A Novel fNIRS Neurofeedback Intervention for Enhancement of Working Memory in Attention Deficit Hyperactivity Disorder (ADHD)

Study Overview
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Brief Summary
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The proposed study is to test and validate a novel intervention that integrates computerized cognitive training with real-time neuromonitoring and neurofeedback to enhance working memory by probing the individualized neural systems underlying working memory. We will test the proposed intervention on children with ADHD with working memory deficits. The R61 proof-of-concept phase will assess the target engagement, effective dose and feasibility.

Official Title
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A Novel Neuromonitoring Guided Cognitive Intervention for Targeted Enhancement of Working Memory

Conditions
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ADHD

Intervention / Treatment
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* Behavioral: Neurofeedback
* Behavioral: Cognitive training


Participation Criteria
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Eligibility Criteria
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Inclusion criteria include: Age from 7 to 11 years Diagnosis and/or current symptoms of ADHD Full-scale Intelligence quotient (IQ) ≥80 Behavior Rating Inventory of Executive Functions (BRIEF), Working Memory Scale t-score > 65 Allowed comorbidities include oppositional defiant disorder, learning disabilities excluding dyslexia, and mild anxiety and/or depression. Exclusion criteria: Presence of severe neurological or psychiatric disease other than those allowed under inclusion Sensory deficits that would preclude participation in assessments or imaging History of significant head trauma with loss of consciousness Contraindications to MRI (e.g. metal implants or claustrophobia) Enrollment in other intervention studies

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 11 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neurofeedback<br>The Neurofeedback group will receive 12 sessions of computerized cognitive intervention combined with neurofeedback in the lab. | Behavioral: Neurofeedback<br>* The Neurofeedback group will receive the proposed intervention which integrates computerized working memory training with neuromonitoring and neurofeedback.<br>|
| Active Comparator: Cognitive Training<br>The Cognitive Training group will receive 12 sessions of computerized cognitive intervention in the lab. | Behavioral: Cognitive training<br>* The Cognitive training group will receive computerized working memory training with performance feedback.<br>|
| No Intervention: Waitlist<br>Both Neurofeedback and Cognitive Training groups will be assigned to waitlist before starting the corresponding intervention. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Target Frontal-parietal Activity | Change in activity in the target frontal-parietal network measured by functional near infrared spectroscopy (fNIRS) during an N-back working memory task. A general linear model is applied to recorded signal and the beta coefficients from the model are extracted as a proxy for brain activity in fronto-pariteal network which subserves working memory function. There is no established population mean for beta coefficient of brain activity. Higher (lower) beta coefficients reflect higher (lower) activation in the target brain network. A positive change indicates increased brain activity. Increased frontal-parietal activity reflects better engagement of this brain network during working memory performance. | baseline and 6 weeks | 
| Change in Working Memory Performance | Accuracy in an N-back working memory task was calculated as the percentage of correct responses to target stimuli. | baseline and 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Behavior Rating Inventory of Executive Function (BRIEF), Working Memory T-score | BRIEF assesses everyday behavior associated with specific domains of the executive functions. BRIEF working memory T-score ranges from <30 to >100 with higher scores indicating larger impairment in working memory. Lower T-scores on BRIEF indicates better working memory. T-score of 50 indicates the population mean with a standard deviation of 10. BRIEF working memory T-score of 65 and higher is indicative of deficits in working memory. | baseline and 6 weeks | 
| Change in Wide Range Assessment of Memory and Learning 2 (WRAML-2), General Memory Index Score | WRAML-2 assesses clinical issues in learning and memory functions. WRAML-2 Working Memory Index score ranges from 50 to 150 with higher scores indicating better working memory performance | baseline and 6 weeks | 
| Change in Conners 3rd Edition ADHD Index Score | Conners 3 will be used to measure changes in clinical ADHD symptoms. Conners 3 ADHD index score ranges from 0 to 100 with higher scores indicating elevated ADHD symptoms. Conners 3 ADHD index score of higher than 65 is indicative of ADHD diagnosis. | baseline and 6 weeks | 
| Change in Conners 3rd Edition Inattention T-score | Conners 3 will be used to measure changes in clinical inattention symptoms. Conners 3 inattention t-score ranges from <30 to >100 with higher scores indicating larger impairment in attention. T-score of 50 indicates the population mean with a standard deviation of 10. Inattention t-score of 65 and higher is indicative of deficits in attention. | baseline and 6 weeks | 
| Change in Developmental NEuroPSYchological Assessment II (NEPSY-II) Composite Score | NEPSY-II consists of a set of subtests measuring cognitive functions required for success in school. The subtests include auditory attention & response, inhibition, word-list interference, and comprehension of instructions. The composite scores were quantified by averaging the scores across sub-scales. A positive change in composite score suggests increased ability in subtest domains. The composite score below 8 suggest deficits. The composite scores range from 0 to 20; lower scores correspond to more deficits, and higher scores correspond to more abilities. | baseline and 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ADHD, Working memory, functional near infrared spectroscopy (fNIRS), magnetic resonance imaging (MRI), Neurofeedback, Cognitive training, Neuromonitoring