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PROBIt Report Summary

Project ID: 682734
Funded under: H2020-EU.1.1.

Periodic Reporting for period 1 - PROBIt (Identifying Predictors of Risk and Resilience for poor neuropsychological Outcome following childhood Brain InsulTs (PROBIt))

Reporting period: 2016-09-01 to 2018-02-28

Summary of the context and overall objectives of the project

The impact of insults to the developing brain upon cognition and behaviour has far-reaching consequences for the child, their family, education and health care systems, and government expenditure. Many variables (illness, environmental) contribute to different outcomes following similar insults, and they exert their influence via the child’s developing brain. Predicting which child will recover from early brain insult and identifying those at risk of poor outcome represents a major challenge, with significant health economic implications. An unexplored question is whether direct measurement of the structure and function of the developing brain can improve our ability to predict outcomes in the long-term. Thus, PROBIt aims to assess the utility of brain imaging biomarkers to predict individual neuropsychological and neurobehavioural outcomes following paediatric brain injury, and to identify those factors that combine optimally to classify outcomes. The proposal adopts an unorthodox approach of combining heterogeneous injury groups to explore the structural and functional consequences of perturbing developing brain networks. PROBIt integrates data from clinically relevant paediatric cognitive and behavioural assessment, neuroimaging and computational modelling in large cohorts of children with brain insults. Multivariate pattern analysis will be used to train a statistical classifier to reliably predict individual child outcomes across three core domains: achievement, behaviour and cognitive ability. PROBIt significantly advances our understanding of features that confer risk and resilience to different neurodevelopmental outcomes and has important implications for clinical diagnosis and rehabilitation of children with early brain insults.

PROBIt's aims will be achieved by completing the following objectives:
1) To establish well-characterised, longitudinal cohorts of children with prenatal and early childhood brain injuries
2) To examine the utility of paediatric brain imaging markers to predict long-term outcomes
3) To determine which imaging modality best predicts different neurodevelopmental outcomes
4) To characterise and test an index of ‘developmental divergence’ to predict outcomes
5) To understand how constitutional and environmental factors contribute to the relationship between
early brain injury and later neuropsychological outcome
6) To perform multivariate pattern analysis, combining brain imaging and clinical data
These objectives (Ob1-Ob6) will cut across three domains that have critical links to children’s future potential: Achievement, Behaviour, and Cognitive ability.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

In the first reporting period we have established an excellent team of young scholars. PROBIt attracts interest from a range of potential collaborators and although we anticipated recruiting from one site in the UK, we have the potential to open up at four others should the need arise.

Work on our existing dataset has led to new analysis methods being developed in the group. This dataset was always intended to act as a ‘test bed’ for analysis pipelines and it has proved extremely fruitful. The PROBIt team will submit eight manuscripts arising directly from our first 18 months work for publication this year. These are in addition to the planned deliverables set out in the original application.

We are conducting new qualitative research to establish current practice in our field so that we are in a position to measure the impact of the eventual study results on the intended stakeholders and society more generally.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Current practice in paediatric neuroimaging excludes or ignores the impact of brain lesions on quantitative measures of brain structure and function. This work is highly challenging and our team is developing new approaches to retain those data so that we can achieve our goal of predicting outcomes at the individual child level. We expect to identify which quantitative MRI measures are the best predictors of long-term outcome. We will characterise neurodevelopmental outcomes for new cohorts for the first time and deliver critical studies on child brain image analysis to the field.
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