Periodic and aperiodic contributions to EEG delta power are translatable and complementary Angelman syndrome biomarkers

Abstract

Angelman syndrome (AS) is a neurodevelopmental disorder caused by loss of maternal UBE3A expression. With promising AS therapies now in clinical trials, there is a pressing need for reliable and translatable biomarkers. Elevated EEG delta power is a hallmark of AS and a promising biomarker, but traditional measures conflate delta oscillations with broadband spectral shifts, limiting interpretability and utility. We dissociated periodic and aperiodic contributions to delta power using spectral parameterization in children with AS and Ube3a mutant mice. In both species, elevated delta power reflected a combination of increased periodic delta oscillations and elevated aperiodic slope and offset. These features were linked to different behavioral domains and followed divergent developmental trajectories, suggesting distinct underlying mechanisms. Together, our findings establish aperiodic changes as a novel translatable EEG biomarker for AS and support the complementary use of periodic and aperiodic features in preclinical and clinical research.