Hearing Research, 48 (1990) 111-124 111 Elsevier HEARES 01416 On the pathophysiology of tinnitus; A review and a peripheral model Jos J. Eggermont Behavioral Neuroscience Research Group, Department of Psychology, The University of Calgary, Calgary, Alberta, Canada (Received 21 December 1989; accepted 28 March 1990) In this paper I investigate the consequences of the assumption that tinnitus is the result of correlated neural activity in auditory nerve fibers under 'no sound' conditions. Two possible pathological conditions capable of causing this correlation are ephaptic excitation of one nerve fiber by neighboring nerve fibers and synchronization of the various synapses in individual hair cells. The first condition is likely to be found in cases suffering from acoustic neuroma where the myelin sheath of the auditory neurons is damaged. The second condition is attributed to a spontaneous excess influx of K + or Ca2+-ions into the hair cell resulting in transient hair cell depolarizations causing synchronous transmitter release at all hair cell synapses. This condition is postulated in noise trauma and ototoxic drug damage of the inner hair cell membrane. The model produces the excess of short interspike intervals found in auditory nerve fiber recordings in animal models of tinnitus as well as the theoretically required correlation in the activity of neighboring neurons. Tinnitus; Neuron model; Ca2+-ion channels; Spontaneous activity Introduction Modeling tinnitus requires a familiarity with the phenomenology of tinnitus and with the prop- erties of spontaneous neural activity in the audi- tory system as well as the changes that occur in this activity when an external sound is presented. For the validation of a computational model for tinnitus one needs to compare the results of the simulation with results from animal models of tinnitus. Therefore in the introduction a compre- hensive review of these aspects of the physiology and pathophysiology of the auditory system is presented, this is followed by the formulation of the necessary components of a theory for tinnitus. This theory forms the basis for a computational model mimicking the phenomena in the hair cell and auditory nerve fibers that may underlie the generation of tinnitus. The model's outcome will Correspondence to: Jos J. Eggermont, Behavioral Neuroscience Research Group, Department of Psychology, The University of Calgary, 2500 University Drive, N.W., Calgary, Alberta, T2N 1N4, Canada. be compared with data from animal studies re- ported in the hterature. Tinnitus Tinnitus can be defined as a sound sensation in the absence of an external stimulus. In some cases tinnitus is caused by internal stimuli such as blood flow pulsations, this is usually called objective tinnitus. In the present paper I will discuss only 'subjective tinnitus'; cases in which there is no physical sound inside or outside the body that can account for the sound sensation. Of 1800 tinnitus cases studied by Meikle and Taylor-Walsh (1984) 57% experienced only one type of sound which was described mostly as ringing (30%) or hissing (10%). It was also found that 52% of the tinnitus cases had bilateral tinni- tus lateralized in the ears, 11% had it localized inside the head. Is the source of tinnitus therefore in the ears or somewhere more central along the auditory pathway? This is the crucial question for anyone attempting to model tinnitus. From the lateralization of tinnitus one cannot readily con- dude that some tinnitus is peripheral and some is central. And although the subject may report tin- 0378-5955/90/$03.50 © 1990 Elsevier Science Publishers B.V. (Biomedical Division)