Diminished Gamma Oscillatory Response in Autism Spectrum Disorder

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder behaviorally defined by a core set of features, including social interaction deficits and restricted and repetitive behaviors. Sensory abnormalities are present in up to 90% of affected individuals, and impairment in cognitive processing is common. Neural oscillations are a key mechanism by which communication and synchronization occur within the brain, in turn driving coordinated cognition and behavior. Gamma band oscillations reflect GABAergic synaptic function, and alterations in the balance between inhibitory GABAergic and excitatory glutamatergic activity have been identified in ASD. Therefore, measurement of gamma oscillations may offer a valuable biological tool to reveal mechanisms underlying cognitive dysfunction and behavioral symptomatology. Auditory steady-state response (ASSR) is a neurological response that occurs when the brain entrains to rapid auditory stimuli presented at a given frequency. ASSR in the gamma frequency range (30-50 Hz) has been identified as a robust measure of abnormal neural oscillations in other disorders where excitatory/inhibitory balance is disrupted. This study used electroencephalography (EEG) to explore gamma oscillations with the ASSR paradigm in order to probe fundamental disruptions in ASD.

Objectives: Test for alterations in gamma band response during entrainment using an ASSR paradigm. Explore the relationship between gamma band response and sensory abnormalities as indexed by clinical self-report measures.

Methods: Seventeen individuals participated in the study, including 8 participants with ASD (63% male, mean age=20.6), and 9 typically-developing (TD) controls (67% male, mean age=22.6). EEGs were recorded at 128 electrode sites using Hydrocel Geodesic Sensor Net and Philips/EGI NetStation software. The auditory stimulus was a 500ms click train with a stimulation rate of 40Hz presented 150 times (inter-trial interval: 50ms). Data were filtered, re-referenced to the average, and segmented to the event onset. We completed artifact detection, bad channel replacement and baseline corrections before conducting time-frequency analyses and calculating absolute power at 40 Hz.

Results: Deficits in 40Hz gamma-band ASSR were found in the ASD group when compared to typically-developing controls (t(15)=-3.99, p<.001). Mean 40Hz power was 0.25±0.09μV² in ASD and 0.43±0.10μV² in TD. Though not significant, a trend was observed between 40Hz power and the Auditory Processing domain of the Adolescent/Adult Sensory Profile (r=-.76, p=.079).

Conclusions: These results reinforce prior findings of diminished ASSR response in ASD. Because it is collected through a passive, non-invasive task, ASSR may be a promising objective biomarker to be used as an ASD screening and stratification tool. For example, ASSR may be diminished in individuals with ASD where GABAergic functioning is disrupted, as in some syndromic forms of ASD caused by rare genetic variants affecting synaptic functioning. In addition, ASSR may be useful as a biomarker for assessing change in clinical trials, particularly for drugs targeting the GABAergic system. Further directions for this work include increasing sample size and diversity to include those that are minimally verbal and/or have cognitive impairments. We similarly seek to implement the paradigm in syndromic ASD populations to test its sensitivity to GABAergic dysfunction in populations with known alterations in this system.