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

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.

FPT, a 2-Aminotetralin, Is a Potent Serotonin 5-HT1A, 5-HT1B, and 5-HT1D Receptor Agonist That Modulates Cortical Electroencephalogram Activity in Adult Fmr1 Knockout Mice

“…This finding is consistent with another preclinical study that showed reduced relative theta power in female Fmr1 KO rats . Clinical studies show decreased cortical alpha (8−13 Hz) power in FXS, ,,, which is similar to our observations of small, but significant, decreases in relative alpha power at baseline in the left somatosensory cortex and auditory cortex in Fmr1 KO mice. Other studies report no alterations in alpha power in Fmr1 KO subjects. ,,− The discrepancies could reflect differences in test subject histories and differences in set and setting.…”

“…Therefore, FPT’s effect of increasing delta power might benefit patients with FXS. However, others report increases in delta power in Fmr1 KO mice and patients with FXS, so it is difficult to make conclusions about the impacts on delta power. There are also irregularities regarding cortical alpha power.…”

“…Clinical studies employing resting-state, non-task-related EEGinvolving mostly male patients on psychotropic medications who were primed to relax and sit quietly during recordingshave revealed alterations in cortical EEG in FXS. The most consistent result across studies is an increase in gamma (30–80 Hz) power, and the next most consistent observation is a decrease in alpha (8–12 Hz) power; − females with FXS present with different resting-state cortical EEG patterns . The increase in gamma power has also been observed in Fmr1 knockout (KO) mouse and rat models and can indicate cortical hyperexcitability. − …”

Genetic modulation of brain dynamics in neurodevelopmental disorders: the impact of copy number variations on resting-state EEG

“…Similar results were also shown in 16p11.2 DEL carriers [66]. Atypical beta and gamma power were found in several neurodevelopmental diagnoses, including ASD [67][68][69] and fragile X syndrome [24,[70][71][72]. Moreover, the increase in beta and gamma power has become a generally accepted marker of schizophrenia [73][74][75].…”

“…The study of resting-state EEG has led to the discovery of deviant brain spectral anomalies and functional organizations in several neurodevelopmental disorders (e.g. [20][21][22][23][24][25][26]). Restingstate EEG has then proven to be an effective method to inform us about the delicate dynamics of neuronal functioning found in neuropsychiatric disorders.…”