Abstract
Qualitative EEG abnormalities are common in Autism Spectrum Disorder (ASD) and hypothesized to reflect disrupted excitation/inhibition (E/I) balance. To test this, we recently introduced a functional measure of network-level E/I ratio (fE/I). Here, we applied fE/I and other EEG measures to alpha oscillations from source-reconstructed data in the EU-AIMS dataset (267 ASD, 209 controls). We analyzed these measures alongside qualitative EEG abnormalities ranging from slowing of activity to epileptiform patterns, aiming to replicate the findings from the SPACE-BAMBI study. Contrary to our previous report, we did not observe increased fE/I variability in ASD compared to controls. EEG abnormalities were rare in adults and could not be statistically assessed. ASD children-adolescents with EEG abnormalities exhibited lower relative alpha power and fE/I compared to those without. However, EEG-abnormality scoring did not stratify the behavioral heterogeneity of ASD using clinical measures. Surprisingly, several controls also exhibited qualitative EEG abnormalities with a strikingly similar anatomical distribution of reduced fE/I, reflecting inhibition-dominated network dynamics in sensory processing regions. The robustness of this association between EEG abnormalities and reduced fE/I was further supported by re-analysis of the SPACE-BAMBI study in source space. Stratification by the presence of EEG abnormalities and their effects on network activity may help understand neurodevelopmental physiological heterogeneity and the difficulties in implementing E/I targeting treatments in unselected cohorts.
Data availability
Due to privacy regulations of human subjects, we cannot provide the EEG files of the subjects included in our study. Analysis scripts to reproduce the figures and statistics, along with the underlying data, will be made available on figshare (https://doi.org/10.6084/m9.figshare.31634182), a website dedicated for sharing scientific data. The code for the fE/I algorithm is publicly available at [https://github.com/rhardstone/fEI](https:/github.com/rhardstone/fEI).
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Acknowledgements
We thank all participants and their families for participating in this study. We also gratefully acknowledge the contributions of all members of the EU-AIMS LEAP group.
Funding
Amsterdam UMC TKI grant BRAINinBALANCE, project number 31556-2012377 (H.B., K.L.-H.). Netherlands Organization for Scientific Research (NWO) Physical Sciences Grant 612.001.123 (K.L.-H.). Netherlands Organization for Scientific Research (NWO) Social Sciences 406-15-256 (A.-E.A.,K.L.-H.). NWA-ORC Call (NWA.1160.18.200) (H.B., K.L.-H.). NWO ‘BRAINMODEL’, project number 10250022110003 (2021–2027) (H.B., K.L.-H.). EU H2020 ‘Human Brain Project’ grant agreement no. 604102 (H.D.M.). EU-AIMS (European Autism Interventions) and AIMS-2-TRIALS programmes which receive support from Innovative Medicines Initiative Joint Undertaking Grant No. 115300 and 777394, the resources of which are composed of financial contributions from the European Union’s FP7 and Horizon2020 programmes, and from the European Federation of Pharmaceutical Industries and Associations (EFPIA) companies’ in-kind contributions, and AUTISM SPEAKS, Autistica and SFARI; and by the Horizon2020 supported programme CANDY Grant No. 847818.
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Conceptualization: H.B., K.L.-H., P.G., J.F.H. Methodology: E.L. J.-M., A.-E.A., S.-S.P., K.L.-H., H.B. Investigation: E.L.J-M, K. L-H, H.B. Visualization: E.L. J.-M., A.-E. A.Acquisition, analysis, or interpretation of data: All authors. Funding acquisition: K. L.-H., H.B. Administrative, technical, or material support: A.-E. A., S.-S.P. Supervision: K. L-H, H.B., H.D.M.Writing – original draft: E. L. J-M, A.-E.A., K. L-H, H. B. Writing – review & editing: all authors.
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H.B., K.L.-H., and S.-S.P. are shareholders of Aspect Neuroprofiles BV, which develops physiology-informed prognostic measures for neurodevelopmental disorders. K.L.-H. has filed the patent claim (PCT/NL2019/050167) “Method of determining brain activity”; with priority date 16 March 2018. TC has served as a paid consultant to F. Hoffmann-La Roche Ltd. and Servier; and has received royalties from Sage Publications and Guilford Publications. A.E.-A. is a paid consultant for Aspect Neuroprofiles BV. J.B. has been in the past 3 years a consultant to / member of advisory board of / and/or speaker for Takeda, Roche, Medice, Angelini, Neuraxpharm, and Servier. He is not an employee of any of these companies, and not a stock shareholder of any of these companies. He has no other financial or material support, including expert testimony, patents, royalties. P.G. and J.F.H. are full-time employees of F. Hoffmann - La Roche Ltd. T.B. served in an advisory or consultancy role for eye level, Infectopharm, Medice, Neurim Pharmaceuticals, Oberberg GmbH and Takeda. He received conference support or speaker’s fee by Janssen-Cilag, Medice and Takeda. He received royalities from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press. The rest of the authors have no competing interests to declare. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.
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Avramiea, AE., Juarez-Martinez, E.L., Garcés, P. et al. Qualitative EEG abnormalities in ASD reflect inhibition-dominated brain dynamics. Sci Rep (2026). https://doi.org/10.1038/s41598-026-42120-y
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DOI: https://doi.org/10.1038/s41598-026-42120-y