Elevated Cortical Reactivity to Auditory Repetition Is Present at 8 but Not 14 Months in Infants with Later ASD

Background: Autism Spectrum Disorders (ASDs) are characterised by difficulties in social communication, restricted interests and repetitive behaviours, as well as sensory perturbations (APA, 2013). Previous work from animal models and the mature adult brain suggests that abnormal cortical excitability could underlie ASD aetiology (Rubenstein & Merzenich, 2003; Lee et al., 2017). Potential atypicalities in regulation of excitation/inhibition balance in early development could alter homeostatic interplay between perceptual mechanisms and result in ASD-phenotype. This would feed into novel treatment approaches to be administered prior to symptom onset and within a stage of augmented plasticity. Recent studies have suggested gamma-band activity may be a candidate neural marker of e/i balance regulation (Rojas, 2008,2014).

Objectives: In this longitudinal study, we examine whether infant siblings with later ASD show a distinct pattern of oscillatory activity and phase-locking responses to auditory repetition relative to those with typical development. We aim to expand on previous reports of atypical gamma-band activity in individuals with ASD and their first-degree relatives.

Methods: Infants with and without family history of ASD were tested in an auditory oddball paradigm at 8 and 14 months. Wavelet analyses were used to examine change in evoked gamma amplitude and low-frequency phase-locking in response to repeated standard tones. Analysis was constrained to location and frequency band where low-risk controls showed habituation effect to repetition, and then the model was applied to high-risk siblings. Infants were followed up at 36 months with standardised assessments of current ASD symptoms.

Results: Relative to high-risk infants with typical development, those with later ASD showed reduced habituation of evoked gamma at 8 months (40-60Hz, 30-150ms; [p=.012, h²=.105]) and greater phase-locking (10-20Hz, 100-180ms; [p = .036, h²= .06]) to repeated tones. A combined index of cortical hyper-reactivity was dimensionally associated with levels of parent-rated social impairment (SRS™) at 3 years as well as with reduced growth in Receptive Language skills between 8 months and 3 years across the whole sample [p = .032]. However, preliminary analysis suggested that reduced habituation did not appear to be present in the ASD group at 14 months (within the same time and frequency bands, all p values are above .05).

Conclusions: We present the first evidence for cortical hyper-reactivity to be present in infants with later ASD, before the onset of behavioural symptoms. The data is consistent with the literature on E/I balance as a potential mechanism underlying neurodevelopmental disorders, further suggesting that an imbalance can be detected during early stages of brain development. This effect did not appear to be present during the 14-month-visit. This could be due to the differences in the nature of the E/I balance itself and possible compensation strategies used by the auditory cortex in response to repetition (Mottron et al., 2006).