Neuronal coupling modes show differential development in the early cortical activity networks of human newborns.

The third trimester is a critical period for the development of functional networks that support the lifelong neurocognitive performance; yet the emergence of neuronal coupling in these networks is poorly understood. Here, we used longitudinal high-density electroencephalographic (EEG) recordings from preterm infants during the period from 33 to 45 weeks of conceptional age to characterize early spatiotemporal patterns in the development of local cortical function and the intrinsic coupling modes (phase-phase, amplitude-amplitude, and phase-amplitude correlations). Absolute local power showed a robust increase with conceptional age across the full frequency spectrum, while local phase-amplitude correlations showed sleep state -specific, biphasic development that peaked a few weeks before normal birth. Amplitude-amplitude and distant phase-amplitude correlations decreased globally at nearly all frequencies. In contrast, the phase-phase correlations showed frequency- and region-selective development, with an increase of coupling strength with conceptional age between frontal, central, and occipital regions at low-delta and alpha frequencies together with a wider-spread decrease at other frequencies. Our findings together present the spectrally and spatially differential development of the distinct intrinsic coupling modes during the neonatal period and provide their developmental templates for future basic and clinical research.Significance statement Neuronal activity coupling in cortical networks is a fundamental mechanism underlying higher brain functions. However, emergence of these functional networks within the structural connectome at early maturation is poorly understood. Here, we study the human development of cortical function and distinct neuronal coupling modes (amplitude-amplitude, phase-phase, and phase-amplitude coupling) by investigating longitudinal high-density electroencephalographic recordings in preterm-born infants and discussing their potential links to established neurophysiological processes. Our findings disclose robust, spatially and spectrally specific developmental trajectories for all coupling modes to be used as developmental baselines for future research. The findings together indicate that neuronal coupling modes develop independently during the early neonatal period, supporting the notion that these modes reflect different coupling mechanisms and should be considered separately.

Transcranial magnetic stimulation set-up for small animals.

Transcranial magnetic stimulation (TMS) is widely applied on humans for research and clinical purposes. TMS studies on small animals, e.g., rodents, can provide valuable knowledge of the underlying neurophysiological mechanisms. Administering TMS on small animals is, however, prone to technical difficulties, mainly due to their small head size. In this study, we aimed to develop an energy-efficient coil and a compatible experimental set-up for administering TMS on rodents. We applied a convex optimization process to develop a minimum-energy coil for TMS on rats. As the coil windings of the optimized coil extend to a wide region, we designed and manufactured a holder on which the rat lies upside down, with its head supported by the coil. We used the set-up to record TMS-electromyography, with electromyography recorded from limb muscles with intramuscular electrodes. The upside-down placement of the rat allowed the operator to easily navigate the TMS without the coil blocking their field of view. With this paradigm, we obtained consistent motor evoked potentials from all tested animals.

Facilitating early parent-infant emotional connection improves cortical networks in preterm infants.

Exposure to environmental adversities during early brain development, such as preterm birth, can affect early brain organization. Here, we studied whether development of cortical activity networks in preterm infants may be improved by a multimodal environmental enrichment via bedside facilitation of mother-infant emotional connection. We examined functional cortico-cortical connectivity at term age using high-density electroencephalography recordings in infants participating in a randomized controlled trial of Family Nurture Intervention (FNI). Our results identify several large-scale, frequency-specific network effects of FNI, most extensively in the alpha frequency in fronto-central cortical regions. The connectivity strength in this network was correlated to later neurocognitive performance, and it was comparable to healthy term-born infants rather than the infants receiving standard care. These findings suggest that preterm neurodevelopmental care can be improved by a biologically driven environmental enrichment, such as early facilitation of direct human connection.

Phase-Based Cortical Synchrony Is Affected by Prematurity.

Inter-areal synchronization by phase-phase correlations (PPCs) of cortical oscillations mediates many higher neurocognitive functions, which are often affected by prematurity, a globally prominent neurodevelopmental risk factor. Here, we used electroencephalography to examine brain-wide cortical PPC networks at term-equivalent age, comparing human infants after early prematurity to a cohort of healthy controls. We found that prematurity affected these networks in a sleep state-specific manner, and the differences between groups were also frequency-selective, involving brain-wide connections. The strength of synchronization in these networks was predictive of clinical outcomes in the preterm infants. These findings show that prematurity affects PPC networks in a clinically significant manner, suggesting early functional biomarkers of later neurodevelopmental compromise that may be used in clinical or translational studies after early neonatal adversity.