Shifted phase of EEG cross-frequency coupling in individuals with Phelan-McDermid syndrome

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Issue Date
2021-04-28Author
Mariscal, Michael G.
Berry-Kravis, Elizabeth
Buxbaum, Joseph D.
Ethridge, Lauren E.
Filip-Dhima, Rajna
Foss-Feig, Jennifer H.
Kolevzon, Alexander
Modi, Meera E.
Mosconi, Matthew W.
Nelson, Charles A.
Powell, Craig M.
Siper, Paige M.
Soorya, Latha
Thaliath, Andrew
Thurm, Audrey
Zhang, Bo
Sahin, Mustafa
Levin, April R.
Publisher
BMC
Type
Article
Article Version
Scholarly/refereed, publisher version
Rights
© The Author(s) 2021. This work is licensed under a Creative Commons Attribution 4.0 International License.
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Show full item recordAbstract
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.
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Citation
Mariscal, M. G., Berry-Kravis, E., Buxbaum, J. D., Ethridge, L. E., Filip-Dhima, R., Foss-Feig, J. H., Kolevzon, A., Modi, M. E., Mosconi, M. W., Nelson, C. A., Powell, C. M., Siper, P. M., Soorya, L., Thaliath, A., Thurm, A., Zhang, B., Sahin, M., Levin, A. R., & Developmental Synaptopathies Consortium (2021). Shifted phase of EEG cross-frequency coupling in individuals with Phelan-McDermid syndrome. Molecular autism, 12(1), 29. https://doi.org/10.1186/s13229-020-00411-9
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