Functional and diffusion MRI reveal the neurophysiological basis of neonates\u2019 noxious-stimulus evoked brain activity

Luke Baxter,Richard Rogers,Marianne Aspbury,Saad Jbabdi,Rebeccah Slater,Fiona Moultrie,Matteo Bastiani,Roshni Mansfield,Eugene Duff,Sean Fitzgibbon

doi:10.1038/s41467-021-22960-0

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-stimulus evoked brain activity. We observe 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-stimulus evoked responses and white matter mean diffusivity. These associations are subsequently confirmed in the original noxious stimulation paradigm dataset, validating the prediction model. Here, we observe that noxious-stimulus evoked brain activity in healthy neonates is coupled to 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.

Highlights

Understanding the neurophysiology underlying neonatal responses to noxious stimulation is central to improving early life pain management
We focus on 16 white matter tracts previously used in a recent Developing Human Connectome Project (dHCP) diffusion MRI (dMRI) publication[35] and three tensor model parameters generated by the dHCP dMRI preprocessing pipeline[35]: mean diffusivity (MD), fractional anisotropy (FA), and mean kurtosis (MK)
Using resting-state fMRI and white matter dMRI, we show that both local and global features of resting-state activity and white matter microstructure provide insight into the neurophysiological basis for neonatal cerebral responses to noxious stimulation

Summary

Introduction

Understanding the neurophysiology underlying neonatal responses to noxious stimulation is central to improving early life pain management. We observe 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-stimulus evoked responses and white matter mean diffusivity. Due to the emergent and multifaceted nature of pain[14,15], we focus on assessing the overall BOLD response amplitude While this BOLD response neither directly reflects nociception, the neural process of encoding noxious stimuli[16], nor pain perception, the unpleasant sensory and emotional subjective experience[16], it is a pertinent and accessible feature of central importance to understanding neonates’ neural responses to noxious input and the neurophysiology of the early developing pain system.

Methods

Results

Conclusion