The rise of synergistic structure in the newborn brain

1227 

Abstract Submission 

Anton Tokariev¹, Thomas Varley², Michael Myers³, Martha Welch³, Sampsa Vanhatalo¹, Olaf Sporns²

¹University of Helsinki, Helsinki, Finland, ²Indiana University, Bloomington, IN, ³Columbia University Medical Center, New York, NY

Anton Tokariev  
University of Helsinki
Helsinki, Finland

Thomas Varley  
Indiana University
Bloomington, IN

Michael Myers  
Columbia University Medical Center
New York, NY

Martha Welch  
Columbia University Medical Center
New York, NY

Sampsa Vanhatalo  
University of Helsinki
Helsinki, Finland

Olaf Sporns  
Indiana University
Bloomington, IN

During the third trimester infant human brain actively self-organises into a unified complex system. Discrete local neurons wire together, their populations connect into large-scale networks, which, in turn, cooperate on a global scale. This happens at both structural and functional levels. Neural dynamics of the whole brain goes far beyond just the sum of its individual elements and this property is known as "synergy". Previously it was shown that synergy is crucial for many complex brain functions and cognition. But the timing of emergence and early formation principles of synergistic system in the human brain is currently unknown. We hypothesized that changing patterns of synergy would be seen during early development of the infant brain, and that the emergence of a consolidated "synergistic scaffold" would be associated with the later neurocognitive performance at individual level.

In this study, we analysed high-density (124-channels) longitudinal EEG data collected from preterm infants (N = 135; born at 31 ± 2.4 weeks) and spanning over period from the third trimester to postnatal age (33–45 weeks). Each subject had 1–3 recordings done during daytime sleep (in total N = 289 recordings). The general cohort included standard care infants (SC; N = 61) and those participated in Family Nurture Intervention (FNI; N = 74) program, which was aimed to enhance mother-infant emotional connection. Artifact-free 5-min-long epochs of quiet sleep EEG were filtered into delta (1.5–4 Hz), theta (4–8 Hz), alpha (8–13 Hz), and beta (13–22 Hz) frequency bands. The filtered signals were source reconstructed into 58 cortical parcel activity using a realistic infant head model and dynamic statistical parametric mapping approach. Next, we estimated O-information (measure of higher-order structure showing the balance between redundancy and synergy) from cortical activity of each infant and correlated to their age (Spearman). Further, we computed nodal frequencies of being a part of the "synergistic scaffold" across different age groups. The developmental trajectories of O-information for each group were computed as mean values in a two-weeks-wide sliding windows and compared within each age bin using two-sample t-test. Finally, we correlated O-information levels at term equivalent age to cognitive outcomes (Bayley) at 18 months.

We found that at ages corresponding to the third trimester, infant brain organization dynamically changes from redundant to synergy-dominated with O-information negatively correlating to age at all frequencies (rho < −0.42, p < 0.001; see Fig.1A for theta band). The size of the "synergistic scaffold" was also increasing with maturation (Fig.1A left). Spatially (Fig.1B), the scaffold mostly consisted of frontal nodes at preterm age (33–36 weeks), but then it expanded over visual areas before term (37–40 weeks) and further incorporated central and temporal cortices during early postnatal period (40–43 weeks). Strikingly, our analysis revealed different developmental trajectories (Fig.1C) between clinical cohorts (SC vs. FNI) with significant group differences at 35 and 38 weeks (p < 0.01). FNI infants showed a steadily decreasing trend, while SC showed bi-phasic trajectory: redundancy was slightly increasing until 38th week ("plateau" phase) followed by abrupt changes towards synergetic structure ("steep" phase). Finally, O-information values around term age were negatively correlated to later cognitive assessments (Fig.1C; rho = −0.45, p = 0.004) suggesting that brain synergy may be a biomarker of future neurodevelopment.

Our results suggest that starting from the third trimester infant human brain rapidly develops synergetic structure and that this predicts later clinical outcomes. Moreover, support of natural mother-infant connection (environmental enrichment) modulates the developmental trajectory of these changes and associates with more gradual reorganization processes in the maturing brain.

Early life, Adolescence, Aging ¹

Normal Brain Development: Fetus to Adolescence ²

Cortex

Development

Electroencephaolography (EEG)

PEDIATRIC

Sleep