Shifted phase of EEG cross-frequency coupling in individuals with Phelan-McDermid syndrome
Michael G. Mariscal, Elizabeth Berry‐Kravis, Joseph D. Buxbaum, Lauren E. Ethridge, Rajna Filip‐Dhima, Jennifer H. Foss‐Feig, Alexander Kolevzon, Meera E. Modi, Matthew W. Mosconi, Charles A. Nelson, Craig M. Powell, Paige M. Siper, Latha Soorya, Andrew Thaliath, Audrey Thurm, Bo Zhang, Mustafa Şahin, April R. Levin
Abstract
BACKGROUND: Phelan-McDermid Syndrome (PMS) is a rare condition caused by deletion or mutation of the SHANK3 gene. Individuals with PMS frequently present with intellectual disability, autism spectrum disorder, and other neurodevelopmental challenges. Electroencephalography (EEG) can provide a window into network-level function in PMS. METHODS: Here, we analyze EEG data collected across multiple sites in individuals with PMS (n = 26) and typically developing individuals (n = 15). We quantify oscillatory power, alpha-gamma phase-amplitude coupling strength, and phase bias, a measure of the phase of cross frequency coupling thought to reflect the balance of feedforward (bottom-up) and feedback (top-down) activity. RESULTS: We find individuals with PMS display increased alpha-gamma phase bias (U = 3.841, p < 0.0005), predominantly over posterior electrodes. Most individuals with PMS demonstrate positive overall phase bias while most typically developing individuals demonstrate negative overall phase bias. Among individuals with PMS, strength of alpha-gamma phase-amplitude coupling was associated with Sameness, Ritualistic, and Compulsive behaviors as measured by the Repetitive Behavior Scales-Revised (Beta = 0.545, p = 0.011). CONCLUSIONS: Increased phase bias suggests potential circuit-level mechanisms underlying phenotype in PMS, offering opportunities for back-translation of findings into animal models and targeting in clinical trials.