Regionally Specific Resting-State Alpha Oscillatory Abnormalities Predict Clinical Impairment in Autism Spectrum Disorders

Background: A disruption in the excitatory/inhibitory balance of neural activity is increasingly thought to characterize autism spectrum disorders (ASD). Despite cellular and molecular evidence (Rubenstein and Merzenich 2003), very few studies to date have investigated an excitatory/inhibitory imbalance in ASD at a macroscopic cortical circuit scale. This putative imbalance can be assessed noninvasively during a resting-state (RS) exam via patterns of neural oscillations, as oscillatory activity reflects the synchronous firing of large populations of neurons mediated by excitatory/inhibitory interactions. In a previous study, our laboratory observed increased parietal-occipital RS alpha activity in non-medicated children with ASD, with increased alpha power associated with higher scores on the Social Responsiveness Scale (Cornew et al. 2012).

Objectives: The present studies sought to replicate and extend our previous findings, examining a new and larger sample of ASD and typically developing children (TDC). In addition, rather than obtaining lobar measures of alpha activity, estimates of RS alpha activity were obtained throughout the brain.

Methods: RS whole-head magnetoencephalography (MEG) was obtained from forty-seven male TDC and forty-one male ASD participants. RS activity was analyzed using a lead-field-based source localization method, Vector-based Spatio-temporal Analysis using L1-minimum norm (VESTAL). Group differences in alpha power and alpha peak frequency were examined. Given a well-documented association between alpha peak frequency and age, hierarchical regressions examined associations between alpha peak frequency and age.

Results: The ASD group had more alpha activity than the TDC group in regions bordering the Central Sulcus as well as parietal association cortices (p < 0.05). In ASD, stronger left Central Sulcus alpha power was associated with higher Social Responsiveness Scale scores (p < 0.05). In both groups the strongest alpha activity was observed in regions bordering both sides of the Calcarine Sulcus. In the Calcarine Sulcus, only the TDC group showed the expected association between age and alpha peak frequency (p < 0.05).

Conclusions: The observation of increased RS alpha activity in primary motor and somatosensory areas in the present study suggests that the ASD brain is potentially underprepared for sensory input. Given the modulating influence of the thalamus on RS alpha activity, findings suggest the possibility that thalamic abnormalities are primary to RS alpha abnormalities in ASD. MEG + DTI studies examining associations between the Central Sulcus and Calcarine Sulcus alpha rhythms and lateral geniculate nucleus and ventral posterior nucleus thalamocortical pathways are of interest.