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

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article number716707
JournalFrontiers in Psychiatry
StatePublished - Nov 11 2021


  • alpha peak frequency
  • development
  • EEG resting-state
  • fragile X syndrome
  • hyperexcitability
  • multiscale entropy
  • neurodevelopmental disorders
  • signal complexity

ASJC Scopus subject areas

  • Psychiatry and Mental health


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