Atypical gut microbiota composition in a mouse model of developmental stuttering.

Developmental stuttering is a complex neurodevelopmental disorder characterized by disfluent speech. It has been associated with mutations in genes involved in lysosomal enzyme trafficking. Mice with mutations in one such gene, Gnptab, exhibit atypical vocalizations analogous to stuttering in humans.

Dissociation Between Linguistic and Nonlinguistic Statistical Learning in Children with Autism.

Statistical learning (SL), the ability to detect and extract regularities from inputs, is considered a domain-general building block for typical language development. We compared 55 verbal children with autism (ASD, 6-12 years) and 50 typically-developing children in four SL tasks. The ASD group exhibited reduced learning in the linguistic SL tasks (syllable and letter), but showed intact learning for the nonlinguistic SL tasks (tone and image).

Exosomes in Epilepsy of Tuberous Sclerosis Complex: Carriers of Pro-Inflammatory MicroRNAs.

Exosomes are a class of small, secreted extracellular vesicles (EV) that have recently gained considerable attention for their role in normal cellular function, disease processes and potential as biomarkers. Exosomes serve as intercellular messengers and carry molecular cargo that can alter gene expression and the phenotype of recipient cells. Here, we investigated alterations of microRNA cargo in exosomes secreted by epileptogenic tissue in tuberous sclerosis complex (TSC), a multi-system genetic disorder that includes brain lesions known as tubers.

Linking Lysosomal Enzyme Targeting Genes and Energy Metabolism with Altered Gray Matter Volume in Children with Persistent Stuttering.

Developmental stuttering is a childhood onset neurodevelopmental disorder with an unclear etiology. Subtle changes in brain structure and function are present in both children and adults who stutter. It is a highly heritable disorder, and 12-20% of stuttering cases may carry a mutation in one of four genes involved in intracellular trafficking.

Association Between Gray Matter Volume Variations and Energy Utilization in the Brain: Implications for Developmental Stuttering.

Purpose The biological mechanisms underlying developmental stuttering remain unclear. In a previous investigation, we showed that there is significant spatial correspondence between regional gray matter structural anomalies and the expression of genes linked to energy metabolism. In the current study, we sought to further examine the relationship between structural anomalies in the brain in children with persistent stuttering and brain regional energy metabolism.

PET imaging of medulloblastoma with an F-labeled tryptophan analogue in a transgenic mouse model.

In vivo positron emission tomography (PET) imaging is a key modality to evaluate disease status of brain tumors. In recent years, tremendous efforts have been made in developing PET imaging methods for pediatric brain tumors. Carbon-11 labelled tryptophan derivatives are feasible as PET imaging probes in brain tumor patients with activation of the kynurenine pathway, but the short half-life of carbon-11 limits its application.

Automated production of 1-(2-[F]fluoroethyl)-l-tryptophan for imaging of tryptophan metabolism.

Automated production of an fluorine-18 labeled tryptophan analogue, 1-(2-[F]fluoroethyl)-l-tryptophan (1-L-[F]FETrp) in a current Good Manufacturing Practice facility was achieved. 1-L-[F]FETrp was produced by a one-pot, two-step strategy with an overall synthesis time of approximately 100 min, a radiochemical yield of 20 ± 5% (decay corrected), radiochemical purity and enantiomeric excess over 90%, and a molar activity of 103 ± 15 GBq/μmol at the end of synthesis (EOS). The dose mass of 1-L-FETrp in four consecutive batches was less than 5 μg.

TLR7 activation in epilepsy of tuberous sclerosis complex.

Background: Neuroinflammation and toll-like receptors (TLR) of the innate immune system have been implicated in epilepsy. We previously reported high levels of microRNAs miR-142-3p and miR-223-3p in epileptogenic brain tissue resected for the treatment of intractable epilepsy in children with tuberous sclerosis complex (TSC). As miR-142-3p has recently been reported to be a ligand and activator of TLR7, a detector of exogenous and endogenous single-stranded RNA, we evaluated TLR7 expression and downstream IL23A activation in surgically resected TSC brain tissue.

Automated production of a N-methyl-D-aspartate receptor radioligand [F]GE179 for clinical use.

N-Methyl-d-aspartate (NMDA) receptors are ligand and voltage-gated heteromeric ion channel receptors. Excessive activation of NMDA receptors is implicated in many neurological and psychiatric disorders, including ischemic stroke, neuropathic pain, epilepsy, drug addition, Alzheimer's disease, and schizophrenia. [F]GE179 is a promising PET probe for imaging functional NMDA receptor alterations (activated or 'open' channel) with a high binding affinity (K = 2.

Linking spherical mean diffusion weighted signal with intra-axonal volume fraction.

Diffusion MRI has been widely used to assess brain tissue microstructure. However, the conventional diffusion tensor imaging (DTI) is inadequate for characterizing fiber direction or fiber density in voxels with crossing fibers in brain white matter. The constrained spherical deconvolution (CSD) technique has been proposed to measure the complex fiber orientation distribution (FOD) using a single high b-value (b ≥ 3000 s/mm) to derive the intra-axonal volume fraction (V) from the calculated FOD.

Minimal number of gradient directions for robust measurement of spherical mean diffusion weighted signal.

Purpose: Determination of the minimum number of gradient directions (N) for robust measurement of spherical mean diffusion weighted signal (S¯).

Methods: Computer simulations were employed to characterize the relative standard deviation (RSD) of the measured spherical mean signal as a function of the number of gradient directions (N). The effects of diffusion weighting b-value and signal-to-noise ratio (SNR) were investigated.

Trajectory of inflammatory and microglial activation markers in the postnatal rabbit brain following intrauterine endotoxin exposure.

Background: Maternal infection is a risk factor for periventricular leukomalacia and cerebral palsy (CP) in neonates. We have previously demonstrated hypomyelination and motor deficits in newborn rabbits, as seen in patients with cerebral palsy, following maternal intrauterine endotoxin administration. This was associated with increased microglial activation, primarily involving the periventricular region (PVR).

A distinct microRNA expression profile is associated with α[C]-methyl-L-tryptophan (AMT) PET uptake in epileptogenic cortical tubers resected from patients with tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is characterized by hamartomatous lesions in various organs and arises due to mutations in the TSC1 or TSC2 genes. TSC mutations lead to a range of neurological manifestations including epilepsy, cognitive impairment, autism spectrum disorders (ASD), and brain lesions that include cortical tubers. There is evidence that seizures arise at or near cortical tubers, but it is unknown why some tubers are epileptogenic while others are not.

Maternal Inflammation Results in Altered Tryptophan Metabolism in Rabbit Placenta and Fetal Brain.

Maternal inflammation has been linked to neurodevelopmental and neuropsychiatric disorders such as cerebral palsy, schizophrenia, and autism. We had previously shown that intrauterine inflammation resulted in a decrease in serotonin, one of the tryptophan metabolites, and a decrease in serotonin fibers in the sensory cortex of newborns in a rabbit model of cerebral palsy. In this study, we hypothesized that maternal inflammation results in alterations in tryptophan pathway enzymes and metabolites in the placenta and fetal brain.

Autism Spectrum Disorders in Africa: Current Challenges in Identification, Assessment, and Treatment: A Report on the International Child Neurology Association Meeting on ASD in Africa, Ghana, April 3-5, 2014.

Prevalence of autism spectrum disorders has increased over recent years, however, little is known about the identification and management of autism spectrum disorder in Africa. This report summarizes a workshop on autism spectrum disorder in Africa under the auspices of the International Child Neurology Association and the African Child Neurology Association through guided presentations and working group reports, focusing on identification, diagnosis, management, and community support. A total of 47 delegates participated from 14 African countries.

Efficacy of Low-Dose Buspirone for Restricted and Repetitive Behavior in Young Children with Autism Spectrum Disorder: A Randomized Trial.

Objectives: To determine safety and efficacy of the 5HT1A serotonin partial agonist buspirone on core autism and associated features in children with autism spectrum disorder (ASD).

Study Design: Children 2-6 years of age with ASD (N = 166) were randomized to receive placebo or 2.5 or 5.

Multi-modal imaging of tumor cellularity and Tryptophan metabolism in human Gliomas.

Background: To assess gliomas using image-based estimation of cellularity, we utilized isotropic diffusion spectrum imaging (IDSI) on clinically feasible diffusion tensor imaging (DTI) and compared it with amino acid uptake measured by α[(11)C]methyl-L-tryptophan positron emission tomography (AMT-PET).

Methods: In 10 patients with a newly-diagnosed glioma, metabolically active tumor regions were defined in both FLAIR hyperintense areas and based on increased uptake on AMT-PET. A recently developed independent component analysis with a ball and stick model was extended to perform IDSI in clinical DTI data.

Cortical Tubers: Windows into Dysregulation of Epilepsy Risk and Synaptic Signaling Genes by MicroRNAs.

Tuberous sclerosis complex (TSC) is a multisystem genetic disorder caused by mutations in the TSC1 and TSC2 genes. Over 80% of TSC patients are affected by epilepsy, but the molecular events contributing to seizures in TSC are not well understood. Recent reports have demonstrated that the brain is enriched with microRNA activity, and they are critical in neural development and function.

Radiosynthesis of (11)C-Levetiracetam: A Potential Marker for PET Imaging of SV2A Expression.

The multistep preparation of (11)C-levetiracetam ((11)C-LEV) was carried out by a one-pot radiosynthesis with 8.3 ± 1.6% (n = 8) radiochemical yield in 50 ± 5.

In vivo detection of reduced Purkinje cell fibers with diffusion MRI tractography in children with autistic spectrum disorders.

Postmortem neuropathology studies report reduced number and size of Purkinje cells (PC) in a majority of cerebellar specimens from persons diagnosed with autism spectrum disorders (ASD). We used diffusion weighted MRI tractography to investigate whether structural changes associated with reduced number and size of PC, could be detected in vivo by measuring streamlines connecting the posterior-lateral region of the cerebellar cortex to the dentate nucleus using an independent component analysis with a ball and stick model. Seed regions were identified in the cerebellar cortex, and streamlines were identified to two sorting regions, the dorsal dentate nucleus (DDN) and the ventral dentate nucleus (VDN), and probability of connection and measures of directional coherence for these streamlines were calculated.

Concurrent quantification of tryptophan and its major metabolites.

An imbalance in tryptophan (TRP) metabolites is associated with several neurological and inflammatory disorders. Therefore, analytical methods allowing for simultaneous quantification of TRP and its major metabolites would be highly desirable, and may be valuable as potential biomarkers. We have developed a HPLC method for concurrent quantitative determination of tryptophan, serotonin, 5-hydroxyindoleacetic acid, kynurenine, and kynurenic acid in tissue and fluids.

Increased risk of very low birth weight, rapid postnatal growth, and autism in underweight and obese mothers.

Purpose: To determine whether prepregnancy weight was associated with children's birth weight, early physical growth, and autism diagnosis.

Design: Early Childhood Longitudinal Study-Birth Cohort data.

Setting: United States.

Automatic detection of primary motor areas using diffusion MRI tractography: comparison with functional MRI and electrical stimulation mapping.

Purpose: As an alternative tool to identify cortical motor areas for planning surgical resection in children with focal epilepsy, the present study proposed a maximum a posteriori probability (MAP) classification of corticospinal tract (CST) visualized by diffusion MR tractography.

Methods: Diffusion-weighted imaging (DWI) was performed in 17 normally developing children and 20 children with focal epilepsy. An independent component analysis tractography combined with ball-stick model was performed to identify unique CST pathways originating from mouth/lip, finger, and leg areas determined by functional magnetic resonance imaging (fMRI) in healthy children and electrical stimulation mapping (ESM) in children with epilepsy.