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Letter to the Editor

The Problem of Patient Heterogeneity and Lack of Proper Training in a Study of EEG Neurofeedback in Children

Rex L. Cannon, PhD; H. E. Pigott, PhD; Tanju Surmeli, MD; Deborah R. Simkin, MD; Robert W. Thatcher, PhD; Werner Van den Bergh, MD; Gerald Gluck, PhD; Joel F. Lubar, PhD; Richard Davis, MS; Dale S. Foster, PhD; Jonathan Douglas, PhD; Atholl T. Malcolm, PhD; Donald Bars, PhD; Kirk Little, PsyD; Wes Center, PhD; Marvin Berman, PhD; Harold Russell, PhD; Barbara Hammer, PhD; and J. Lucas Koberda, MD, PhD

Published: March 15, 2014

See reply by van Dongen-Boomsma et al and related article by van Dongen-Boomsma et al.

The Problem of Patient Heterogeneity and Lack of Proper Training in a Study of EEG Neurofeedback in Children

To The Editor: A recent article1 reported results demonstrating that electroencephalographic (EEG) neurofeedback was not different from placebo neurofeedback in improving attention-deficit/hyperactivity disorder (ADHD) symptoms in children with ADHD. Thus, we would request the title and clinical points be changed to reflect the findings of the study in an accurate manner. The issues that support this modification are listed below in order of importance.

1. The percentage of reward (80%) utilized in this study precludes a significant learning effect in an operant conditioning paradigm. This article failed to demonstrate acquisition at the neural level for the stimulus being trained, which is the most basic principle of operant learning.2-6 In both respondent and operant conditioning, an individual acquires a behavior that was not previously possessed.7-9

2. Importantly, pre-quantitative and post-quantitative EEG at the group level would have also been desired given the comorbidity10 and medication issues in addition to reward parameters.11 It would also be advantageous to examine the EEG changes in the placebo group as a result of the procedure to better understand the nature of self-regulation and its global effects. To this end, we have calculated the effect size for each of the study variables shown in Table 2 of the article. The effect sizes range from 0.63 to 0.36; the highest effect sizes are shown for the inattention symptoms at 0.63.

3. The current work includes patients with ADHD) with comorbid oppositional defiant disorder (ODD), anxiety, and learning disorders. Thus, approximately 39% of this study population may not have received proper training with known protocols utilized for treatment of ADHD, anxiety, ODD, or learning disorders;12-14 such protocols with differential features to address these particular syndromes,15-17 with or without comorbid ADHD, would be different from the SMR/theta protocols used in this study. These differences in protocols undoubtedly contributed to the lack of significantly different findings between groups and should have been considered in the differential grouping and analyses of the study data.

4. Although the reduction in symptoms occurred in both groups, psychometric measures were not utilized for diagnostic or classification purposes nor were they obtained to confirm or deny this outcome,18 given that we clinicians would want to see improvement within the individual across treatment sessions.19 Therefore we hypothesize that this classification system may have produced effects on the outcome of the study.15-17 Further, data for 14 (8 neurofeedback and 6 placebo) of the total 41 patients had previously been analyzed and reported. As we have noted in this letter, there are standardized protocols that have worked well with ADHD across studies,18,19 and may have added to the quality of the article.

Simply stated, it is not unreasonable to consider the effects of neurofeedback across a heterogenous sample of comorbidity, since this is highly likely to be encountered in the clinical setting. However, to report the findings of such a study in one disorder is misleading and unrepresentative of the data. Thus, the title and clinical points of this study fall under these confounding issues and should be adjusted accordingly.

References

1. van Dongen-Boomsma M, Vollebregt MA, Slaats-Willemse D, et al. A randomized placebo-controlled trial of electroencephalographic (EEG) neurofeedback in children with attention-deficit/hyperactivity disorder. J Clin Psychiatry. 2013;74(8):821-827. PubMed doi:10.4088/JCP.12m08321

2. Sterman MB. Sensorimotor EEG operant conditioning: experimental and clinical effects. Pavlov J Biol Sci. 1977;12(2):63-92. PubMed

3. Sterman MB. Neurophysiologic and clinical studies of sensorimotor EEG biofeedback training: some effects on epilepsy. Semin Psychiatry. 1973;5(4):507-525. PubMed

4. Sterman MB, Friar L. Suppression of seizures in an epileptic following sensorimotor EEG feedback training. Electroencephalogr Clin Neurophysiol. 1972;33(1):89-95. PubMed doi:10.1016/0013-4694(72)90028-4

5. Cannon RL, Congedo M, Lubar JF, et al. Differentiating a network of executive attention: LORETA neurofeedback in anterior cingulate and dorsolateral prefrontal cortices. Int J Neurosci. 2009;119(3):404-441. PubMed doi:10.1080/00207450802480325

6. Cannon RL, Lubar JF, Congedo M, et al. The effects of neurofeedback training in the cognitive division of the anterior cingulate gyrus. Int J Neurosci. 2007;117(3):337-357. PubMed doi:10.1080/00207450500514003

7. Pear J. The Science of Learning. New York, NY: Psychology Press; 2001.

8. Eliot LS, Kandel ER, Hawkins RD. Modulation of spontaneous transmitter release during depression and posttetanic potentiation of Aplysia sensory-motor neuron synapses isolated in culture. J Neurosci. 1994;14(5 pt 2):3280-3292. PubMed

9. Kandel ER, Spencer WA. Electrophysiological properties of an archicortical neuron. Ann N Y Acad Sci. 1961;94(2):570-603. PubMed doi:10.1111/j.1749-6632.1961.tb35560.x

10. Gevensleben H, Kleemeyer M, Rothenberger LG, et al. Neurofeedback in ADHD: further Pieces of the Puzzle [published online ahead of print April 6, 2013]. Brain Topogr. 2013. PubMed doi:10.1007/s10548-013-0285-y

11. Wangler S, Gevensleben H, Albrecht B, et al. Neurofeedback in children with ADHD: specific event-related potential findings of a randomized controlled trial. Clin Neurophysiol. 2011;122(5):942-950 PubMed.

12. Hammond DC. Neurofeedback with anxiety and affective disorders. Child Adolesc Psychiatr Clin N Am. 2005;14(1):105-123, vii. PubMed doi:10.1016/j.chc.2004.07.008

13. Fernández T, Herrera W, Harmony T, et al. EEG and behavioral changes following neurofeedback treatment in learning disabled children. Clin Electroencephalogr. 2003;34(3):145-152. PubMed

14. Otero GA, Pliego-Rivero FB, Fernández T, et al. EEG development in children with sociocultural disadvantages: a follow-up study. Clin Neurophysiol. 2003;114(10):1918-1925. PubMed doi:10.1016/S1388-2457(03)00173-1

15. Eichstedt JA, Tobon JI, Phoenix E, et al. Worried no more: the effects of medication status on treatment response to a CBT group for children with anxiety in a community setting. Clin Child Psychol Psychiatry. 2011;16(2):265-277. PubMed

16. Hannesdottir DK, Doxie J, Bell MA, et al. A longitudinal study of emotion regulation and anxiety in middle childhood: associations with frontal EEG asymmetry in early childhood. Dev Psychobiol. 2010;52(2):197-204. PubMed

17. Clarke AR, Barry RJ, McCarthy R, et al. Coherence in children with attention-deficit/hyperactivity disorder and excess beta activity in their EEG. Clin Neurophysiol. 2007;118(7):1472-1479. PubMed doi:10.1016/j.clinph.2007.04.006

18. Klingberg T, Fernell E, Olesen PJ, et al. Computerized training of working memory in children with ADHD—a randomized, controlled trial. J Am Acad Child Adolesc Psychiatry. 2005;44(2):177-186. PubMed doi:10.1097/00004583-200502000-00010

19. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Arlington, VA: American Psychiatric Association; 2000.

Rex L. Cannon, PhD

[email protected]

H. E. Pigott, PhD

Tanju Surmeli, MD

Deborah R. Simkin, MD

Robert W. Thatcher, PhD

Werner Van den Bergh, MD

Gerald Gluck, PhD

Joel F. Lubar, PhD

Richard Davis, MS

Dale S. Foster, PhD

Jonathan Douglas, PhD

Atholl T. Malcolm, PhD

Donald Bars, PhD

Kirk Little, PsyD

Wes Center, PhD

Marvin Berman, PhD

Harold Russell, PhD

Barbara Hammer, PhD

J. Lucas Koberda, MD, PhD

Author affiliations: Psychoeducational Network, Assessment/Neuroregulation, Knoxville, Tennessee.

Potential conflicts of interest: Dr Pigott has been a consultant to the International Society of Neurofeedback and Research and is a stock shareholder in NeuroAdvantage, LLC. Dr Simkin has received grant/research support from Pfizer, Eli Lilly, and Novartis. Drs Cannon, Surmeli, Thatcher, Van den Bergh, Gluck, Lubar, Foster, Douglas, Malcolm, Bars, Little, Center, Berman, Russell, Hammer, and Koberda and Mr Davis report no conflicts of interest relevant to the subject of this letter.

Funding/support: None reported.

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