Neurovascular coupling refers to the mechanism that links the transient neural activity to the subsequent change in cerebral blood flow, which is regulated by both chemical signals and mechanical effects. Recent studies suggest that neurovascular coupling in neonates and preterm born infants is different compared to adults. The hemodynamic response after a stimulus is later and less pronounced and the stimulus might even result in a negative (hypoxic) signal. In addition, studies both in animals and neonates confirm the presence of a short hypoxic period after a stimulus in preterm infants. In clinical practice, different methodologies exist to study neurovascular coupling. The combination of functional magnetic resonance imaging or functional near-infrared spectroscopy (brain hemodynamics) with EEG (brain function) is most commonly used in neonates. Especially near-infrared spectroscopy is of interest, since it is a non-invasive method that can be integrated easily in clinical care and is able to provide results concerning longer periods of time. Therefore, near-infrared spectroscopy can be used to develop a continuous non-invasive measurement system, that could be used to study neonates in different clinical settings, or neonates with different pathologies. The main challenge for the development of a continuous marker for neurovascular coupling is how the coupling between the signals can be described. In practice, a wide range of signal interaction measures exist. Moreover, biomedical signals often operate on different time scales. In a more general setting, other variables also have to be taken into account, such as oxygen saturation, carbon dioxide and blood pressure in order to describe neurovascular coupling in a concise manner. Recently, new mathematical techniques were developed to give an answer to these questions. This review discusses these recent developments.

Graphs can be used to describe a great variety of real-world situations and have therefore been used extensively in different fields. In the present analysis, we use graphs to study the interaction between cerebral function, brain hemodynamics, and systemic variables in premature neonates. We used data from a propofol dose-finding and pharmacodynamics study as a model in order to evaluate the performance of the graph measures to monitor signal interactions. Concomitant measurements of heart rate, mean arterial blood pressure, arterial oxygen saturation, regional cerebral oxygen saturation-measured by means of near-infrared spectroscopy-and electroencephalography were performed in 22 neonates undergoing INSURE (intubation, surfactant administration, and extubation). The graphs used to study the interaction between these signal modalities were constructed using the RBF kernel. Results indicate that propofol induces a decrease in the signal interaction up to 90 minutes after propofol administration, which is consistent with clinical observations published previously. The clinical recovery phase is mainly determined by the EEG dynamics, which were observed to recover much slower compared to the other modalities. In addition, we found a more pronounced loss in cerebral-systemic interactions with increasing propofol dose.

BACKGROUND The altered neurodevelopment of children operated on during the neonatal period might be due to perioperative changes in the homeostasis of brain perfusion. Monitoring of vital signs is a standard of care, but it does not usually include monitoring of the brain. OBJECTIVES To evaluate methods of monitoring the brain that might be of value. We also wanted to clarify if there are specific risk factors that result in peri-operative changes and how this might be evaluated. DESIGN Systematic review. DATA SOURCES A structured literature search was performed in MEDLINE in Ovid, Embase, Cochrane CENTRAL, Web of Science and Google Scholar. ELIGIBILITY CRITERIA Studies in neonates who received peri-operative neuromonitoring were eligible for inclusion; studies on neurosurgical procedures or cardiac surgery with cardiopulmonary bypass and/or deep hypothermia cardiac arrest were excluded. RESULTS Nineteen of the 24 included studies, totalling 374 infants, reported the use of near-infrared spectroscopy. Baseline values of cerebral oxygenation greatly varied (mean 53 to 91%) and consequently, no coherent results were found. Two studies found a correlation between cerebral oxygenation and mean arterial blood pressure. Five studies, with in total 388 infants, used (amplitude-integrated) electroencephalography to study peri-operative brain activity. Overall, the brain activity decreased during anaesthesia and epileptic activity was more frequent in the peri-operative phase. The association between intra-operative cerebral saturation or activity and neuro-imaging abnormalities and/ or neurodevelopmental outcome was investigated in six studies, but no association was found. CONCLUSION Neuromonitoring with the techniques currently used will neither help our understanding of the altered neonatal pathophysiology, nor enable early detection of deviation from the norm. The modalities lack specificity and are not related to clinical (long-term) outcome or prognosis. Accordingly, we were unable to draw up a monitoring guideline.