Download This Paper
Preprints with The Lancet is a collaboration between The Lancet Group of journals and SSRN to facilitate the open sharing of preprints for early engagement, community comment, and collaboration. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early-stage research papers that have not been peer-reviewed. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. The findings should not be used for clinical or public health decision-making or presented without highlighting these facts. For more information, please see the FAQs.
Inferring the Infant Pain Experience: A Translational fMRI-Based Signature Study
18 Pages Posted: 30 Jul 2020
More...Abstract
Background: In the absence of verbal communication it is challenging to infer an individual’s sensory and emotional experience. In communicative adults, fMRI has been used to develop multivariate brain activity signatures, which reliably capture elements of human pain experience. We 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.
Methods: A cohort of adults (n=10; mean age=28.3 years) and 2 cohorts of healthy infants (Cohort A: n=15; Cohort B: n=22; mean postnatal age=3 days) were stimulated with low intensity nociceptive stimuli (64-512mN) during acquisition of functional MRI data. fMRI pain signatures were applied directly to the adult data and transformed such that they could be applied to the infant brain. In each cohort, we assessed the concordance of the signatures with the brain responses using cosine-similarity scores, and we assessed stimulus intensity encoding of the signature responses using Spearman rank correlation. Brain activity in ‘pro-pain’ and ‘anti-pain’ components of the signatures were also examined.
Findings: The Neurologic Pain Signature (NPS), which reflects aspects of nociceptive pain experience, was activated in both the adults and infants, and reliably encoded stimulus intensity. However, the Stimulus Intensity Independent Pain Signature (SIIPS1), which reflects higher-level cognitive modulation of nociceptive input, was only expressed in adults. ‘Pro-pain’ brain regions showed similar activation patterns in adults and infants, whereas, ‘anti-pain’ brain regions exhibited divergent responses.
Interpretation: Basic intensity encoding of nociceptive information is similar in adults and infants. However, translation of adult brain signatures into infants reveals significant differences in infant cerebral processing of nociceptive information, which may reflect their lack of expectation, motivation and contextualisation. This study expands the use of brain activity pain signatures to non-verbal patients and provides a potential approach to assess analgesic interventions in infancy.
Funding Statement: This work was funded by Wellcome (Senior Research Fellowship awarded to Prof. Rebeccah Slater) and SSNAP “Support for Sick and Newborn Infants and their Parents” Medical Research Fund (University of Oxford Excellence Fellowship awarded to Dr Eugene Duff).
Declaration of Interests: Dr. Wager reports In addition, Dr. Wager has a patent US 2018/0055407 CU4199B-PPA1 issued. All other authors have nothing to declare.
Ethics Approval Statement: The infants were studied under ethical approval from the National Research Ethics Service and the adult study was granted approval by the University of Oxford Central University Research Ethics Committee. Both studies were conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines.
Keywords: pain, fMRI, infant, brain
Suggested Citation: Suggested Citation