EEG Signal Complexity Is Reduced During Resting-State in Fragile X Syndrome

Mélodie Proteau-Lemieux; Inga Sophia Knoth; Kristian Agbogba; Valérie Côté; Hazel Maridith Barlahan Biag; Angela John Thurman; Charles-Olivier Martin; Anne-Marie Bélanger; Cory Rosenfelt; Flora Tassone; Leonard J Abbeduto; Sébastien Jacquemont; Randi Hagerman; François Bolduc; David Hessl; Andrea Schneider; Sarah Lippé

doi:10.3389/fpsyt.2021.716707

EEG Signal Complexity Is Reduced During Resting-State in Fragile X Syndrome

Front Psychiatry. 2021 Nov 11:12:716707. doi: 10.3389/fpsyt.2021.716707. eCollection 2021.

Authors

Mélodie Proteau-Lemieux^{1

2}, Inga Sophia Knoth², Kristian Agbogba², Valérie Côté², Hazel Maridith Barlahan Biag³, Angela John Thurman³, Charles-Olivier Martin², Anne-Marie Bélanger², Cory Rosenfelt⁴, Flora Tassone^{3

5}, Leonard J Abbeduto^{3

6}, Sébastien Jacquemont^{2

7}, Randi Hagerman³, François Bolduc⁴, David Hessl^{3

6}, Andrea Schneider^{3

8}, Sarah Lippé^{1

2}

Affiliations

¹ Department of Psychology, University of Montreal, Montreal, QC, Canada.
² Research Center of the Sainte-Justine University Hospital, Montreal, QC, Canada.
³ University of California Davis Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, Sacramento, CA, United States.
⁴ Department of Pediatric Neurology, University of Alberta, Edmonton, AB, Canada.
⁵ Department of Biochemistry and Molecular Medicine, University of California Davis School of Medicine, Sacramento, CA, United States.
⁶ Department of Psychiatry and Behavioral Sciences, University of California Davis School of Medicine, Sacramento, CA, United States.
⁷ Department of Pediatrics, University of Montreal, Montreal, QC, Canada.
⁸ California North State University, College of Psychology, Rancho Cordova, CA, United States.

Abstract

Introduction: Fragile X syndrome (FXS) is a genetic disorder caused by a mutation of the fragile X mental retardation 1 gene (FMR1). FXS is associated with neurophysiological abnormalities, including cortical hyperexcitability. Alterations in electroencephalogram (EEG) resting-state power spectral density (PSD) are well-defined in FXS and were found to be linked to neurodevelopmental delays. Whether non-linear dynamics of the brain signal are also altered remains to be studied. Methods: In this study, resting-state EEG power, including alpha peak frequency (APF) and theta/beta ratio (TBR), as well as signal complexity using multi-scale entropy (MSE) were compared between 26 FXS participants (ages 5-28 years), and 7 neurotypical (NT) controls with a similar age distribution. Subsequently a replication study was carried out, comparing our cohort to 19 FXS participants independently recorded at a different site. Results: PSD results confirmed the increased gamma, decreased alpha power and APF in FXS participants compared to NT controls. No alterations in TBR were found. Importantly, results revealed reduced signal complexity in FXS participants, specifically in higher scales, suggesting that altered signal complexity is sensitive to brain alterations in this population. The replication study mostly confirmed these results and suggested critical points of stagnation in the neurodevelopmental curve of FXS. Conclusion: Signal complexity is a powerful feature that can be added to the electrophysiological biomarkers of brain maturation in FXS.

Keywords: EEG resting-state; alpha peak frequency; development; fragile X syndrome; hyperexcitability; multiscale entropy; neurodevelopmental disorders; signal complexity.