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 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Brain development in the first 2 years after birth is extremely dynamic and likely plays an important role in neurodevelopmental disorders, including autism and schizophrenia. Knowledge regarding this period is currently quite limited. We studied structural brain development in healthy subjects from birth to 2. Ninety-eight children received structural MRI scans on a Siemens head-only 3T scanner with magnetization prepared rapid gradient echo T1-weighted, and turbo spin echo, dual-echo (proton density and T2 weighted) sequences: 84 children at 2-4 weeks, 35 at 1 year and 26 at 2 years of age. Tissue segmentation was accomplished using a novel automated approach. Lateral ventricle, caudate, and hippocampal volumes were also determined. Total brain volume increased 101% in the first year, with a 15% increase in the second. The majority of hemispheric growth was accounted for by gray matter, which increased 149% in the first year; hemispheric white matter volume increased by only 11%. Cerebellum volume increased 240% in the first year. Lateral ventricle volume increased 280% in the first year, with a small decrease in the second. The caudate increased 19% and the hippocampus 13% from age 1 to age 2. There was robust growth of the human brain in the first two years of life, driven mainly by gray matter growth. In contrast, white matter growth was much slower. Cerebellum volume also increased substantially in the first year of life. These results suggest the structural underpinnings of cognitive and motor development in early childhood, as well as the potential pathogenesis of neurodevelopmental disorders.
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PMID:A structural MRI study of human brain development from birth to 2 years. 1902 11

Recent developments in functional imaging as well as the emergence of new anatomical imaging techniques suited for the study of white matter have shifted investigational paradigms from a localized to a more holistic network approach. Aside from detecting local activity, functional MRI can be applied to the study of connectivity. However, the concept of "functional connectivity" remains broad, and specific designs and analyses may affect the results. In addition, connectivity cannot be viewed in isolation. Rather, from a developmental perspective, connectivity and local cortical architecture are intimately related. Therefore, combined approaches examining local organization and connectivity are the most promising avenues for elucidating disturbances of neurofunctional organization in developmental disorders. Here this approach is illustrated via data obtained from autism research that suggest impaired local cortical architecture and reduced long-range connectivity between cerebral regions.
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PMID:From loci to networks and back again: anomalies in the study of autism. 1907 5

A number of studies have documented that autism has a neurobiological basis, but the anatomical extent of these neurobiological abnormalities is largely unknown. In this paper, we apply advanced computational techniques to extract 3D models of the corpus callosum (CC) and subsequently analyze the volumetric deficit of the total CC and its five sub-regions in a homogeneous group of autistic children. Moreover, we explore new MRI traits based on the oriented bounding rectangle of the CC, which are the length, width and aspect ratio of the bounding rectangle. These measurements as well as the volumes are compared between patients and controls using t-tests. The results reveal significant reduction in all sub-regions of the CC and some MRI traits in the patients.
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PMID:Abnormalities in MRI traits of corpus callosum in autism subtype. 1916 65

This study explored white matter abnormalities in a group of Chinese children with high functioning autism (HFA). Twelve male children with HFA and ten matched typically developing children underwent diffusion tensor imaging (DTI) as well three-dimensional T1-weighted MRI for voxel-based morphometry (VBM). We found a significant decrease of the white matter density in the right frontal lobe, left parietal lobe and right anterior cingulate and a significant increase in the right frontal lobe, left parietal lobe and left cingulate gyrus in the HFA group compared with the control group. The HFA group also had decreased FA in the frontal lobe and left temporal lobe. By combining DT-MRI FA and MRI volumetric analyses based on the VBM model, the results showed consistent white matter abnormalities in a group of Chinese children with HFA.
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PMID:White matter impairments in autism, evidence from voxel-based morphometry and diffusion tensor imaging. 1923 48

Interstitial deletions of 7q11.23 cause Williams-Beuren syndrome, one of the best characterized microdeletion syndromes. The clinical phenotype associated with the reciprocal duplication however is not well defined, though speech delay is often mentioned. We present 14 new 7q11.23 patients with the reciprocal duplication of the Williams-Beuren syndrome critical region, nine familial and five de novo. These were identified by either array-based MLPA or by array-CGH/oligonucleotide analysis in a series of patients with idiopathic mental retardation with an estimated population frequency of 1:13,000-1:20,000. Variable speech delay is a constant finding in our patient group, confirming previous reports. Cognitive abilities range from normal to moderate mental retardation. The association with autism is present in five patients and in one father who also carries the duplication. There is an increased incidence of hypotonia and congenital anomalies: heart defects (PDA), diaphragmatic hernia, cryptorchidism and non-specific brain abnormalities on MRI. Specific dysmorphic features were noted in our patients, including a short philtrum, thin lips and straight eyebrows. Our patient collection demonstrates that the 7q11.23 microduplication not only causes language delay, but is also associated with congenital anomalies and a recognizable face.
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PMID:Fourteen new cases contribute to the characterization of the 7q11.23 microduplication syndrome. 1924 92

Autism is a developmental disorder characterized by social deficits, impaired communication, and restricted and repetitive patterns of behaviour. Emerging theories indicate interregional functional and anatomical brain connectivity as a likely key feature in autism pathophysiology. Corpus callosum (CC) represents a natural target of autism connectivity research, being the expression of interhemispheric communication. In this paper, a novel method for a robust morphometric analysis of CC data is presented. The standard morphometric approach is based on the analysis of the size and shape of the CC midsagittal cross-section. As there are no gross anatomical landmarks that clearly delimit anatomically or functionally distinct CC regions, several geometric partitioning schemes have been proposed in the literature for morphometric analysis, subdividing CC into subregions whose fiber topography is expected to target different hemispheric cortical regions. A novel tool of morphometric analysis, based on the automated subdivision of a high number of partitions from a CC centroid and on the consequent determination of the CC anatomical landmarks is presented, allowing an automated analysis of CC volumes, shapes and curvatures, suitable for an automated application in clinical environment. Moreover the proposed tool can be used for original post-processing and visualization techniques that may help in the analysis of possible alterations of CC and in the correlations with autism-related diseases. The proposed morphometric tool has been validated and applied for clinical investigation on brain morphometry in children (age 3-11 years) with autism or with other autism spectrum disorders (DSA) and on healthy control subjects who underwent volumetric MRI T1 weighted acquisitions.
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PMID:A novel tool for the morphometric analysis of corpus callosum: applications to the diagnosis of autism - biomed 2009. 1936 3

Autism spectrum disorders (ASD) impact social functioning and communication, and individuals with these disorders often have restrictive and repetitive behaviors. Accumulating data indicate that ASD is associated with alterations of neural circuitry. Functional MRI (FMRI) studies have focused on connectivity in the context of psychological tasks. However, even in the absence of a task, the brain exhibits a high degree of functional connectivity, known as intrinsic or resting connectivity. Notably, the default network, which includes the posterior cingulate cortex, retro-splenial, lateral parietal cortex/angular gyrus, medial prefrontal cortex, superior frontal gyrus, temporal lobe, and parahippocampal gyrus, is strongly active when there is no task. Altered intrinsic connectivity within the default network may underlie offline processing that may actuate ASD impairments. Using FMRI, we sought to evaluate intrinsic connectivity within the default network in ASD. Relative to controls, the ASD group showed weaker connectivity between the posterior cingulate cortex and superior frontal gyrus and stronger connectivity between the posterior cingulate cortex and both the right temporal lobe and right parahippocampal gyrus. Moreover, poorer social functioning in the ASD group was correlated with weaker connectivity between the posterior cingulate cortex and the superior frontal gyrus. In addition, more severe restricted and repetitive behaviors in ASD were correlated with stronger connectivity between the posterior cingulate cortex and right parahippocampal gyrus. These findings indicate that ASD subjects show altered intrinsic connectivity within the default network, and connectivity between these structures is associated with specific ASD symptoms.
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PMID:Abnormalities of intrinsic functional connectivity in autism spectrum disorders. 1940 98

Using aCGH, we have identified a pericentromeric deletion, spanning about 8.2 Mb, within 16p11.2-p12.2 in a patient with developmental delay (DD) and dysmorphic features. This deletion arose de novo and is flanked by segmental duplications. The proposita was the only child of healthy nonconsanguineous parents, born after an uneventful pregnancy, at 40 weeks gestation, by normal delivery. She was referred to us at age 3 10/12 years for evaluation of DD and absent speech. On examination, there were a flat face; low-set, posteriorly rotated ears; high-arched palate; hypotonic face; right single palmar crease; long, thin fingers; and a sacral dimple. Her height was at the 50th centile, weight at the 25th, and OFC at the 30th. Results of DNA FraX, HRB chromosomes, metabolic work-up, audiologic evaluation, brain MRI, electroencephalogram, and heart/abdomen ultrasonography were normal. When last seen, aged 8 years, she had a moderate intellectual disability (ID) and poor speech. She was hyperactive with short attention span and difficulty in concentration, but, based on formal testing, did not have autism. Our patient shows common clinical features to the four individuals described by Ballif et al. [Ballif et al. (2007); Nat Genet 39:1071-1073], and further characterizes the new microdeletion syndrome of 16p11.2-p12.2. aCGH suggests that the deletions of all cases share the same distal breakpoint. Of note, the proximal breakpoint of our proposita overlaps the distal breakpoint of the autistic patients studied by Kumar et al. [Kumar et al. (2008); Hum Mol Genet 17:628-638] and Weiss et al. [Weiss et al. (2008); N Eng J Med 358:667-675], confirming that the 16p region carrying susceptibility to autism is more centromeric. Our observation further defines two different, contiguous 16p genomic regions, responsible for a distinct MCA/ID syndrome, and for autism, respectively.
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PMID:Further characterization of the new microdeletion syndrome of 16p11.2-p12.2. 1944 18

Prenatal viral infection has been associated with the development of schizophrenia and autism. Our laboratory has previously shown that viral infection causes deleterious effects on brain structure and function in mouse offspring following late first trimester (E9) and late second trimester (E18) administration of influenza virus. We hypothesized that middle second trimester infection (E16) in mice may lead to a different pattern of brain gene expression and structural defects in the developing offspring. C57BL6 mice were infected on E16 with a sublethal dose of human influenza virus or sham-infected using vehicle solution. Male offspring of the infected mice were collected at P0, P14, P35, and P56, their brains removed and cerebella dissected and flash frozen. Microarray, DTI and MRI scanning, as well as qRT-PCR and SDS-PAGE and western blotting analyses were performed to detect differences in gene expression and brain atrophy. Expression of several genes associated with myelination, including Mbp, Mag, and Plp1 were found to be altered, as were protein levels of Mbp, Mag, and DM20. Brain imaging revealed significant atrophy in cerebellum at P14, reduced fractional anisotropy in white matter of the right internal capsule at P0, and increased fractional anisotropy in white matter in corpus callosum at P14 and right middle cerebellar peduncle at P56. We propose that maternal infection in mouse impacts myelination genes.
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PMID:Abnormal expression of myelination genes and alterations in white matter fractional anisotropy following prenatal viral influenza infection at E16 in mice. 1948 9

The hippocampus governs memory formation and emotional regulation, and there is widespread evidence of hippocampal dysfunction in psychiatric disorders, including schizophrenia and autism. There is abundant evidence that prenatal viral infection may play a role in the development of these two disorders. In the current study, we have examined gene expression and structural changes of the hippocampi of exposed neonates following maternal infection at embryonic day (E) 16 (middle second trimester). We observed significant changes in gene expression in the offspring at postnatal day (P) 0 (birth), P14 (childhood), and P56 (adulthood), including a number of candidate genes for autism and schizophrenia. qRT-PCR verified the direction and magnitude of change for 5 of the genes from the microarray data set and revealed mRNA changes for additional genes associated with schizophrenia and autism. MRI revealed a decrease in hippocampal volume at P35 (adolescence). Our results demonstrate altered gene expression and reduced hippocampal volume in the offspring following prenatal viral infection at E16.
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PMID:Prenatal viral infection of mice at E16 causes changes in gene expression in hippocampi of the offspring. 1950 87


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