251 research outputs found
Prenatal maternal immune activation causes epigenetic differences in adolescent mouse brain
Epigenetic processes such as DNA methylation have been implicated in the pathophysiology of neurodevelopmental disorders including schizophrenia and autism. Epigenetic changes can be induced by environmental exposures such as inflammation. Here we tested the hypothesis that prenatal inflammation, a recognized risk factor for schizophrenia and related neurodevelopmental conditions, alters DNA methylation in key brain regions linked to schizophrenia, namely the dopamine rich striatum and endocrine regulatory centre, the hypothalamus. DNA methylation across highly repetitive elements (long interspersed element 1 (LINE1) and intracisternal A-particles (IAPs)) were used to proxy global DNA methylation. We also investigated the Mecp2 gene because it regulates transcription of LINE1 and has a known association with neurodevelopmental disorders. Brain tissue was harvested from 6 week old offspring of mice exposed to the viral analog PolyI:C or saline on gestation day 9. We used Sequenom EpiTYPER assay to quantitatively analyze differences in DNA methylation at IAPs, LINE1 elements and the promoter region of Mecp2. In the hypothalamus, prenatal exposure to PolyI:C caused significant global DNA hypomethylation (t=2.44, P=0.019, PolyI:C mean 69.67%, saline mean 70.19%), especially in females, and significant hypomethylation of the promoter region of Mecp2, (t=3.32, P=0.002; PolyI:C mean 26.57%, saline mean 34.63%). IAP methylation was unaltered. DNA methylation in the striatum was not significantly altered. This study provides the first experimental evidence that exposure to inflammation during prenatal life is associated with epigenetic changes, including Mecp2 promoter hypomethylation. This suggests that environmental and genetic risk factors associated with neurodevelopmental disorders may act upon similar pathways. This is important because epigenetic changes are potentially modifiable and their investigation may open new avenues for treatment
Evaluation of a Screening Instrument for Autism Spectrum Disorders in Prisoners
There have been concerns that individuals with autism spectrum disorders (ASDs) are over-represented but not recognised in prison populations. A screening tool for ASDs in prisons has therefore been developed
Impaired Communication Between the Motor and Somatosensory Homunculus Is Associated With Poor Manual Dexterity in Autism Spectrum Disorder
ABSTRACTBackgroundFine motor skill impairments are common in autism spectrum disorder (ASD), significantly affecting quality of life. Sensory inputs reaching the primary motor cortex (M1) from the somatosensory cortex (S1) are likely involved in fine motor skill and specifically motor learning. However, the role of these connections has not been directly investigated in humans. This study aimed to investigate, for the first time, the role of the S1-M1 connections in healthy subjects in vivo and whether microstructural alterations are associated with motor impairment in ASD.MethodsSixty right-handed neurotypical adult men aged 18 to 45 years, and 60 right-handed age- and sex-matched subjects diagnosed with ASD underwent fine motor skill assessment and scanning with diffusion tensor imaging (DTI). The streamlines of the hand region connecting S1-M1 of the motor-sensory homunculus were virtually dissected using TrackVis, and diffusion properties were extracted. The face/tongue region connections were used as control tracts.ResultsThe ASD group displayed lower motor performances and altered DTI measurements of the hand-region connection. Behavioral performance correlated with hand-region DTI measures in both groups, but not with the face/tongue connections, indicating anatomical specificity. There was a left-hemisphere association of motor ability in the control group and an atypical rightward shift in the ASD group.ConclusionsThese findings suggest that direct interaction between S1 and M1 may contribute to the human ability to precisely interact with and manipulate the environment. Because electrophysiological evidence indicates that these connections may underpin long-term potentiation in M1, our findings may lead to novel therapeutic treatments for motor skill disorders
Shifting brain inhibitory balance and connectivity of the prefrontal cortex of adults with autism spectrum disorder
Age-related grey matter volume correlates of response inhibition and shifting in Attention Deficit Hyperactivity Disorder
Background Children with attention-deficit hyperactivity disorder (ADHD) have difficulties with executive function and impulse control which may improve with age. Aims To map the brain correlates of executive function in ADHD and determine age-related changes in reaction times and brain volumes. Method Attention-deficit hyperactivity disorder and control groups were compared on the change task measures of response inhibition (stop signal reaction time, SSRT) and shifting (change response reaction time, CRRT). voxel-wise magnetic resonance imaging (MRI) correlations of reaction times and grey matter volume were determined, along with bivariate correlations of reaction times, brain volumes and age.Results Individuals in the ADHD group had longer SSRTs and CRRTs. Anterior cingulate, striatal and medial temporal volumes highly correlated with SSRT. Striatal and cerebellar volumes strongly correlated with CRRT. Older children had faster reaction times and larger regional brain volumes. In controls, orbitofrontal, medial temporal and cerebellar volumes correlated with CRRT but not SSRT. Neither reaction times nor regional brain volumes were strongly age- dependent. Conclusions Our evidence supports delayed brain maturation in ADHD and implies that some features of ADHD improve with age.link_to_subscribed_fulltex
Author Correction: Effects of route of administration on oxytocin-induced changes in regional cerebral blood flow in humans
MRI Study of Minor Physical Anomaly in Childhood Autism Implicates Aberrant Neurodevelopment in Infancy
Background: MPAs (minor physical anomalies) frequently occur in neurodevelopmental disorders because both face and brain are derived from neuroectoderm in the first trimester. Conventionally, MPAs are measured by evaluation of external appearance. Using MRI can help overcome inherent observer bias, facilitate multi-centre data acquisition, and explore how MPAs relate to brain dysmorphology in the same individual. Optical MPAs exhibit a tightly synchronized trajectory through fetal, postnatal and adult life. As head size enlarges with age, inter-orbital distance increases, and is mostly completed before age 3 years. We hypothesized that optical MPAs might afford a retrospective 'window' to early neurodevelopment; specifically, inter-orbital distance increase may represent a biomarker for early brain dysmaturation in autism. Methods: We recruited 91 children aged 7-16; 36 with an autism spectrum disorder and 55 age- and gender-matched typically developing controls. All children had normal IQ. Inter-orbital distance was measured on T1-weighted MRI scans. This value was entered into a voxel-by-voxel linear regression analysis with grey matter segmented from a bimodal MRI data-set. Age and total brain tissue volume were entered as covariates. Results: Intra-class coefficient for measurement of the inter-orbital distance was 0.95. Inter-orbital distance was significantly increased in the autism group (p = 0.03, 2-tailed). The autism group showed a significant relationship between inter-orbital distance grey matter volume of bilateral amygdalae extending to the unci and inferior temporal poles. Conclusions: Greater inter-orbital distance in the autism group compared with healthy controls is consistent with infant head size expansion in autism. Inter-orbital distance positively correlated with volume of medial temporal lobe structures, suggesting a link to "social brain" dysmorphology in the autism group. We suggest these data support the role of optical MPAs as a "fossil record" of early aberrant neurodevelopment, and potential biomarker for brain dysmaturation in autism. © 2011 Cheung et al.published_or_final_versio
Effects of gestational age at birth on perinatal structural brain development in healthy term-born babies
Infants born in early term (37-38 weeks gestation) experience slower neurodevelopment than those born at full term (40-41 weeks gestation). While this could be due to higher perinatal morbidity, gestational age at birth may also have a direct effect on the brain. Here we characterise brain volume and white matter correlates of gestational age at birth in healthy term-born neonates and their relationship to later neurodevelopmental outcome using T2 and diffusion weighted MRI acquired in the neonatal period from a cohort (n = 454) of healthy babies born at term age (>37 weeks gestation) and scanned between 1 and 41 days after birth. Images were analysed using tensor-based morphometry and tract-based spatial statistics. Neurodevelopment was assessed at age 18 months using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). Infants born earlier had higher relative ventricular volume and lower relative brain volume in the deep grey matter, cerebellum and brainstem. Earlier birth was also associated with lower fractional anisotropy, higher mean, axial, and radial diffusivity in major white matter tracts. Gestational age at birth was positively associated with all Bayley-III subscales at age 18 months. Regression models predicting outcome from gestational age at birth were significantly improved after adding neuroimaging features associated with gestational age at birth. This work adds to the body of evidence of the impact of early term birth and highlights the importance of considering the effect of gestational age at birth in future neuroimaging studies including term-born babies
Development of microstructural and morphological cortical profiles in the neonatal brain
Interruptions to neurodevelopment during the perinatal period may have long-lasting consequences. However, to be able to investigate deviations in the foundation of proper connectivity and functional circuits, we need a measure of how this architecture evolves in the typically developing brain. To this end, in a cohort of 241 term-born infants, we used magnetic resonance imaging to estimate cortical profiles based on morphometry and microstructure over the perinatal period (37-44 weeks postmenstrual age, PMA). Using the covariance of these profiles as a measure of inter-areal network similarity (morphometric similarity networks; MSN), we clustered these networks into distinct modules. The resulting modules were consistent and symmetric, and corresponded to known functional distinctions, including sensory-motor, limbic, and association regions, and were spatially mapped onto known cytoarchitectonic tissue classes. Posterior regions became more morphometrically similar with increasing age, while peri-cingulate and medial temporal regions became more dissimilar. Network strength was associated with age: Within-network similarity increased over age suggesting emerging network distinction. These changes in cortical network architecture over an 8-week period are consistent with, and likely underpin, the highly dynamic processes occurring during this critical period. The resulting cortical profiles might provide normative reference to investigate atypical early brain development
ANS: Aberrant Neurodevelopment of the Social Cognition Network in Adolescents with Autism Spectrum Disorders
Background: Autism spectrum disorders (ASD) are characterized by aberrant neurodevelopment. Although the ASD brain undergoes precocious growth followed by decelerated maturation during early postnatal period of childhood, the neuroimaging approach has not been empirically applied to investigate how the ASD brain develops during adolescence. Methodology/Principal Findings: We enrolled 25 male adolescents with high functioning ASD and 25 typically developing controls for voxel-based morphometric analysis of structural magnetic resonance image. Results indicate that there is an imbalance of regional gray matter volumes and concentrations along with no global brain enlargement in adolescents with high functioning ASD relative to controls. Notably, the right inferior parietal lobule, a role in social cognition, have a significant interaction of age by groups as indicated by absence of an age-related gain of regional gray matter volume and concentration for neurodevelopmental maturation during adolescence. Conclusions/Significance: The findings indicate the neural correlates of social cognition exhibits aberrant neurodevelopment during adolescence in ASD, which may cast some light on the brain growth dysregulation hypothesis. The period of abnormal brain growth during adolescence may be characteristic of ASD. Age effects must be taken into account while measures of structural neuroimaging have been clinically put forward as potential phenotypes for ASD
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