Original Research ARTICLE
Early pain exposure influences functional brain connectivity in very preterm neonates
- 1Neuroradiology Unit, Giannina Gaslini Institute (IRCCS), Italy
- 2Neonatal Intensive Care Unit, Giannina Gaslini Institute (IRCCS), Italy
- 3Child Neuropsychiatry Unit, Giannina Gaslini Institute (IRCCS), Italy
Early exposure to nociceptive events may cause brain structural alterations in preterm neonates (PN), with long-lasting consequences on neurodevelopmental outcome. Little is known on the extent to which early pain may affect brain connectivity. We aim to evaluate brain functional connectivity changes in PN that underwent multiple invasive procedures during the postnatal period, and to correlate them with the neurodevelopmental outcome at 24 months.
In this prospective case-control study, we collected information about exposure to painful events during the early postnatal period and resting-state BOLD-fMRI data at term equivalent age from two groups of PN: 33 subjected to painful procedures during the neonatal intensive care (mean gestational age 26.9±1.8 weeks) and 13 who did not require invasive procedures (average gestational age 31.2±2.1 weeks). A data-driven principal-component-based multivariate pattern analysis (MVPA) was used to investigate the effect of early pain exposure on brain functional connectivity, and the relationship between connectivity changes and neurodevelopmental outcome at 24 months, assessed with Griffiths’Developmental Scale-Revised:0-2.
Early pain was associated with decreased functional connectivity between thalami and bilateral somatosensory cortex, and between the right insular cortex and ipsilateral amygdala and hippocampal regions, with a more evident effect in PN undergoing more invasive procedures. Functional connectivity of the right thalamocortical pathway was related to neuromotor outcome at 24 months (P=.003).
Early exposure to pain is associated with abnormal functional connectivity of developing networks involved in the modulation of noxious stimuli in PN, contributing to the neurodevelopmental consequence of preterm birth.
Keywords: Preterm neonatal brain, fMRI, Pain, Functional Connectivity, neonatal neuroimaging, nociceceptive modulation, brain connectitvity, resting state
Received: 14 Apr 2019;
Accepted: 12 Aug 2019.
Edited by:Alessandra Griffa, VU University Amsterdam, Netherlands
Reviewed by:Chiara Nosarti, King's College London, United Kingdom
Ruth E. Grunau, University of British Columbia, Canada
Lynne J. Williams, BC Children's Hospital MRI Research Facility, Canada
Lorenzo Fabrizi, University College London, United Kingdom
Copyright: © 2019 Tortora, Severino, Di Biase, Malova, Parodi, Minghetti, Traggiai, Uccella, Boeri, Morana, Rossi and Ramenghi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Dr. Domenico Tortora, Giannina Gaslini Institute (IRCCS), Neuroradiology Unit, Genoa, Italy, email@example.com
Dr. Andrea Rossi, Giannina Gaslini Institute (IRCCS), Neuroradiology Unit, Genoa, Italy, firstname.lastname@example.org