Abstract
The purpose of this study was to evaluate the effect of neurofeedback on depressive symptoms and electrophysiological disturbances in patients with major depressive disorder. We recruited participants suffering from depression to evaluate efficacy of left prefrontal beta with alpha/theta training. An 8-week, prospective, open-label study was undertaken. Twenty participants were recruited. The treatment protocol was twice or three times a week training of beta at F3 with alpha/theta at Pz for 8 weeks. When every visit, patients were received beta training for 30 min, and then alpha/theta training for 30 min. Baseline, 4 and 8 week scores of; the Hamilton rating scale for Depression (HAM-D), the Hamilton rating scale for Anxiety (HAM-A), the Beck Depression Inventory (BDI)-II, the Beck Anxiety Inventory (BAI), Clinical global impression-severity (CGI-S), and pre- and post-treatment resting state EEGs were compared. Interhemispheric alpha power asymmetry (A score) was computed for homologous sites F3–F4. Pre- and post-training clinical assessments revealed significant improvements in HAM–D, HAM-A, BDI, and CGI-S scores. Cumulative response rates by HAM-D were 35.0 and 75.0 % at 4 and 8 weeks, respectively, corresponding cumulative remission rates by HAM-D were 15.0 and 55.0 %, respectively. No significant differences were found between pre- and post-treatment A score. Neurofeedback treatment could improve depressive symptoms significantly. In addition, anxiety symptoms and clinical illness severity decreased significantly after neurofeedback treatment. Despite its several limitations, such as, small sample size and lack of a control group, this study suggested neurofeedback has significant effects in patients with major depressive disorder.

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References
American Psychiatric Association. (2000). Diagnostic criteria from DSM-IV-TR. Washington, D.C.: American Psychiatric Association.
Baehr, E., & Baehr, R. (1997). The use of neurofeedback as adjunctive therapeutic treatment for depression: Three case studies. Biofeedback, 25, 10–11.
Baehr, E., Rosenfeld, J. P., & Baehr, R. (2001). Clinical use of an alpha asymmetry neurofeedback protocol in the treatment of mood disorders: Follow-up study one to five years post therapy. Journal of Neurotherapy, 4(4), 11–18.
Bagby, R. M., Ryder, A. G., Schuller, D. R., & Marshall, M. B. (2006). The Hamilton depression rating scale: Has the gold standard become a lead weight? The American Journal of Psychiatry, 161, 2163–2177.
Baxter, L. R. Jr., Schwartz, J. M., Phelps, M. E., Mazziotta, J. C., Guze, B. H., Selin, C. E., et al. (1989). Reduction of prefrontal cortex glucose metabolism common to three types of depression. Archives of General Psychiatry, 46(3), 243–250.
Beck, A. T., & Steer, R. A. (1990). Beck anxiety inventory manual. San Antonio, TX: Psychological Corporation.
Beck, A. T., Steer, R. A., & Brown, G. K. (1996). Manual for beck depression inventory-II. San Antonio, TX: Psychological Corporation.
Bench, C. J., Friston, K. J., Brown, R. G., Frackowiak, R. S., & Dolan, R. J. (1993). Regional cerebral blood flow in depression measured by positron emission tomography: The relationship with clinical dimensions. Psychological Medicine, 23(3), 579–590.
Bench, C. J., Friston, K. J., Brown, R. G., Scott, L. C., Frackowiak, R. S., & Dolan, R. J. (1992). The anatomy of melancholia–focal abnormalities of cerebral blood flow in major depression. Psychological Medicine, 22(3), 607–615.
Bonnet, M. H., & Arand, D. L. (2001). Impact of activity and arousal upon spectral EEG parameters. Physiology & Behavior, 74(3), 291–298.
Bouyer, J. J., Montaron, M. F., Vahnée, J. M., Albert, M. P., & Rougeul, A. (1987). Anatomical localization of cortical beta rhythms in cat. Neuroscience, 22(3), 863–869.
Brody, A. L., Barsom, M. W., Bota, R. G., & Saxena, S. (2001). Prefrontal-subcortical and limbic circuit mediation of major depressive disorder. Seminars in Clinical Neuropsychiatry, 6(2), 102–112.
Busner, J., & Targum, S. D. (2007). The clinical global impressions scale: Applying a research tool in clinical practice. Psychiatry (Edgmont), 4(7), 28–37.
Busner, J., Targum, S. D., & Miller, D. S. (2009). The clinical global impressions scale: Errors in understanding and use. Comprehensive Psychiatry, 50(3), 257–262. doi:10.1016/j.comppsych.2008.08.005.
Cheon, E. J., Koo, B. H., Seo, W. S., Lee, J. Y., Choi, J. H., & Song, S. H. (2015). Effects of neurofeedback on adult patients with psychiatric disorders in a naturalistic setting. Applied Psychophysiology and Biofeedback, 40(1), 17–24. doi:10.1007/s10484-015-9269-x.
Choi, S. W., Chi, S. E., Chung, S. Y., Kim, J. W., Ahn, C. Y., & Kim, H. T. (2011). Is alpha wave neurofeedback effective with randomized clinical trials in depression? A pilot study. Neuropsychobiology, 63(1), 43–51. doi:10.1159/000322290.
Conca, A., Koppi, S., Konig, P., Swoboda, E., & Krecke, N. (1996). Transcranial magnetic stimulation: A novel antidepressive strategy? Neuropsychobiology, 34(4), 204–207.
Davidson, R. J. (1998). Anterior electrophysiological asymmetries, emotion, and depression: Conceptual and methodological conundrums. Psychophysiology, 35(5), 607–614.
Davidson, R. J., & Henriques, J. B. (2000). Regional brain function in sadness and depression. In J. Borod (Ed.), The neuropsychology of emotion (pp. 269–297). New York: Oxford University Press.
Dias, A. M., & van Deusen, A. (2011). A new neurofeedback protocol for depression. The Spanish Journal of Psychology, 14(1), 374–384.
Drevets, W. C., Price, J. L., Simpson, J. R., Todd, R. D., Reich, T., Vannier, M., et al. (1997). Subgenual prefrontal cortex abnormalities in mood disorders. Nature, 386, 824–827.
Drevets, W. C., Videen, T. O., Price, J. L., Preskorn, S. H., Carmichael, S. T., & Raichle, M. E. (1992). A functional anatomical study of unipolar depression. The Journal of Neuroscience, 12, 3628–3641.
Earnest, C. (1999). Single case study of EEG asymmetry biofeedback for depression: An independent replication in an adolescent. Journal of Neurotherapy, 3(2), 28–35.
Galynker, I. I., Cai, J., Ongseng, F., Finestone, H., Dutta, E., & Serseni, D. (1998). Hypofrontality and negative symptoms in major depressive disorder. The Journal of Nuclear Medicine, 39(4), 608–612.
George, M. S., Wassermann, E. M., Williams, W. A., Callahan, A., Ketter, T. A., Basser, P., et al. (1995). Daily repetitive transcranial magnetic stimulation (rTMS) improves mood in depression. NeuroReport, 6(14), 1853–1856.
Gruzelier, J. (2009). A theory of alpha/theta neurofeedback, creative performance enhancement, long distance functional connectivity and psychological integration. Cognitive Processing, 10(Suppl 1), S101–S109. doi:10.1007/s10339-008-0248-5. (Epub 2008 Dec 11).
Hamilton, M. (1959). The assessment of anxiety states by rating. British Journal of Medical Psychology, 32, 50–55.
Hammond, D. C. (2000). Neurofeedback treatment of depression with the Roshi. Journal of Neurotherapy, 4(2), 45–56.
Hammond, D. C. (2005). Neurofeedback treatment of depression and anxiety. Journal of Adult Development, 12(2), 131–137.
Henriques, J. B., & Davidson, R. J. (1990). Regional brain electrical asymmetries discriminate between previously depressed and healthy control subjects. Journal of Abnormal Psychology, 99(1), 22–31.
Kato, T., Shioiri, T., Murashita, J., Hamakawa, H., Takahashi, Y., Inubushi, T., et al. (1995). Lateralized abnormality of high energy phosphate metabolism in the frontal lobes of patients with bipolar disorder detected by phase-encoded 31P-MRS. Psychological Medicine, 25, 557–566.
Kung, S., Alarcon, R. D., Williams, M. D., Poppe, K. A., Jo Moore, M., & Frye, M. A. (2013). Comparing the Beck Depression Inventory-II (BDI-II) and Patient Health Questionnaire (PHQ-9) depression measures in an integrated mood disorders practice. Journal of Affective Disorder, 145(3), 341–343. doi:10.1016/j.jad.2012.08.017.
Larsen, S., & Sherlin, L. (2013). Neurofeedback an emerging technology for treating central nervous system dysregulation. Psychiatric Clininics of North America, 36, 163–168.
Leyfer, O. T., Ruberg, J. L., & Woodruff-Borden, J. (2006). Examination of the utility of the Beck Anxiety Inventory and its factors as a screener for anxiety disorders. Journal of Anxiety Disorders, 20(4), 444–458.
Martinot, J. L., Hardy, P., Feline, A., Huret, J. D., Mazoyer, B., Attar-Levy, D., et al. (1990). Left prefrontal glucose hypometabolism in the depressed state: A confirmation. The American Journal of Psychiatry, 147(10), 1313–1317.
Mayberg, H. S. (2003). Modulating dysfunctional limbic-cortical circuits in depression: Towards development of brain-based algorithms for diagnosis and optimised treatment. British Medical Bulletin, 65, 193–207.
Murthy, V. N., & Fetz, E. E. (1992). Coherent 25- to 35-Hz oscillations in the sensorimotor cortex of awake behaving monkeys. Proceedings of the National Academy of Sciences of the United States of America, 89(12), 5670−5674.
Niv, S. (2013). Clinical efficacy and potential mechanisms of neurofeedback. Personality and Individual Differences, 54(6), 676–686. doi:10.1016/j.paid.2012.11.037.
Osman, A., Barrios, F. X., Aukes, D., Osman, J. R., & Markway, K. (1993). The Beck Anxiety Inventory: Psychometric properties in a community population. Journal of Psychopathology and Behavioral Assessment, 15, 287–297.
Osuch, E. A., Ketter, T. A., Kimbrell, T. A., George, M. S., Benson, B. E., Willis, M. W., et al. (2000). Regional cerebral metabolism associated with anxiety symptoms in affective disorder patients. Biological Psychiatry, 48, 1020–1023.
Pascual-Leone, A., Peris, M., Tormos, J. M., Pascual, A. P., & Catala, M. D. (1996). Reorganization of human cortical motor output maps following traumatic forearm amputation. NeuroReport, 7(13), 2068–2070.
Paus, T., Castro-Alamancos, M. A., & Petrides, M. (2001). Cortico-cortical connectivity of the human mid-dorsolateral frontal cortex and its modulation by repetitive transcranial magnetic stimulation. European Journal of Neuroscience, 14(8), 1405–1411.
Peniston, E. G., & Kulkosky, P. J. (1989). Alpha-theta brainwave training and beta-endorphin levels in alcoholics. Alcoholism Clininical and Experimental Research, 13(2), 271–279.
Reischies, F. M., Hedde, J. P., & Drochner, R. (1989). Clinical correlates of cerebral blood flow in depression. Psychiatry Research, 29(3), 323–326.
Rosenfeld, J. P. (1997). EEG biofeedback of frontal alpha asymmetry in affective disorders. Biofeedback, 25(1), 8–25.
Rosenfeld, J. P. (2000). An EEG biofeedback protocol for affective disorders. Clinical Electroencephalography, 31(1), 7–12.
Rosenfeld, J. P., Cha, G., Blair, T., & Gotlib, I. H. (1995). Operant (biofeedback) control of left-right frontal alpha power differences: Potential neurotherapy for affective disorders. Biofeedback Self Regulation, 20(3), 241–258.
Rush, A. J., Trivedi, M. H., Ibrahim, H. M., Carmody, T. J., Arnow, B., Klein, D. N., et al. (2003). The 16-item quick inventory of depressive symptomatology (QIDS), clinician rating (QIDS-C), and self-report (QIDSSR): A psychometric evaluation in patients with chronic major depression. Biological Psychiatry, 54, 573–583.
Rush, A. J., Trivedi, M. H., Stewart, J. W., Nierenberg, A. A., Fava, M., Kurian, B. T., & Wisniewski, S. R. (2011). Combining medications to enhance depression outcomes (CO-MED): Acute and long-term outcomes of a single-blind randomized study. The American Journal of Psychiatry, 168(7), 689–701. doi:10.1176/appi.ajp.2011.10111645.
Saxby, E., & Peniston, E. G. (1995). Alpha-theta brainwave neurofeedback training: An effective treatment for male and female alcoholics with depressive symptoms. Journal of Clinical Psychology, 51(5), 685–693.
Scott, W. C., Kaiser, D., Othmer, S., & Sideroff, S. I. (2005). Effects of an EEG biofeedback protocol on a mixed substance abusing population. The American Journal of Drug and Alcohol Abuse, 31(3), 455–469.
Shear, M. K., Vander Bilt, J., Rucci, P., Endicott, J., Lydiard, B., Otto, M. W., & Frank, D. M. (2001). Reliability and validity of a structured interview guide for the Hamilton anxiety rating scale (SIGH-A). Depression and Anxiety, 13(4), 166–178.
Tomarken, A. J., Davidson, R. J., Wheeler, R. E., & Kinney, L. (1992). Psychometric properties of resting anterior EEG asymmetry: Temporal stability and internal consistency. Psychophysiology, 29(5), 576–592.
United States, Depression Guideline Panel, & United States, Agency for Health Care Policy and Research. (1993). Depression in primary care. Rockville, Md. Washington, D.C: U.S. Dept. of Health and Human Services.
Walker, J. E., & Lawson, R. (2013). FP02 beta training for drug-resistant depression—a new protocol that usually reduces depression and keeps it reduced. Journal of Neurotherapy, 17, 198–200.
Walker, J. E., Lawson, R., & Kozlowski, G. (2007). Current status of QEEG and neurofeedback in the treatment of clinical depression. In J. R. Evans (Ed.), The handbook of neurofeedback (pp. 341–351). Binghampton, NY: Haworth Medical Press.
Zimmerman, M., Chelminski, I., & Posternak, M. (2004). A review of studies of the Hamilton depression rating scale in healthy controls: Implications for the definition of remission in treatment studies of depression. The Journal of Nervous and Mental Disease, 192(9), 595–601.
Acknowledgments
This work was supported by a Yeungnam University Research Grant (2012). We deeply appreciate to our colleagues, Dai-Seg Bai Ph.D., Hye-Guem Kim M.D., Young-Ji Lee M.D., Seung-Woo Lee, M.D., Jae-Hwa Choi M.D., Su-Hong Ha M.A. for helping in this study.
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Cheon, EJ., Koo, BH. & Choi, JH. The Efficacy of Neurofeedback in Patients with Major Depressive Disorder: An Open Labeled Prospective Study. Appl Psychophysiol Biofeedback 41, 103–110 (2016). https://doi.org/10.1007/s10484-015-9315-8
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DOI: https://doi.org/10.1007/s10484-015-9315-8