21473
Spontaneous Beta Oscillations Are a Biomarker of Duplication 15q11.2-q13.1 Syndrome

Thursday, May 12, 2016: 11:30 AM-1:30 PM
Hall A (Baltimore Convention Center)
J. Frohlich1, D. Senturk2, P. Golshani3, R. Sankar4 and S. S. Jeste5, (1)University of California, Los Angeles, Los Angeles, CA, (2)Biostatistics, University of California, Los Angeles, Los Angeles, CA, (3)Neurology, University of California, Los Angeles, Los Angeles, CA, (4)Pediatrics, Neurology, University of California, Los Angeles, Los Angeles, CA, (5)Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA
Background: Duplications of 15q11.2-q13.1—referred to as Dup15q syndrome—account for roughly 1% of autism spectrum disorder (ASD) cases while also conferring strong risk for intellectual disability (ID) and epilepsy. Interstitial cases of Dup15q syndrome feature extra copies of duplicated genes on the q-arm of chromosome 15, generally resulting in partial trisomy. Isodicentric cases of the same disorder feature an extranumerary chromosome and generally result in partial tetrasomy as well as greater overall clinical impairment [Battaglia 2008]. All cases of Dup15q syndrome include duplications of gamma-aminobutyric acid(GABA)A receptor subunit genes GABRA5, GABRB3, and GABRG3. Recently, case reports have identified spontaneous beta oscillations (SBOs) resembling benzodiazepine-induced activity in clinical electroencephalography (EEG) recordings from children with Dup15q syndrome [Ageeli et al 2014; Urraca et al 2013]. 

Objectives: Herein, we sought to quantify SBOs in resting-state EEG recordings from children and compare a cohort of children with Dup15q syndrome with (A) a comparison group of age-matched typically developing (TD) children and (B) another comparison group of age and intelligence quotient (IQ) matched children with nonsyndromic ASD. 

Methods: We measured SBOs from resting-state EEG recordings of children with Dup15q syndrome (n = 11) using 129 channel high-density EEG nets and compared these recordings to those from TD children (n = 9) and children with nonsyndromic ASD (n = 10). Because beta is traditionally examined as two frequency bands, we quantified SBOs as both low beta and high beta power. Relative power in delta (1 – 4 Hz), theta (4 – 8 Hz), alpha (8 – 12 Hz), low beta (12 – 20 Hz), high beta (20 – 30 Hz), and gamma (30 – 48 Hz) frequency bands was computed for 9 scalp regions of interest (ROIs). Any child being treated with benzodiazepines—drugs which induce beta oscillations and enhance inhibitory currents through GABAA receptors—was excluded from analysis.

Results:  High beta power was significantly higher in children with Dup15q syndrome compared with both the TD (p < 1.0 x 10-4, FDR corrected) and ASD (p < 1.0 x 10-4, FDR corrected) comparison groups. Similarly, resting low beta power was significantly higher in children with Dup15q syndrome than in either comparison group (TD, p = 0.0108, FDR corrected; ASD, p = 6.5 x 10-3, FDR corrected). Delta power was also significantly lower in children with Dup15q syndrome than in either comparison group (TD, p = 8.1 x 10-3, FDR corrected; ASD, p= 0.0126, FDR corrected).  

Conclusions: SBOs represent a clear diagnostic biomarker of a genetically distinct subgroup of children with neurodevelopmental disorders. Given evidence that beta oscillations relate to GABAergic tone [Gaetz et al., 2011; Van Lier et al., 2004], these SBOs represent a potential biomarker of cortical inhibition in this population that may facilitate not only the diagnosis but also treatment monitoring in a subgroup of children within the autism spectrum. Our finding of lower delta power in children with Dup15q syndrome may relate to a shift in spectral energy from slow to fast frequencies (i.e., delta to beta) resulting from GABAA receptor gene upregulation in this disorder.

See more of: Brain Function (fMRI, fcMRI, MRS, EEG, ERP, MEG)
See more of: Brain Function (fMRI, fcMRI, MRS, EEG, ERP, MEG)