Source Localization Analyses of Preattentive Auditory Discrimination Processing in Japanese Children with Autism Spectrum Disorders

Background: Children with autism spectrum disorders (ASD) are often characterized as having atypicalities in information processing deficits, spanning from low level sensory processing to higher-order cognitive functions. Mismatch negativity (MMN) and P3a, which is considered to be promising neurophysiological indexes in translational research of psychiatry, are event related potential (ERP) components that are automatically elicited in response to unattended changes in ongoing, repetitive stimuli. Recent studies suggest that investigation of these preattentive auditory discrimination processing might extend understanding of the atypical neurophysiological basis of ASD. However, to our knowledge, the neural substrates of these atypical responses in ASD are not fully understood.

Objectives: To evaluate the preattentive auditory discrimination processing (MMN and P3a) and their generators in Japanese children with ASD and typical development (TD), and, to evaluate their relationship to quantitative autistic traits.

Methods: In this study, 8 children with ASD and 26 with TD underwent 64 channel EEG testing using a multi-feature auditory oddball paradigm (3 types of deviant: duration, frequency, omission) while passively watching a silent video. We separately average the ERPs in response to the standards and the oddball stimuli, and then subtract the standard responses to get difference waveforms reflecting just the additional processing associated with the oddball stimuli. Based on the electric potential distribution of ERP difference waveform, the exact low resolution brain electromagnetic tomography (eLORETA) software was used to compute the cortical three-dimensional distribution of electric neuronal activity, current density of MMN (latency: 135-205 msec) and P3a (latency: 250-300 msec) components in the subjects as well as the brain regions associated with atypicalities observed among ASD children. ASD characteristics of all subjects were assessed by Social Responsive Scale (SRS).

Results: The current density components of MMN and P3a responses to duration and frequency oddball mapped onto neural sources broadly distributed across temporal, frontal, and parietal regions in children with ASD and TD. Non-parametric voxel-by-voxel regression analysis after logarithmic transformation of the current density data revealed significant negative association between duration-deviant MMN current density of right inferior frontal gyrus and SRS total score. Duration-deviant P3a current density of right inferior, middle, superior frontal gyrus was negatively associated with SRS social cognition subscale.

Conclusions: Our findings support the idea of atypical preattentive auditory discrimination processing in ASD. Further investigations are required to reveal the contribution of the neural sources to atypical higher-order psychosocial cognitive functions in ASD.