Individualized Upper Alpha Neurofeedback for ADHD

Study Overview
=================
Brief Summary
-----------------
Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent neurodevelopmental disorders, characterised by inattention, hyperactivity, and impulsivity. Although pharmacotherapy is considered the first-line treatment for ADHD at all ages (at least for severe cases), non-pharmacological therapies might be equally effective without the risk of drug side effects. Some studies have shown that electroencephalographic (EEG) neurofeedback improves parent-rated ADHD symptoms in children and adolescents. However, whether neurofeedback is an effective treatment for ADHD is still under debate. Several issues may hinder the evaluation of the effectiveness of neurofeedback treatment in previous studies. Firstly, previous neurofeedback studies did not utilize effective neurophysiological markers for ADHD. Theta/Beta ratio, the most common neurofeedback marker for treating ADHD in the past two decades, has recently been suggested to be only weakly correlated to individuals' attention. Secondly, previous studies mostly used the norm of the EEG markers in age/gender matched healthy children as the training target for ADHD children, which largely ignored the individual variations in EEG acquisition. Third, most of the previous studies lack a rigorous study design, for comparing neurofeedback with a 'placebo' condition and evaluating its specific and non-specific effects. In the current studies, we propose to conduct a sham-controlled, triple-blind trial to evaluate the effectiveness of an individual-based neurofeedback treatment for ADHD children and adolescents. The EEG marker for neurofeedback in treating ADHD would be the individualized upper alpha band power, based on the recent methodological advances in EEG spectrum processing (1/f model fit and individualized peak alpha frequency modelling) . The training target will be individualized and defined according to the neurophysiological pattern shown in pre-training resting-state conditions, and thus each participant will be trained to achieve their own optimum state of engagement. Sham neurofeedback will be used as a placebo condition, controlling for the non-specific effect of neurofeedback. The study will be triple-blinded (i.e, participants, individuals who administered treatment or intervention, and those who assessed the outcomes were masked).

Detailed Description
-----------------
120 ADHD children will be invited to join the RCT neurofeedback training. They will be randomly assigned to one of two groups (neurofeedback group, sham feedback group, ). For the neurofeedback group participants will undergo an 4-week neurofeedback training (twice a week); for the sham feedback group， participants will undergo an 4-week sham feedback training (twice a week), All the groups will conduct cognitive and EEG tests before and after the 4-week period and the investigators will follow up with all the participants immediately after the training, 3-month and 12-month after the training. When recruiting, participants and parents of the participants will be notified that their children are likely to be assigned to one of the three groups, and for the neurofeedback and sham feedback group, the parents and participants will not know which condition they are enrolled in, until the end of the study. By the end of the study, participants from the sham feedback group will be given an opportunity to rejoin a neurofeedback session for compensation.

Official Title
-----------------
Examine the Effectiveness of Individualized Upper Alpha Neurofeedback for Children With ADHD, a Triple Blinded Randomised Control Trial

Conditions
-----------------
ADHD

Intervention / Treatment
-----------------
* Behavioral: Individual upper alpha neurofeedback
* Behavioral: Sham neurofeedback


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Fulfilment of the DSM-IV-TR criteria for ADHD No intention to use any medication during the intervention period. Exclusion Criteria: Diagnosis of cerebral palsy/ history of structural brain abnormalities on CT/ MRI; full-scale IQ score (FSIQ) < 70; A history of seizure or prior electroencephalogram abnormalities related to epilepsy. Having comorbid psychiatric disorders including schizophrenia or schizoaffective disorder, bipolar disorder, borderline personality disorder, epilepsy, or traumatic brain injury; current substance abuse or dependence Planned other behavioural/durg treatment during the intervention period

Ages Eligible for Study
-----------------
Minimum Age: 4 Years
Maximum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Once eligible participants are enrolled in this study, they will be randomly allocated either to the neurofeedback intervention group or the sham feedback group. Participants in both groups will receive treatment/sham treatment at the same period.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Individual upper alpha neurofeedback<br> | Behavioral: Individual upper alpha neurofeedback<br>* The aim of the neurofeedback is to uptrain the upper alpha frequency band power of human EEG. Before the training participants will undergo a 2-minute resting-state EEG recording and the individual alpha peak frequency (IAF) will automatically calculated by algorithm. The IAF value will be calculated before each training session and for each session, the upper alpha frequency band is defined as IAF   IAF +2 Hz. The relative upper alpha band power = band power[IAF, IAF+2]/band power[0,IAF]. The relative upper alpha band power will be visualised in a gauge on the screen. Real time visual feedback will be given the participants, such that as the relative upper alpha power increases (relative to the mean value in the pre-training resting state EEG recording) a car on the screen will move (the movement is correspondent to the magnitude of relative upper alpha power change), and the animation will change based on EEG parameter every 500 ms.<br>|
| Sham Comparator: Sham neurofeedback<br> | Behavioral: Sham neurofeedback<br>* The sham neurofeedback protocol was identical to the verum neurofeedback protocol except for the origin of the EEG signal displayed on the participants' screens. In the sham condition, participants were presented with a pre-recorded signal from an individual who participated in the verum neurofeedback group of the study. Therefore, at the beginning of the training, a computer program allocated each participant of the sham neurofeedback condition to a participant of the verum neurofeedback condition and this assignment remained stable throughout the treatment<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Strengths and Weaknesses of Attention-Deficit/Hyperactivity Symptoms and Normal Behavior Scale (SWAN) | The Chinese SWAN is a validated instrument for the assessment of ADHD symptoms in Chinese children in Hong Kong. The SWAN questionnaire was originally devised by Swanson et al in 2005 based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for ADHD. | prior to the intervention, immediate after the intervention, 3 months & 12 months after the intervention | 
| Conners CPT (Conners Continuous Performance Test) | The Conners Continuous Performance Test (CPT) is a computerized neuropsychological assessment designed to evaluate attention, impulsivity, and vigilance in children and adolescents aged 8-18 years. The test involves the presentation of letters on a computer screen, where the participant must respond to specific target letters while ignoring others. The Conners CPT provides measures of response time, errors, and variability, which can aid in the identification of attention deficit hyperactivity disorder (ADHD) and other attention-related problems. | prior to the intervention, immediate after the intervention, 3 months & 12 months after the intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PedsQL (Pediatric Quality of Life Inventory) | The Pediatric Quality of Life Inventory (PedsQL) is a reliable and validated instrument for assessing health-related quality of life in children and adolescents aged 2-18 years. It consists of 23 items, covering four domains: physical functioning, emotional functioning, social functioning, and school functioning. The PedsQL is designed to measure the impact of various health conditions on children's daily lives and well-being. | prior to the intervention, immediate after the intervention, 3 months & 12 months after the intervention | 
| SDQ (Strengths and Difficulties Questionnaire) | The Strengths and Difficulties Questionnaire (SDQ) is a brief behavioral screening questionnaire for children and adolescents aged 2-17 years. It consists of 25 items, covering five domains: emotional symptoms, conduct problems, hyperactivity/inattention, peer relationship problems, and prosocial behavior. The SDQ is designed to help identify mental health problems and promote emotional well-being in children and adolescents. | prior to the intervention, immediate after the intervention, 3 months & 12 months after the intervention | 
| BRIEF (Behavior Rating Inventory of Executive Function) | The Behavior Rating Inventory of Executive Function (BRIEF) is a standardized questionnaire for assessing executive function behaviors in children and adolescents aged 5-18 years. It consists of 86 items, covering eight clinical scales: inhibit, shift, emotional control, initiate, working memory, plan/organize, organization of materials, and monitor. The BRIEF is designed to identify executive function difficulties in school and home settings. | prior to the intervention, immediate after the intervention, 3 months & 12 months after the intervention | 
| RAVEN (Raven's Progressive Matrices) | Raven's Progressive Matrices is a non-verbal, multiple-choice test that measures abstract reasoning and fluid intelligence in children and adolescents. The test consists of a series of visual patterns, where the participant must identify the missing piece from a set of options. Raven's Progressive Matrices are widely used in educational and clinical settings to assess general cognitive abilities, as they are relatively unaffected by language, cultural, and educational background. | prior to the intervention, immediate after the intervention, 3 months & 12 months after the intervention | 
| the Wechsler Intelligence Scale for Children (WISC): | The Wechsler Intelligence Scale for Children (WISC) is a comprehensive, standardized intelligence test designed for children and adolescents aged 6-16 years. The WISC measures cognitive abilities across various domains, including verbal comprehension, visual-spatial abilities, fluid reasoning, working memory, and processing speed. The test consists of several subtests, each designed to assess different aspects of cognitive functioning. The WISC is widely used in educational and clinical settings to help identify learning difficulties, intellectual giftedness, and other cognitive issues that may impact a child's academic performance and daily functioning | prior to the intervention, immediate after the intervention, 3 months & 12 months after the intervention | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ADHD, Neurofeedback