Rapid and objective assessment of neural function in autism spectrum disorder using transient visual evoked potentials

OBJECTIVE: There is a critical need to identify biomarkers and objective outcome measures that can be used to understand underlying neural mechanisms in autism spectrum disorder (ASD). Visual evoked potentials (VEPs) offer a noninvasive technique to evaluate the functional integrity of neural mechanisms, specifically visual pathways, while probing for disease pathophysiology. METHODS: Transient VEPs (tVEPs) were obtained from 96 unmedicated children, including 37 children with ASD, 36 typically developing (TD) children, and 23 unaffected siblings (SIBS). A conventional contrast-reversing checkerboard condition was compared to a novel short-duration condition, which was developed to enable objective data collection from severely affected populations who are often excluded from electroencephalographic (EEG) studies. RESULTS: Children with ASD showed significantly smaller amplitudes compared to TD children at two of the earliest critical VEP components, P60-N75 and N75-P100. SIBS showed intermediate responses relative to ASD and TD groups. There were no group differences in response latency. Frequency band analyses indicated significantly weaker responses for the ASD group in bands encompassing gamma-wave activity. Ninety-two percent of children with ASD were able to complete the short-duration condition compared to 68% for the standard condition. CONCLUSIONS: The current study establishes the utility of a short-duration tVEP test for use in children at varying levels of functioning and describes neural abnormalities in children with idiopathic ASD. Implications for excitatory/inhibitory balance as well as the potential application of VEP for use in clinical trials are discussed

Does Cognitive Impairment Explain Behavioral and Social Problems of Children with Neurofibromatosis Type 1?

Thirty NF1-patients (mean age 11.7 years, SD = 3.3) and 30 healthy controls (mean age 12.5 years, SD = 3.1) were assessed on social skills, autistic traits, hyperactivity-inattention, emotional problems, conduct problems, and peer problems. Cognitive control, information processing speed, and social information processing were measured using 5 computer tasks. GLM analyses of variance showed significant group differences, to the disadvantage of NF1-patients, on all measures of behavior, social functioning and cognition. General cognitive ability (a composite score of processing speed, social information processing, and cognitive control) accounted for group differences in emotional problems, whereas social information processing accounted for group differences in conduct problems. Although reductions were observed for group differences in other aspects of behavior and social functioning after control for (specific) cognitive abilities, group differences remained evident. Training of cognitive abilities may help reducing certain social and behavioral problems of children with NF1, but further refinement regarding associations between specific aspects of cognition and specific social and behavioral outcomes is required

PhagoSight: an open-source MATLAB® package for the analysis of fluorescent neutrophil and macrophage migration in a zebrafish model

Neutrophil migration in zebrafish larvae is increasingly used as a model to study the response of these leukocytes to different determinants of the cellular inflammatory response. However, it remains challenging to extract comprehensive information describing the behaviour of neutrophils from the multi-dimensional data sets acquired with widefield or confocal microscopes. Here, we describe PhagoSight, an open-source software package for the segmentation, tracking and visualisation of migrating phagocytes in three dimensions. The algorithms in PhagoSight extract a large number of measurements that summarise the behaviour of neutrophils, but that could potentially be applied to any moving fluorescent cells. To derive a useful panel of variables quantifying aspects of neutrophil migratory behaviour, and to demonstrate the utility of PhagoSight, we evaluated changes in the volume of migrating neutrophils. Cell volume increased as neutrophils migrated towards the wound region of injured zebrafish. PhagoSight is openly available as MATLAB® m-files under the GNU General Public License. Synthetic data sets and a comprehensive user manual are available from http://www.phagosight.org