DOI: 10.3886/e198003v1
title: Double-Blind 2-Site Randomized Clinical Trial of Neurofeedback for ADHD

description: <b>Importance:</b> The first large
double-blind randomized controlled trial of neurofeedback (EEG biofeedback) for
attention-deficit/hyperactivity disorder (ADHD).

 

<br><b>Objective:</b> Determine how much of
reported neurofeedback benefit is specific to deliberate continuous brain-wave-contingent
reinforcement and how enduring the effect is. 

 

<br><b>Design</b>: Double-blind trial with
randomization 3:2 to active neurofeedback vs. a yoked control of equal duration/intensity/appearance.
Assessments at baseline, mid-treatment, treatment-end, and 6-, 13-, and
25-month follow-ups. Treatment was completed June 2018 and 13-month follow-ups
June 2019.

 

<br><b>Setting:</b> Two sites: An Ohio university
center and a North Carolina neurofeedback clinic.

<b> </b>

<br><b>Participants:</b> Children age 7-10 with
moderate/severe ADHD and EEG theta-beta power ratio&gt;4.5. Mainly
middle/upper class; 78% boys; 36% inattentive, 64% combined. Of 329 screened,
305 passed categorical and dimensional ADHD criteria; 235 had Theta-Beta Ratio.&gt;4.5;
144 completely eligible, randomized; 2 withdrew early, leaving 142 as modified
ITT population: 84 active, 58 controls.

 <br>

<b>Interventions:
</b>Neurofeedback
(38 sessions at 3X/week) to reduce theta and increase beta power, using
systematic reinforcement (game- and money-points) for meeting individualized
manually set thresholds. The yoked-control reinforcements were based on
pre-recorded EEGs with participant’s live artifacts superimposed to maintain
blind. Conditions were programmed via internet by an off-site
statistician-guided co-investigator. 

 

<br><b>Main
Outcomes/Measures:</b>
Primary outcome was composited parent- and teacher-rated inattention at treatment
end and follow-ups.

 <br>

<b>Results:</b> Both neurofeedback and controls had large
pre-post treatment-end benefits (d=1.5, p&lt;0.001) for parent/teacher-rated inattention
but were not significantly different. Hyperactive-impulsive symptoms and
impairment showed similar results. Responders (CGI-I=1-2) were 61% of NF and 53%
of Controls. Adverse events were
proportional. 13-month follow-up found further nonsignificant improvement of inattention
from treatment end for NF (d=0.1), but not controls (d= -0.07), with remission
rates 39.7% for NF vs. 18.5% for Controls (p=.011). 

<b> </b>

<br><b>Conclusions:
</b>This
study failed to support a significant specific effect of deliberate continuous EEG-power-contingent
reinforcement post-treatment but demonstrated large improvements in inattention
for both neurofeedback and control. After 13 months, benefit was maintained,
with small further improvement for neurofeedback, which had twice the remission
rate of controls. These results suggest strong non-specific lasting effects and
the possibility of delayed specific effect of TBR neurofeedback, being checked
in 25-month follow-ups.
description: Presence of Common Scales: CGI-I (improvement) -- Clinical Global Impressions ScaleCGI-S (severity) -- Clinical Global Impressions ScaleCHIPS -- Coping Health Inventory for Parents CHIPS Interview (Performed by Clinician)Conners - ParentConners -TeacherCSHQ -- Children's Sleep Habits Questionnaire -- ParentFAC - Parent --Functional Assessment Checklist, Parent CompletedFAC - Teacher -- Functional Assessment Checklist, Teacher CompletedNORS -- Neurofeedback Observer Rating ScalePPDS -- Modified Petersen Pubertal Development ScaleSBQ -- Suicide Behaviors QuestionnaireSCT-23 -- Sluggish Cognitive TempoTMT -- Time Math TestWASI -- Wechsler Abbresviate Scale IntelligenceWIAT -- Wechsler Individual Achevement TEsWJ -- Woodcock-Johnson Cognitive Abilities test
description: children under the age of 12 who have been diagnosed with ADHD. .
description: coded video observation; cognitive assessment test; computer-assisted self interview (CASI); face-to-face interview; on-site questionnaire; The design
was a 2-site, parallel-group, double-blind randomized comparison of active NF
to “sham” NF (Control) for up to 38 treatments in a 14-week period, with 6-, 13-,
and 25-month FU, in children with ADHD and TBR&gt;4.5.  At each of two sites, consented eligible
children were randomized to NF vs. Control in a 3:2 ratio, stratified by site and current ADHD
medication. Randomization was supervised by the study biostatistician
and implemented remotely in the software
by an unblinded co-investigator who had no contact with participants. The
follow-ups were considered an integral part of the RCT because enduring benefit
was important to justify the expense and effort of labor-intensive NF.<br><br>Treatment consisted of downtraining theta power
and uptraining beta power for 38 active NF treatments vs. 38 control treatments.
The yoked-control condition used pre-recorded EEGs instead of the live EEG to
determine rewards. Treatment was conducted with EEGer NF software (EEG Software
LLC, Northridge, CA), using a ProComp Infiniti (Though Technology, Toronto) or
Atlantis (BrainMaster, Bedford, OH) amplifier. EEGer was configured for training four EEG parameters: preventing high
overall amplitudes and gross movement (1-60 Hz), reducing theta (4-8 Hz),
increasing beta (13-21 Hz), and reducing muscle movements (EMG, 45-60 Hz). Reinforcement consisted of points that could be cashed for money. Each
session, the child participated in 5 training periods (blocks). Each period
lasted 5 minutes at the beginning and gradually increased to 9 minutes per period
in later sessions. Details of the reinforcement algorithm can be found in the
supplementary materials.<br><br><b>Mid-treatment
Decision about Continuing: </b>Review of prior studies found that participants
who did not show at least 10% improvement in parent/teacher ratings by 19
treatments did not respond after 38 treatments 17,22. Therefore, those who did not show a 10%
improvement in the average of parent and teacher ratings at the midpoint
assessment exited neurofeedback per protocol –in a blinded fashion,
irrespective of assigned group- but were retained for assessments. 

 <br><br>Measures

The standardized diagnostic interview at
screening and follow-ups was the Children’s Interview for Psychiatric Syndromes-child
(ChIPS) and -parent (P-ChIPS) versions 23.

Repeated
outcome measures (unmedicated at major assessments) included: 

Parent-rated
scales: Conners
-3rd Edition: Long Version (C-3:P, 24) and Functional Assessment Checklist (FAC; 25). 

Teacher-rated
scales: Teacher
versions of the C-3 (C-3T) and FAC for Teachers (FACT; 26). We recruited from August through February so
the child could have the same teacher for baseline, mid-treatment, and
end-of-treatment assessments in the 3-month treatment. DSM-5 ADHD symptoms from
the parent and teacher C-3 were used for the severity inclusion criterion (1.5 SD
above norm).

Clinician
& staff ratings: Clinical
Global Impression (CGI).

Adverse
effects and changes in concomitant treatments: Adverse
Events Tracking Form and Concomitant Treatment/Education Services Form.

Blinding
Checks.  Consumer Satisfaction and Blinding
Questionnaire (parent and child) and trainer Blinding Questionnaire measured parent, child, and trainer blinding to assigned
treatment.

Clinical
response and remission: Response was defined as CGI-Improvement (CGI-I) rating of 1 or 2. Remission
(loss of diagnostic severity) was defined in two ways: as a CGI-severity rating
of 1 or 2, and an ADHD symptom rating item mean &lt;1.003,27.


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