Highlights • Sex-differences were observed in white matter alterations among adolescents with FASD. • Associations between white matter alterations and gonadal hormone levels were altered among ...adolescents with FASD. • Present results suggest underlying neuroendocrine alterations in adolescents with FASD.
Written and verbal languages are neurobehavioral traits vital to the development of communication skills. Unfortunately, disorders involving these traits—specifically reading disability (RD) and ...language impairment (LI)—are common and prevent affected individuals from developing adequate communication skills, leaving them at risk for adverse academic, socioeconomic and psychiatric outcomes. Both RD and LI are complex traits that frequently co‐occur, leading us to hypothesize that these disorders share genetic etiologies. To test this, we performed a genome‐wide association study on individuals affected with both RD and LI in the Avon Longitudinal Study of Parents and Children. The strongest associations were seen with markers in ZNF385D (OR = 1.81, P = 5.45 × 10−7) and COL4A2 (OR = 1.71, P = 7.59 × 10−7). Markers within NDST4 showed the strongest associations with LI individually (OR = 1.827, P = 1.40 × 10−7). We replicated association of ZNF385D using receptive vocabulary measures in the Pediatric Imaging Neurocognitive Genetics study (P = 0.00245). We then used diffusion tensor imaging fiber tract volume data on 16 fiber tracts to examine the implications of replicated markers. ZNF385D was a predictor of overall fiber tract volumes in both hemispheres, as well as global brain volume. Here, we present evidence for ZNF385D as a candidate gene for RD and LI. The implication of transcription factor ZNF385D in RD and LI underscores the importance of transcriptional regulation in the development of higher order neurocognitive traits. Further study is necessary to discern target genes of ZNF385D and how it functions within neural development of fluent language.
ZNF385D associates with comorbid reading disability and language impairment, as well as overall fiber tract and brain volumes.
Mapping brain maturation Toga, Arthur W.; Thompson, Paul M.; Sowell, Elizabeth R.
Trends in neurosciences,
03/2006, Volume:
29, Issue:
3
Journal Article
Peer reviewed
Open access
Human brain maturation is a complex, lifelong process that can now be examined in detail using neuroimaging techniques. Ongoing projects scan subjects longitudinally with structural magnetic ...resonance imaging (MRI), enabling the time-course and anatomical sequence of development to be reconstructed. Here, we review recent progress on imaging studies of development. We focus on cortical and subcortical changes observed in healthy children, and contrast them with abnormal developmental changes in early-onset schizophrenia, fetal alcohol syndrome, attention-deficit–hyperactivity disorder (ADHD) and Williams syndrome. We relate these structural changes to the cellular processes that underlie them, and to cognitive and behavioral changes occurring throughout childhood and adolescence.
Sex differences in age- and puberty-related maturation of human brain structure have been observed in typically developing age-matched boys and girls. Because girls mature 1-2 years earlier than ...boys, the present study aimed at assessing sex differences in brain structure by studying 80 adolescent boys and girls matched on sexual maturity, rather than age. We evaluated pubertal influences on medial temporal lobe (MTL), thalamic, caudate, and cortical gray matter volumes utilizing structural magnetic resonance imaging and 2 measures of pubertal status: physical sexual maturity and circulating testosterone. As predicted, significant interactions between sex and the effect of puberty were observed in regions with high sex steroid hormone receptor densities; sex differences in the right hippocampus, bilateral amygdala, and cortical gray matter were greater in more sexually mature adolescents. Within sex, we found larger volumes in MTL structures in more sexually mature boys, whereas smaller volumes were observed in more sexually mature girls. Our results demonstrate puberty-related maturation of the hippocampus, amygdala, and cortical gray matter that is not confounded by age, and is different for girls and boys, which may contribute to differences in social and cognitive development during adolescence, and lasting sexual dimorphisms in the adult brain.
This study asked whether previously identified developmental changes in the gray matter of the left inferior frontal gyrus are associated with maturation of a linguistic skill. To test this ...hypothesis, we examined whether thickening of this region was correlated with developmental improvements in phonological processing but not hand motor skills in a unique longitudinal data set of 45 normally developing children (between ages 5 and 11 years) studied over a 2-year interval. We analyzed structural magnetic resonance imaging data using cortical pattern matching methods and correlated within-individual changes in cortical thickness with 2 neurocognitive scores. As predicted, gray matter thickening in the left inferior frontal cortex was associated with improving phonological processing scores but not with improving hand motor skills. By contrast, motor skill improvement was associated with thinning in the hand region of the left motor cortex, and cortical change in this region was not associated with phonological processing. This study illustrates a specific correspondence between regional gray matter thickness change and language skill change in normally developing children.
Findings from previous magnetic resonance imaging studies of sex differences in gray matter have been inconsistent, with some showing proportionally increased gray matter in women and some showing no ...differences between the sexes. Regional sex differences in gray matter thickness have not yet been mapped over the entire cortical surface in a large sample of subjects spanning the age range from early childhood to old age. We applied algorithms for cortical pattern matching and techniques for measuring cortical thickness to the structural magnetic resonance images of 176 healthy individuals between the ages of 7 and 87 years. We also mapped localized differences in brain size. Maps of sex differences in cortical thickness revealed thicker cortices in women in right inferior parietal and posterior temporal regions even without correcting for total brain volume. In these regions, the cortical mantle is up to 0.45 mm thicker, on average, in women than in men. Analysis of a subset of 18 female and 18 male subjects matched for age and brain volume confirmed the significance of thicker gray matter in temporal and parietal cortices in females, independent of brain size differences. Further analyses were conducted in the adult subjects where gender differences were evaluated using height as a covariate, and similar sex differences were observed even when body size differences between the sexes were controlled. Together, these results suggest that greater cortical thickness in posterior temporal inferior parietal regions in females relative to males are independent of differences in brain or body size. Age-by-sex interactions were not significant in the temporoparietal region, suggesting that sex differences in these regions are present from at least late childhood and then are maintained throughout life. Male brains were larger than female brains in all locations, though male enlargement was most prominent in the frontal and occipital poles, bilaterally. Given the large sample and the large range of ages studied, these results help to address controversies in the study of central nervous system sexual dimorphisms.
Previous in vivo morphometric studies of human brain maturation between childhood and young adulthood have revealed a spatial and temporal pattern of progressive brain changes that is consistent with ...the post mortem cytoarchitectonic and cognitive developmental literatures. In this study, we mapped age differences in structural asymmetries at the cortical surface in groups of normally developing children (7–11 years), adolescents (12–16 years) and young adults (23–30 years) using novel surface-based mesh modeling image analytic methods. We also assessed relationships between cortical surface sulcal asymmetry and the local density of the underlying cortical gray matter. Results from this study reveal that perisylvian sulcal asymmetries are much more prominent in the adults than in the children studied. The superior posterior extent of the Sylvian fissure in the right hemisphere is ~7 mm more superior in the average adult than in the average child studied, whereas little difference is observed during this age range in the location of this anatomical structure in the left hemisphere. Age-related differences in Sylvian fissure asymmetry were significant (P = 0.0129, permutation test), showing increased asymmetry with increasing age. We also show age-related increases in local gray matter proportion bilaterally in the temporo-parietal cortices that are anatomically and temporally related to the sulcal asymmetries. Results from this cross-sectional study imply that asymmetries in the Sylvian fissure are dynamically changing into young adulthood and show that variability in brain tissue density is related to asymmetry in this region. These morphological differences may be related to changing cognitive abilities and are relevant in interpreting results from studies of abnormal brain development where perisylvian brain regions are implicated.
We used magnetic resonance imaging and cortical matching algorithms to map gray matter density (GMD) in 176 normal individuals ranging in age from 7 to 87 years. We found a significant, nonlinear ...decline in GMD with age, which was most rapid between 7 and about 60 years, over dorsal frontal and parietal association cortices on both the lateral and interhemispheric surfaces. Age effects were inverted in the left posterior temporal region, where GMD gain continued up to age 30 and then rapidly declined. The trajectory of maturational and aging effects varied considerably over the cortex. Visual, auditory and limbic cortices, which are known to myelinate early, showed a more linear pattern of aging than the frontal and parietal neocortices, which continue myelination into adulthood. Our findings also indicate that the posterior temporal cortices, primarily in the left hemisphere, which typically support language functions, have a more protracted course of maturation than any other cortical region.
Functional magnetic resonance imaging (fMRI) reveals brain activation abnormalities during visuo-spatial attention and working memory among those with fetal alcohol spectrum disorders (FASD) in ...cross-sectional reports, but little is known about how activation changes over time during development within FASD or typically developing children. We studied 30 controls and 31 individuals with FASD over 2 years (7-14 years at first participation) with a total of 122 scans, as part of the Collaborative Initiative on Fetal Alcohol Spectrum Disorders. Despite comparable performance, there were significant group differences in visuo-spatial activation over time bilaterally in frontal, parietal, and temporal regions. Controls showed an increase in signal intensity in these multiple regions whereas FASD participants showed a decrease in brain activation. Effects were also found in 2 small independent samples from the USA, corroborating the findings from the larger group. Results suggest that the long-lasting effect of prenatal alcohol may impact the maturation of visuo-spatial attention and differentiate those with FASD from controls. Based on this first longitudinal fMRI study in FASD children, our novel findings suggest a possible neural mechanism for attention deficits common among individuals with FASD.
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