Somatosensory prediction in premature neonates: iatrogenic pain experience increases repetition suppression and deviance detection of innocuous stimuli in a tactile oddball protocol

TL;DR

This study investigates how premature birth and neonatal pain exposure influence the development of somatosensory prediction in neonates, revealing that pain exposure accelerates certain neural markers of sensory processing.

Contribution

It provides novel evidence that painful neonatal procedures enhance neural indices of somatosensory prediction in premature infants, challenging assumptions about neurodevelopmental risk factors.

Findings

Premature neonates show neural markers of sensory prediction at 35 weeks GA.

Painful procedures increase the amplitude of neural responses related to prediction.

Higher pain exposure correlates with accelerated maturation of somatosensory processing.

Abstract

Sensory prediction (SP) is a fundamental mechanism of perception that supports cognitive development. Atypical SP has been reported across multiple neurodevelopmental disorders (ND), suggesting it may constitute an early cross-syndromic marker. Premature birth is a major risk factor for ND, with risk increasing as gestational age (GA) at birth decreases. However, how perinatal risk factors shape the development of SP remains poorly understood. We do not know if untimely birth itself, or exposure to iatrogenic pain during neonatal intensive care, cause neurodevelopmental impairments. In this study, we first assessed whether SP can be detected in the brains of premature neonates at 35 weeks corrected GA using a tactile oddballomission paradigm with EEG. We then examined the effects of the degree of prematurity and of the exposure to painful care procedures on neural indices of SP. Results demonstrate the presence of repetition suppression (RS) and a mismatch response (MMR) to deviant stimuli in the contralateral somatosensory cortex of premature neonates. The amplitude of these SP proxies was significantly affected by the number of painful procedures experienced since birth, independently of the effect of GA at birth. Contrary to our initial hypothesis that greater neurodevelopmental risk would be associated with less mature SP, infants with higher exposure to pain exhibited more robust indices of SP. These findings suggest that increased ex utero experience, even painful, is associated with accelerated maturation of predictive somatosensory processing. Longitudinal follow-up of participants at age 2 will explore how these early markers relate to developmental outcomes.