Translating Adult Electrophysiology Findings to Younger Patient Populations: Difficulty Measuring 40-Hz Auditory Steady-State Responses in Typically Developing Children and Children with Autism Spectrum Disorder
Authors: Edgar J. Christopher , Fisk 4th Charles L. , Liu Song , Pandey Juhi , Herrington John D. , Schultz Robert T. , Roberts Timothy P.L. 
Published: January 2016

<b><i>Background:</i></b> &#947; (∼30-80 Hz) brain rhythms are thought to be abnormal in neurodevelopmental disorders such as schizophrenia and autism spectrum disorder (ASD). In adult populations, auditory 40-Hz click trains or 40-Hz amplitude-modulated tones are used to assess the integrity of superior temporal gyrus (STG) 40-Hz &#947;-band circuits. As STG 40-Hz auditory steady-state responses (ASSRs) are not fully developed in children, tasks using these stimuli may not be optimal in younger patient populations. The present study examined this issue in typically developing (TD) children as well as in children with ASD, using source localization to directly assess activity in the principal generators of the 40-Hz ASSR in the left and right primary/secondary auditory cortices. <b><i>Methods:</i></b> 40-Hz amplitude-modulated tones of 1 s duration were binaurally presented while magnetoencephalography data were obtained from 48 TD children (45 males; 7-14 years old) and 42 ASD children (38 males; 8-14 years old). T1-weighted structural MRI was obtained. Using single dipoles anatomically constrained to each participant's left and right Heschl's Gyrus, left and right 40-Hz ASSR total power (TP) and intertrial coherence (ITC) measures were obtained. Associations between 40-Hz ASSR TP, ITC and age as well as STG gray matter cortical thickness (CT) were assessed. Group STG function and structure differences were also examined. <b><i>Results:</i></b> TD and ASD did not differ in 40-Hz ASSR TP or ITC. In TD and ASD, age was associated with left and right 40-Hz ASSR ITC (p < 0.01). The interaction term was not significant, indicating in both groups a ∼0.01/year increase in ITC. 40-Hz ASSR TP and ITC were greater in the right than left STG. Groups did not differ in STG CT, and no associations were observed between 40-Hz ASSR activity and STG CT. Finally, right STG transient &#947; (50-100 ms and 30-50 Hz) was greater in TD versus ASD (significant for TP, trend for ITC). <b><i>Conclusions:</i></b> The 40-Hz ASSR develops, in part, via an age-related increase in neural synchrony. Greater right than left 40-Hz ASSRs (ITC and TP) suggested earlier maturation of right versus left STG neural network(s). Given a ∼0.01/year increase in ITC, 40-Hz ASSRs were weak or absent in many of the younger participants, suggesting that 40-Hz driving stimuli are not optimal for examining STG 40-Hz auditory neural circuits in younger populations. Given the caveat that 40-Hz auditory steady-state neural networks are poorly assessed in children, the present analyses did not point to atypical development of STG 40-Hz ASSRs in higher-functioning children with ASD. Although groups did not differ in 40-Hz auditory steady-state activity, replicating previous studies, there was evidence for greater right STG transient &#947; activity in TD versus ASD.