Elsevier

Hearing Research

Volume 206, Issues 1–2, August 2005, Pages 200-226
Hearing Research

Tinnitus as a plastic phenomenon and its possible neural underpinnings in the dorsal cochlear nucleus

https://doi.org/10.1016/j.heares.2005.02.013Get rights and content

Abstract

Tinnitus displays many features suggestive of plastic changes in the nervous system. These can be categorized based on the types of manipulations that induce them. We have categorized the various forms of plasticity that characterize tinnitus and searched for their neural underpinnings in the dorsal cochlear nucleus (DCN). This structure has been implicated as a possible site for the generation of tinnitus-producing signals owing to its tendency to become hyperactive following exposure to tinnitus inducing agents such as intense sound and cisplatin. In this paper, we review the many forms of plasticity that have been uncovered in anatomical, physiological and neurochemical studies of the DCN. Some of these plastic changes have been observed as consequences of peripheral injury or as fluctuations in the behavior and chemical activities of DCN neurons, while others can be induced by stimulation of auditory or even non-auditory structures. We show that many parallels can be drawn between the various forms of plasticity displayed by tinnitus and the various forms of neural plasticity which have been defined in the DCN. These parallels lend further support to the hypothesis that the DCN is an important site for the generation and modulation of tinnitus-producing signals.

Introduction

Over the past decade, there has been increasing evidence that the dorsal cochlear nucleus (DCN) plays an important role in the etiology of tinnitus. This structure was first implicated as a source of tinnitus-generating signals in studies conducted in hamsters (Kaltenbach et al., 1996, Kaltenbach et al., 1998; Kaltenbach and McCaslin, 1996). These and several more recent investigations in the same species (Kaltenbach and Afman, 2000; Kaltenbach et al., 2000, Kaltenbach et al., 2004) showed that neurons become hyperactive in the DCN following exposure to intense sound. The hyperactivity was originally observed as increases in spontaneous activity at the multiunit level, although more recent studies have demonstrated sound exposure-induced hyperactivity in the DCN at the single unit level (Brozoski et al., 2002). Evidence for intense sound-induced hyperactivity in the DCN has now been observed in four other species, including rats (Zhang and Kaltenbach, 1998), chinchillas (Brozoski et al., 2002), gerbils (Wallhausser-Franke et al., 2003) and mice (Kaltenbach et al., 2001) suggesting that it may be a general phenomenon across species.

It is not yet known whether intense noise-exposure causes hyperactivity to develop in the DCN of humans. However, several studies have implicated the DCN as an important component involved in the modulation of tinnitus in humans. Soussi and Otto (1994) reported that tinnitus loudness could be negatively modulated by applying electrical stimuli directly to the DCN surface. In 6 out of 7 patients, stimulation of the DCN resulted in decreasing the loudness of tinnitus or eliminating it altogether. A role of the DCN in the modulation of tinnitus has also been inferred from studies of patients with somatic tinnitus. In these patients, tinnitus percepts can be modulated by certain manipulations of the head and neck (Levine, 1999; Levine et al., 2003). An interesting aspect of this modulation is that in cases with unilateral tinnitus the modulatory effect was described as always coming from the ear ipsilateral to the side of the somatic manipulation (Levine, 1999). It was hypothesized that the DCN is a structure that may underlie somatically modulated tinnitus because it integrates auditory with mainly ipsilateral rather than contralateral somatosensory pathways (El-Kashlan and Shore, 2004; Weinberg and Rustioni, 1987; Young et al., 1995; Wright and Ryugo, 1996). More recent studies showing that stimulation of the trigeminal nerve or ganglion can modulate spontaneous activity of DCN cells, including fusiform cells, is consistent with this hypothesis (Kanold and Young, 2001; Shore, 2004).

Evidence that hyperactivity in the DCN represents a source of tinnitus-generating signals comes from studies in which electrophysiological recordings from the DCN were complemented by behavioral tests for tinnitus. These studies suggest that noise-exposure conditions which cause hyperactivity in the DCN also cause animals to develop tinnitus-like percepts (Bauer, 2003; Bauer and Brozoski, 2001; Brozoski et al., 2002; Heffner and Harrington, 2002). Moreover, when behavioral and electrophysiological tests were conducted in the same animals, a significant correlation was found between the level of activity in the DCN and the behavioral evidence for tinnitus (Kaltenbach et al., 2004). A correlation, however, does not prove a cause and effect relationship. It is possible that both DCN hyperactivity and tinnitus result from hearing loss, and yet be causally unrelated to each other. However, this explanation was cast in doubt by Brozoski et al. (2002) who exposed chinchillas to low levels of sound (80 dB SPL) and succeeded in demonstrating that both hyperactivity in the DCN and behavioral evidence of tinnitus were induced in chinchillas even after recovery from temporary hearing loss.

In the present study, we sought additional evidence that tinnitus and DCN hyperactivity are related. We set out to determine whether hyperactivity and related phenomena in the DCN might show similar patterns of plasticity as those that are characteristic of tinnitus. This search requires comparison of data from neurophysiological, anatomical and neurochemical studies of the DCN with the features of tinnitus that have been cited as evidence for plasticity. The term ‘plasticity’ is used in many ways in the literature and there is no universal agreement on its definition. We apply the term at the physiological level to refer to short and long-term secondary changes in neuronal sensitivity or excitability that result from alterations or manipulations of synaptic input. Changes in excitability commonly reflect changes at the synaptic level, but may also arise from changes in membrane properties. It is reasonable to suppose that both types of change begin with alterations in the expression of related genes. This definition thus encompasses changes that are triggered by alterations of input, either pathological or normal, but which go beyond the primary changes that would be expected based on the passive properties of neurons, such as immediate elevations of response thresholds due to a failure of peripheral receptor function. The term ‘plasticity’ can also be useful at the psychophysical level. In the present discussion, we will apply the term in reference to both the process by which tinnitus is induced as well as the changes in tinnitus percepts that are experienced over time, either spontaneously without obvious cause, or as a result of experimental manipulations of input. It is assumed that the plastic features of tinnitus are the perceptual manifestations of the plastic changes in neural excitability. Thus, it is reasonable to expect that if DCN hyperactivity contributes to the percepts of tinnitus, we should expect to find numerous parallels between the plastic features of tinnitus, or what we will refer to hereinafter as tinnitus plasticity, and DCN plasticity. The purpose of this paper is to examine this issue in detail.

Section snippets

Plasticity of tinnitus

The literature describes a wealth of psychophysical attributes of tinnitus that can be considered hallmarks of plasticity. Not only is the process by which tinnitus is induced thought to involve plasticity, the post-induction perceptual features of tinnitus can change spontaneously over time or be modulated by certain manipulations of sensory input. To facilitate this discussion, we have categorized various forms of tinnitus plasticity into four types, based on the kinds of events that trigger

DCN plasticity and hyperactivity

We now turn to the issue of whether there are any known properties of DCN organization and function that might serve as underlying correlates of the plastic features of tinnitus that have just been reviewed. Focus on the DCN is justified here because the hyperactivity that develops in this structure after acoustic injury has been found to be associated with tinnitus percepts (see Section 1). If the DCN contributes to the generation of tinnitus, then it is natural to expect that the various

DCN plasticity and the search for a final common path for tinnitus

The search for a final common path underlying tinnitus has been complicated by the multiple forms of tinnitus, the numerous potential mechanisms that have been proposed, and by evidence for the involvement of many brain areas. While our focus on the DCN might be viewed as an oversimplification of this search, it should be apparent from the foregoing analysis that the DCN possesses many characteristics that one would expect of a major center for the generation of tinnitus and its various forms

Summary and conclusion

This article has reviewed various forms of plasticity that characterize tinnitus, including its induction by injuries and hearing loss, its fluctuant behavior over time, its changes in psychophysical attributes following use of non-traumatic acoustic maskers, and its modulations that occur with certain somatic manipulations. Each of these forms of plasticity has one or more parallels that can be found at the neuronal level in the DCN. These parallels lend further support to the hypothesis that

Acknowledgements

Much of the work reviewed in this paper was supported by grants from the National Institute of Deafness and Other Communication Disorders (R01 DC03258) and by the Tinnitus Research Consortium.

References (195)

  • R.D. Cook et al.

    Effects of conductive hearing loss on auditory nerve activity in gerbil

    Hear. Res.

    (2002)
  • J.J. Eggermont et al.

    The neuroscience of tinnitus

    Trends Neurosci.

    (2004)
  • H.K. El-Kashlan et al.

    Effects of trigeminal ganglion stimulation on the central auditory system

    Hear. Res.

    (2004)
  • H.W. Francis et al.

    Effects of deafferentation on the electrophysiology of ventral cochlear nucleus neurons

    Hear. Res.

    (2000)
  • H. Furue et al.

    Sensory processing and functional reorganization of sensory transmission under pathological conditions in the spinal dorsal horn

    Neurosci. Res.

    (2004)
  • M.M. Garcia et al.

    Deafferentation-induced changes in protein kinase C expression in the rat cochlear nucleus

    Hear. Res.

    (2000)
  • D.A. Godfrey et al.

    Contribution of centrifugal innervation to choline acetyltransferase activity in the cat cochlear nucleus

    Hear. Res.

    (1990)
  • G.W. Harding et al.

    DPOAE level shifts and ABR threshold shifts compared to detailed analysis of histopathological damage from noise

    Hear. Res.

    (2002)
  • H.E. Heffner et al.

    Tinnitus in hamsters following exposure to intense sound

    Hear. Res.

    (2002)
  • K. Itoh et al.

    Direct projections from the dorsal column nuclei and the spinal trigeminal nuclei to the cochlear nuclei in the cat

    Brain Res.

    (1987)
  • P.J. Jastreboff et al.

    Neurophysiological model of tinnitus: dependence of the minimal masking level on treatment outcome

    Hear. Res.

    (1994)
  • P.J. Jastreboff et al.

    Tinnitus retraining therapy for patients with tinnitus and decreased sound tolerance

    Otolaryngol. Clin. North Am.

    (2003)
  • J.A. Kaltenbach et al.

    Hyperactivity in the dorsal cochlear nucleus after intense sound exposure and its resemblance to tone-evoked activity: a physiological model for tinnitus

    Hear. Res.

    (2000)
  • J.A. Kaltenbach et al.

    Tone-induced stereocilia lesions as a function of exposure level and duration in the hamster cochlea

    Hear. Res.

    (1992)
  • J.A. Kaltenbach et al.

    Changes in spontaneous neural activity in the dorsal cochlear nucleus following exposure to intense sound: relation to threshold shift

    Hear. Res.

    (1998)
  • J.A. Kaltenbach et al.

    Plasticity of spontaneous neural activity in the dorsal cochlear nucleus after intense sound exposure

    Hear. Res.

    (2000)
  • J.A. Kaltenbach et al.

    Activity in the dorsal cochlear nucleus of hamsters previously tested for tinnitus following intense tone exposure

    Neurosci. Lett.

    (2004)
  • J. Kim et al.

    Degeneration of axons in the brainstem of the chinchilla after auditory overstimulation

    Hear. Res.

    (1997)
  • R.A. Levine

    Somatic (craniocervical) tinnitus and the dorsal cochlear nucleus hypothesis

    Am. J. Otolaryngol.

    (1999)
  • M.C. Liberman et al.

    Single-neuron labeling and chronic cochlear pathology. II. Stereocilia damage and alterations of spontaneous discharge rates

    Hear. Res.

    (1984)
  • P.W. Alberti

    Tinnitus in occupational hearing loss: nosological aspects

    J. Otolaryngol.

    (1987)
  • G.R. Atherley et al.

    Study of tinnitus induced temporarily by noise

    J. Acoust. Soc. Am.

    (1968)
  • C.A. Bauer et al.

    Assessing tinnitus and prospective tinnitus therapeutics using a psychophysical animal model

    J. Assoc. Res. Otolaryngol.

    (2001)
  • A. Axelsson et al.

    Tinnitus in noise-induced hearing loss

    Br. J. Audiol.

    (1985)
  • R.D. Bacsik et al.

    The cytoarchitecture of the human anteroventral cochlear nucleus

    J. Comp. Neurol.

    (1973)
  • D.M. Barrs et al.

    Translabyrinthine nerve section: effect on tinnitus

    J. Laryngol. Otol. Suppl.

    (1984)
  • T.E. Benson et al.

    Postsynaptic targets of type II auditory nerve fibers in the cochlear nucleus

    J. Assoc. Res. Otolaryngol.

    (2004)
  • O. Bernhardt et al.

    Signs of temporomandibular disorders in tinnitus patients and in a population-based group of volunteers: results of the Study of Health in Pomerania

    J. Oral. Rehabil.

    (2004)
  • N.D. Biggs et al.

    Gaze-evoked tinnitus following acoustic neuroma resection: a de-afferentation plasticity phenomenon?

    Clin. Otolaryngol.

    (2002)
  • M.C. Brown

    Antidromic responses of single units from the spiral ganglion

    J. Neurophysiol.

    (1994)
  • W.E. Brownell

    Outer hair cell electromotility and otoacoustic emissions

    Ear Hear.

    (1990)
  • T.J. Brozoski et al.

    Elevated fusiform cell activity in the dorsal cochlear nucleus of chinchillas with psychophysical evidence of tinnitus

    J. Neurosci.

    (2002)
  • E.M. Burns

    A comparison of variability among measurements of subjective tinnitus and objective stimuli

    Audiology

    (1984)
  • A.T. Cacace et al.

    Auditory perceptual and visual–spatial characteristics of gaze-evoked tinnitus

    Audiology

    (1994)
  • S. Chery-Croze et al.

    Is the test of medial efferent system function a relevant investigation in tinnitus

    Br. J. Audiol.

    (1994)
  • D.Y. Chung et al.

    Factors affecting the prevalence of tinnitus

    Audiology

    (1984)
  • M.L. Coad et al.

    Characteristics of patients with gaze-evoked tinnitus

    Otol. Neurotol.

    (2001)
  • R.R.A. Coles

    Classification of causes, mechanisms of patient disturbance and associated counciling

  • R.R.A. Coles et al.

    The relationship between noise-induced hearing loss and tinnitus and its management

  • A.W. Curtis

    Myofascial pain-dysfunction syndrome: the role of nonmasticatory muscles in 91 patients

    Otolaryngol. Head Neck Surg.

    (1980)
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