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An EEG Biomarker of Delayed Sensitive Period Onset in Autism Spectrum Disorder
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder thought to result from dysregulated sensitive periods in development. Sensitive periods are windows of increased neuroplasticity when experiences get embedded in brain function with lifelong effects on cognition and behavior. Neural measures of sensitive periods in animal models have shown that the timing of sensitive periods is regulated by maturing inhibition, which shifts the balance of spontaneous neural activity and experience-induced neural activity (the S/E ratio). Specifically, the S/E ratio decreases during sensitive period onset relative to pre-sensitive period levels.
Objectives:
The present study sought to translate the S/E ratio measure of sensitive period onset into human ASD neurodevelopment with longitudinal high-density electroencephalography (EEG) from 3 to 12 months of age. Specifically, this study tested how the language phoneme sensitive period manifests in ASD neurodevelopment, as language deficits are frequent ASD symptoms. We hypothesized that reduced neural inhibition in ASD may delay the developmental timing when inhibition is robust enough to reduce the S/E ratio (i.e. delayed sensitive period opening).
Methods:
Data were contributed by 79 typically developing infants (TD), 67 high-risk infants without ASD at 3 years (HR-), and 24 high-risk infants with ASD diagnoses at 3 years of age (ASD+). Spontaneous EEG power was collected with a silent baseline recording, while experience-induced EEG power was generated by a phoneme oddball paradigm. All EEG data were processed through HAPPE software, optimized for developmental EEG data. The ratio of spontaneous EEG power to phoneme induced EEG power was calculated over auditory cortex to generate the S/E ratio.
Results:
The S/E ratio in TD infants decreased between 3 and 6 months of age, consistent with the native phoneme sensitive period onset behaviorally (p < 0.05, n = 79). However, the S/E ratio in ASD+ infants remained elevated at 6 months of age, and was significantly higher than both HR- and TD infants (p = 0.015, n = 170), consistent with a delayed phoneme sensitive period. HR- infant S/E ratios did not differ from those of TD infants at any timepoint. Post-hoc analyses showed the elevated 6-month S/E ratio in the ASD+ infants was due to elevated spontaneous EEG power, consistent with the model of hyper-excitability in early ASD neurodevelopment. The S/E ratio in ASD+ infants was significantly negatively associated with later receptive language scores at 12 months (p < 0.05, n = 24).
Conclusions:
These findings suggest early auditory sensitive periods may be delayed in ASD with ramifications for later language development. This delay appears to be specific to infants who go on to ASD diagnoses, rather than reflecting high-risk for ASD. Moreover, the S/E ratio measure may serve as a translational sensitive period biomarker that can link ASD animal model insights to human brain and behavior development.