Phase-Amplitude Coupling in Autism Spectrum Disorder: Results from the Autism Biomarkers Consortium for Clinical Trials

BackgroundAutism spectrum disorder (ASD) is defined behaviorally, but measures that probe underlying neural mechanisms may provide clues to biomarker discovery and brain-based patient stratification with clinical utility. Phase-amplitude coupling (PAC) has been posited as a measure of the balance between top-down and bottom-up processing in cortex, as well as a marker for sensory processing and predictive coding difficulties in ASD. We evaluate differences in PAC metrics of resting-state brain dynamics between children with and without ASD and relate PAC measures to age and behavioral assessments. MethodsWe analyzed electroencephalography data collected by the Autism Biomarkers Consortium for Clinical Trials, including 225 (192 male) ASD and 116 (81 male) typically-developing children aged 6-11 years. We evaluated the strength and phase preference of PAC and the test-retest reliability of PAC across sessions. ResultsThere was significantly increased alpha-gamma and theta-gamma PAC strength in ASD. When considering all participants together, we found significant associations of whole brain theta-gamma PAC strength with measures of social communication (Beta = 0.185; p = 0.006) and repetitive behaviors (Beta = 0.166; p = 0.009) as well as age (Beta = 0.233; p < 0.0001); however, these associations did not persist when considering the ASD group alone. There are also group differences in theta-gamma phase preference. ConclusionsThis large, rigorously collected sample indicated altered PAC strength and phase bias in ASD. These findings suggest opportunities for back-translation into animal models as well as clinical potential for stratification of brain-based subgroups in ASD.