Delta power robustly predicts cognitive function in Angelman syndrome

Area of Science:

• Neuroscience
• Genetics
• Developmental Biology

Background:

• Angelman syndrome (AS) is a severe neurodevelopmental disorder resulting from the loss of the UBE3A gene function in neurons.
• Current research focuses on disease-modifying treatments to restore UBE3A expression, necessitating early indicators of treatment efficacy.
• Increased delta power in EEG is observed in AS and linked to genotype, but its correlation with clinical symptoms is not well-established.

Purpose of the Study:

• To evaluate delta power as a reliable biomarker for cognitive function in individuals with Angelman syndrome.
• To assess the robustness of delta power as a biomarker across different states of consciousness and recording methods.
• To determine if delta power can predict specific clinical symptoms and developmental assessments in AS.

Main Methods:

• Analysis of combined EEG recordings and developmental assessments in a cohort of 82 individuals with AS (ages 1.08-28.16 years).
• Evaluation of delta power as a predictor of the Bayley Cognitive Score, controlling for age, genotype, and repeat assessments.
• Examination of model performance across varying states of consciousness, recording techniques, and analysis procedures, including raw data excluding frontal channels.

Main Results:

• Delta power significantly predicted the Bayley Scale cognitive score (P < 10^-5, R^2 = 0.9374), demonstrating excellent cross-validation (R^2 = 0.95).
• Model performance was consistent across different states of consciousness and EEG montages.
• Models utilizing raw data excluding frontal channels showed superior predictive power for cognitive function, expressive and receptive communication, and fine motor skills.

Conclusions:

• Delta power serves as a straightforward and direct measure of neuronal activity that accurately correlates with cognitive function in Angelman syndrome.
• This electrophysiological biomarker provides an objective and clinically relevant endpoint for evaluating treatment response in ongoing and future clinical trials for AS.
• The findings support the use of delta power as a key outcome measure in therapeutic development for Angelman syndrome.