cortical-source-analysis-of-high-density-eeg-recordings-in-children

Cortical Source Analysis of High-Density EEG Recordings in Children

EEG is traditionally described as a neuroimaging technique with high temporal and low spatial resolution. Recent advances in biophysical modelling and ...

University College London

Patients with Crigler-Najjar Type 1 (CN-1) disorder have an unconjugated hyperbilirubinaemia due to the complete absence in activity of uridinediphosphate glucuronosyltransferase, a bilirubin-conjugating enzyme. In pregnant women with CN-1, the foetus is at high risk of being adversely affected by the bilirubin, as unconjugated bilirubin can cross the placenta and is potentially neurotoxic. We report the long-term outcomes of two infants born to women with CN-1. These infants had exchange transfusions soon after birth and have normal neurodevelopmental outcomes at 18 months and four years of age, respectively. We propose that this intervention might have improved the neurological outcome of these infants.

Normal neurological outcome in two infants treated with exchange transfusions born to mothers with Crigler-Najjar Type 1 disorder.

Autism is thought to be associated with a bias towards detail-focussed processing. While the cognitive basis remains controversial, one strong hypothesis is that there are high processing costs associated with changing from local into global processing. A possible neural mechanism underlying this processing style is abnormal neural connectivity; specifically reduced structural or functional connectivity between brain regions might lead to good exemplar-based processing but poor generalisation. Abnormal neural connectivity has also been suggested to account for the increased incidence of macrocephaly in autism (increased head/brain size). The present study therefore investigated the effect of head size on the ability to switch between global and local processing in autism. 49 high-functioning 7-12 year olds with autism (12 with macrocephaly) were compared to 25 normally developing children in their performance on a Local-Global Switching task. Those children with autism who also had macrocephaly showed a greater processing cost when switching into global processing, or 'zooming out', than both the remaining children with autism and the control children. A second experiment revealed that macrocephaly in the context of normal development is not associated with difficulty switching into global processing but rather occurs in children who are physically large. Macrocephaly in the context of autism may therefore be a biological marker of abnormal neural connectivity, and of a local processing bias.

Big heads, small details and autism.

Introduction: Brain injury in the newborn is a major cause of death and lifelong disability. The newborn brain is vulnerable to injury from a variety of causes, including hypoxia-ischaemia, haemorrhage and infection, yet has a remarkable capacity for repair. New neuroprotective therapies are being developed that have the potential to improve neurodevelopmental outcome in this vulnerable population. Brain imaging has revolutionised our understanding of the aetiology, pathophysiology and prognosis of damage in both term and preterm infants. Areas covered: This paper reviews the main clinical imaging methodologies, principally ultrasound and magnetic resonance imaging, and describes new clinical and research techniques being developed using a range of imaging modalities. This paper provides an overview of perinatal brain injury and the importance of imaging in the management of these patients. Expert opinion: Conventional brain imaging is important in neonatal care. However, the challenge is to correlate brain structure with function, and new technologies will provide new insights into the function of the developing brain. Imaging is also going to play a key role as an early biomarker facilitating trials of new neuroprotective therapies.

Advances in imaging the neonatal brain.

There is increasing interest in applying connectivity analysis to brain measures (Rubinov and Sporns, 2010), but most studies have relied on fMRI, which substantially limits the participant groups and numbers that can be studied. High-density EEG recordings offer a comparatively inexpensive easy-to-use alternative, but require channel-level connectivity analysis which currently lacks a common analytic framework and is very limited in spatial resolution. To address this problem, we have developed a new technique for studies of network development that overcomes the spatial constraint and obtains functional networks of cortical areas by using EEG source reconstruction with age-matched average MRI templates (He et al., 1999). In contrast to previously reported channel-level analysis, this approach provides information about the cortical areas most likely to be involved in the network as well as their functional relationship (Babiloni et al., 2005; De Vico Fallani et al., 2007). In this study, we applied source reconstruction with age-matched templates to task-free high-density EEG recordings in typically-developing children between 2 and 6 years of age (O'Reilly, 2012). Graph theory was then applied to the association strengths of 68 cortical regions of interest based on the Desikan-Killiany atlas. We found linear increases of mean node degree, mean clustering coefficient and maximum betweenness centrality between 2 years and 6 years of age. Characteristic path length was negatively correlated with age. The correlation of the network measures with age indicates network development towards more closely integrated networks similar to reports from other imaging modalities (Fair et al., 2008; Power et al., 2010). We also applied eigenvalue decomposition to obtain functional modules (Clayden et al., 2013). Connection strength within these modules did not change with age, and the modules resembled hub networks previously described for MRI (Hagmann et al., 2010; Power et al., 2010). The high temporal resolution of EEG additionally allowed us to distinguish between frequency bands potentially reflecting dynamic coupling between different neural oscillators. Generally, network parameters were similar for networks based on different frequency bands, but frequency band did emerge as a significant factor for clustering coefficient and characteristic path length. In conclusion, the current analysis shows that source reconstruction of high-density EEG recordings with appropriate head models offers a valuable tool for estimating network parameters in studies of brain development. The findings replicate the pattern of closer functional integration over development described for other imaging modalities (Fair et al., 2008; Power et al., 2010).

Functional brain network organisation of children between 2 and 5 years derived from reconstructed activity of cortical sources of high-density EEG recordings.

Previous research has suggested that the local processing bias often reported in studies of Autism Spectrum Condition may only be typical of a subgroup of individuals with autism also presenting with macrocephaly. The current study examined a group of children with autism, with and without macrocephaly, on the Children's Embedded Figures Test (CEFT), a well-established measure of local processing bias. The results demonstrated that the children with autism and macrocephaly performed significantly better on the CEFT than children with autism without macrocephaly, indicative of a local bias. These results lend support to the proposal that both macrocephaly in autism and a local processing bias may arise from the same underlying neural processes and these characteristics represent an endophenotype in a subgroup of individuals with ASC worthy of further investigation.

Article	Year
Normal neurological outcome in two infants treated with exchange transfusions born to mothers with Crigler-Najjar Type 1 disorder. European journal of pediatrics\| PubMed ID: 18551316	2009
Big heads, small details and autism. Neuropsychologia\| PubMed ID: 19428391	2009
Advances in imaging the neonatal brain. Expert opinion on medical diagnostics\| PubMed ID: 23480584	2011
Functional brain network organisation of children between 2 and 5 years derived from reconstructed activity of cortical sources of high-density EEG recordings. NeuroImage\| PubMed ID: 23769920	2013
Is macrocephaly a neural marker of a local bias in autism? Developmental cognitive neuroscience\| PubMed ID: 24161549	2013

Helen O'Reilly

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