Neurophysiological Model of Tinnitus, Its Clinical Implications and Clinical Results

• Jastreboff, P.J. Phantom auditory perception (Tinnitus): mechanisms of generation and perception. Neuroscience Research, 8:221-254, 1990.
  
  This is a fundamental paper in which the model is introduced and other approaches to tinnitus are discussed. Rather difficult. Not recommended as initial reading.

• Jastreboff, P.J. Tinnitus as a phantom perception: Theories and clinical implications. In: Mechanisms of Tinnitus, eds. J. Vernon and A. Moller, Allyn & Bacon, Massachusetts, Chapter 8, pp. 73-87, 1995.
  A chapter describing the updated version of the model and its clinical implication. Much more accessible to read than the above paper.

• Jastreboff, P.J., Hazell, J.W.P., Graham, R.L. Neurophysiological model of tinnitus: Dependence of the minimal masking level on treatment outcome. Hearing Research, 80:216-232, 1994.
  The introduction in this paper provides a concise comparison of previous models and approaches to tinnitus with the neurophysiological model. The clinical data presented support our model and argue against common errors, such as the belief that treatment outcome is related to tinnitus loudness or its maskability -- it is not! This paper is somewhat difficult, but I would recommend reading the introduction and discussion.

• Jastreboff, P.J., Hazell, J.W.P. A neurophysiological approach to tinnitus: clinical implications. British Journal of Audiology, 27:7-17, 1993.
  A paper focused on translating theory into clinical implication.

• Jastreboff, P.J., Hazell, J.W.P. Treatment of tinnitus based on a neurophysiological model. In: Treatments for Tinnitus, ed. K. Farnsworth, Allyn & Bacon, Massachusetts, in press.
  This chapter was written as simply as possible for patients. It may be the easiest reading on the model.

• Jastreboff, P.J., Gray, W.C., Gold, S.L. Neurophysiological approach to tinnitus patients. American Journal of Otology, 17:236-240, 1996.
  A description of the model and results presented in a well recognized journal.

• Jastreboff, P.J. Processing of the tinnitus signal within the brain. Proceedings of the 5th International Tinnitus Seminar, Portland, Oregon, 1995, eds. G. Reich and J. Vernon, American Tinnitus Association, Portland, Oregon, pp58-67, 1996.
  Updated the theory and emphasizes the relation of theory and findings from the animal model.

• Jastreboff, P.J. Usefulness of the psychoacoustical characterization of tinnitus. Proceedings of the 5th International Tinnitus Seminar, Portland, Oregon, 1995, eds. G. Reich and J. Vernon, American Tinnitus Association, Portland, Oregon, pp. 58-166, 1996.
  An analysis of the value of audiological evaluation, stressing the importance of evaluating hyperacusis in tinnitus patients.

The following three papers describe the practical aspects and results of treatment in our Center.

• Jastreboff, P.J. Clinical implication of the neurophysiological model of tinnitus. Proceedings of the 5th International Tinnitus Seminar, Portland, Oregon, 1995, eds. G. Reich and J. Vernon, American Tinnitus Association, Portland, Oregon, pp. 500-507, 1996.
• Gray, W.C., Jastreboff, P.J. Medical evaluation, diagnosis, and counseling. Proceedings of the 5th International Tinnitus Seminar, Portland, Oregon, 1995, eds. G. Reich and J. Vernon, American Tinnitus Association, Portland, Oregon, pp. 494-497, 1996.
• Gold, S.L., Gray, W.C., Jastreboff, P.J. Audiological evaluation and follow up. Proceedings of the 5th International Tinnitus Seminar, Portland, Oregon, 1995, eds. G. Reich and J. Vernon, American Tinnitus Association, Portland, Oregon, pp. 485-487, 1996.
• Sheldrake, J.B., Jastreboff, P.J., Hazell, J.W.P. Perspectives for total elimination of tinnitus perception. Proceedings of the 5th International Tinnitus Seminar, Portland, Oregon, 1995, eds. G. Reich and J. Vernon, American Tinnitus Association, Portland, Oregon, pp. 531-537, 1996.
  Presents the results of a long-term study showing that about 20% of the patients treated with our approach exhibited periods of time, up to a few weeks, when they were not able to hear their tinnitus even when they tried to. The study was done on 150 patients, and presently we are continuing to collect data from an additional 100 patients.

Two papers on instruments.

• Jastreboff, P.J. Instrumentation and tinnitus: A neurophysiological approach. Hearing Instruments 45:7-11, 1994.
• Gold, S.L., Gray, W.C., Jastreboff, P.J. Selection and fitting of noise generators and hearing aids for tinnitus patients. Proceedings of the 5th International Tinnitus Seminar, Portland, Oregon, 1995, eds. G. Reich and J. Vernon, American Tinnitus Association, Portland, Oregon, pp. 312-314, 1996.

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Other Clinical Works

• Jastreboff, P.J., Ikner, C.L., Hassen, A. An approach to objective evaluation of tinnitus in humans. In: Tinnitus '91: Proceedings IV International Tinnitus Seminar, Bordeaux, France 1991, ed. Jean©Marie Aran, Kugler Publications, Amsterdam, pp. 331-340, 1992.
  An application of a mathematical method, used for discrimination between tinnitus and non tinnitus subjects in a blind study.

• Hazell, J.W.P., Jastreboff, P.J., Meerton, L.E., Conway, M.J. Electrical tinnitus suppression: frequency dependence of effects. Audiology, 32:68-77, 1993.
  The results of work with extracochlear electrical stimulation; rather promising, however due to a high success rate with habituation techniques, this approach has been limited to totally deaf patients who are getting a cochlear implant.

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An Animal Model of Tinnitus

• Jastreboff, P.J., Brennan, J.F., Sasaki, C.T. Phantom auditory sensation in rats: An animal model for tinnitus. Behavioral. Neuroscience, 102:811-822, 1988.
  The main paper describing the principle and the results of our behavioral paradigm for inducing and detecting tinnitus in rats.

• Jastreboff, P.J., Brennan, J.F., Sasaki, C.T. An animal model for tinnitus. Laryngoscope, 98:280-286, 1988.
  The outline of the model presenting both behavior and electrophysiology.

• Chen, G-D., Jastreboff, P.J. Salicylate-induced abnormal activity in the inferior colliculus of rats. Hearing Research, 82:158-178, 1995.
  To my knowledge, this is the first paper to present abnormal neuronal activity which may be related to tinnitus in a large number of neurons, and recorded under conditions when animals were shown to perceive tinnitus. Notably, the results point out specific categories of mechanisms involved in tinnitus and suggest types of drugs which may be effective.

Series of papers on the animal model presented at the IV International Seminar in Bordeaux; the titles are self explanatory.

• Jastreboff, P.J., Brennan, J.F. Animal model of tinnitus: Recent developments. In: Tinnitus '91: Proceedings IV International Tinnitus Seminar, Bordeaux, France 1991, ed. Jean-Marie Aran, Kugler Publications, Amsterdam, pp. 283-292, 1992.
• Jastreboff, P.J., Brennan, J.F. The psychoacoustical characteristics of tinnitus in rats. Tinnitus '91: Proceedings IV International Seminar, Bordeaux, France 1991, ed. Jean-Marie Aran, Kugler Publications, Amsterdam, pp. 305-309, 1992.
• Jastreboff, P.J., Nguyen, Q., Brennan, J.F., Sasaki, C.T. Calcium and calcium channel involvement in tinnitus. In: Tinnitus '91: Proceedings IV International Tinnitus Seminar, Bordeaux, France 1991, ed. Jean-Marie Aran, Kugler Publications, Amsterdam, pp. 109-114, 1992.
• Jastreboff, P.J. Appropriateness of salicylate-based models of tinnitus. In: Tinnitus '91: Proceedings IV International Tinnitus Seminar, Bordeaux, France 1991, ed. Jean-Marie Aran, Kugler Publications, Amsterdam, pp. 309-313, 1992.
• Jastreboff, P.J., Sasaki, C.T. An animal model of tinnitus: A decade of development. American Journal of Otology, 15:19-27, 1994.
  A summary of the main stages of work on the animal model, initially presented at the 126th Annual Meeting of American Otological Society.

• Jastreboff, P.J., Brennan, J.F. Evaluating the loudness of phantom auditory perception (tinnitus) in rats. Audiology, 33:202-217, 1994.
  The work created the basis for evaluating drugs capable of only partial attenuation of tinnitus.

• Zhou, S., Kwapisz, U., Jastreboff, M.M., Gryczynska, U., Jastreboff, P. J. Evaluation of the effectiveness of EGb 761 in an animal model of tinnitus. Proceedings of the 5th International Tinnitus Seminar, Portland, Oregon, 1995, eds. G. Reich and J. Vernon, American Tinnitus Association, Portland, Oregon, pp. 245-247, 1996.
  Evaluation of ginkgo biloba on the animal model.

• Jastreboff, P.J., Brennan, J.F., Jastreboff, M.M., Hu, S., Zhou, S., Chen, G.-D., Gryczynska, U., Kwapisz, U. Recent findings from an animal model of tinnitus. Proceedings of the 5th International Tinnitus Seminar, Portland, Oregon, 1995, eds. G. Reich and J. Vernon, American Tinnitus Association, Portland, Oregon, pp. 114-126, 1996.
  A summary of the main achievements during the last four years.

• Jastreboff, M.M., Jastreboff, P.J. Tinnitus-related modulation of c-fos expression. Proceedings of the 5th International Tinnitus Seminar, Portland, Oregon, 1995, eds. G. Reich and J. Vernon, American Tinnitus Association, Portland, Oregon, pp. 426-428, 1996.
  To my knowledge, these preliminary results represent the first work with c-fos and tinnitus. These studies should allow for mapping the plastic changes associated with tinnitus emergence.

• Jastreboff, M.M., Jastreboff, P.J. Modification of metabolic activity within the auditory pathways related to salicylate-induced tinnitus. Proceedings of the 5th International Tinnitus Seminar, Portland, Oregon, 1995, eds. G. Reich and J. Vernon, American Tinnitus Association, Portland, Oregon, pp. 423-425, 1996.
  Similar to the c-fos work, but on metabolic activity.

• Jastreboff, P.J., Brennan, J.F. Mechanisms of L-type calcium channel antagonist on tinnitus. Proceedings of the 5th International Tinnitus Seminar, Portland, Oregon, 1995, eds. G. Reich and J. Vernon, American Tinnitus Association, Portland, Oregon, pp. 234-236, 1996.
  Nimodipine is a drug that has been indicated as potentially helpful and we are testing it now in the center.

• Hu, S., Zhou, S., Jastreboff, M.M., Jastreboff, P.J. Influence of tinnitus-inducing drugs on cochlear active processes. Proceedings of the 5th International Tinnitus Seminar, Portland, Oregon, 1995, eds. G. Reich and J. Vernon, American Tinnitus Association, Portland, Oregon, pp. 231-233, 1996.
  A study testing the relation of tinnitus to active processes in the cochlea.

• Hu, S., Zhou, S., Jastreboff, M.M., Jastreboff, P.J. Aging and the functionality of the outer hair cell system. Proceedings of the 5th International Tinnitus Seminar, Portland, Oregon, 1995, eds. G. Reich and J. Vernon, American Tinnitus Association, Portland, Oregon, pp. 420-422, 1996.
  An element of our continuing investigation of aging and tinnitus.

• Jastreboff, P.J., Zhou, S., Jastreboff, M.M., Kwapisz, U., Gryczynska, U. Testing the efficacy of Ginkgo biloba extract (EGb 761) for tinnitus attenuation in an animal model. In: Advances in Ginkgo biloba Extract Research. Effects of Ginkgo biloba Extract (EGb 761) on Neural Plasticity (eds. Y. Christen, M.T. Droy-Lefaix, J.F. Macais-Nunez) Elsevier, Paris, Volume 5, pp. 101-112, 1996.
  Presents results of our investigation of the effectiveness of ginkgo biloba on an animal model of tinnitus.

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Salicylate and mortality

These two papers report that salicylate in interaction with noise or stress is literally deadly. The results have been reproduced in three independent laboratories.

• Brennan, J.F., Jastreboff, P.J. Interaction of salicylate and noise results in mortality of rats. Experientia, 45:731-734, 1989.
• Jastreboff, P.J., Brennan, J.F. Alleviation of mortality induced by salicylate and stress. Experientia, 50:469-474, 1994.

Furthermore, the following books can be useful for a general overview of tinnitus:

1. McFadden, D. Tinnitus: Facts, theories, and treatments, Washington, D.C. National Academy Press, 1982.
2. Tinnitus, ed. Hazell, J.W.P.Edinburgh: Churchill Livingstone, 1987. Proceeding of the III International Tinnitus Seminar, Muenster, edited by Feldmann, H.Karlsruhe: Harsch Verlag, 1987.
3. Tinnitus 91. Proceedings IV International Tinnitus Seminar, Bordeaux, France, 1991, eds. Aran, J. and Dauman, R.Amsterdam: Kugler Publications, 1992.
4. Proceedings of the 5th International Tinnitus Seminar 1995, eds. G. Reich and J. Vernon, American Tinnitus Association, Portland, Oregon, 1996.

Additionally, a book on the tinnitus is presently under preparation.

• Jastreboff, P.J. and Hazell J.W.P. A Neurophysiological Approach to Tinnitus: Theory & Practice. Cambridge University Press, expected to be published at the end of 1998.

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