EEG Time-Frequency and Phase-Locking Alterations during Auditory Processing in SYNGAP1 Mutation Individuals

Poster Presentation
Saturday, May 4, 2019: 11:30 AM-1:30 PM
Room: 710 (Palais des congres de Montreal)
V. Côté1, S. Lippe2, I. S. Knoth2, F. Barlaam2, S. Jacquemont3, P. Major4, K. Agbogba5, J. Michaud6 and L. Côté7, (1)Psychology, University of Montreal, Montreal, QC, Canada, (2)Neurosciences of Early Development Lab, CHU Sainte-Justine, Montreal, QC, Canada, (3)CHU Sainte Justine, University of Montreal, Montreal, QC, Canada, (4)Division of Child Neurology, CHU Sainte-Justine, Montreal, QC, Canada, (5)Electrical Engineering Department, École de Technologie Supérieure (ÉTS), Montreal, QC, Canada, (6)Centre de recherche, CHU Sainte-Justine, Montreal, QC, Canada, (7)Neurology, CHU Sainte-Justine, Montreal, QC, Canada
Background: Alterations in basic sensory processing have been reported in various genetic syndromes related to neurodevelopmental disorders. SYNGAP1 is a mutation thought to be a common cause of intellectual disability (ID), epilepsy and autism spectrum disorder (ASD). Excitation/ inhibition imbalance at the molecular level has been shown in several genetic neurodevelopmental disorders involving ID and ASD. Haploinsufficiency of the SYNGAP1 gene affects the GABAergic circuit function and oscillatory activity in mice (Berryer et al., 2016). In electroencephalography, these imbalances impair synchronisation in brain rhythms oscillations (Garrido et al., 2009; Larrain-Valenzuela et al., 2017; Lee et al., 2017; Rojas & Wilson, 2014).

Objectives: Here we assessed brain response oscillation and synchronisation in the time-frequency domain of individuals with SYNGAP1 mutation.

Methods: We recorded EEG in 61 participants ranging from 3 to 19 years of age (SYNGAP1 n = 8, neurotypical n = 37 and Down syndrome (DS) n=16) with an auditory stimulus (broadband white noise). We investigated auditory evoked potentials (AEP), time-frequency (TF) and inter-trial coherence (ITC) in SYNGAP1 mutation compared to DS and neurotypicals. Group comparisons were performed using ANOVA and Gabriel or Tamhane post hoc tests.

Results: ANOVA revealed a group effect on P2 latency and amplitude where DS shows a tendency of longer latency. TF analysis demonstrated delayed responses in SYNGAP1 mutation carriers compared to other groups. Specifically, they showed more power in late beta-low gamma band (18-35 Hz/ 150-300 ms) compared to neurotypicals (p=.046) and low gamma (30-40 Hz/ 250-380 ms) in comparison to neurotypicals (p=.004) and DS (p=.022). Importantly, SYNGAP1 mutation carriers showed less phase locking ITC compared to controls in early time windows and lower frequency bands. Specifically, they showed less ITC compared to neurotypicals and DS in theta-alpha (6-10Hz/ 300-450ms; vs. neurotypicals (p=.003); vs. DS (p=.012)) and less ITC compared to neurotypicals in early theta band (3-5 Hz/ 0-300ms; p=.014), (3-6Hz/ 100-350 ms; p=.035). Further, SYNGAP1 individuals expressed less ITC in low beta (16-19 Hz/ 0-100ms; p=.001) and early alpha (7-12Hz/ 50-300 ms; p<.001) compared to neurotypicals, and DS (p=.015). ITC in SYNGAP1 mutation carriers is also significantly reduced in later theta-alpha bands (6-10Hz/ 300-450ms) compared to neurotypicals (p=.003) and DS (p=.012).

Conclusions: SYNGAP1 mutation carriers showed delayed brain responses to auditory sensory stimulations that were also less synchronized in the theta, alpha and beta bands. Beta/low gamma oscillations also occur delayed compared to neurotypicals and DS. Lack of synchronisation in SYNGAP1 individuals could reflect the imbalance of excitation/ inhibition found at the molecular level in several animal models of ID/ASD. Further research is needed to investigate how these auditory processing characteristics in SYNGAP1 relate to cognition and behavior.