Excess EEG beta-band oscillations in Dup15q syndrome correlate with clinical severity

Dup15q syndrome is a rare genetic neurodevelopmental disorder caused by copy number gains of 15q11.2-q13.1, which include UBE3A and three GABA-A receptor subunit genes among several other genes. The contribution of the different genes to etiology remains elusive. Excess EEG beta-band power is a characteristic electrophysiological phenotype of this syndrome and a candidate biomarker of increased GABA-A receptor activity. Here we investigate the link between clinical and EEG phenotypes. We implemented a method to isolate oscillatory activity in the beta-band (16-32 Hz) from the background of the EEG power spectrum, i.e., locally referenced power (LRP_β) and applied it to EEGs from children with Dup15q syndrome (n = 52) and age-matched typically developing children (n = 14). We then investigated the relationship of LRP_β with cognitive ability (assessed with the Mullen Scales of Early Learning or the Differential Ability Scale), and adaptive behaviors (assessed with the Vineland Adaptive Behavior Scales). LRP_β was strongly elevated in individuals with Dup15q syndrome compared to typically developing children (effect size, Hedges' g = +1.84). LRP_β significantly correlated with both cognitive ability (developmental quotient; r = -0.48, p = 0.008) and adaptive functioning (Adaptive behavior composite score; r = -0.56, p = 0.002) in individuals without a history of epilepsy. Our results suggest that excess GABA-A receptor function is a relevant component of Dup15q syndrome pathophysiology and further substantiates the relevance of EEG beta-band power as a biomarker in Dup15q syndrome.