medRxiv
Enhanced local synchronization with impaired large-scale recruitment of NREM slow waves in pediatric disorders of arousal
By Bergamo, D., Pereno, M., Lombardi, G. and 5 others.
Abstract
NREM slow waves emerge from the synchronization of neuronal activity across multiple spatial scales. During childhood, local synchronization and large-scale propagation undergo distinct maturational trajectories, paralleling cortical synaptic remodeling and the maturation of long-range brain connectivity. How alterations in this local-to-global organization relate to arousal instability remains poorly understood. Here, we used 256-channel high-density EEG to characterize NREM oscillatory organization in 17 children with disorders of arousal (DOA) and 17 age- and sex-matched healthy controls. Children with DOA showed a marked dissociation between local synchronization and large-scale coordination: slow waves were locally larger, steeper and more synchronized, yet recruited the cortex less globally and exhibited a more spatially restricted distribution of origins. This phenotype preferentially involved Type 1 slow waves, a subtype associated with widespread cortical and subcortico-cortical recruitment and late developmental maturation. Children with DOA also showed reduced centro-posterior slow spindle density, providing convergent evidence for altered coordination of distributed NREM oscillations. These microstructural abnormalities occurred despite largely preserved conventional sleep architecture. Together, our findings reveal an altered local-to-global organization of NREM sleep in pediatric DOA and suggest that vulnerability to incomplete arousals may emerge when strong local synchronization is not matched by effective large-scale network coordination during brain development.



