Delta rhythmicity is a reliable EEG biomarker in Angelman syndrome: a parallel mouse and human analysis

Abstract

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.

Lovastatin suppresses hyperexcitability and seizure in Angelman syndrome model

“…The seizure phenotype is reported to be more prominent in AS patients with a maternal deletion of chromosomal 15q11-q13 region, presumably due to the haploinsufficiency of a cluster of GABA receptors including GABRB3 in the distal end (Dan 2009; DeLorey et al 1998; Egawa et al 2008). The electroencephalogram (EEG) in AS patients has a characteristic pattern of large-amplitude slow-spike waves at 1–2 or 4–6 Hz (Sidorov et al 2017; Vendrame et al 2012). A significant fraction of clinical seizures is medically intractable and the quality of life is significantly compromised in these individuals (Tan and Bird 2016).…”

Emergence of consciousness and complexity amidst diffuse delta rhythms: the paradox of Angelman syndrome

“…In apparent contradiction to the above arguments and data, children with Angelman syndrome (AS) display the rich spectrum of purposeful behavior that implies conscious awareness (as seen here) [33][34][35] while exhibiting the chanting EEG phenotype typical of states of reduced consciousness ( Fig. 1) [36][37][38][39] . Although the AS EEG phenotype has long been described in clinical reports 40 , we are the first to characterize the degree to which the awake EEG in children with AS can support complex dynamics and, moreover, that these dynamics are demonstrably lowered as consciousness decreases during sleep.…”

Social–emotional processing in nonverbal individuals with Angelman syndrome: evidence from brain responses to known and novel names

“…) that were also observed in animal models of AS (Sidorov et al . ). However, the connection between these EEG characteristics and behavioural or cognitive features of AS is currently unknown.…”

“…Measures of electrical brain activity may offer another way to assess social information processing in AS. To date, electroencephalography (EEG) studies in AS noted distinct patterns of delta-band activity (Vendrame et al 2012) that were also observed in animal models of AS (Sidorov et al 2017). However, the connection between these EEG characteristics and behavioural or cognitive features of AS is currently unknown.…”