Abstract
Dysregulation of cortical excitation/inhibition (E/I) has been proposed as a neuropathological mechanism underlying core symptoms of autism spectrum disorder (ASD). Determining whether dysregulated E/I could contribute to the emergence of behavioural symptoms of ASD requires evidence from human infants prior to diagnosis. In this prospective longitudinal study, we examine differences in neural responses to auditory repetition in infants later diagnosed with ASD. Eight-month-old infants with (high-risk: n = 116) and without (low-risk: n = 27) an older sibling with ASD were tested in a non-linguistic auditory oddball paradigm. Relative to high-risk infants with typical development (n = 44), infants with later ASD (n = 14) showed reduced repetition suppression of 40–60 Hz evoked gamma and significantly greater 10–20 Hz inter-trial coherence (ITC) for repeated tones. Reduced repetition suppression of cortical gamma and increased phase-locking to repeated tones are consistent with cortical hyper-reactivity, which could in turn reflect disturbed E/I balance. Across the whole high-risk sample, a combined index of cortical reactivity (cortical gamma amplitude and ITC) was dimensionally associated with reduced growth in language skills between 8 months and 3 years, as well as elevated levels of parent-rated social communication symptoms at 3 years. Our data show that cortical ‘hyper-reactivity’ may precede the onset of behavioural traits of ASD in development, potentially affecting experience-dependent specialisation of the developing brain.
Highlights
Autism spectrum disorder (ASD) is defined by difficulties in social communication, as well as the presence of restricted interests, repetitive behaviours, and sensory anomalies[1]
To exploit the full dimensional nature of the high-risk design, we examined whether a cortical reactivity index (CRI) was associated with dimensional variation in later language skills across the whole cohort (LR, high-risk infants with typical development (HR-TD), HRAtyp, HR-ASD45,64)
Alterations in excitatory and inhibitory signalling are a feature of several leading neurobiological theories of sensory perturbations observed in autism spectrum disorder (ASD), with some researchers proposing that behavioural symptomology is the cumulative developmental consequence of altered excitatory and inhibitory coordination within cortical systems[2,3,6,7,89]
Summary
Autism spectrum disorder (ASD) is defined by difficulties in social communication, as well as the presence of restricted interests, repetitive behaviours, and sensory anomalies[1]. Symptoms emerge in the first years of life, and can be reliably identified through behavioural assessments from toddlerhood. Several recent theories have implicated dysregulated coordination of excitatory and inhibitory signals (E/I) in cortical processing and associated homoeostatic/autoregulatory feedback loops as one potential common mechanism through which multiple background genetic and environmental risk factors could converge to produce behavioural symptoms of autism[2,3,4,5,6,7]. In animal models of ASD, emerging evidence from stem cell studies have implicated an over-production of GABA-ergic neurons[15], while several animal models provide support for both
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
