Infant Excitation/Inhibition Balance Interacts with Executive Attention to Predict Autistic Traits in Childhood

the EDEN, STAARS Teams, Virginia Carter Leno*, Jannath Begum-Ali, Amy Goodwin, Luke Mason, Greg Pasco, Andrew Pickles, Shruti Garg, Jonathan Green, Tony Charman, Mark H. Johnson, Emily J.H. Jones, Grace Vassallo, Emma Burkitt-Wright, Judith Eelloo, D. Gareth Evans, Siobhan West, Eileen Hupton, Lauren LewisLouise Robinson, Angus Dobbie, Ruth Drimer, Helen Bethell, Rachel Jones, Susan Musson, Catherine Prem, Miranda Splitt, Karen Horridge, Diana Baralle, Carolyn Redman, Helen Tomkins, Ankita Bhojwani, Shannon Connelly, Francesca Conti, Beth Evans, Meg Jackson, Emily Powell, Mary Agyapong, Tessel Bazelmans, Leila Dafner, Mutluhan Ersoy, Teea Gliga, Rianne Haartsen, Hanna Halkola, Alexandra Hendry, Rebecca Holman, Sarah Kalwarowsky, Anna Kolesnik, Nisha Narvekar, Chloë Taylor

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)
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Background: Autism is proposed to be characterised by an atypical balance of cortical excitation and inhibition (E/I). However, most studies have examined E/I alterations in older autistic individuals, meaning that findings could in part reflect homeostatic compensation. To assess the directionality of effects, it is necessary to examine alterations in E/I balance early in the lifespan before symptom emergence. Recent explanatory frameworks have argued it is also necessary to consider how early risk features interact with later developing modifier factors to predict autism outcomes.
Method: We indexed E/I balance in early infancy by extracting the aperiodic exponent of the slope of the electroencephalogram (EEG) power spectrum (‘1/f’). To validate our index of E/I balance we tested for differences in the aperiodic exponent in 10-month-old infants with (n=22) and without (n=27) Neurofibromatosis type 1 (NF1), a condition thought to be characterised by alterations to cortical inhibition. We then tested for E/I alterations in a larger heterogeneous longitudinal cohort of infants with and without a family history of neurodevelopmental conditions (n=150) who had been followed to early childhood. We tested the relevance of alterations in E/I balance and our proposed modifier, executive attention, by assessing whether associations between 10-month aperiodic slope and 36-month neurodevelopmental traits were moderated by 24-month executive attention. Analyses adjusted for age at EEG assessment, sex and number of EEG trials.
Results: Infants with NF1 were characterised by a higher aperiodic exponent, indicative of greater inhibition, supporting our infant measure of E/I. Longitudinal analyses showed a significant interaction between aperiodic slope and executive attention, such that higher aperiodic exponents predicted greater autistic traits in childhood, but only in infants who also had weaker executive functioning abilities.
Limitations: The current study relied on parent report of infant executive functioning-type abilities; future work is required to replicate effects with objective measures of cognition.
Conclusions: Results suggest alterations in E/I balance are on the developmental pathway to autism outcomes, and that higher executive functioning abilities may buffer the impact of early cortical atypicalities, consistent with proposals that stronger executive functioning abilities may modify the impact of a wide range of risk factors.
Original languageEnglish
Article number46
JournalMolecular Autism
Issue number1
Publication statusPublished - Dec 2022


  • ADHD
  • Autism
  • E/I balance
  • Executive functioning
  • Infants
  • NF1


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