Kevin Head

Children's Brain Development Benefits from Longer Gestation.

Disruptions to brain development associated with shortened gestation place individuals at risk for the development of behavioral and psychological dysfunction throughout the lifespan. The purpose of the present study was to determine if the benefit for brain development conferred by increased gestational length exists on a continuum across the gestational age spectrum among healthy children with a stable neonatal course. Neurodevelopment was evaluated with structural magnetic resonance imaging in 100 healthy right-handed 6- to 10-year-old children born between 28 and 41 gestational weeks with a stable neonatal course. Data indicate that a longer gestational period confers an advantage for neurodevelopment. Longer duration of gestation was associated with region-specific increases in gray matter density. Further, the benefit of longer gestation for brain development was present even when only children born full term were considered. These findings demonstrate that even modest decreases in the duration of gestation can exert profound and lasting effects on neurodevelopment for both term and preterm infants and may contribute to long-term risk for health and disease.

Structural brain variation and general intelligence

Total brain volume accounts for about 16% of the variance in general intelligence scores (IQ), but how volumes of specific regions-of-interest (ROIs) relate to IQ is not known. We used voxel-based morphometry (VBM) in two independent samples to identify substantial gray matter (GM) correlates of IQ. Based on statistical conjunction of both samples (N = 47; P < 0.05 corrected for multiple comparisons), more gray matter is associated with higher IQ in discrete Brodmann areas (BA) including frontal (BA 10, 46, 9), temporal (BA 21, 37, 22, 42), parietal (BA 43 and 3), and occipital (BA 19) lobes and near BA 39 for white matter (WM). These results underscore the distributed neural basis of intelligence and suggest a developmental course for volume--IQ relationships in adulthood.

The neuroanatomy of general intelligence: sex matters

We examined the relationship between structural brain variation and general intelligence using voxel-based morphometric analysis of MRI data in men and women with equivalent IQ scores. Compared to men, women show more white matter and fewer gray matter areas related to intelligence. In men IQ/gray matter correlations are strongest in frontal and parietal lobes (BA 8, 9, 39, 40), whereas the strongest correlations in women are in the frontal lobe (BA10) along with Brocas area. Men and women apparently achieve similar IQ results with different brain regions, suggesting that there is no singular underlying neuroanatomical structure to general intelligence and that different types of brain designs may manifest equivalent intellectual performance.

Maternal cortisol over the course of pregnancy and subsequent child amygdala and hippocampus volumes and affective problems

Stress-related variation in the intrauterine milieu may impact brain development and emergent function, with long-term implications in terms of susceptibility for affective disorders. Studies in animals suggest limbic regions in the developing brain are particularly sensitive to exposure to the stress hormone cortisol. However, the nature, magnitude, and time course of these effects have not yet been adequately characterized in humans. A prospective, longitudinal study was conducted in 65 normal, healthy mother–child dyads to examine the association of maternal cortisol in early, mid-, and late gestation with subsequent measures at approximately 7 y age of child amygdala and hippocampus volume and affective problems. After accounting for the effects of potential confounding pre- and postnatal factors, higher maternal cortisol levels in earlier but not later gestation was associated with a larger right amygdala volume in girls (a 1 SD increase in cortisol was associated with a 6.4% increase in right amygdala volume), but not in boys. Moreover, higher maternal cortisol levels in early gestation was associated with more affective problems in girls, and this association was mediated, in part, by amygdala volume. No association between maternal cortisol in pregnancy and child hippocampus volume was observed in either sex. The current findings represent, to the best of our knowledge, the first report linking maternal stress hormone levels in human pregnancy with subsequent child amygdala volume and affect. The results underscore the importance of the intrauterine environment and suggest the origins of neuropsychiatric disorders may have their foundations early in life.

High pregnancy anxiety during mid-gestation is associated with decreased gray matter density in 6-9-year-old children.

Because the brain undergoes dramatic changes during fetal development it is vulnerable to environmental insults. There is evidence that maternal stress and anxiety during pregnancy influences birth outcome but there are no studies that have evaluated the influence of stress during human pregnancy on brain morphology. In the current prospective longitudinal study we included 35 women for whom serial data on pregnancy anxiety was available at 19 (+/-0.83), 25 (+/-0.9) and 31 (+/-0.9) weeks gestation. When the offspring from the target pregnancy were between 6 and 9 years of age, their neurodevelopmental stage was assessed by a structural MRI scan. With the application of voxel-based morphometry, we found regional reductions in gray matter density in association with pregnancy anxiety after controlling for total gray matter volume, age, gestational age at birth, handedness and postpartum perceived stress. Specifically, independent of postnatal stress, pregnancy anxiety at 19 weeks gestation was associated with gray matter volume reductions in the prefrontal cortex, the premotor cortex, the medial temporal lobe, the lateral temporal cortex, the postcentral gyrus as well as the cerebellum extending to the middle occipital gyrus and the fusiform gyrus. High pregnancy anxiety at 25 and 31 weeks gestation was not significantly associated with local reductions in gray matter volume.This is the first prospective study to show that a specific temporal pattern of pregnancy anxiety is related to specific changes in brain morphology. Altered gray matter volume in brain regions affected by prenatal maternal anxiety may render the developing individual more vulnerable to neurodevelopmental and psychiatric disorders as well as cognitive and intellectual impairment.

Fetal Glucocorticoid Exposure Is Associated with Preadolescent Brain Development

BACKGROUND Glucocorticoids play a critical role in normative regulation of fetal brain development. Exposure to excessive levels may have detrimental consequences and disrupt maturational processes. This may especially be true when synthetic glucocorticoids are administered during the fetal period, as they are to women in preterm labor. This study investigated the consequences for brain development and affective problems of fetal exposure to synthetic glucocorticoids. METHODS Brain development and affective problems were evaluated in 54 children (56% female), aged 6 to 10, who were full term at birth. Children were recruited into two groups: those with and without fetal exposure to synthetic glucocorticoids. Structural magnetic resonance imaging scans were acquired and cortical thickness was determined. Child affective problems were assessed using the Child Behavior Checklist. RESULTS Children in the fetal glucocorticoid exposure group showed significant and bilateral cortical thinning. The largest group differences were in the rostral anterior cingulate cortex (rACC). More than 30% of the rACC was thinner among children with fetal glucocorticoid exposure. Furthermore, children with more affective problems had a thinner left rACC. CONCLUSIONS Fetal exposure to synthetic glucocorticoids has neurologic consequences that persist for at least 6 to 10 years. Children with fetal glucocorticoid exposure had a thinner cortex primarily in the rACC. Our data indicating that the rACC is associated with affective problems in conjunction with evidence that this region is involved in affective disorders raise the possibility that glucocorticoid-associated neurologic changes increase vulnerability to mental health problems.

Application of an automated voxel-based morphometry technique to assess regional gray and white matter brain atrophy in a canine model of aging

In recent years, voxel-based morphometry (VBM) has emerged as a technique to examine regional brain changes associated with normal and pathological aging. Despite its popularity in studies of human aging, application of VBM to animal models of brain aging is rare. In the present study, VBM techniques were developed to validate earlier region of interest (ROI) measures of brain aging in the dog and to provide a more comprehensive analysis of local changes in a canine model of brain aging. Consistent with previous findings, frontal lobe atrophy increased with age, most notably in aged male dogs. Age-related gray matter reductions were also observed in parietal and temporal lobes, thalamus, cerebellum, and brainstem. Temporal lobe atrophy was particularly prominent in old females. A number of age-related changes in white matter not previously explored in the dog were also identified with VBM. Specifically, aged males exhibited greater decreases in the internal capsula and cranial nerve bundles compared to decreased volumes in the alveus of the hippocampus in old female dogs. Together, the present results indicate that application of VBM techniques in a canine model of aging yields more comprehensive information regarding topographical patterns of brain aging in male and female dogs than previously reported using traditional manual ROI methods.

Cortical and subcortical changes in typically developing preadolescent children

There is evidence that abnormal cerebral development during childhood is a risk factor for various cognitive and psychiatric disorders. There is not, however, sufficient normative data available on large samples of typically developing children, especially within the narrow preadolescent age range. We analyzed high resolution MRI images from 126 normally developing children between ages 6 and 10 years. Age related differences in cortical thickness and in the volumes of major subcortical structures were assessed. Thinner cortices were observed in the occipital, parietal and somatosensory regions as well as in distinct regions of the temporal and frontal lobes with increasing age. Among the major subcortical structures analyzed in this study, only the thalamus showed increased volume with age after accounting for intracranial volume. Within the age range studied age-related cortical and subcortical differences were similar for boys and girls except for the right insula, where girls showed a slight increase in thickness with age. The findings reveal age-associated changes in brain anatomy, providing information about the trajectory of normal brain development during late childhood.

Structural brain variation, age, and response time

Response time (RT) generally slows with aging, but the contribution of structural brain changes to this slowing is unknown. We used voxel-based morphometry (VBM) to determine gray matter (GM) and white matter (WM) brain volumes in 9 middle-aged adults (38–58 years old) and 9 seniors (66–82 years old). We correlated brain volumes with RT assessed in both a simple visual stimulus-response task and a visual continuous recognition memory task. No GM correlations with simple RT were significant; there was one WM correlation in the right fusiform gyrus. In the memory task, faster RT was correlated (p<.05, corrected) with less GM in the globus pallidus, the parahippocampus, and the thalamus for both groups. Several Brodmann areas (BA) differed between the groups such that in each area, less GM was correlated with slower RTs in the middle-aged group but with faster RTs in the senior group (BAs 19, 37, 46, 9, 8, 6, 13, 10, 41, and 7). The results suggest that individual differences in specific brain structure volumes should be considered as potential moderating factors in cognitive brain imaging studies.

Magnetic resonance imaging demonstrates long-term changes in brain structure in children born preterm and exposed to chorioamnionitis

OBJECTIVE We sought to determine if children born preterm and exposed to chorioamnionitis have differences in brain structure measured at 6-10 years of age using magnetic resonance imaging (MRI). STUDY DESIGN Structural MRI was performed with 11 preterm children (8.5 ± 1.7 years) with chorioamnionitis and 16 preterm children (8.7 ± 1.4 years) without chorioamnionitis. Cortical surface reconstruction and volumetric segmentation were performed with FreeSurfer image analysis software. Subcortical structures were analyzed using multivariate analysis. RESULTS Widespread regional differences in cortical thickness were observed. With chorioamnionitis, the frontal and temporal lobes were primarily affected by decreased cortical thickness, and the limbic, parietal, and occipital lobes were primarily affected by increased cortical thickness when compared to the comparison group. Subcortical differences were observed in the hippocampus and lateral ventricle. CONCLUSION Using MRI, chorioamnionitis is associated with longterm widespread regional effects on brain development in children born prematurely. Our study is limited by its small sample size.