Interhemispheric Alpha-Band Hypoconnectivity in Children with Autism Spectrum Disorder (ASD)

Background: Autism Spectrum Disorder (ASD) has been associated with, and likely results from, aberrant neural connectivity, with patterns of decreased short range and increased long range connectivity generally described (Wass, 2011). The dynamics of neural oscillations in the alpha range (6-12 Hz) are exquisitely sensitive to healthy development of (Varokin, 2012), and disruptions to (Hinkley, 2011), functional and structural connectivity. Here we used electroencephalography (EEG) to quantify alpha-band functional connectivity in children with ASD across a range of cognitive abilities. Employing a data driven approach to analyze all possible short and long range connections allowed for an unbiased examination of all possible atypical connectivity patterns.

Objectives: We asked: (1) whether alpha band coherence in both long and short-range networks distinguishes children with ASD from typically developing (TD) children, and (2) whether alpha band coherence relates to developmental level and cognitive function within the autism spectrum.

Methods: We studied 59 children with ASD (mean age 69 months; range: 25-126) with nonverbal IQ ranging from 10-145 (mean NVIQ: 75) and 39 age matched TD children (mean age: 72 months; range: 29-146; mean NVIQ: 113). Spontaneous EEG was recorded using a high density 128 channel hydrocel geodesic sensor net (EGI inc.), and extensively cleaned through both manual inspection, and independent component analysis (ICA). To mitigate the effects of volume conduction, EEG data were transformed into current source density (CSD) using a spherical spline Laplacian transform. CSD estimates were then decomposed into the time-frequency domain using fast Fourier transform. Phase coherence within the alpha range was calculated between every possible electrode pair. A permutation test with a false discovery rate (FDR) adjustment for multiple testing was used to identify electrode pairs which demonstrated significantly different phase coherence between ASD and TD participants.

Results: Using a conservative FDR correction of 0.05, one electrode pair between left and right temporal regions showed significantly decreased phase coherence in ASD compared to TD children (t(96)=4.20, P=.000). Alpha phase coherence for this electrode pair was not associated with either age or IQ in the ASD group (age: P=.193; non-verbal IQ: P=.267, verbal IQ: P=.215).

Conclusions: Long range alpha band coherence between left and right temporal regions distinguished TD children from a heterogeneous group of ASD children. No association was found between long range connectivity and cognitive ability. Our results are consistent with previous research, suggesting that interhemispheric temporal hypoconnectivity represents a fundamental brain difference in children with ASD across a wide cognitive range. The findings presented here may reflect structural factors causing decreased neural communication (such as white mater disturbances), or increased signal variability at one (or both) temporal sites in ASD (neural noise). Future research will address the earliest developmental origins of aberrant spontaneous functional connectivity in infants at risk for ASD and will examine the specific behavioral consequences of these connectivity patterns.