The relationship between gamma-band neural oscillations and language skills in youth with Autism Spectrum Disorder and their first-degree relatives

Background Most children with Autism Spectrum Disorder (ASD) have co-occurring language impairments and some of these autism-specific language difficulties are also present in their non-autistic first-degree relatives. One of the possible neural mechanisms associated with variability in language functioning is alterations in cortical gamma-band oscillations, hypothesized to be related to neural excitation and inhibition balance. Methods We used a high-density 128-channel electroencephalography (EEG) to register brain response to speech stimuli in a large sex-balanced sample of participants: 125 youth with ASD, 121 typically developing (TD) youth, and 40 unaffected siblings (US) of youth with ASD. Language skills were assessed with Clinical Evaluation of Language Fundamentals. Results First, during speech processing, we identified significantly elevated gamma power in ASD participants compared to TD controls. Second, across all youth, higher gamma power was associated with lower language skills. Finally, the US group demonstrated an intermediate profile in both language and gamma power, with nonverbal IQ mediating the relationship between gamma power and language skills. Limitations We only focused on one of the possible neural contributors to variability in language functioning. Also, the US group consisted of a smaller number of participants in comparison to the ASD or TD groups. Finally, due to the timing issue in EEG system we have provided only non-phase-locked analysis. Conclusions Autistic youth showed elevated gamma power, suggesting higher excitation in the brain in response to speech stimuli and elevated gamma power was related to lower language skills. The US group showed an intermediate pattern of gamma activity, suggesting that the broader autism phenotype extends to neural profiles. Supplementary Information The online version contains supplementary material available at 10.1186/s13229-024-00598-1.

ROI.This supplementary analysis addresses a model that includes ROI as a factor.The structure of the model is as follows: gamma power as a dependent variable, condition, group, and condition*group interaction as main effects, sex and ROI as factors, and participants as random intercept.The results of the model are presented in Table S1.The model revealed a main effect of group in gamma power, so as the TD group had lower power when comparing to the ASD group.We also observed main effects of ROIs, poinJng to a regional-specific differences in gamma power.

Composite whole-head EEG measure (gamma power averaged across all ROIs)
The previous model demonstrated that there is a main effect of ROI, however, there is a main effect of group as well (see Table S1).The main effect of group across all ROIs brough up the quesJon whether composite whole-head EEG measure (gamma power averaged across all ROIs) can be used to replicate the results of ROI-by-ROI analysis (between-group difference in gamma power as well as the relationship between gamma power and language skills).The models with the same structure as for the main analysis were used with 1) gamma power as a dependent variable, condition, group, and condition*group interaction as main effects, sex as a factor, and participants as a random intercept (to assess betweengroup difference); and 2) gamma power as a dependent variable, CELF Core Language SS as a predictor, sex and age as factors, and participants as a random intercept.See results in Tables S2 and S3 with models outcomes.
Table S2.The output of the model (between-group difference in composite EEG power) For the first model, we revealed similar effects as for ROIs analysis: main effect of group, so that the TD group had lower power, and a main effect of sex, as the male group had higher power.At the same time, for the second model, we did not reveal a relationship between gamma power averaged across all ROIs and language skills, pointing to the idea that this effect can be a regional-specific.

MediaCon models for the ASD and TD groups
The main analysis showed that the group of unaffected siblings (US) of youth with ASD showed an intermediate pa;ern (between the ASD and TD groups) in both behavioral language skills (CELF-4 Core Language Standard Score) and neural funcJoning (lower gamma power in comparison to the ASD group but higher when comparing to TD group).To explore which phenotypic characterisJcs inform the relaJonship between gamma power and language skills of US parJcipants, we provided mediaJon analysis.The model assessed the direct effects of gamma power on language skills as well as indirect effects through all mediators included in the models (age, sex, nonverbal IQ, verbal IQ, Vineland SocializaJon Standard Score, and SRS-2 total raw score).The results showed that nonverbal IQ played a mediaJon role in the relaJonship between gamma power and language skills.
To assess if this indirect effect is unique or universal, we provided the same mediaJon models for the ASD and TD groups.The results did not show any indirect paths between gamma power and language skills in both groups, indicaJng hypotheJcally that this effect can be specific to the US group.See Tables S4 and   S5 with full model outcomes.Fit indexes of the mediation model: SRMR = 0.151, AIC = 12117.853,TLI = 0.336, CFI = 0.644.

Table S1 .
Between-group difference in gamma power, considering ROI as a factor

Table S3 .
The output of the model (relationship between composite EEG gamma power and language skills)

Table S4 .
The output of the mediaJon model for central midline region of interest (TD group).

Table S5 .
The output of the mediaJon model for central midline region of interest (ASD group).