EEG Repetition Suppression in Children with Neurofibromatosis Type 1: Evidence from Time-Frequency Analysis

Background: Neurofibromatosis type 1 (NF1) is a genetic disorder associated with neurodevelopmental disorders, including autism spectrum disorder (ASD), the prevalence of which in this population is approximately 25% (Garg et al., 2013). Studies on animal models of NF1 have identified deficits in habituation, a simple form of repetition learning that is conserved across species and crucial for the development of higher cognitive functions (Larkin et al., 2010; Wolman et al., 2014). Repetition suppression (RS), the reduction of brain activity in response to repeated presentations of a single stimulus, is considered the neurophysiological equivalent of habituation and can be measured using electroencephalography (EEG). However, RS has not yet been investigated in humans with NF1.

Objectives: The purpose of this study is to explore RS in children with NF1 ranging from 4 to 16 years of age. We investigate RS in the time-frequency domain through the variation of event-related spectral power, hypothesizing that the NF1 group would present habituation deficits reflected by lower RS compared to controls.

Methods: EEG was recorded in 13 participants with NF1 and 13 age-matched neurotypical controls using a 128-channel EEG system (Electrical Geodesics System Inc.) in a soundproof room at the CHU Sainte-Justine hospital. Participants were presented with recordings of thirty pseudowords read by a female native French speaker, which were repeated six times each and allowed us to observe auditory RS in a previous study using a similar design (Knoth et al., 2018). Timeframes of -400 ms (pre-stimulus) to 1400 ms were segmented for each presentation of a pseudoword. Artifact-free segments were averaged according to presentation order (first through sixth presentation of a pseudoword) and analysed in the time-frequency domain using the Morlet decomposition.

Results: A mixed-design ANOVA controlling for IQ revealed a significant interaction between repetition and group (F (5,115) = 3.770, p = 0.03) in the lower theta band (3-5 Hz), between 800 and 1400 ms. Post-hoc one-way ANOVAs controlling for IQ revealed a significant difference between the two groups at the third repetition of the pseudowords (F (1,23) = 9.006, p = 0.006), with higher suppression of theta power in the control group (Bonferroni-corrected, p = 0.036). A repeated measures ANOVA controlling for IQ revealed a significant RS effect in the control group (F (5,55) = 3.929, p = 0.004), but not in the NF1 group (F (5,55) = 0.310, p = 0.905).

Conclusions: Considering the role of theta activity in language processing and memory (Bastiaansen et Hagoort, 2003), the absence of repetition suppression for that frequency range in the NF1 group could reflect an altered habituation process in response to auditory presentations of language stimuli. Thus, RS alterations in NF1 may help us understand language, memory and learning deficits that are common in this population (Batista, Lemos, Rodrigues et de Rezende, 2014). Also, EEG markers of habituation promise to be highly relevant translational markers of basic learning mechanisms for clinical trials aimed at learning disabilities in NF1.