Electroencephalographic Spectral Power as a Marker of Cortical Function and Disease Severity in Girls With Rett Syndrome

Abstract

Objective: Rett syndrome (RTT) is a neurodevelopmental disorder caused by a mutation in the X-linked MECP2 gene. Individuals with RTT typically develop normally until around 18 months of age before undergoing a developmental regression, and the disorder can lead to cognitive, motor, sensory, and autonomic dysfunction. Understanding the mechanism of developmental regression represents a unique challenge when viewed through a neuroscience lens. Are circuits that were previously established erased, and are new ones built to supplant old ones One way to examine circuit-level changes is with the use of electroencephalography (EEG). Using EEG, it is possible to study neural oscillations, and power spectral analysis allows for the decomposition of the EEG signal into frequency components linked to various neurological processes. Previous studies of the EEG in RTT have focused on morphological characteristics, but few have explored spectral power, including power as an index of brain function or disease severity. This study sought to determine if EEG power differs in girls with RTT and typically developing (TD) girls and among girls with RTT based on various clinical characteristics in order to better understand neural connectivity and cortical organization in individuals with this disorder. Methods: Resting state EEG data were acquired from girls with RTT (n=57) and typically developing children (n=37). Clinical data such as disease stage, performance on the Mullen Scales of Early Learning (MSEL), and Clinical Severity Score (CSS) were also collected for girls with RTT. EEG power across several brain regions in numerous previously defined frequency bands was then compared between girls with RTT and TD controls, and power in girls with RTT was compared based on scores on the previously collected clinical and cognitive measures. Additionally, power in all participants was related to participant age, and for a subset of participants, power was compared between a first study visit and a second visit approximately one year later. Results: Girls with RTT demonstrate significantly lower power in the middle-range alpha and beta frequency bands across multiple brain regions. Additionally, girls with RTT that are postregression demonstrate significantly higher power in the lower frequency theta band in the frontal region. EEG power was not found to change significantly over one year in girls with RTT or TD controls. Increased power in these lower frequency bands in girls with RTT trended with lower scores on the MSEL in all domains, and delta and theta power were observed to increase with age in girls with Rett syndrome but decrease with age in TD controls. Interpretation: Increased power in the lower frequency bands, as well as decreased power in the middle frequency bands, is consistent with previous studies demonstrating a “slowing” of the background EEG in RTT and is consistent with EEG patterns seen in other progressive neurological disorders. This increase, particularly in the delta band, could represent abnormal cortical inhibition due to dysfunctional GABAergic signaling or circuitry and could potentially be used as a marker of disease severity due to its associations with more severe RTT phenotypes and worsening with disease progression.