Detection of regularities in auditory sequences before and at term-age in human neonates.

During the last trimester of gestation, fetuses and preterm neonates begin to respond to sensory stimulation and to discover the structure of their environment. Yet, neuronal migration is still ongoing. This late migration notably concerns the supra-granular layers neurons, which are believed to play a critical role in encoding predictions and detecting regularities. In order to gain a deeper understanding of how the brain processes and perceives regularities during this stage of development, we conducted a study in which we recorded event-related potentials (ERP) in 31-wGA preterm and full-term neonates exposed to alternating auditory sequences (e.g. "ba ga ba ga ba"), when the regularity of these sequences was violated by a repetition (e.g., ``ba ga ba ga ga''). We compared the ERPs in this case to those obtained when violating a simple repetition pattern ("ga ga ga ga ga" vs. "ga ga ga ga ba"). Our results indicated that both preterm and full-term neonates were able to detect violations of regularity in both types of sequences, indicating that as early as 31 weeks gestational age, human neonates are sensitive to the conditional statistics between successive auditory elements. Full-term neonates showed an early and similar mismatch response (MMR) in the repetition and alternating sequences. In contrast, 31-wGA neonates exhibited a two-component MMR. The first component which was only observed for simple sequences with repetition, corresponded to sensory adaptation. It was followed much later by a deviance-detection component that was observed for both alternation and repetition sequences. This pattern confirms that MMRs detected at the scalp may correspond to a dual cortical process and shows that deviance detection computed by higher-level regions accelerates dramatically with brain maturation during the last weeks of gestation to become indistinguishable from bottom-up sensory adaptation at term.

The frontal sharp transient in newborns: An endogenous neurobiomarker concomitant to the physiological and critical transitional period around delivery?

The frontal sharp transient (FST) consists of transient electrical activity recorded around the transitional period from the in to ex utero environment. Although its positive predictive value is assumed, nothing is known about its functionality or origin. The objectives were (i) to define its characteristics and (ii) to develop functional hypothesis. The 128-channels high-resolution electroencephalograms of 20 healthy newborns (37.1-41.6 weeks) were studied. The morphological and time-frequency characteristics of 418 FSTs were analyzed. The source localization of the FSTs was obtained using a finite element head model (5 layers and fontanels) and various source localization methods (distributed and dipolar). The characteristics (duration, slopes, and amplitude) and the localization of FSTs were not modulated by the huge developmental neuronal processes that occur during the very last period of gestation. The sources were located beneath the ventral median part of the frontal lobe around the interhemispheric fissure, suggesting that the olfactory bulbs and orbitofrontal cortex, essential in olfaction and the mother-infant attachment relationship, are likely candidates for the generation of FSTs. FSTs may contribute to the implementation of the functionalities of brain structures involved in the higher-order processing necessary for survival ahead of delivery, with a genetic fingerprint.

The intimate relationship between coalescent generators in very premature human newborn brains: Quantifying the coupling of nested endogenous oscillations.

Temporal theta slow-wave activity (TTA-SW) in premature infants is a specific neurobiomarker of the early neurodevelopment of perisylvian networks observed as early as 24 weeks of gestational age (wGA). It is present at the turning point between non-sensory driven spontaneous networks and cortical network functioning. Despite its clinical importance, the underlying mechanisms responsible for this spontaneous nested activity and its functional role have not yet been determined. The coupling between neural oscillations at different timescales is a key feature of ongoing neural activity, the characteristics of which are determined by the network structure and dynamics. The underlying mechanisms of cross-frequency coupling (CFC) are associated with several putative functions in adults. In order to show that this generic mechanism is already in place early in the course of development, we analyzed electroencephalography recordings from sleeping preterm newborns (24-27 wGA). Employing cross-frequency phase-amplitude coupling analyses, we found that TTAs were orchestrated by the SWs defined by a precise temporal relationship. Notably, TTAs were synchronized to the SW trough, and were suppressed during the SW peak. Spontaneous endogenous TTA-SWs constitute one of the very early signatures of the developing temporal neural networks with key functions, such as language and communication. The presence of a fine-tuned relationship between the slow activity and the TTA in premature neonates emphasizes the complexity and relative maturity of the intimate mechanisms that shape the CFC, the disruption of which can have severe neurodevelopmental consequences.