Increased Phase-Amplitude Coupling in Children with Autism at 18, 24, and 36 Months

Background: Phase-Amplitude Coupling (PAC), the modulation of higher frequency activity by the phase of lower frequency activity, can be derived from the nested oscillations seen in electroencephalography recordings. PAC may serve as a mechanism for the processing of information as well as for functional connectivity in the brain¹. Greater PAC has been demonstrated in children with autism spectrum disorder (ASD) with an average age of 9.5 years².

Objectives: Here we examine if and when differences in PAC emerge through infancy and early childhood among children at high familial risk who develop ASD, as compared to those who develop typically.

Methods: Baseline electroencephalography (EEG) data was collected in infants at 3, 6, 9, 12, 18, 24, and 36 months of age as a part of a prospective, longitudinal investigation (n=108; not all participants provided useable data at each time point). Participants were at a high risk for autism (HRA) by virtue of having an older sibling with ASD. We measured PAC across multiple frequency combinations for each individual at each time point. Diagnosis of ASD(+) or lack thereof(-) was determined at 24-36 months using the Autism Diagnostic Observation Schedule (ADOS) and best clinical estimate (HRA+: n = 35; HRA-: n = 73).

Results: The HRA+ group shows greater PAC (p < .05, independent samples Mann-Whitney U test) than the HRA- group at 18, 24, and 36 months. Differences were not significant in the 3, 6, 9, and 12 month age groups.

Conclusions: We find increased PAC in children later diagnosed with ASD, beginning at around 18 months. We find children later diagnosed with ASD are not born with, but develop, increased PAC. Notably, the timing at which PAC becomes excessive in the HRA+ group is similar to the timing at which symptoms of ASD tend to become more prominent.