Transcranial Direct Current Stimulation in Children With Autism Spectrum Disorder

The executive function of the children with ASD will be assessed using the Executive Composite score, which will be derived by summing the scores from the test battery of executive functions.

Simple-task processing speed will be evaluated using the CANTAB® 5-choice Reaction Time (RTI) task. Complex-task processing speed will be assessed using the computerized version of the Wisconsin Card Sorting Test (WCST). The mean reaction time is calculated for the trials giving a correct answer during WCST.

The reaction time measured from both tasks will be converted to standard scores and averaged to yield an executive composite score. Lower scores indicate poorer executive functioning.

RTI assesses motor and mental response speeds, reaction time, response accuracy and impulsivity. It consists of 30 trials with five potential targets and requires participants to make flexible responses as fast as possible to the target stimulus (shown in yellow). Specifically, movement and reaction time will be measured, where shorter duration reflects faster processing speed.

SST assesses the ability of inhibition control. The participant must respond to an arrow stimulus, by selecting one of two options, depending on the direction in which the arrow points. If an audio tone is present, the subject must withhold making that response (inhibition). Accuracy will be measured, where higher accuracy indicates better inhibition control.

MTT assesses the ability to resolve the interference of task-irrelevant information (stroop-like effect). The test displays an arrow which can appear on either the left or right side of the screen and can point to either the left or right side. In each trial, participants are presented with a cue that indicates which button to press according to two different rules. And the rules that participants have to follow may change from trial to trial in a randomized order. Participant's response latencies will be measured.

MTT assesses the ability to resolve the interference of task-irrelevant information (stroop-like effect). The test displays an arrow which can appear on either the left or right side of the screen and can point to either the left or right side. In each trial, participants are presented with a cue that indicates which button to press according to two different rules. And the rules that participants have to follow may change from trial to trial in a randomized order. Participant's error scores will be measured.

ERT assesses ability to identify six basic emotions in facial expressions along a continuum of expression magnitude. The participants must select which emotion the facial image displayed 0.2s ago. Accuracy and its percentage, as well as response latencies will be measured.

The VFT assesses an individual's ability of working memory retrieval and executive control by instructing the individual to generate words for given semantic categories within a limited time. The VFT experimental paradigm is designed and presented with E-prime 3 (Psychology Software Tools Inc., Sharpsburg, PA, USA). During the experimental blocks, which will be counterbalanced across individuals to avoid order effects, a category word (i.e. 'transportation' or 'country') will be shown on the screen. Participants will be asked to focus their eye gaze on the center of the screen and continuously repeat '1, 2, 3, 4' slowly during the given period of time. Their responses will be recorded by an audio recorder and then transferred into written form on an Excel spreadsheet. The number of unique and correct words generated will be counted for each of the participants. This test will be paired with fNIRS recording.

EEG resting-state theta coherence (4-7.5 Hz) will be computed from EEG signals collected from the 19 electrode positions collected from 5-min eye opened resting. Raw data will be processed with the EEGLAB Toolbox using MATLAB® R2019a. Automatic channel rejection, re-referencing, finite impulse response filtering will be performed. To filter artifacts, visual inspection of the EEG data will also be performed. Independent component analysis (ICA) will be used to further remove muscle and eyeblink artifacts. The E/I ratio will be calculated using the method described by Bruining et al (2020). the correlation between amplitude and fluctuation will be calculated for each EEG channel to yield the E/I ratio.

fNIRS data will be collected from 15 channel positions and processed using the NIRSIT Lite Analysis Tool version 3.1.0 (OBELAB Inc., Seoul, Korea), which is a MATLAB® R2019a compatible graphical user interface. The raw light intensity data for resting-state and task-based recordings (i.e. VFT) will be converted into changes in oxyhemoglobin (oxy-Hb) concentration according to the modified Beer-Lambert Law. To remove the physiological noise and movement artifacts, a 0.005-0.05 Hz bandpass filter will be used. To avoid the contamination of data caused by head movements, which are observed as spikes or significant shifts from baseline values, two additional channel rejection measures will be taken. Baseline corrections will be performed for task-based recordings based on the mean pretask baseline values defined by 5s prior to the task blocks to control for task-irrelevant [oxy-Hb] changes. The block average fNIRS data will be used for subsequent statistical analyses.