Neuroimaging of neonatal nociception

Thesis

Newborn infants undergo painful procedures during standard clinical care. However, pain assessment in non-verbal infants is challenging. Improving understanding of infant pain neurophysiology, including anticipating pain responses, is central to improving pain management. Magnetic resonance imaging (MRI) is an ideal technique for examining the structure and function of the infant pain system, allowing whole-brain coverage at relatively high spatial resolutions. However, major differences between the adult and infant brain necessitate the use of infant- optimised data analysis methods.

The first study involved outlining and validating an optimised infant noxious- response functional MRI data analysis pipeline to improve data quality. Using a cohort of 15 healthy newborn infants, five key analysis steps were assessed. Adopting the Developing Human Connectome Project functional MRI preprocessing pipeline improved motion and distortion correction and spatial normalisation outputs, and including spatial ICA-based denoising and minimal spatial filtering furthered these improvements. Of three term infant haemodynamic response function parameterisations, the double gamma function was most suitable. Relative to a standard adult analysis pipeline adapted for infants, the infant-optimised pipeline significantly improved data quality.

The second study involved predicting infants’ cerebral haemodynamic noxious- response amplitudes from resting-state activity demonstrating the potential for infant-unique brain activity to inform infant pain management. Using a cohort of 18 healthy newborn infants, nine resting-state networks were robustly identifiable, and the infants’ resting-state network amplitudes predicted noxious-response amplitudes with statistically significant accuracy. Noxious-response amplitudes were related to white matter complexity using diffusion MRI, suggesting the response amplitudes were infant trait effects. Finally, the specific pattern of functional and structural neural correlates of the haemodynamic noxious-response amplitudes suggested the responses reflected brain maturity.

This work advances our understanding of the newborn infant’s pain system, un- derscores the central importance of MRI in furthering this basic understanding, and helps form the foundations on which further infant pain research can be conducted.

Authors: Baxter, L

• DOI: 10.5287/ora-bdv2pjjrn
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: noxious; developing human connectome project; diffusion magnetic resonance imaging; fMRI; preprocessing; infant; functional magnetic resonance imaging; pain; dMRI
• Subjects: Newborn infants; Pain; Magnetic resonance imaging