 40,000 individuals from CHARGE, ENIGMA and the UK-Biobank. We show that variability in subcortical volumes is heritable, and identify 25 significantly associated loci (20 novel). Annotation of these loci utilizing gene expression, methylation, and neuropathological data identified 62 candidate genes implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.

Cortical morphology as a shared neurobiological substrate of attention-deficit/hyperactivity symptoms and executive functioning : a population-based pediatric neuroimaging study

Abstract: Background: Attention-deficit/hyperactivity symptoms have repeatedly been associated with poor cognitive functioning. Genetic studies have demonstrated a shared etiology of attention-deficit/hyperactivity disorder (ADHD) and cognitive ability, suggesting a common underlying neurobiology of ADHD and cognition. Further, neuroimaging studies suggest that altered cortical development is related to ADHD. In a large population-based sample we investigated whether cortical morphology, as a potential neurobiological substrate, underlies the association between attention-deficit/hyperactivity symptoms and cognitive problems. Methods: The sample consisted of school-aged children with data on attention-deficit/hyperactivity symptoms, cognitive functioning and structural imaging. First, we investigated the association between attention-deficit/hyperactivity symptoms and different domains of cognition. Next, we identified cortical correlates of attention-deficit/hyperactivity symptoms and related cognitive domains. Finally, we studied the role of cortical thickness and gyrification in the behaviour–cognition associations. Results: We included 776 children in our analyses. We found that attention-deficit/hyperactivity symptoms were associated specifically with problems in attention and executive functioning (EF; b = –0.041, 95% confidence interval [CI] –0.07 to –0.01, p = 0.004). Cortical thickness and gyrification were associated with both attention-deficit/hyperactivity symptoms and EF in brain regions that have been previously implicated in ADHD. This partly explained the association between attention-deficit/hyperactivity symptoms and EF (bindirect = –0.008, bias-corrected 95% CI –0.018 to –0.001). Limitations: The nature of our study did not allow us to draw inferences regarding temporal associations; longitudinal studies are needed for clarification. Conclusion: In a large, population-based sample of children, we identified a shared cortical morphology underlying attention-deficit/hyperactivity symptoms and EF.

Cortical Structures Associated With Sports Participation in Children: A Population-Based Study.

Abstract: We studied cortical morphology in relation to sports participation and type of sport using a large sample of healthy children (n = 911). Sports participation data was collected through a parent-reported questionnaire. Magnetic resonance scans were acquired, and different morphological brain features were quantified. Global volumetric measures were not associated with sports participation. We observed thicker cortex in motor and premotor areas associated with sports participation. In boys, team sports participation, relative to individual sports, was related to thinner cortex in prefrontal brain areas involved in the regulation of behaviors. This study showed a relationship between sports participation and brain maturation.

Infant Neuromotor Development and Childhood Problem Behavior.

Abstract: BACKGROUND: Research of adults and school-aged children suggest a neurodevelopmental basis for psychiatric disorders. We examined whether infant neuromotor development predicted internalizing and externalizing problems in young children. METHODS: In Generation R, a population-based cohort in the Netherlands (2002–2006), trained research assistants evaluated the neuromotor development of 4006 infants aged 2 to 5 months by using an adapted version of Touwen’s Neurodevelopmental Examination (tone, responses, and senses and other observations). We defined nonoptimal neuromotor development as scores in the highest tertile. Mothers and fathers rated their children’s behavior at ages 1.5, 3, 6, and 10 years with the Child Behavior Checklist (n = 3474, response: 86.7%). The associations were tested with generalized linear mixed models. RESULTS: Overall, neuromotor development predicted internalizing scores, but no association was observed with externalizing scores. Nonoptimal muscle tone was associated with higher internalizing scores (mothers’ report: β = .07; 95% confidence interval [CI]: 0.01 to 0.13; fathers’ report: β = .09, 95% CI: 0.00 to 0.16). In particular, nonoptimal low muscle tone was associated with higher internalizing scores (mothers’ report: β = .11; 95% CI: 0.05 to 0.18; fathers’ report: β = .13; 95% CI: 0.04 to 0.22). We also observed an association between senses and other observations with internalizing scores. There was no relationship between high muscle tone or reflexes and internalizing scores. CONCLUSIONS: Common emotional problems in childhood have a neurodevelopmental basis in infancy. Neuromotor assessment in infancy may help identify vulnerability to early internalizing symptoms and offer the opportunity for targeted interventions.

Mapping Cortical Brain Asymmetry in 17,141 Healthy Individuals Worldwide via the ENIGMA Consortium

Abstract: Hemispheric asymmetry is a cardinal feature of human brain organization. Altered brain asymmetry has also been linked to some cognitive and neuropsychiatric disorders. Here the ENIGMA consortium presents the largest ever analysis of cerebral cortical asymmetry and its variability across individuals. Cortical thickness and surface area were assessed in MRI scans of 17,141 healthy individuals from 99 datasets worldwide. Results revealed widespread asymmetries at both hemispheric and regional levels, with a generally thicker cortex but smaller surface area in the left hemisphere relative to the right. Regionally, asymmetries of cortical thickness and/or surface area were found in the inferior frontal gyrus, transverse temporal gyrus, parahippocampal gyrus, and entorhinal cortex. These regions are involved in lateralized functions, including language and visuospatial processing. In addition to population-level asymmetries, variability in brain asymmetry was related to sex, age, and brain size (indexed by intracranial volume). Interestingly, we did not find significant associations between asymmetries and handedness. Finally, with two independent pedigree datasets (N = 1,443 and 1,113, respectively), we found several asymmetries showing modest but highly reliable heritability. The structural asymmetries identified, and their variabilities and heritability provide a reference resource for future studies on the genetic basis of brain asymmetry and altered laterality in cognitive, neurological, and psychiatric disorders.

Anxiety and Social Responsiveness Moderate the Effect of Situational Demands on Children's Donating Behavior

Abstract: This study examined dispositional and situational correlates of donating behavior in a sample of 221 eight-year-old children. Children were shown a promotional clip for a charity, including a donation call. For a random half of the children, the video fragment ended with a probe of a same-sex peer donating money to the charity. Seeing a peer donate was associated with higher donations. Empathy and inhibition were not related to donating. Anxiety and social responsiveness moderated the effect of the situational manipulation on donating. Anxious children and children with less social responsiveness problems donated more after seeing the donating peer than did less anxious children and children with more social responsiveness problems. Moreover, in absence of the donating peer, anxious children donated less money than did less anxious children. Our results indicate that donating behavior is dependent on situational demands, and the situational effect differs depending on children’s levels of anxiety or social responsiveness.

The structural disconnectome: A pathology-sensitive extension of the structural connectome

Abstract: Brain connectivity is increasingly being studied using connectomes. Typical structural connectome definitions do not directly take white matter pathology into account. Presumably, pathology impedes signal transmission along fibres, leading to a reduction in function. In order to directly study disconnection and localize pathology within the connectome, we present the disconnectome, which only considers fibres that intersect with white matter pathology. To show the potential of the disconnectome in brain studies, we showed in a cohort of 4199 adults with varying loads of white matter lesions (WMLs) that: (1) Disconnection is not a function of streamline density; (2) Hubs are more affected by WMLs than peripheral nodes; (3) Connections between hubs are more severely and frequently affected by WMLs than other connection types; and (4) Connections between region clusters are often more severely affected than those within clusters.