Revisiting the functional monitoring of brain development in premature neonates. A new direction in clinical care and research

The first 1000 days of life are of paramount importance for neonatal development. Premature newborns are exposed early to the external environment, modifying the fetal exposome and leading to overexposure in some sensory domains and deprivation in others. The resulting neurodevelopmental effects may persist throughout the individual's lifetime. Several neonatal neuromonitoring techniques can be used to investigate neural mechanisms in early postnatal development. EEG is the most widely used, as it is easy to perform, even at the patient's bedside. It is not expensive and provides information with a high temporal resolution and relatively good spatial resolution when performed in high-density mode. Functional near-infrared spectroscopy (fNIRS), a technique for monitoring vascular network dynamics, can also be used at the patient's bedside. It is not expensive and has a good spatial resolution at the cortical surface. These two techniques can be combined for simultaneous monitoring of the neuronal and vascular networks in premature newborns, providing insight into neurodevelopment before term. However, the extent to which more general conclusions about fetal development can be drawn from findings for premature neonates remains unclear due to considerable differences in environmental and medical situations. Fetal MEG (fMEG, as an alternative to EEG for preterm infants) and fMRI (as an alternative to fNIRS for preterm infants) can also be used to investigate fetal neurodevelopment on a trimester-specific basis. These techniques should be used for validation purposes as they are the only tools available for evaluating neuronal dysfunction in the fetus at the time of the gene-environment interactions influencing transient neuronal progenitor populations in brain structures. But what do these techniques tell us about early neurodevelopment? We address this question here, from two points of view. We first discuss spontaneous neural activity and its electromagnetic and hemodynamic correlates. We then explore the effects of stimulating the immature developing brain with information from exogenous sources, reviewing the available evidence concerning the characteristics of electromagnetic and hemodynamic responses. Once the characteristics of the correlates of neural dynamics have been determined, it will be essential to evaluate their possible modulation in the context of disease and in at-risk populations. Evidence can be collected with various neuroimaging techniques targeting both spontaneous and exogenously driven neural activity. A multimodal approach combining the neuromonitoring of different functional compartments (neuronal and vascular) is required to improve our understanding of the normal functioning and dysfunction of the brain and to identify neurobiomarkers for predicting the neurodevelopmental outcome of premature neonate and fetus. Such an approach would provide a framework for exploring early neurodevelopment, paving the way for the development of tools for earlier diagnosis in these vulnerable populations, thereby facilitating preventive, rescue and reparative neurotherapeutic interventions.