Abstract
SummaryBackgroundIn the absence of verbal communication, it is challenging to infer an individual's sensory and emotional experience. In communicative adults, functional MRI (fMRI) has been used to develop multivariate brain activity signatures, which reliably capture elements of human pain experience. We aimed to translate whole-brain fMRI signatures that encode pain perception in adults to the newborn infant brain, to advance understanding of functional brain development and pain perception in early life.MethodsIn this cross-sectional, observational study, we recruited adults at the University of Oxford (Oxford, UK) and infants on the postnatal wards of John Radcliffe Hospital (Oxford, UK). Healthy full-term infants were eligible for inclusion if they were clinically stable, self-ventilating in air, and had no neurological abnormalities. Infants were consecutively recruited in two cohorts (A and B) due to the installation of a new fMRI scanner using the same recruitment criteria. Adults (aged ≥18 years) were eligible if they were postgraduate students or staff at the University of Oxford. Participants were stimulated with low intensity nociceptive stimuli (64, 128, 256, and 512 mN in adults; 64 and 128 mN in infants) during acquisition of fMRI data. fMRI pain signatures (neurologic pain signature [NPS] and stimulus intensity independent pain signature-1 [SIIPS1]), and four control signatures (the vicarious pain signature, the picture-induced negative emotion signature [PINES], the social rejection signature, and a global signal signature) were applied directly to the adult data and translated to the infant brain. We assessed the concordance of the signatures with the brain responses of adults and infants using cosine similarity scores, and we assessed stimulus intensity encoding of the signature responses using a Spearman rank correlation test. We also assessed brain activity in pro-pain and anti-pain components of the signatures.FindingsBetween May 22, 2013, and Jan 29, 2018, we recruited ten healthy participants to the adult cohort (five women and five men; mean age 28·3 years [range 23–36]), 15 infants to infant cohort A (six girls and nine boys; mean postnatal age 4 days [range 1–11]), and 22 infants to infant cohort B (11 girls and 11 boys; mean postnatal age 3 days [range 1–10]). The NPS was activated in both the adults and infants, and reliably encoded stimulus intensity. The NPS was activated in the adult cohort (p<0·0001) and both infant cohorts (p=0·048 for infant cohort A; p=0·001 for infant cohort B). The SIIPS1 was only expressed in adults. Pro-pain brain regions showed similar activation patterns in adults and infants, whereas responses in anti-pain brain regions were divergent.InterpretationBasic intensity encoding of nociceptive information is similar in adults and infants. However, translation of adult brain signatures to infants indicated substantial differences in infant cerebral processing of nociceptive information, which might reflect their absence of expectation, motivation, and contextualisation associated with pain. This study expands the use of brain activity pain signatures to non-verbal patients and provides a potential research approach to assess the impact of analgesic interventions on brain function in infants.FundingWellcome Trust, Supporting the Sick Newborn and their Parents Medical Research Fund.
Highlights
In the absence of verbal communication, the perceptions of pain in infants are not known
Considering that pain perception is encoded by the brain, neuroimaging provides a proxy measure of neural activity that can be compared between infants and adults to make www.thelancet.com/digital-health Vol 2 September 2020
We have shown that the basic encoding of the sensory discriminative aspects of pain, as represented by the neurologic pain signature (NPS), occurs in both adults and infants, whereas higher-level cognitive modulation of pain, represented by the stimulus intensity independent pain signature-1, is only present in adults and not observed in infants
Summary
In the absence of verbal communication, the perceptions of pain in infants are not known. Behavioural cues such as grimacing and vocalisation are relied on to make inferences regarding an infant’s perception of pain,[1] which are broadly based on the experiences of older children and adults capable of verbalisation. Considering that pain perception is encoded by the brain, neuroimaging provides a proxy measure of neural activity that can be compared between infants and adults to make www.thelancet.com/digital-health Vol 2 September 2020
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