Transcranial Direct Current Stimulation in Autism Spectrum Disorder

NCT03814083 | Completed

• 1 other identifier: HSEARS20171230001
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Transcranial Direct Current Stimulation (tDCS) is a form of non-invasive brain stimulation that has aroused increased interests in the past decade. Not only that it is transient with little side-effects, and can be well-tolerated by children, it is also affordable and readily accessible, making it an appealing treatment option for autism spectrum disorder (ASD). Objective: (1) To assess the therapeutic effects of tDCS when combined with cognitive training for 10 consecutive weekdays on improving cognitive processing in adolescents with ASD, relative to control group receiving sham-stimulation, and (2) to evaluate the associated neural mechanisms underlying the treatment effect of tDCS on adolescents with ASD. Methods: 105 adolescents with ASD will be randomly assigned to active- (n=35), sham- (n=35) tDCS, or no-treatment control (n=35) groups. Twenty minute sessions of 1 mA cathodal stimulation to the left dorsolateral prefrontal cortex (DLPRC) in conjunction with cognitive training exercise will be provided on 10 consecutive weekdays. EEGs, functional near-infrared spectroscopy, and neuropsychological tests will be administered before, 1 day and 6 months after the series of tDCS sessions. Hypothesis: We hypothesized that cathodal (inhibitory) tDCS over the left DLPRC will induce (1) stimulation-linked facilitation of learning and enhanced processing speed and resultant improvement of cognitive functioning, in executive function, relative to the sham-tDCS and the wait-list controls, (2) active-tDCS, but not sham-tDCS and wait-list controls, will modulate the intra- and inter-hemispheric neural connectivity, indexed by altered level EEG theta coherence and aberrant fNIRS haemodynamic measures, across brain areas implicated in executive functioning.

Conditions

Transcranial Direct Current Stimulation; Autistic Disorders Spectrum; Electroencephalography

Outcome Measures

Primary Outcomes (12)

• Change in behavioral measures - Early Adolescent Temperament Questionnaire - Revised - Effortful control subscale (EATQ-R-EC)

  EATQ-R-EC is an 18-item self-rated questionnaire composed of 3 sub-components under effortful control, namely attentional control, inhibitory control and activation control.

  First day of intervention,1 day and 6 months after the last day of intervention (3 time points)

• Change in behavioral measures - Autism Quotient (AQ)

  AQ serves as a screening test for autism spectrum disorders. Given its sensitivity to subtle autistic features, it is thus adopted in present study to rule out possibilities of children having unidentified autism. The questionnaire is rated on a 4-point Likert scale, from 0 (definitely agree) to 3 (definitely disagree) on a total of 50 items. Higher scores suggest greater severity level of autistic features.

  First day of intervention,1 day and 6 months after the last day of intervention (3 time points)

• Change in behavioral measures - Social Responsiveness Scales (SRS)

  SRS-2 for measures participants' social communication abilities that are highly related to frontal lobe dysfunction. It is a 4-point scale tapping on the aspects of social awareness, social cognition, social communication, social motivation, and restricted interests and repetitive behavior. Higher scores indicate greater difficulties in socialization.

  First day of intervention,1 day and 6 months after the last day of intervention (3 time points)

• Change in CANTAB® cognitive test - Stop Signal Task (SST)

  Cambridge Neuropsychological Test Automated Battery (CANTAB®) includes computerized tests correlated to neural networks and have demonstrated high sensitivity in detecting changes in neuropsychological performance. SST assesses a participants' motor inhibition of a prepotent response. The participant is required to 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 the response.

  First day of intervention,1 day and 6 months after the last day of intervention (3 time points)

• Change in CANTAB® cognitive test - Reaction Time (RTI)

  RTI assesses motor and mental response speeds, reaction time, response accuracy and impulsivity. Participants are required to react as soon as a yellow dot appears on screen. Specifically, movement and reaction time will be measured, where shorter duration reflects faster processing speed.

  First day of intervention,1 day and 6 months after the last day of intervention (3 time points)

• Change in CANTAB® cognitive test - One Touch Stockings of Cambridge (OTS)

  OTS assesses the spatial planning ability. The participant is required to determine the number of steps required to move the balls such that the pattern copies the desired patterns (correct answer). The OTS comprises of 4 problem sets to reflect increasing demands on planning.

  First day of intervention,1 day and 6 months after the last day of intervention (3 time points)

• Change in CANTAB® cognitive test - Multitasking Test (MTT)

  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 and error scores will be measured.

  First day of intervention,1 day and 6 months after the last day of intervention (3 time points)

• Change in CANTAB® cognitive test - Emotion Recognition Task (ERT)

  ERT assesses emotional recognition ability of an individual. The participant is required to determine the emotion of the face displayed from 6 options (i.e. sadness, happiness, fear, anger, disgust or surprise) after viewing the facial features of real individuals for 200 milliseconds.

  First day of intervention,1 day and 6 months after the last day of intervention (3 time points)

• Change in n-back task

  The N-back paradigm consists of 0-back (i.e., low working memory load), 1-back (i.e., medium working memory load), and 2-back (i.e., high working memory load) conditions. For the 0-back condition, participants have to press the left button of a mouse when the digit "0" (i.e., target) appeared whereas to press the right button for occurrence of other digits. For 1-back condition, participants are required to press the left button when the presented digit was identical to the one presented in the previous trial (i.e., target), otherwise, press the right button. For 2-back condition, participants are required to press the left button when the presented digit was identical to the one presented two trials before (i.e., target), otherwise, press the right button. The accuracy rate and reaction time of each block across different conditions will be measured to reflect the capacity of working memory and processing speed.

  First day of intervention,1 day and 6 months after the last day of intervention (3 time points)

• Change in the Attention Network Task (ANT)

  The computerized ANT paradigm measures different levels of attention network, namely alerting, orienting and conflicting monitoring. To measure alerting and/or orienting, 3 warning conditions will be presented - no-cue (baseline), center-cue (alerting) and spatial-cue (alerting plus orienting). Stimuli consisted of a row of 5 objects, with the object in the center being an arrow pointing either to the left or right, and 4 remaining objects being diamond-shaped stimuli. To assess conflict monitoring, the central arrow will be "flanked by congruent or incongruent stimuli". The target is flanked on either side by two arrows in the same direction (congruent) or in the opposite direction (incongruent). The participants are required to identify the direction of the arrow presented in the middle by pressing the left and right button respectively. Reaction times will be calculated to reflect subjects' performance.

  First day of intervention,1 day and 6 months after the last day of intervention (3 time points)

• Change in Electroencephalography (EEG) coherence measure

  EEG coherence measure is a useful indicator of cortical connectivity between functional areas in the brain. It reflects the levels of synchronization between two cortical areas at different sites of the scalp. High coherence indicates a high level of synchronization between the two brain areas, whereas low coherence indicates a low level of synchronization. It has been shown that different EEG frequency bands correlate with different cognitive and emotional processes. EEG signals collected from the 19 electrode positions (Fp1, Fp2, F3, F4, F7, F8, Fz, T3, T4, T5, T6, C3, C4, Cz, P3, P4, Pz, O1, and O2) will be used.

  First day of intervention,1 day and 6 months after the last day of intervention (3 time points)

• Change in functional near-infrared spectroscopy (fNIRS) recording

  NIRS is a non-invasive neuroimaging procedure used to measure hemodynamic changes, in terms of oxyhemoglobin (HbO), deoxyhemoglobin (HbR) and total haemoglobin (HbT), associated with neuronal activities of the cerebral cortex in response to attending a task within a given period of time. In addition, functional connectivity will be measured, in which the synchronized responses to cognitive stimuli between and within the left and right frontal cortex will be computed in terms of zero lagged correlation. During the NIRS session, participants will be tested on the Attention Network Task (ANT), and the n-back task while their hemodynamic data are collected using the NIRS system.

  First day of intervention,1 day and 6 months after the last day of intervention (3 time points)

Study Arms (3)

Active-tDCS and Sham-tDCS

EXPERIMENTAL

For active-tDCS condition, participants will receive stimulation on the dorsolateral prefrontal cortex with ramp up and ramp down mode for 10 seconds, eliciting a tingling sensation on the scalp that fades over seconds. Following that, a twenty-minute executive functional training task will be initiated five minutes subsequent to the stimulation mode, and the stimulation will be terminated when the training task ends. On the other hand, for sham-tDCS condition, participants will receive initial stimulation with ramp up and ramp down mode for 30 seconds, eliciting a tingling sensation on the scalp then it will be discontinued. Participant will also receive the twenty-minute executive functional training task five minutes subsequent to the stimulation mode.

Device: Active-tDCS; Device: Sham-tDCS

Active-tDCS and wait-list

ACTIVE COMPARATOR

For active-tDCS condition, participants will receive stimulation on the dorsolateral prefrontal cortex with ramp up and ramp down mode for 10 seconds, eliciting a tingling sensation on the scalp that fades over seconds. Following that, a twenty-minute executive functional training task will be initiated five minutes subsequent to the stimulation mode, and the stimulation will be terminated when the training task ends. On the other hand, participants in the wait-list control group will not receive any intervention.

Device: Active-tDCS; Other: Wait-list

Sham-tDCS and wait-list

SHAM COMPARATOR

For sham-tDCS condition, participants will receive initial stimulation with ramp up and ramp down mode for 30 seconds, eliciting a tingling sensation on the scalp then it will be discontinued. Participant will also receive the twenty-minute executive functional training task five minutes subsequent to the stimulation mode. On the other hand, participants in the wait-list control group will not receive any intervention.

Device: Sham-tDCS; Other: Wait-list

Interventions

Active-tDCS DEVICE

Active-tDCS over 10 sessions in 2 weeks (once per day, for 10 consecutive working days), while performing the executive function training tasks. Also, participants will complete an online cognitive training program while they receive active tDCS stimulation for 10 training sessions. The training session will last for 20 minutes and the online cognitive training program is comprised of 5 exercises targeting at information processing speed and executive function capacities. Each exercise lasts for approximately 4 minutes, totaling approximately 20 minutes.

Active-tDCS and Sham-tDCS; Active-tDCS and wait-list

Sham-tDCS DEVICE

Sham-tDCS stimulation over 10 sessions in 2 weeks (once per day, for 10 consecutive working days), while performing the executive function training tasks. Also, participants will complete an online cognitive training program while they receive sham-tDCS stimulation for 10 training sessions. The training session will last for 20 minutes and the online cognitive training program is comprised of 5 exercises targeting at information processing speed and executive function capacities. Each exercise lasts for approximately 4 minutes, totaling approximately 20 minutes.

Active-tDCS and Sham-tDCS; Sham-tDCS and wait-list

Wait-list OTHER

No intervention

Active-tDCS and wait-list; Sham-tDCS and wait-list

Eligibility Criteria

• Age: 14 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Individuals who are confirmed by a clinical psychologist based on the Diagnostic and Statistical Manual of Mental Disorders-5th Ed (DSM-V) criteria of Autism spectrum disorder and structured interview with their parents or primary caregivers on their developmental history using the Autism Diagnostic Interview-Revised (ADI-R).
• Individuals with intelligence quotient above 70
• Individuals who demonstrate the ability to comprehend testing and stimulation instructions

You may not qualify if:

• Individuals with severe motor dysfunctions that would hinder their participation, and those with history of other neurological and psychiatric disorders and head trauma, or on psychiatric medication will be excluded from the study

Sponsors & Collaborators

• The Hong Kong Polytechnic University: lead
• Chinese University of Hong Kong: collaborator

Study Sites (1)

The Hong Kong Polytechnic University

Hung Hom, Kowloon, Hong Kong

Location

Related Publications (1)

• Han YMY, Chan MMY, Shea CKS, Lai OL, Krishnamurthy K, Cheung MC, Chan AS. Neurophysiological and behavioral effects of multisession prefrontal tDCS and concurrent cognitive remediation training in patients with autism spectrum disorder (ASD): A double-blind, randomized controlled fNIRS study. Brain Stimul. 2022 Mar-Apr;15(2):414-425. doi: 10.1016/j.brs.2022.02.004. Epub 2022 Feb 15.

  PMID: 35181532 DERIVED

MeSH Terms

Conditions

Child Development Disorders, Pervasive

Interventions

Waiting Lists

Condition Hierarchy (Ancestors)

Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Appointments and Schedules; Organization and Administration; Health Services Administration

Study Officials

• Yvonne Han, PhD

  The Hong Kong Polytechnic University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: January 11, 2019
• First Posted: January 23, 2019
• Study Start: July 23, 2019
• Primary Completion: February 28, 2022
• Study Completion: August 31, 2022
• Last Updated: November 15, 2022

Record last verified: 2022-11

Locations

HK (1)