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Advancing brain research in children’s developmental neurocognitive disorders

Periodic Reporting for period 2 - ChildBrain (Advancing brain research in children’s developmental neurocognitive disorders)

Reporting period: 2017-03-01 to 2019-02-28

Many children are affected by developmental neurocognitive disorders, such as problems of attention or reading difficulties, or neurocognitive problems associated with hearing loss and epilepsy (each affecting from 1% up to about 10% of children). These disorders carry an increased risk of societal exclusion and place a significant economic burden on Europe’s healthcare and educational systems. There is hence a need to improve preventive actions, differential diagnosis and appropriate interventions, which need to be evidence-based and aided by research. The European Brain Council (http://www.europeanbraincouncil.org/projects/CDBE/2010) has suggested that EU should emphasize more research into the causes of neurocognitive disorders, and that training on neurocognitive disorders should be present in all health professions, and encourage industry to engage in brain research. The ChildBrain ETN addresses these concerns using brain imaging techniques.

There are critical technical and scientific challenges associated with brain imaging in children. These techniques have been developed primarily for the adult brain anatomy. However, differences in child brain anatomy can lead to erroneous results in characterizing brain activity using standard methods. Therefore, a detailed understanding of developmental changes is needed for applying brain imaging in clinical or educational settings in children. The next generation of scientists should understand the mathematical and analytical challenges of using brain imaging data, brain development, as well as clinical applications of these techniques.

With these challenges in mind, the ChildBrain (www.childbrain.eu) European Training Network (ETN) has trained interdisciplinary scientists to contribute to the development of new diagnostic tools. ChildBrain has created a cross-disciplinary network of experts with skills and professional connections to drive innovations in the application of brain imaging and has created links between industry and academia for the training of Early Stage Researchers (ESRs) and to develop new analytical methods. ChildBrain has acquired significant child datasets that improve our understanding of brain development, and neurodevelopmental disorders, and has developed new commercial and open-source products to guide clinical work and basic research.
ChildBrain has been structured along three interlinked scientific themes and work packages (WPs), in which the individual ESR projects have been carried out, and two network-wide training WPs.

1. Childhood neurodevelopmental disorders
WP1 focussed on neurocognitive disorders: dyslexia and attention-deficit hyperactivity disorder (ADHD), as well as neuronal changes due to cochlear implantation. Two projects focussed on ADHD, one investigating the relationship between brain structure and oscillatory brain activity with MEG in children with and without ADHD, and the other attentional sub-processes with EEG. Two projects investigated the brain basis of dyslexia. In one, biomarkers for dyslexia were explored using magnetic resonance imaging (MRI) revealing anatomical differences in specific reading-related regions of the brain present prior to reading instruction onset. The other dyslexia project explored the hemispheric asymmetry of language-related brain areas in dyslexia bridging the gap between the molecular genetic level and the behavioural outcome of dyslexia. The fifth project focused on cochlear implantation and the effects of restoration of auditory function on brain maturation using auditory steady state responses in EEG.

2. Brain development
WP2 examined how processing of sensory information in the brain changes with development and experience in children in four projects. One project focused on using MEG to characterize the developmental trajectory of functional and structural connectivity between brain areas and in relation to genetic profile. The second study worked on developing analysis methods for auditory brainstem-cortical connectivity patterns using EEG during very early development. The third study focussed, using MEG, on neural underpinnings of audiovisual integration during childhood as well as short- and long-term learning effects on brain activity. The fourth project studied timing and stability of brain responses, measured with EEG and MEG, as a function of maturation.

3. Brain research methods
WP3 introduced and evaluated methods for analysing brain data from children that make better use of accurate anatomical models and improved algorithms. One project focused on improved and automatic registration and segmentation for labelling of reduced-quality child MRIs. The second project developed, tested and validated novel child-adjusted anatomical and dMRI pipelines. The third project investigated a new approach for EEG analysis using fast acquisition of head surface and electrode information with a 3D camera. The fourth project developed and validated novel forward approaches for EEG and MEG source analysis. The fifth project investigated the use of somatosensory evoked potential and field data to calibrate the head model and thereby enable a combined analysis of EEG, MEG and MRI data for an improved presurgical epilepsy diagnosis. The sixth project focused on robust approaches for paediatric and clinical MEG source analysis, and on reduction of the effect of head movement during MEG data acquisition.

4. Training
Training was built through network-wide workshops and a winter and summer school, in addition to the local training containing scientific, theoretical, and methodological as well as transferable and entrepreneurial skill training. The major focus of the training was in interdisciplinary exposure, accomplished in the interaction and collaboration between the researchers with varied backgrounds in, for example, biomedical engineering, mathematics, and psychology. This focus was further strengthened by the interdisciplinary supervisory arrangements and visits to other research groups.

Dissemination and outreach
Outreach activities included a public science slam in the winter school, demonstrations and presentations at open lab days and science fairs, and lectures for the general public. Research news and public activities were published on ChildBrain web-site http://www.childbrain.eu/ Facebook page https://www.facebook.com/childbrain15/ and on Twitter (https://twitter.com/childbrainitn).
ChildBrain projects have produced new ways to analyse the child specific data of typically developing children and those with neurocognitive disorders. The knowledge produced in ChildBrain research increases understanding of these disorders, their brain signatures and risk-factors. This information is applicable for clinicians and educational practitioners. ChildBrain methodological development has resulted in both commercial applications and open source tools and pipelines available for wider research and user community.

Some highlights of ChildBrain outcomes:
Measuring the head shape fast and easy: youtube video https://www.youtube.com/watch?v=d6FZlZTf-Hg

How combining information from vision and hearing impact reading skills: https://www.frontiersin.org/articles/10.3389/fnhum.2018.00304/full

How attention processes can be measured in children using EEG: https://www.nature.com/articles/s41598-018-36947-3

User-friendly version of child head modeling for brain research: https://arxiv.org/abs/1901.02874
ChildBrain team in action
ChildBrain methodological approaches