5.8 Clinical and Genetic Influences on Functional Brain Networks in Preterm Infants

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Abstract

Preterm birth is associated with adverse neurodevelopmental outcomes. The pathological mechanisms leading to adverse outcomes involve several pathways, which are not fully understood. Current methods of assessing neurological injury associated with preterm birth have limited scope and low prognostic value. Whilst structural MRI may provide detailed anatomical information about the neonatal brain, there is imperfect mapping between structure and function. A supplementary approach is the use of functional MRI (fMRI) to infer functional connectivity (FC), evaluating integration of neural activity within the brain. There is emerging evidence that children who were born preterm show long term changes in FC, and early detection of such changes offers potential to improve understanding of pathophysiology of preterm brain injury. These functional changes may be influenced by both neonatal course and underlying susceptibilities to abnormal development, including genetic risk factors.

We used resting state fMRI (rs-fMRI) at 3T to examine functional brain connectivity in 20 infants born at <32 weeks of gestation, scanned at term. Infants also had genetic testing to examine polymorphisms in the EAAT2 glutamate transporter, previously associated with variation in preterm neurodevelopmental outcomes. Using a multivariate model to examine the independent contributions of demographic, genetic and clinical characteristics of the infants to FC, we identified multiple dissociable influences on functional brain networks. This is the first report of genetic variability in cerebral glutamate homeostasis influencing neonatal brain connectivity. We discuss the impact on understanding preterm brain injury, and the potential for predicting neurodevelopmental outcome by non-invasive measurement of functional brain connectivity.

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