Depression and fatigue are common symptoms of multiple sclerosis (MS) and are the primary determinants of impaired quality of life in this demyelinating neurological disease. Untreated depression is associated with suicidal ideation, impaired cognitive function and poor adherence to immunomodulatory treatment. For these reasons, systematic screening and management of depressive symptoms and fatigue is recommended for all patients with MS. The objective of this study was to evaluate the effectiveness of neurofeedback in treating depression and fatigue in persons with MS. We conducted a randomized trial with 24 MS patients with primary fatigue and depression. Participants were randomized into two groups: neurofeedback training group (16 sessions of NFB) or treatment as usual. Participants were evaluated at 3 time points (baseline, end of the treatment, and 2-month follow-up) using the Fatigue Severity Scale and Depression subscale of the Hospital Anxiety and Depression Scale as outcome measures. A repeated measures analysis of variance was used to examine differences between the groups. NFB significantly reduced symptoms of depression and fatigue in patients with MS patients, compared to treatment as usual (p < .05), and these effects were maintained the 2-month follow-up (p < .05).
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Aikens, J. E., Fischer, J. S., Namey, M., & Rudick, R. A. (1997). A replicated prospective investigation of life stress, coping, and depressive symptoms in multiple sclerosis. Journal of Behavioral Medicine, 5, 433–445.
Aronson, K. (1996). Quality of life among persons with multiple sclerosis and their caregivers. Neurology, 48, 74–80.
Baehr, E., Miller, L., Rosenfeld, J., & Baehr, R. (2004). Changes in frontal brain asymmetry associated with premenstrual dysphoric disorder: A single case study. Journal of Neurofeedback, 8(1), 29–42.
Baehr, E., Rosenfeld, J., & Baehr, R. (1997). The clinical use of an alpha asymmetry protocol in the neurofeedback treatment of depression: Two case studies. Journal of Neurofeedback, 2(3), 10–23.
Baehr, E., Rosenfeld, J., & Baehr, R. (2001). The clinical use of an alpha asymmetry protocol in the treatment of mood disorders: Follow-up study one to five years post therapy. Journal of Neurofeedback, 4(4), 11–18.
Baehr, E., Rosenfeld, J. P., Baehr, R., & Earnest, C. (1999). Clinical use of an alpha asymmetry neurofeedback protocol in the treatment of mood disorders. In J. R. Evans & A. Abarbanel (Eds.), Introduction to quantitative EEG and neurofeedback (pp. 181–200). New York: Academic Press.
Bakshi, R., Shaikh, Z. A., Miletich, R. S., Czarnecki, D., Dmochowski, J., Henschel, K., et al. (2000). Fatigue in multiple sclerosis and its relationship to depression and neurologic disability. Multiple Sclerosis, 6, 181–185.
Bergamaschi, R., Romani, A., Versino, M., Poli, R., & Cosi, V. (1997). Clinical aspects of fatigue in multiple sclerosis. Functional Neurology, 12, 247–251.
Bjelland, I., Dahl, A. A., Haug, T. T., & Neckelmann, D. (2002). The validity of the Hospital Anxiety and Depression Scale: An updated review. Journal of Psychiatric Research, 52, 69–77.
Braley, T. J., & Chervin, R. D. (2010). Fatigue in multiple sclerosis: Mechanisms, evaluation, and treatment. Sleep, 33, 1061–1067.
Clark, C. M., Fleming, J. A., Li, D., Oger, J., Klonoff, H., & Paty, D. (1992). Sleep disturbance, depression, and lesion site in patients with multiple sclerosis. Archive of Neurology, 49, 641–643.
Colosimo, C., Millefiorini, E., Grasso, M. G., Vinci, F., Fiorelli, M., Koudriavtseva, T., et al. (1995). Fatigue in MS is associated with specific clinical features. Acta Neurologica Scandinavica, 92, 353–355.
Comi, G., Leocani, L., Rossi, P., & Colombo, B. (2001). Physiopathology and treatment of fatigue in multiple sclerosis. Journal of Neurology, 248(174), 9.
Davidson, R. J. (1992). Emotion and affective style: Hemispheric substrates. Psychological Science, 3, 39–43.
Davidson, R. J. (1995). Cerebral asymmetry, emotion and affective style. In R. J. Davidson & K. Hugdahl (Eds.), Brain asymmetry (pp. 361–387). Boston: MIT Press.
Davidson, R. J. (1998a). Affective style and affective disorders: Perspectives from affective neuroscience. Cognition and Emotion, 12, 307–330.
Davidson, R. J. (1998b). Anterior electrophysiological asymmetries, emotion, and depression: Conceptual and methodological conundrums. Psychophysiology, 35, 607–614.
Dawson, G., Klinger, L. G., Panagiotides, H., Hill, D., & Spieker, S. (1992a). Frontal lobe activity and affective behavior of infants of mothers with depressed symptoms. Child Development, 63, 725–737.
Dawson, G., Klinger, L. G., Panagiotides, H., Spieker, S., & Frey, K. (1992b). Infants of mothers with depressed symptoms: electroencephalographic and behavioral findings related to attachment status. Development and Psychopathology, 4, 67–80.
Dursun, E., Dursun, N., & Alican, D. (2004). Effects of biofeedback treatment on gait in children with cerebral palsy. Disability and Rehabilitation, 26, 116–120.
Egner, T., Strawson, E., & Gruzelier, J. H. (2002). EEG signature and phenomenology of alpha-theta neurofeedback training versus mock feedback. Applied Psychophysiology and Biofeedback, 27, 261–270.
Fassbender, K., Schmidt, R., Mobner, R., Kischka, U., Kuhnen, J., Schwartz, A., et al. (1998). Mood disorders and dysfunction of the hypothalamic-pituitary-adrenal axis in multiple sclerosis. Archive of Neurology, 55, 66–72.
Feinstein, A. (2002). An examination of suicidal intent in patients with multiple sclerosis. Neurology, 59, 674–678.
Fisk, J. D., Pontefract, A., Ritvo, P. G., Archibald, C. J., & Murray, T. J. (1994). The impact of fatigue on patients with multiple sclerosis. Canadian Journal of Neurological Sciences, 21, 9–14.
Flachenecker, P., Kumpfel, T., Kallmann, B., Gottschalk, M., Grauer, O., Rieckmann, P., et al. (2002). Fatigue in multiple sclerosis: A comparison of different rating scales and correlation to clinical parameters. Multiple Sclerosis, 8, 523–526.
Foong, J., & Ron, M. A. (2003). Neuropsychiatry: cognition and mood disorders. In W. I. McDonald & J. H. Noseworthy (Eds.), Multiple sclerosis—2 (pp. 115–124). Philadelphia: Butterworth-Heinemann Publishers.
Ford, H., Trigwell, P., & Johnson, M. (1998). The nature of fatigue in multiple sclerosis. Journal of Psychosomatic Research, 45, 33–38.
Freal, J., Kraft, G. H., & Coryell, J. (1984). Symptomatic fatigue in multiple sclerosis. Archive of Neurology, 53, 185–188.
Goodkine, D. (1992). The natural history of multiple sclerosis. New York: Springer-Verlag.
Halper, J. (2007). The psychosocial effect of multiple sclerosis: The impact of relapses. Journal of the Neurological Science, 256, 34–38.
Hammond, D. C. (2000). Neurofeedback treatment of depression with the Roshi. Journal of Neurotherapy, 4(2), 45–56.
Hammond, D. C. (2003). QEEG-guided neurofeedback in the treatment of obsessive compulsive disorder. Journal of Neurotherapy, 7(2), 25–52.
Hammond, D. (2005a). Neurofeedback treatment of depression and anxiety. Journal of Adult Development, 12(2/3), 131–1377.
Hammond, D. (2005b). Neurofeedback with anxiety and affective disorders. Child and Adolescent Psychiatric Clinics of North America, 14, 105–123.
Hanslmayr, S., Sauseng, P., Doppelmayr, M., Schabus, M., & Klimesch, W. (2005). Increasing individual upper alpha power by Neurofeedback improves cognitive performance in human subjects. Applied Psychophysiology and Biofeedback, 30(1), 1–10.
Hauser, S. L., & Goodkin, D. E. (2001). MS & demyelinating disease. In T. R. Harrison, E. Brown, A. S. Fauci, D. L. Kasper, S. L. Hauser, & D. L. Longo (Eds.), Harrison’s principles of internal medicine (15th ed., Vol. 4, pp. 2452–2460). New York: McGraw- Hill.
Hendin, H. (1999). Suicide, assisted suicide, and medical illness. Journal of Clinical Psychiatry, 60, 46–50.
Henriques, J. B., & Davidson, R. J. (1991). Left frontal hypoactivation in depression. Journal of Abnormal Psychology, 100, 535–545.
Heron, R., McCann, G., & O’Leary, C. P. (1999). The influence of multiple sclerosis on fatigue levels and physical activity levels. Multiple Sclerosis, 5, 37.
How long do the effects of neurofeedback training last?(2010). http://www.aboutneurofeedback.com/.
Iwasaki, Y., Iwamoto, K., Igarashi, O., Kiyozuka, T., Aoyagi, J., Hirano, K., et al. (2005). Depression in multiple sclerosis. Acta Neurologica Scandinavica, 111, 209.
Janardhan, V., & Bakshi, R. (2002). Quality of life in patients with multiple sclerosis: The impact of fatigue and depression. Journal of eurological Science, 205, 51–58.
Kaminska, M., Kimoff, R. J., Schwartzman, K., & Trojan, D. A. (2011). Sleep disorders and fatigue in multiple sclerosis: Evidence for association and interaction. Journal of Neurological Science, 302, 7–13.
Kano, K., Nakamura, M., Matsuoka, T., Iida, H., & Nakajima, T. (1992). The topographical features of EEGs in patients with affective disorders. Electroencephalography Clinical Neurophysiology, 83, 124–129.
Kayıran, S., Dursun, E., Dursun, N., Ermutlu, N., & Karamursel, S. (2010). Neurofeedback intervention in fibromyalgia syndrome: A randomized, controlled, rater blind clinical trial. Applied Psychophysiology and Biofeedback, 35, 293–302.
Kroencke, D. C., Lynch, S. G., & Denney, D. R. (2000). Fatigue in multiple sclerosis: relationship to depression, disability, and disease pattern. Multiple Sclerosis, 6, 131–136.
Krupp, L. B., Alvarez, L., LaRocca, N., & Scheinberg, L. (1988). Fatigue in multiple sclerosis. Archive of Neurology, 45, 435–437.
Krupp, L. B., LaRocca, N., Muir-Nash, J., & Steinberg, A. D. (1989). The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. Archive of Neurology, 46(10), 1121–1123.
Lubar, J. F. (1997). Neocortical dynamics: Implications for understanding the role of neurofeedback and related techniques for the enhancement of attention. Applied Psychophysiology and Biofeedback, 22, 111–126.
Marrie, R. A., Horowitz, R., Cutter, G., Tyry, T., Campagnolo, D., & Vollmer, T. (2009). The burden of mental comorbidity in multiple sclerosis: frequent, underdiagnosed and undertreated. Multiple Sclerosis, 15, 385–392.
McDonald, W. I., Compston, A., Edan, G., Goodkin, D., Hartung, H. P., Lublin, F. D., et al. (2001). Recommended diagnostic criteria for multiple sclerosis: guidelines from the international panel on the diagnosis of multiple sclerosis. Annals of Neurology, 50, 121–127.
McGuigan, C., & Hutchinson, M. (2006). Unrecognised symptoms of depression in a community-based population with multiple sclerosis. Journal of Neurology, 253, 219–223.
Minden, S. L., Orav, J., & Reich, P. (1987). Depression in multiple sclerosis. General Hospital Psychiatry, 9, 426–434.
Mohr, D. C., Hart, S. L., Fonareva, I., & Tasch, E. S. (2006). Treatment of depression for patients with multiple sclerosis in neurology clinics. Multiple Sclerosis, 12, 204–208.
Muller, H. H., Donaldson, C. C. S., Nelson, D. V., & Layman, M. (2001). Treatment of fibromyalgia incorporating EEG-driven stimulation: a clinical study. Journal of Clinical Psychology, 57(7), 925–933.
Multiple Sclerosis Council for Clinical Practice Guidelines. (1998). Fatigue and multiple sclerosis: Evidence-based management strategies for fatigue in multiple sclerosis. Multiple Sclerosis Council for Clinical Practice Guidelines.
Murray, T. J. (1985). Amantadine therapy for fatigue in multiple sclerosis. Canadian Journal of Neurological Sciences, 12, 251–254.
Neurofeedback and multiple sclerosis.(2009).http://www.sinhaclinic.com/ .
Nocentini, U. (2006). Clinical assessment for depression. Neurological Sciences, 27, 341–343.
Patten, S., Metz, L. M., & Reimer, M. A. (2000). Biopsychosocial correlates of life time major depression in a multiple sclerosis population. Multiple Sclerosis, 6, 115–120.
Provinciali, L., Ceravolo, M. G., Bartolini, M., Logullo, F., & Danni, M. (1999). A multidimensional assessment of multiple sclerosis: relationships between disability domains. Acta Neurologica Scandinavica, 100, 156–162.
Putman, J. A. (2001). EEG biofeedback on a female patient stroke patient with depression: a case study. Journal of Neurotherapy, 5(3), 27–38.
Rickards, H. (2005). Depression in neurological disorders: Parkinson’s disease, multiple sclerosis and stroke. Journal of Neurology, Neurosurgery and Psychiatry, 76, 48–52.
Ros, T., Munneke, M. A. M., Ruge, D., Gruzelier, J. H., & Rothwell, J. C. (2010). Endogenous control of waking brain rhythms induces neuroplasticity in humans. European Journal of Neuroscience, 31, 770–778.
Rosenfeld, J. P., Cha, G., Blair, T., & Gotlib, I. (1995). Operant biofeedback control of left-right frontal alpha power differences. Biofeedback Self Regulation, 20, 241–258.
Salehpoor, G. H., Rezaei, S., & Hossininezhad, M. (2013). Psychometric properties of fatigue severity scale in patients with multiple sclerosis. Journal of Kerman University of Medical Sciences, 20(3), 263–278.
Sevène, A., Akrour, B., Galimard-Maisonneuve, E., Kutneh, M., Royer, P., & Sevène, M. (2009). Multiple sclerosis and sexuality: A complex model. Sexologies, 18, 86–90.
Sharrack, B., & Hughes, R. A. (1996). Clinical scales for multiple sclerosis. Journal of Neurological Science, 135, 1–9.
Siegert, R., & Abernethy, D. (2006). Depression in multiple sclerosis: A review. Journal of Neurology Neurosurgery Psychiatry, 76, 469–475.
Sollom, A. C., & Kneebone, I. (2007). Treatment of depression in people who have multiple sclerosis. Multiple Sclerosis, 13, 632–635.
Stein, M. B., Cox, B. J., Afifi, T. O., Belik, S., & Sareen, J. (2006). Does comorbid illness magnify the impact of chronic physical illness? A population based perspective. Psychological Medicine, 36, 587–596.
Stenager, E. N., & Stenager, E. (2000). Physical illness and suicidal behavior. In K. Hawton & K. van Heeringen (Eds.), The international handbook of suicide and attempted suicide. New York: Wiley.
Sterman, M. B. (1999). Atlas of topometric clinical displays: Functional interpretations and neurofeedback strategies. Los Angeles: Sterman-Kaiser Imaging Laboratory.
Sterman, M. B., & Kaiser, D. (2001). Comodulation: A new QEEG analysis metric for assessment of structural and functional disorders of the central nervous system. Journal of Neurotherapy, 4(3), 73–83.
Vanathy, S., Sharma, P. S. V. N., & Kumar, K. B. (1998). The efficacy of alpha and theta neurofeedback training in treatment of generalized anxiety disorder. Indian Journal of Clinical Psychology, 25(2), 136–143.
Vernon, D., Egner, T., Cooper, N., Compton, T., Neilands, C., Sheri, A., et al. (2003). The effect of training distinct neurofeedback protocols on aspects of cognitive performance. International Journal of Psychophysiology, 47(1), 75–85.
Walker, J. (2007). Current status of QEEG and neurofeedback in the treatment of clinical depression. In J. R. Evans (Ed.), Handbook of neurofeedback: Dynamic and clinical applications (pp. 341–352). New York: Haworth Medical Press.
Williams, R. M., Turner, A. P., Hatzakis, M., Bowen, J. D., Rodriquez, A. A., & Haselkorn, J. K. (2005). Prevalence and correlates of depression among veterans with multiple sclerosis. Neurology, 64, 75–80.
Wilson, V. E., Peper, E., & Moss, D. (2006). Professional issue “The mind room’’ in Italian soccer training: the use of biofeedback and neurofeedback for optimum performance. Biofeedback, 34, 79–810.
Yucha, C., & Gilbert, C. (2004). Evidence-based practice in biofeedback and neurofeedback. Wheat Ridge CO: Association for Applied Psychophysiology and Biofeedback.
Yucha, C., & Montgomery, D. (2008). Evidence-based practice in biofeedback and neurofeedback. Wheat Ridge: Association for Applied Psychophysiology and Biofeedback.
Ziemssen, T. (2009). Multiple sclerosis beyond EDSS: depression and fatigue. Journal of the Neurological Science, 277, 37–41.
Zigmond, A. S., & Snaith, R. P. (1983). The hospital anxiety and depression scale. Acta Psychiatry Scandinavia, 67(6), 361–370.
The authors would like to thank all the patients for their participation, the Editor-in-Chief and the anonymous reviewers for their constructive and detailed comments that helped improve very much the quality of this paper.
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Choobforoushzadeh, A., Neshat-Doost, H.T., Molavi, H. et al. Effect of Neurofeedback Training on Depression and Fatigue in Patients with Multiple Sclerosis. Appl Psychophysiol Biofeedback 40, 1–8 (2015). https://doi.org/10.1007/s10484-014-9267-4
- Multiple sclerosis
- Fatigue Severity Scale
- Hospital Anxiety and Depression Scale