Abstract
Fetal and neonatal brain connectivity development is highly complex. Studies have shown that functional networks change dramatically during development. The purpose of the current study was to determine how the mean phase lag index (mPLI), a measure of functional connectivity (FC), assessed with electroencephalography (EEG), changes with postmenstrual age (PMA) during the early stages of brain development after birth. Neonates (N = 131) with PMA 27.6–45.3 weeks who underwent an EEG for a medical reason were retrospectively studied. For each recording, global FC was assessed by obtaining a whole-head average of all local PLI values (pairwise between sensor space EEG signals). Global FC results were consequently correlated with PMA values in seven frequency bands. Local results were obtained for the frequency band with the strongest global association. There was a strong negative correlation between mPLI and PMA in most frequency bands. The strongest association was found in the delta frequency band (R = −0.616, p < 0.001) which was therefore topographically explored; the strongest correlations were between pairs of electrodes with at least one electrode covering the central sulcus. Even in this heterogeneous group of neonates, global FC strongly reflects PMA. The decrease in PLI may reflect the process of segregation of specific brain regions with increasing PMA. This was mainly found in the central brain regions, in parallel with myelination of these areas during early development. In the future, there may be a role for PLI in detecting atypical FC maturation. Moreover, PLI could be used to develop biomarkers for brain maturation and expose segregation processes in the neonatal brain.
Highlights
The development of the fetal and neonatal brain is highly complex
The objective of this study is to investigate how the phase lag index’’ (PLI) develops over time during the very early stages of brain development in a diverse group of preterm and full-term born neonates who underwent an EEG in clinical practice
The group consisted of 131 subjects with postmenstrual age (PMA) between 27–46 weeks, in whom an EEG had been recorded for a medical reason
Summary
The development of the fetal and neonatal brain is highly complex. The brain follows an elaborate developmental trajectory, involving the formation of 10 billion cortical neurons, which migrate from their origin in the ventricular and the laterformed sub-ventricular zones to their final position and start to grow their own synaptic connections (van den Heuvel et al, 2015; Fernández et al, 2016). Myelination is already seen in the white matter by 28 weeks, and between 34 and 46 weeks it becomes more prominently visible in the cortex bordering the central sulcus, extending in the posterior limb of the internal capsule (Sie et al, 1997; Counsell et al, 2002) These highly plastic changes make it a challenge to study the active neonatal brain, and to distinguish normal from abnormal development patterns. The signals that are recorded with the electrodes reflect synchronous neuronal activity of the cortex, in particular excitatory and inhibitory post-synaptic potentials of pyramidal cells in layer three and five related to synaptic currents. Little is known about the development of functional brain networks in these early stages
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