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

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

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.

Study Overview

• Status: Completed
• Conditions: ADHD
• Intervention / Treatment: Behavioral: Neurofeedback; Behavioral: Cognitive training

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 11 years (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Parent Stress Index 4th Edition (PSI-IV)	PSI-IV evaluates the magnitude of stress in the parent-child system	baseline and 6 weeks
Change in Continuous Performance Test (CPT) Accuracy	CPT is standard test for measuring vigilance, sustained attention and inhibitory control.	baseline and 6 weeks
Change in California Verbal Learning Test - Children's Version (CVLT-C) Score	CVLT-C test measures performance in learning and recalling verbal materials	baseline and 6 weeks

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Hadi Hosseini, Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2019
• Primary Completion (Actual): August 26, 2022
• Study Completion (Actual): September 14, 2022

Study Registration Dates

• First Submitted: June 24, 2019
• First Submitted That Met QC Criteria: June 26, 2019
• First Posted (Actual): June 28, 2019

Study Record Updates

• Last Update Posted (Estimated): December 13, 2023
• Last Update Submitted That Met QC Criteria: November 22, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: ADHD; Working memory; Neurofeedback; Cognitive training; magnetic resonance imaging (MRI); Neuromonitoring; functional near infrared spectroscopy (fNIRS)
• Other Study ID Numbers: 328066; R61MH119289 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No