We directly assessed mesial temporal activity in two Alzheimer’s disease (AD) patients without a history or EEG evidence of seizures, using intracranial foramen ovale electrodes. We detected clinically silent hippocampal seizures and epileptiform spikes during sleep, a period when both were most likely to interfere with memory consolidation. These index cases support a model in which early development of occult hippocampal hyperexcitability may contribute to the pathogenesis of AD.

BackgroundClinicians have qualitatively described rhythmic delta activity as a prominent EEG abnormality in individuals with Angelman syndrome, but this phenotype has yet to be rigorously quantified in the clinical population or validated in a preclinical model. Here, we sought to quantitatively measure delta rhythmicity and evaluate its fidelity as a biomarker.MethodsWe quantified delta oscillations in mouse and human using parallel spectral analysis methods and measured regional, state-specific, and developmental changes in delta rhythms in a patient population.ResultsDelta power was broadly increased and more dynamic in both the Angelman syndrome mouse model, relative to wild-type littermates, and in children with Angelman syndrome, relative to age-matched neurotypical controls. Enhanced delta oscillations in children with Angelman syndrome were present during wakefulness and sleep, were generalized across the neocortex, and were more pronounced at earlier ages.ConclusionsDelta rhythmicity phenotypes can serve as reliable biomarkers for Angelman syndrome in both preclinical and clinical settings.Electronic supplementary materialThe online version of this article (doi:10.1186/s11689-017-9195-8) contains supplementary material, which is available to authorized users.