Reciprocal white matter alterations due to 16p11.2 chromosomal deletions versus duplications.

Copy number variants at the 16p11.2 chromosomal locus are associated with several neuropsychiatric disorders, including autism, schizophrenia, bipolar disorder, attention-deficit hyperactivity disorder, and speech and language disorders. A gene dosage dependence has been suggested, with 16p11.

The Contribution of the Corpus Callosum to Language Lateralization.

Unlabelled: The development of hemispheric lateralization for language is poorly understood. In one hypothesis, early asymmetric gene expression assigns language to the left hemisphere. In an alternate view, language is represented a priori in both hemispheres and lateralization emerges via cross-hemispheric communication through the corpus callosum.

White Matter Changes of Neurite Density and Fiber Orientation Dispersion during Human Brain Maturation.

Diffusion tensor imaging (DTI) studies of human brain development have consistently shown widespread, but nonlinear increases in white matter anisotropy through childhood, adolescence, and into adulthood. However, despite its sensitivity to changes in tissue microstructure, DTI lacks the specificity to disentangle distinct microstructural features of white and gray matter. Neurite orientation dispersion and density imaging (NODDI) is a recently proposed multi-compartment biophysical model of brain microstructure that can estimate non-collinear properties of white matter, such as neurite orientation dispersion index (ODI) and neurite density index (NDI).

Aberrant white matter microstructure in children with 16p11.2 deletions.

Copy number variants (CNVs) of the chromosomal locus 16p11.2, consisting of either deletions or duplications, have been implicated in autism, schizophrenia, epilepsy, and other neuropsychiatric disorders. Since abnormal white matter microstructure can be seen in these more broadly defined clinical disorders, we used diffusion magnetic resonance imaging and tract-based spatial statistics to investigate white matter microstructural integrity in human children with 16p11.

Both rare and de novo copy number variants are prevalent in agenesis of the corpus callosum but not in cerebellar hypoplasia or polymicrogyria.

Agenesis of the corpus callosum (ACC), cerebellar hypoplasia (CBLH), and polymicrogyria (PMG) are severe congenital brain malformations with largely undiscovered causes. We conducted a large-scale chromosomal copy number variation (CNV) discovery effort in 255 ACC, 220 CBLH, and 147 PMG patients, and 2,349 controls. Compared to controls, significantly more ACC, but unexpectedly not CBLH or PMG patients, had rare genic CNVs over one megabase (p = 1.

Resting-state networks and the functional connectome of the human brain in agenesis of the corpus callosum.

The corpus callosum is the largest white matter fiber bundle connecting the two cerebral hemispheres. In this work, we investigate the effect of callosal dysgenesis on functional magnetic resonance imaging (fMRI) resting-state networks and the functional connectome. Since alternate commissural routes between the cerebral hemispheres exist, we hypothesize that bilateral cortical networks can still be maintained in partial or even complete agenesis of the corpus callosum (AgCC).

Test-retest reliability of computational network measurements derived from the structural connectome of the human brain.

Structural magnetic resonance (MR) connectomics holds promise for the diagnosis, outcome prediction, and treatment monitoring of many common neurodevelopmental, psychiatric, and neurodegenerative disorders for which there is currently no clinical utility for MR imaging (MRI). Before computational network metrics from the human connectome can be applied in a clinical setting, their precision and their normative intersubject variation must be understood to guide the study design and the interpretation of longitudinal data. In this work, the reproducibility of commonly used graph theoretic measures is investigated, as applied to the structural connectome of healthy adult volunteers.

The structural connectome of the human brain in agenesis of the corpus callosum.

Adopting a network perspective, the structural connectome reveals the large-scale white matter connectivity of the human brain, yielding insights into cerebral organization otherwise inaccessible to researchers and clinicians. Connectomics has great potential for elucidating abnormal connectivity in congenital brain malformations, especially axonal pathfinding disorders. Agenesis of the corpus callosum (AgCC) is one of the most common brain malformations and can also be considered a prototypical genetic disorder of axonal guidance in humans.

The role of corpus callosum development in functional connectivity and cognitive processing.

The corpus callosum is hypothesized to play a fundamental role in integrating information and mediating complex behaviors. Here, we demonstrate that lack of normal callosal development can lead to deficits in functional connectivity that are related to impairments in specific cognitive domains. We examined resting-state functional connectivity in individuals with agenesis of the corpus callosum (AgCC) and matched controls using magnetoencephalographic imaging (MEG-I) of coherence in the alpha (8-12 Hz), beta (12-30 Hz) and gamma (30-55 Hz) bands.

Laterality of brain and ocular lesions in Aicardi syndrome.

This study reports a large case series of children with Aicardi syndrome. A new severity scoring system is established to assess sidedness of ocular and brain lesions. Thirty-five children were recruited from Aicardi syndrome family conferences.

Genetic and functional analyses identify DISC1 as a novel callosal agenesis candidate gene.

Agenesis of the corpus callosum (AgCC) is a congenital brain malformation that occurs in approximately 1:1,000-1:6,000 births. Several syndromes associated with AgCC have been traced to single gene mutations; however, the majority of AgCC causes remain unidentified. We investigated a mother and two children who all shared complete AgCC and a chromosomal deletion at 1q42.

Diffusion tensor imaging of Aicardi syndrome.

Aicardi syndrome is a congenital neurodevelopmental disorder associated with significant cognitive and motor impairment. Diffusion tensor imaging was performed on two subjects with Aicardi syndrome, as well as on two matched subjects with callosal agenesis and cortical malformations but not a clinical diagnosis of Aicardi syndrome. Whole-brain three-dimensional fiber tractography was performed, and major white matter tracts were isolated using standard tracking protocols.

Agenesis of the corpus callosum, optic coloboma, intractable seizures, craniofacial and skeletal dysmorphisms: an autosomal recessive disorder similar to Temtamy syndrome.

Agenesis of the corpus callosum (ACC) is a common brain anomaly with a birth incidence of at least 1 in 4,000. ACC can occur as an isolated malformation or as a component of a syndrome. Here, we report on an autosomal recessive syndrome with ACC, optic coloboma, craniofacial dysmorphism, skeletal anomalies, and intractable seizures in a brother and sister from a consanguineous family.