Despite over 65 years of electroencephalography (EEG) in newborn infants, our understanding of the rhythmic cortical activity patterns associated with normal development and brain injury remains largely speculative. The long term goal of the current project is to create a developmental activity atlas in which abberant EEG patterns in the at-risk newborn are matched to specific disruptions in brain areas and neuronal types. A first step towards this goal requires an un-anesthetized preclinical model with demonstrated homology to fetal and neonatal human cortical activity in which cells can be genetically manipulated and the underlying effects on cortical circuits rigorously probed. By measuring activity in vivo through the depth of cortex and corresponding thalamic networks in developing neonatal rodents, we will provide insight into the circuit changes that may underlie human fetal thalamo-cortical development to inform future studies of subcortical injury in infants and non-human primates. By manipulating the activity of thalamic neurons we will assay the distinct contributions of the thalamic relay and inhibitory neurons to the maturation of specific features of the EEG common to developing humans and rodents. Given the challenges of imaging and diagnosis in the fragile at-risk newborn, EEG has the potential to be a valuable and inexpensive bedside diagnostic tool. An improved understanding of the control of cortical activity development will inform diagnosis after neonatal brain injury and improve targeting of treatments for the cognitive and intellectual disability that often results.
The electroencephalogram (EEG) is an essential tool for diagnosis of neurological problems in newborn infants, yet we know little about the neural circuits that produce the EEG signal at this age. This project will explore the contribution of cortical and sub-cortical neuronal activity to the rapid developmental changes observed a validated animal model of EEG development. Our long term objective is to apply knowledge gained from the animal model to the developing infant EEG to improve diagnosis of neonatal brain injury, allow more targeted treatments, and improve neurological outcome for infants at risk of brain injury.
