# Electrophysiological biomarkers of sleep and cognition in Dup15q syndrome

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $185,566

## Abstract

Project Abstract
Duplications of 15q11.3-21.1 (Dup15q syndrome) are highly penetrant for intellectual disability (ID), autism
spectrum disorder (ASD) and epilepsy (Finucane et al., 2016). Several genes in the region, particularly UBE3A
and a cluster of GABAA receptor genes, are critical for neural development, disrupting synaptic protein
synthesis and degradation as well as inhibitory neurotransmission. In a previous study, we identified an
electrophysiological biomarker of this syndrome defined by increased beta band oscillations that likely reflect
aberrant GABAergic neurotransmission (Frohlich et al., 2016). As we further explored properties of this
biomarker, we discovered that the sleep physiology in these children is profoundly abnormal, with grossly
attenuated slow wave sleep and reduced sleep spindle density. Healthy sleep physiology is necessary for
robust cognitive development, from early infancy through adulthood, (den Bakker et al., 2018; Fogel & Smith,
2011; Hahn et al., 2018; Tham, Schneider, & Broekman, 2017), and there is extensive evidence of
physiological sleep impairment in neurodevelopmental disorders (Gruber & Wise, 2016; Kose, Yilmaz,
Ocakoglu, & Ozbaran, 2017; Tessier et al., 2015). We hypothesize that abnormal sleep physiology directly
undermines cognitive development in Dup15q syndrome and may serve as a quantifiable and modifiable
target for pharmacological or even behavioral interventions. Through a partnership with the Dup15q Alliance
(patient advocacy group) and our UCLA Intellectual and Developmental Disabilities Research Center (IDDRC),
we propose a comprehensive study of sleep electrophysiology and cognition in Dup15q syndrome. We will
collect previously recorded overnight clinical EEG’s from children with Dup15q syndrome across the country
and compare these EEG’s to those of children with nonsyndromic ID and typical development. We will ask
whether sleep physiology, specifically (1) spindle density, (2) percent slow wave sleep, (3) percent spikes in
slow wave sleep and (4) absolute beta power in stage 1 and 2 of sleep differentiates Dup15q syndrome from
these comparison groups and whether these variables relate to cognition and adaptive skills. The field of
neurodevelopmental disorders has sorely lacked quantifiable electrophysiological biomarkers that relate to
disease mechanisms, and sleep EEG may represent a robust biomarker that sheds light on the etiology of
cognitive impairment while also serving as a surrogate endpoint in clinical trials, particularly for Dup15q
syndrome. Moreover, the pipeline that we have developed, from building a remote clinical EEG repository to
performing semi-automated sleep EEG signal processing can inform other biomarker studies in syndromic and
nonsyndromic forms of ID.

## Key facts

- **NIH application ID:** 9989179
- **Project number:** 5R21HD099686-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Shafali Spurling Jeste
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $185,566
- **Award type:** 5
- **Project period:** 2019-08-05 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989179

## Citation

> US National Institutes of Health, RePORTER application 9989179, Electrophysiological biomarkers of sleep and cognition in Dup15q syndrome (5R21HD099686-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9989179. Licensed CC0.

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