Functional and diffusion MRI reveal the functional and structural basis of infants’ noxious-evoked brain activity

Abstract Understanding the neurophysiology underlying neonatal responses to noxious stimulation is central to improving early life pain management. In this neonatal multimodal MRI study, we use resting-state and diffusion MRI to investigate inter-individual variability in noxious-evoked brain activity. We demonstrate that cerebral haemodynamic responses to experimental noxious stimulation can be predicted from separately acquired resting-state brain activity (n=18). Applying this prediction model to independent Developing Human Connectome Project data (n=215), we identify negative associations between predicted noxious-evoked responses and white matter mean diffusivity. These associations are subsequently confirmed in the original noxious stimulation paradigm dataset, validating the prediction model. This study in healthy neonates demonstrates that noxious-evoked brain activity is tightly coupled to both resting-state activity and white matter microstructure, that neural features can be used to predict responses to noxious stimulation, and that the dHCP dataset could be utilised for future exploratory research of early life pain system neurophysiology.