Infant excitation/inhibition balance interacts with executive attention to predict autistic traits in childhood

Abstract

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.

Neonatal brain dynamic functional connectivity in term and preterm infants and its association with early childhood neurodevelopment

“…This was the basis for development of the Q-CHAT 27,39 . There is also accumulating evidence across different modalities that infants who go on to receive a diagnosis of autism have differences in their neurobiology and physiology from as young as 6-9 months [63][64][65][66][67][68] Thus our work links emerging social cognitive profile relevant to ASD, also to dynamic functional connectivity at birth, especially within sensory networks. This correlation between higher scores on an instrument, which captures early features relevant to ASD (though not necessarily diagnostic) to the dynamics of sensory systems, is in agreement with the importance of sensory processes throughout the lifespan in individuals who have an ASD diagnosis.…”

The developmental trajectory of functional excitation‐inhibition balance relates to language abilities in autistic and allistic children

“…Deviations in EI development in human infants could thus impact the processing of spectro-temporal speech information, which is, amongst others, crucial for phonemes (i.e., speech sounds) and pitch (involved in speech prosody and intonation). Some recent evidence suggests that autism is related to differences in EI balance already during infancy (Carter Leno et al, 2022), which could thus affect acoustic fine-tuning of the auditory cortex. It has recently been shown that electrophysiological processing of acoustic-phonological information in infancy predicts later language development (Menn, Ward, et al, 2022).…”

Changes in high-frequency aperiodic 1/f slope and periodic activity reflect post-stimulus functional inhibition in the visual cortex

“…The aperiodic slope becomes an increasingly popular index of the E/I ratio in neuropsychiatric and neurodevelopmental disorders, such as schizophrenia (Molina et al, 2020), attention deficit hyperactivity disorders (Arnett, Rutter, & Stein, 2022; Ostlund, Alperin, Drew, & Karalunas, 2021; Robertson et al, 2019), obsessive-compulsive disorder (Perera, Mallawaarachchi, Bailey, Murphy, & Fitzgerald, 2023), depression (Veerakumar et al, 2019), Rett syndrome (Roche et al, 2019), Fragile X syndrome (Wilkinson & Nelson, 2021) and autism spectrum disorders (Carter Leno et al, 2022). Many of these recent studies used EEG and estimated a single aperiodic slope in a broad frequency range (e.g.…”