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<div><p>Autism spectrum disorder (ASD) has been postulated to involve impaired neuronal cooperation in large-scale neural networks, including cortico-cortical interhemispheric circuitry. In the context of ASD, alterations in both peripheral and central auditory processes have also attracted a great deal of interest because these changes appear to represent pathophysiological processes; therefore, many prior studies have focused on atypical auditory responses in ASD. The auditory evoked field (AEF), recorded by magnetoencephalography, and the synchronization of these processes between right and left hemispheres was recently suggested to reflect various cognitive abilities in children. However, to date, no previous study has focused on AEF synchronization in ASD subjects. To assess global coordination across spatially distributed brain regions, the analysis of Omega complexity from multichannel neurophysiological data was proposed. Using Omega complexity analysis, we investigated the global coordination of AEFs in 3–8-year-old typically developing (TD) children (n = 50) and children with ASD (n = 50) in 50-ms time-windows. Children with ASD displayed significantly higher Omega complexities compared with TD children in the time-window of 0–50 ms, suggesting lower whole brain synchronization in the early stage of the P1m component. When we analyzed the left and right hemispheres separately, no significant differences in any time-windows were observed. These results suggest lower right-left hemispheric synchronization in children with ASD compared with TD children. Our study provides new evidence of aberrant neural synchronization in young children with ASD by investigating auditory evoked neural responses to the human voice.</p></div

Scatter plot of log-transformed Omega complexity (250–300 ms) and age in months for ASD and TD children.

<p>(A) During the 0–50 ms time window, there was no significant correlation between Omega complexity and age in months for either TD children or children with ASD. (B) For TD children, a significant correlation between Omega complexity and age in months was only detected during the 250–300 ms time window. TD, typically developing. ASD, autism spectrum disorder. Solid blue line, regression line for TD children. Broken red line, regression line for ASD children. *, P < 0.0031.</p

Sound waveform of the /ne/ voice stimulus.

<p>The total time of a /ne/ stimulus was approximately 342 ms; the time length of the consonant /n/ was approximately 65 ms; and the time length of the post consonantal vowel sound /e/ was approximately 277 ms. The time point of 50 ms after stimulation onset was defined as 0 ms, and the time-window of -50–0 ms was used as baseline period.</p

The magnitude of the AEF for the whole head in TD and ASD children.

<p>(A) RMSs were calculated by 151 sensors (whole head) in TD and ASD children. (B) For each time-window of 50 milliseconds, RMSs were compared between TD and ASD children with unpaired two-tailed <i>t</i>-tests for each time window. No significant differences were observed in any time-windows. RMS, root mean square. AEF, auditory evoked field. TD, typically developing. ASD, autism spectrum disorder. Faint colored zones represent 1 standard deviation.</p

Demographic characteristics of the study participants.

<p>Demographic characteristics of the study participants.</p

Omega complexity of AEFs for the whole head in TD and ASD children.

<p>(A) Omega complexities were calculated by 151 sensors (whole head) in TD and ASD children for each time-window of 50 milliseconds. (B) Log-10 transformed Omega complexities are compared between TD and ASD children with unpaired, two-tailed <i>t</i>-tests for each time window. Children with ASD exhibited significantly higher Omega complexities compared with TD children in the time-window of 0–50 ms (t = 3.90, <i>P</i> = 0.0002). (C) The time-window of 0–50 ms included the early stage of the P1m component. AEF, auditory evoked field. TD, typically developing. ASD, autism spectrum disorder. The error bars represent 1 standard deviation.</p

Magnitude topographies of whole-head AEFs for TD and ASD children.

<p>The magnitude topographies of the AEFs calculated for each 151-sensor (whole-head) examination of TD (A) and ASD children (B). For each 50 ms time window, an unpaired two-tailed <i>t</i>-test was used to compare the magnitudes observed for TD and ASD children. No significant differences between the two types of children were observed in any time window (P > 0.0031 for all comparisons). AEF, auditory evoked field. TD, typically developing. ASD, autism spectrum disorder.</p

Omega complexity of AEFs for the left and right hemispheres in TD and ASD children.

<p>Omega complexities were calculated in 40 sensors corresponding to the left (A) and right (C) hemisphere. The Omega complexities of TD children and children with ASD were compared with unpaired two-tailed <i>t</i>-tests for 16 time windows in the left (B) and right (D) hemisphere. No significant differences were observed in any time-windows. AEF, auditory evoked field. TD, typically developing. ASD, autism spectrum disorder. The error bars represent 1 standard deviation.</p

Pearson correlation coefficients between Omega complexity in AEFs for the whole head and either age or K-ABC mental processing scale score for children with ASD (n = 50) and TD children (n = 50).

<p>Pearson correlation coefficients between Omega complexity in AEFs for the whole head and either age or K-ABC mental processing scale score for children with ASD (n = 50) and TD children (n = 50).</p

The magnitude of AEFs for the left and right hemispheres in TD and ASD children.

<p>(A) Selected 40 sensors that cover the AEF for each hemisphere. Red areas indicate magnetic field flux-out, and blue areas indicate magnetic field flux-in for P1m. RMSs were calculated in 40 sensors corresponding to the left (B) and right (D) hemisphere. The RMSs of TD children and children with ASD were compared with unpaired, two-tailed <i>t</i>-tests for 16 time windows in the left (C) and right (E) hemisphere. No significant differences were observed in any time-windows. RMS, root mean square. AEF, auditory evoked field. TD, typically developing. ASD, autism spectrum disorder. Faint colored zones represent 1 standard deviation.</p