The Potential of EEG Biofeedback for Immune System Disorders by Gary J. Schummer, Ph.D.

INTRODUCTION

Biofeedback practitioners have avoided EEG biofeedback (or neurofeedback) because they perceive the field as complex and somewhat intimidating. We may remember the high school science teacher being more than a little apprehensive when she had to cover neuroanatomy. The truth is that the brain is complex - and we should be grateful for the complexity! As someone once said, if the brain were simpler in its complexity we would be that much less able to comprehend it. Overall, the neurofeedback field is fresh and extremely inviting. One might consider approaching neurofeedback as an adventure or an exploration into the unknown. Since beginning my study of the field and the central nervous system, I have been encouraged that no one seems to know very much about how the brain works. Somehow the community formed by these inquisitive types is fascinating and engaging.
It is interesting to note that rather small changes in central nervous system (CNS) functioning can produce extreme "downstream" effects. This can be readily seen in the sudden mood shifts prevalent in a bipolar patient due to, as yet, unmeasurable changes in certain neurotransmitters. These changes can shift a patientís mood from suicidal depression to grandiose self-confidence within minutes. As we ponder the powerful effects of small CNS changes, we realize that, with neurofeedback, the possibilities for enhancing the human condition are profound. To demystify this area is one of my purposes in writing this article. We need more researchers and clinicians working together and communicating the results they see in their laboratories, clinical settings, and through careful observation of life. This article will present the opportunities and challenges facing this new application neurofeedback to immune enhancement and consider certain theoretical models which may be applicable. In addition, the limited yet provocative literature in this area will be surveyed.

NEUROFEEDBACK AS A TOOL FOR CHANGE

To gain an understanding of how neurofeedback might be an effective tool, let us look at some things we know. Instability of the central nervous system is seen in seizure disorder, attention deficit disorder, closed head injury, and other central nervous system disorders currently being successfully treated with neurofeedback. Disregulation of brain function is thought to be the basis of certain psychological disorders (depression, mania, obsessive-compulsive disorder, anxiety, etc.) which likewise respond to neurofeedback treatment. Given what we know to be true, the following working hypothesis may be generated: IF seizure thresholds can be raised, attention and concentration skills can be refined, and neurons can be reeducated and/or recruited to produce more normal full-spectrum functioning in closed head injury; THEN a disregulated, down-regulated, or unstable immune system be stabilized and/or modulated utilizing neurofeedback.
Correlation of EEG patterns with behavior, cognition, and emotion are now being intensely studied and defined. Equipped with newer and better instrumentation, the data indicate that subjects may learn to control previously uncontrollable physiology (self-regulation). Furthermore, individuals who utilize neurofeedback state that they perceive reality with greater clarity, have improved mental acuity, as well as acquire greater control over fluctuations in mood and behavior. As stated above, we know that small changes in brain activity produced by drugs, trauma, neurotransmitter shifts, or mood can yield profound effects. Neurofeedback, which reorganizes and reorients brain electrical activity, can, in all probability, be utilized to positively modulate the immune response. We must remember however, that although this is a logical extension of currently accepted knowledge and protocols it has yet to be subjected to the rigors of scientific inquiry.

TWO NEUROPHYSIOLOGICAL MODELS FOR CHANGE

From systems theory we learn that feedback corrects incremental deviations from a desired course and creates stability via the integration of new knowledge. When a disregulated or unstable CNS is given neurofeedback it can yield greater regulation and stability. Often that is desirable. Given what we know of the plasticity of the human brain (Diamond, 1988), it is certainly reasonable to assert the hypothesis that EEG biofeedback can alter immune function within an individual. This paper will discuss two well documented models for this assertion. The first is based upon what we know about the effect of stress on immunity (a field of study known as psycho-neuro-immunology), and the second is based upon what we are learning about the intricate feedback mechanisms "hard wired" within the CNS, the immune system, and the endocrine system. This is an exciting and growing body of literature which is more clearly defining the bi-directional feedback circuits existing within these three systems.
I . STRESS AND IMMUNITY

The human exists in a state of dynamic equilibrium called homeostasis. The body reacts when homeostasis is challenged by intrinsic or extrinsic forces (stress). Research demonstrates that exposure to pathogens, toxic odors, marital conflict, depression and grief suppress immune function. Conversely, vitamin C, sleep, stimulating positive experiences, physical fitness, exposure to humor, even light boosts immune function. To date, more than 20 hormones and neurotransmitters have known immunological modulation potential (Khansari, 1990). Likewise, many neurotransmitters either increase or decrease in response to stress or to drugs that help us cope with the effects of stress.
Few experts dispute the role of stress in determining, or at least modulating, how healthy an individual is at any point in time. With increased stress or perceived threat, the hypothalamus releases corticotropin-releasing factor (CRF) a hormone which triggers release of adrenocorticotropin (ACTH) by the pituitary gland which, in turn, stimulates the release of corticosterone by the adrenal glands. Corticosterone is a known suppresser of immune function and its role is much more complex in modulating immunity than has been previously understood. Both the hypothalamus and its neighbor the pituitary gland are part of, and therefore regulated by, the CNS. This is why relaxation training is thought to have beneficial effects and explains why people who meditate experience significantly less physical symptomatology.
The sympathetic nervous system, which is innervated under the "fight or flight" condition and often accompanies acute stress, has undergone extensive study as it relates to immune system modulation. It is thought that sympathetic nervous system changes that accompany anxiety and depression (common sequelae during bereavement) play a role in immune suppression or "down-regulation." Other studies indicate that T-cell mediated natural killer cell activity is significantly decreased as observed in college students who are not coping with the demands of school (Rogers, 1979). Epinephrine and norepinephrine, the primary stress response hormones, consistently decrease immune response making the body more vulnerable to disease (for a more complete discussion of this please see my article "Self-Regulation of the Immune System" in Megabrain Report, Volume 3, Number 1, pages 30-39, 1996).

I I . CNS - ENDOCRINE FEEDBACK AND IMMUNITY

Research has elucidated extensive mediating mechanisms with a dense communication network that interfaces the central nervous system (CNS) with both the endocrine and immune systems. The brain communicates with the immune system through two known pathways, the autonomic nervous system and the hypothalamic pituitary adrenal axis - HPA (Angeli, 1994). Recent discoveries yield consistent evidence that the immune process provides protection against infection and that its impairment seems to be involved in the development of autoimmune disorders, malignancies and rapid advancement of the AIDS virus.
Karen Bulloch (1990) demonstrated that autonomic servous system fibers are directly connected to the thymus where T-cells mature. More recently, Felten and Felten (1991) have demonstrated that primary lymphoid organs are heavily innervated by fibers from the sympathetic nervous system. A relatively new field called "immunoendocrinology" is uncovering numerous bilateral interactions between the immune system and neuroendocrine circuits. Researchers' Derijk and Berkenbosch (1991) discuss evidence indicating that an immunoendocrine feedback loop, which they term "immune-hypothalamo-pituitary-adrenal system" is an important factor in immune system modulation. Maladaptive neuroendocrine responses, i.e., disregulation of the stress system, often lead to disturbances in growth and development, and cause psychiatric, endocrine/metabolic, and/or autoimmune diseases or vulnerability to such disease (Stratakis, 1995).
The dedicated work of many scientists in their search for neuromodulatory mechanisms has led us to conclude that the immune system, endocrine system, and central nervous system contain a web of "hard-wired" feedback loops. The exact mechanism of action of these immune modulating feedback loops await further research, however they will become more and more important in describing how neurofeedback can enhance the immune systemís ability to either maintain health and ward off disease or become impaired thus creating sickness. At the present time, our ability to describe an exact mechanism is limited by our elementary understanding of how the immune system communicates with the brain at the electrical and biochemical level.

THE HISTORY OF SELF-REGULATION AND IMMUNITY

The novelty inherent in the application of biofeedback and neurofeedback to immune disorders becomes obvious as one scans relevant literature in this area. The few studies that do exist are generally flawed by poor immune system assays or lack of control groups. Additionally, decreases in physical symptomalogy, a relatively poor second order immune system marker, is generally used. The ability to properly assay the immune system is rather expensive and therefore limits clinicians and/or researchers. The heterogeneity of the diseased individual (psychologically, socially, and physically), the variability of assays, and the clinical relevance of observed changes further complicate the interpretation of research.

BIOFEEDBACK AND IMMUNITY

To briefly summarize the relevant biofeedback literature let us begin with Peavy, et al (1985). He administered EMG and thermal biofeedback with relaxation training to a group of subjects and found significant increases in phagocyte (a cell that engulfs and absorbs unwanted microorganisms) activity comparing pre and post treatment blood work. In 1993, Farber utilized biofeedback with meditation to successfully treat psoriasis, often thought to be a stress-related disease.
Gruber, et al (1988) conducted two studies involving metastatic breast cancer. The first, a pilot study, involved 10 subjects given biofeedback and guided imagery over a one year period. Blood samples taken monthly indicated significant increases in multiple immune system markers. In 1993, the same author reported on an 18 month study showing positive shifts in immune system markers (natural killer cells and lymphocytes) and psychological changes with stage one breast cancer when subjects were given biofeedback, guided imagery, and relaxation training (Gruber, et al, 1993). McGrady, et al (1992) reported increased lymphocyte growth as well as positive shifts in white blood cell count in fourteen subjects trained with EMG and thermal biofeedback-assisted relaxation for four weeks. The author also reported that the subjects with lower initial anxiety scores and forehead muscle tension levels showed larger increases in lymphocyte growth and larger decreases in neutrophils (white blood cells known for their excellent ability to destroy unwanted microorganisms) than subjects with higher initial anxiety and muscle tension levels.
Auerbach, et al (1992) conducted a study on 26 HIV+ males who were assigned to either a treatment group, consisting of thermal biofeedback, guided imagery and hypnosis or a wait list control for eight weeks. Although no significant changes were found in T-4 level in the treatment condition, significant decreases were noted in HIV related symptoms as well as increases in energy. For a further understanding of relaxation, imagery and biofeedback-assisted strategies as well as the use of humor, emotional factors, hypnosis and conditioning paradigms, the reader may reference an article titled, "Self-regulation of the immune system through biobehavioral strategies" in Biofeedback and Self-Regulation (March, 1991).

NEUROFEEDBACK AND IMMUNITY

Neurofeedback is so new that there are currently very few studies. Michael Tansey (1994) published the first peer reviewed article as to the curative effect of 14 Hz. EEG neurofeedback on multiple cases of Chronic Fatigue Syndrome (CFS). Fran Lowe (1994) likewise reported positive effects on five subjects with CFS utilizing 13-14 Hz. beta training. Both Tansey and Lowe measured improvement on psychometric measures rather than direct measurement of immune system factors (i.e., Ebstein-Barr virus).
Subjects with HIV make excellent candidates for study since the progress of the disease was fairly consistent especially in the days prior to the advent of protease inhibitors and combination drug treatments. Since the disease was continuous and progressive, increases in T-4, especially in group data, would have been highly unlikely and would most likely be due to a treatment that strengthens the immune system. A single case study was presented at the Society for the Study of Neuronal Regulation conference in 1994 by Ellen Saxby. In this study she recruited one HIV+ subject and utilized 14 Hz. enhancement of C1-C2 utilizing EEG-driven photo-stimulation for five sessions. The subject increased T-4 absolute count from 110 to 264, a 140% increase. Saxby's results are suggestive but the single case design is scientifically inconclusive and limits generalization.
A neurofeedback pilot study that is "in press" was completed by me along with co-investigators: M. Crane, L. Wong, and C. Aguirre. The study is titled "The effect of alpha and theta neurofeedback and alpha-stim treatment on immune function, physical symptoms, and subjective stress within a group of HIV+ subjects, a controlled study". Due to the current publication status of the study, I can only summarize the results here. The goal of the study was to document previously observed changes and to justify the utility of further investigation. Forty subjects were assigned to one of three treatment conditions and a control group. Of the 20 subjects given alpha neurofeedback training over four months at O-z, one group of 10 subjects averaged a 31% increase in T-4 count, the other group of ten increased 25%. The alpha-stim only and control group showed no change. In addition, all the subjects given neurofeedback reported a significant decrease in physical symptoms and subjective stress within the first month of the study. These results have been extremely compelling in favor of the possibility of positive immune modulation with neurofeedback. At the present time we are attempting to raise funds for further research to replicate and refine these results. Likewise, we intend on expanding the scope of our research to other immune problems. Future studies will have better measures of immune function and examine electrode placement issues for maximum benefit.

WHERE DO WE GO FROM HERE?

As the complexity involved in the interaction between the central nervous, immune, and the endocrine systems become better understood many questions will be resolved. Certainly the immune system has a level of sophistication and organization that we are just beginning to comprehend. Neurofeedback as a science is still in its infancy because so little is known about how changes in cortical EEG effect deeper brain structures (the thalamus, hypothalamus, etc.). The interface between these deeper brain structures appear to be modulated by the cerebral cortex. Hopefully, changes in cortical EEG can positively modulate the immune and endocrine systems. Surface electrode placement must be further investigated. A logical extension of work done by M.B. Sterman, J. Lubar, S. Othmer, P. Rosenfeld, M. Diamond and others indicate that higher cortical regions better regulate and perhaps stimulate lower, primary input areas (Schummer, 1989). Extending this further, Kang, et al (1991) showed significant differences in natural killer cell activity inversely correlated with right frontal activation. This finding supports the hypothesis that there is a specific association between frontal brain asymmetry and certain immune responses. Dr. Marian Diamond (1996) stated that as early as 1980 the French reported significant increases in immune system function were observed with removal of the left cerebral cortex. She found in her own lab that removal of the adrenals significantly decreased cortical activity and that placing thymus and pituitary cells into mice that do not have these cells increased the number of T-4 and T-8 (or CD4 and CD8) cells. These factors would indicate that an electrode placement over the central or left frontal cortex would probably yield even more significant results than the occipital placement referenced in our research. Further study is necessary to confirm these hypotheses.
At this point in time there are many more questions than answers. However, as more knowledge presents itself regarding neural pathways for the propagation of positive modulation of the immune system we can correlate these changes with cortical EEG patterns utilizing sophisticated EEG brain mapping technology. Once correlation is quantified between the EEG and immune function, research can be designed to change cortical EEG utilizing the operant conditioning paradigm inherent in biofeedback. Advances in computer technology, more sophisticated methods of recording brain activity, possible utilization of photic stimulation and such techniques as guided imagery will likely yield better and quicker learning curves to reorganize and reorient brain electrical activity to match desired frequency-amplitude patterns. Cerebral blood flow may also come under scrutiny since new provocative research indicates that increased blood flow enhances cortical growth and may more efficiently regulate or stabilize the brain. Methods to measure and feedback cerebral blood flow are currently under development.
As researchers, it is important to adhere to the discipline inherent in the scientific method so that the results we see will be real and stand up to replication. Neurofeedback is perhaps one of technology's greatest gifts to humankind. Some have said that we can look forward to freedom from autonomic control and thereby maximize human potential as it relates to physiology. The new frontier of neurofeedback will allow for immune enhancement as well as broadening the applications to the various disorders of the central nervous system already under investigation. Ultimately neurofeedback can, and undoubtedly will, facilitate the growth and development of human potential, communication, and consciousness. As Dr. James Hardt stated, "Neurofeedback will eventually allow humanity to transcend our present limited consciousness as we experience true liberation from automatic stress responses, addiction, chronic pain, anxiety, depression, and a variety of other cognitive, emotional, and physical limitations" (1994).

REFERENCES

Felten, S.Y., and Felten, D.L. The innervation of lymphoid tissue. Psychoneuroimmunology, 2nd edition, edited by Ader, R., Cohen, N., and Felten, D.L., Academic Press, New York, pp. 27-70, 1991.
Angeli, A., Masera, R.G., Staurenghi, A.H., Solomon, S., Bateman, A., Sartori, M.L., Lazzero, A., Griot, G. (1994) The expanding field of hypothalamic pituitary adrenal modulation of human natural killer cell activity [Review]. Annals of the New York Academy of Sciences, 719:328-342.
Auerbach, J.E., Oleson, T.D., and Solomon, G.F. A behavioral medicine intervention as an adjunctive treatment for HIV related illness. Psychology and Health, 6:325-334, 1992.
Bulloch, K., Tollefson, L. (1990). Dual-label retrograde transpost: CNS innervation of the mouse thymus distinct from other mediastinum viscera. J Neurosci Res 25, 20-28.
Derijk, R. and Berkenbosch, F. The immune-hypothalamo-pituitary-adrenal axis and autoimmunity [Review]. International Journal of Neuroscience, 59(1-3):91-100, 1991.
Diamond, M.C. Enriching Heredity. Free Press, New York, 1988.
Diamond, M.C. Enrichment Speaker - Invited Address at the 22nd Annual BSC Convention, South San Francisco, Nov 8, 1996.
Farber, E.M. and Nall, L. Psoriasis: a stress-related disease [Review]. Cutis, 51(5):322-326, 1993.
Gruber, B.L., Hall, N.R., Hersh, S.P., Dubois, P. Immune system and psychological changes in metastatic cancer patients while using ritualized relaxation and guided imagery: A pilot study. Scandinavian Journal of Behavior Therapy, 17:25-46, 1988.
Gruber, B.L., Hersh, S.P., Hall, N.R., Waletzky, L. R., Kunz, J.F., Carpenter, J.K. (1993)Immunological responses of breast cancer patients to behavioral interventions. Biofeedback and Self Regulation, 18(1)1-22.
Hardt, J. A Tale of Self-Discovery. Megabrain Report, 2(3):2-16, 1994.
Halley, F.M. (1991). Self regulation of the immune system. Biofeedback and Self-Regulation, 16:1,55-74.
Kang, D.H., Davidson, R.J., Coe, C.L., Wheeler, R.F., Tomarken, A.J., Ershler, W.B. (1991)Frontal brain asymmetry and immune function. Behavioral Neuroscience, 105(6):860-869.
Khansari, D.N., Murgo, A.J., and Faith, R.E. Effects of Stress on the Immune System. Immunol. Today, 11:170-175, 1990.
Lowe, F. A controlled study of the treatment of Chronic Fatigue Syndrome with 13-14 Hz. beta band EEG biofeedback. Reported on at SSNR Conference, Las Vegas, 1994.
McGrady, A., Conran, P., Dickey, D., Garman, D., Farria, E., Schumann-Brezinski, C. (1992)The effects of biofeedback-assisted relaxation on cell mediated immunity, cortisol, and white blood cell count in healthy adult subjects. Journal of Behavioral Medicine, 15:343-354.
Peavey, B.S., Lawlis, G.F, and Goven, A. Biofeedback-assisted relaxation: Effects on phagocytic capacity. Biofeedback and Self-Regulation, 10:33-47, 1985
Rogers, M.P., Dubey, D., and Reich, P. The influence of the psyche and the brain on immunity and disease susceptibility: A critical review. Psychosom. Med., 41: 147-164, 1979.
Schummer, G.J. Rationale for the utilization of the sersorimotor cortex in the neurofeedback treatment of the learning disabilities. Symposium: "Methodological Issues in EEG Training," AAPB Conference, San Diego, CA, 1989.
Schummer, G.J. Self-regulation of the immune system. Megabrain Report, 3(1);30-39, 1996.
Schummer, G.J., Crane, M., Wong, L., Aguirre, C. (1996) The effect of alpha and theta neurofeedback and alpha-stim treatment on immune function, physical symptoms, and subjective stress within a group of HIV+ subjects, a controlled study (in press).
Stratakis, C.A. Neuroendocrinology and pathophysiology of the stress system. Ann NY Acad Sci., 771:1-18, 1995.
Tansey, M.A. Neurofeedback and Chronic Fatigue Syndrome: New findings with respect to diagnosis and treatment. The CFIDS Chronicle, 9:30-32, 1993; Reported on at SSNR Conference, Las Vegas, 1994.


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