Association Between Magnetoencephalographic Interictal Epileptiform Discharge and Cognitive Function in Young Children With Typical Development and With Autism Spectrum Disorders

Electroencephalograms of individuals with autism spectrum disorders (ASD) show higher rates of interictal epileptiform discharges (IEDs), which are known to have an inverse association with cognitive function in typically developed (TD) children. Nevertheless, that phenomenon has not been investigated adequately in children with ASD. From university and affiliated hospitals, 163 TD children (84 male, 79 female, aged 32–89 months) and 107 children (85 male, 22 female, aged 36–98 months) with ASD without clinical seizure were recruited. We assessed their cognitive function using the Kaufman Assessment Battery for Children (K-ABC) and recorded 10 min of MEG. Original waveforms were visually inspected. Then a linear regression model was applied to evaluate the association between the IED frequency and level of their cognitive function. Significantly higher rates of IEDs were found in the ASD group than in the TD group. In the TD group, we found significant negative correlation between mental processing scale scores (MPS) and the IED frequency. However, for the ASD group, we found significant positive correlation between MPS scores and the IED frequency. In terms of the achievement scale, correlation was not significant in either group. Although we found a correlative rather than a causal effect, typically developed children with higher IED frequency might better be followed up carefully. Furthermore, for children with ASD without clinical seizure, clinicians might consider IEDs as less harmful than those observed in TD children

Gamma-band auditory steady-state response after frontal tDCS: A double-blind, randomized, crossover study

<div><p>The effects of transcranial direct current stimulation (tDCS) likely depend on cortical N-methyl-D-aspartic acid (NMDA) neurotransmission; however, no previous studies have reported tDCS-mediated modulation of cortical NMDA neurotransmission in humans. The gamma-band auditory steady-state response (ASSR) to a 40 Hz stimulation likely reflects the integrity of cortical NMDA neurotransmission. The present study tested whether the effect of tDCS is reflected in gamma-band ASSRs during a 40 Hz stimulation. Using a double-blind, randomized, crossover study, we performed magnetoencephalography (MEG) and measured the ASSR in 24 healthy participants during 40 Hz of auditory stimulation after prefrontal tDCS (2 mA) or sham (i.e., placebo) treatment. Our results failed to reveal significant differences in any brain between the two conditions after the application of a frequency of approximately 40 Hz. Based on these results, the ASSR is an insufficient method to detect the effect of tDCS on cortical NMDA neurotransmission. Unexpectedly, the results revealed an enhanced beta-band event-related spectral perturbation (ERSP) in the left motor cortex after tDCS compared with that observed after the sham stimuli. Given that beta-band oscillations reflect many functions in motor cortices, the tDCS for the frontal areas had some effect on the left motor cortex while the participants were focusing on not pressing the button with their right index finger. An additional study with an adequate psychological task is necessary to draw a conclusion regarding this unexpected result.</p></div

Study design: A double-blind, randomized, crossover study.

<p>Twenty-four participants were recruited and randomly assigned to receive either tDCS or sham stimulation during the first trial. After an interval of at least four weeks, the second trial was conducted. The order of the two stimulation conditions (i.e., tDCS or sham) was counterbalanced across participants. After delivering one of the two stimulus conditions, ASSRs were recorded using MEG. We excluded two participants from the statistical analysis because they met the exclusion criteria. ASSR, auditory steady-state response.</p

ERSPs in the left precentral gyrus.

<p>(A) <i>T</i>-maps of the differences in the ERSPs between the tDCS and sham conditions. The threshold of <i>p</i> < 0.05 (FDR corrected) is highlighted with a red rectangle. The color indicates the <i>t</i>-values at each time-frequency point. Significantly higher ERSPs were observed in the beta-band (20 Hz; a red rectangle) after tDCS than after the sham condition. (B) The grand average of the time-frequency maps of ERSPs in the left precentral gyrus under both tDCS (upper row) and sham (lower row) conditions. In each map, the x-axis indicates time (ms), and the y-axis indicates frequency (Hz). The color indicates ERSPs at each time-frequency point (reflected as the percentage change from baseline).</p

The grand average of the time-frequency maps for the ITPC in the transverse temporal gyrus under both tDCS and sham conditions.

<p>In each map, the x-axis indicates time (ms), and the y-axis indicates frequency (Hz). The color indicates the ITPCs at each time-frequency point. The ITPC peak in the gamma-band (40 Hz) was clearly observed during the 40 Hz auditory stimulation.</p

Electrode placement.

<p>(A) Anodal (F3) and cathodal (F4) electrodes marked on the scalp surface. (B) The computational simulation of brain current flow during the delivery of the tDCS. Major changes in the brain current flow were observed in the dorsal-frontal areas during stimulation [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0193422#pone.0193422.ref037" target="_blank">37</a>].</p

<i>T</i>-maps of the differences in ERSPs (upper row) and ITPCs (lower row) in the transverse temporal gyrus between the tDCS and sham conditions.

<p>Color indicates <i>t</i>-values at each time-frequency point. No significant differences were found in either ERSPs or ITPCs when the statistical threshold was set to <i>p</i> < 0.05 with an FDR correction.</p