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Recording multimodal responses to sensory stimuli in infants provides an integrative approach to investigate the developing nervous system. Accurate time-locking across modalities is essential to ensure that responses are interpreted correctly, and could also improve clinical care, for example, by facilitating automatic and objective multimodal pain assessment. Here we develop and assess a system to time-lock stimuli (including clinically-required heel lances and experimental visual, auditory and tactile stimuli) to electrophysiological research recordings and data recorded directly from a hospitalised infant's vital signs monitor. The electronic device presented here (that we have called 'the PiNe box') integrates a previously developed system to time-lock stimuli to electrophysiological recordings and can simultaneously time-lock the stimuli to recordings from hospital vital signs monitors with an average precision of 105 ms (standard deviation: 19 ms), which is sufficient for the analysis of changes in vital signs. Our method permits reliable and precise synchronisation of data recordings from equipment with legacy ports such as TTL (transistor-transistor logic) and RS-232, and patient-connected networkable devices, is easy to implement, flexible and inexpensive. Unlike current all-in-one systems, it enables existing hospital equipment to be easily used and could be used for patients of any age. We demonstrate the utility of the system in infants using visual and noxious (clinically-required heel lance) stimuli as representative examples. [ABSTRACT FROM AUTHOR]

Infants in neonatal intensive care units frequently experience clinically necessary painful procedures, which elicit a range of behavioral, physiological, and neurophysiological responses. However, the measurement of pain in this population is a challenge and no gold standard exists. The aim of this study was to investigate how noxious-evoked changes in facial expression, reflex withdrawal, brain activity, heart rate, and oxygen saturation are related and to examine their accuracy in discriminating between noxious and non-noxious stimuli. In 109 infants who received a clinically required heel lance and a control non-noxious stimulus, we investigated whether combining responses across each modality, or including multiple measures from within each modality improves our ability to discriminate the noxious and non-noxious stimuli. A random forest algorithm was used to build data-driven models to discriminate between the noxious and non-noxious stimuli in a training set which were then validated in a test set of independent infants. Measures within each modality were highly correlated, while different modalities showed less association. The model combining information across all modalities had good discriminative ability (accuracy of 0.81 in identifying noxious and non-noxious stimuli), which was higher than the discriminative power of the models built from individual modalities. This demonstrates the importance of including multiple modalities in the assessment of infant pain., Competing Interests: The authors declare no conflicts of interest., (© 2019 The Authors. Paediatric and Neonatal Pain published by John Wiley & Sons Ltd.)