Infant excitation/inhibition balance interacts with executive attention to predict autistic traits in childhood.
Creators: name: Carter Leno, Virginia
name: Begum-Ali, Jannath
name: Goodwin, Amy
name: Mason, Luke
name: Pasco, Greg
name: Pickles, Andrew
name: Garg, Shruti
name: Green, Jonathan
name: Charman, Tony
name: Johnson, Mark H
name: Jones, Emily JH
name: EDEN
name: STAARS Teams
Publisher: name: Apollo - University of Cambridge Repository
Year: 2022
Subjects: Research
Infants
Autism
ADHD
NF1
E/I balance
Executive functioning

description: Funder: Action for Medical Research
description: Funder: Great Ormond Street Hospital Children’s Charity
description: Funder: Horizon 2020; doi: http://dx.doi.org/10.13039/501100007601
description: Funder: EFPIA
description: Funder: Autism Speaks; doi: http://dx.doi.org/10.13039/100000073
description: Funder: Autistica; doi: http://dx.doi.org/10.13039/100011706
description: Funder: Simons Foundation Autism Research Initiative; doi: http://dx.doi.org/10.13039/100014370
description: 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 that 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.