Tinnitus: animal models and findings in humans

Current opinion in otolaryngology & head and neck surgery, 2012

Tinnitus is the sensation of hearing a sound when no external auditory stimulus is present. Most individuals experience tinnitus for brief, unobtrusive periods. However, chronic sensation of tinnitus affects approximately 17% (44 million people) of the general US population. Tinnitus, usually a benign symptom, can be constant, loud and annoying to the point that it causes significant emotional distress, poor sleep, less efficient activities of daily living, anxiety, depression and suicidal ideation/attempts. Tinnitus remains a major challenge to physicians because its pathophysiology is poorly understood and there are few management options to offer to patients. The purpose of this article is to describe the current understanding of central neural mechanisms in tinnitus and to summarize recent developments in clinical approaches to tinnitus patients. Recently developed animal models of tinnitus provide the possibility to determine neuronal mechanisms of tinnitus generation and to te...

Brain Research, 2012

Tinnitus, the perception of a phantom sound, is a common consequence of damage to the auditory periphery. A major goal of tinnitus research is to find the loci of the neural changes that underlie the disorder. Crucial to this endeavor has been the development of an animal behavioral model of tinnitus, so that neural changes can be correlated with behavioral evidence of tinnitus. Three major lines of evidence implicate the dorsal cochlear nucleus (DCN) in tinnitus. First, elevated spontaneous activity in the DCN is correlated with peripheral damage and tinnitus. Second, there are somatosensory inputs to the DCN that can modulate spontaneous activity and might mediate the somatic-auditory interactions seen in tinnitus patients. Third, we have found a subpopulation of DCN neurons in the adult rat that express doublecortin, a plasticity-related protein. The expression of this protein may reflect a role of these neurons in the neural reorganization causing tinnitus. However, there is a problem in extending the findings in the rodent DCN to humans. Classic studies state that the structure of the primate DCN is quite different from that of rodents, with primates lacking granule cells, the recipients of somatosensory input. To address the possibility of major species differences in DCN organization, we compared Nissl-stained sections of the DCN in five different species. In contrast to earlier reports, our data suggest that the organization of the primate DCN is not dramatically different from that of the rodents, and validate the use of animal data in the study of tinnitus.

Frontiers in Systems Neuroscience, 2012

2012

Tinnitus is an auditory phantom sensation (ringing of the ears) experienced when no external sound is present. Most but not all cases are associated with hearing loss induced by noise exposure or aging. Neuroscience research has begun to reveal how tinnitus is generated by the brain when hearing loss occurs, and to suggest new avenues for management and prevention of tinnitus following hearing injuries. Downregulation of intracortical inhibition induced by damage to the cochlea or to auditory projection pathways highlights neural processes that underlie the sensation of phantom sound.

Neuron, 2019

Hearing Research, 2015

Tinnitus, the phantom perception of sound, is physiologically characterized by an increase in spontaneous neural activity in the central auditory system. However, as tinnitus is often associated with hearing impairment, it is unclear how a decrease of afferent drive can result in central hyperactivity. In this review, we first assess methods for tinnitus induction and objective measures of the tinnitus percept in animal models. From animal studies, we discuss evidence that tinnitus originates in the cochlear nucleus (CN), and hypothesize mechanisms whereby hyperactivity may develop in the CN after peripheral auditory nerve damage. We elaborate how this process is likely mediated by plasticity of auditory esomatosensory integration in the CN: the circuitry in normal circumstances maintains a balance of auditory and somatosensory activities, and loss of auditory inputs alters the balance of auditory somatosensory integration in a stimulus timing dependent manner, which propels the circuit towards hyperactivity. Understanding the mechanisms underlying tinnitus generation is essential for its prevention and treatment.

Journal of Neuroscience, 2010

with hearing impairment. This symposium will consider evidence that deafferentation of tonotopically organized central auditory structures leads to increased neuron spontaneous firing rates and neural synchrony in the hearing loss region. This region covers the frequency spectrum of tinnitus sounds, which are optimally suppressed following exposure to band-limited noise covering the same frequencies. Cross-modal compensations in subcortical structures may contribute to tinnitus and its modulation by jaw-clenching and eye movements. Yet many older individuals with impaired hearing do not have tinnitus, possibly because age-related changes in inhibitory circuits are better preserved. A brain network involving limbic and other nonauditory regions is active in tinnitus and may be driven when spectrotemporal information conveyed by the damaged ear does not match that predicted by central auditory processing.

The Journal of Neuroscience, 2010

Tinnitus is a phantom sound (ringing of the ears) that affects quality of life for millions around the world and is associated in most cases with hearing impairment. This symposium will consider evidence that deafferentation of tonotopically organized central auditory structures leads to increased neuron spontaneous firing rates and neural synchrony in the hearing loss region. This region covers the frequency spectrum of tinnitus sounds, which are optimally suppressed following exposure to band-limited noise covering the same frequencies. Cross-modal compensations in subcortical structures may contribute to tinnitus and its modulation by jaw-clenching and eye movements. Yet many older individuals with impaired hearing do not have tinnitus, possibly because age-related changes in inhibitory circuits are better preserved. A brain network involving limbic and other nonauditory regions is active in tinnitus and may be driven when spectrotemporal information conveyed by the damaged ear does not match that predicted by central auditory processing.

Frontiers in Systems Neuroscience

Tinnitus is one of the most prevalent auditory disorders worldwide, manifesting in both chronic and acute forms. The pathology of tinnitus has been mechanistically linked to induction of harmful neural plasticity stemming from traumatic noise exposure, exposure to ototoxic medications, input deprivation from age-related hearing loss, and in response to injuries or disorders damaging the conductive apparatus of the ears, the cochlear hair cells, the ganglionic cells of the VIIIth cranial nerve, or neurons of the classical auditory pathway which link the cochlear nuclei through the inferior colliculi and medial geniculate nuclei to auditory cortices. Research attempting to more specifically characterize the neural plasticity occurring in tinnitus have used a wide range of techniques, experimental paradigms, and sampled at different windows of time to reach different conclusions about why and which specific brain regions are crucial in the induction or ongoing maintenance of tinnitus-related plasticity. Despite differences in experimental methodologies, evidence reveals similar findings that strongly suggest that immediate and prolonged activation of non-classical auditory structures (i.e., amygdala, hippocampus, and cingulate cortex) may contribute to the initiation and development of tinnitus in addition to the ongoing maintenance of this devastating condition. The overarching focus of this review, therefore, is to highlight findings from the field supporting the hypothesis that abnormal early activation of non-classical sensory limbic regions are involved in tinnitus induction, with activation of these regions continuing to occur at different temporal stages. Since initial/early stages of tinnitus are difficult to control and to quantify in human clinical populations, a number of different animal paradigms have been developed and assessed in experimental investigations. Reviews of traumatic noise exposure and ototoxic doses of sodium salicylate, the most prevalently used animal models to induce experimental tinnitus, indicate early limbic

AVR Journal, 2019

Background and Aim: Tinnitus is a perception of sound in ears or head in the absence of any external stimuli. Despite its high prevalence in various age groups, tinnitus has still no effective treatment because its physiological and pathological mechanisms have remained unknown. Since the study of cellular-molecular mechanisms of tinnitus production and stability in human is not feasible, animal models have been used to shed some light on tinnitus induction and propagation mechanisms. This study reviewed some of these research studies. The present review article is based on articles published during 1967-2018 in which keywords such as “salicylate,” “noise,” “tinnitus in the animal model,” and “tinnitus mechanism” were used. These articles were searched in databases such as Science Direct, Google Scholar, PubMed, and Scopus. Recent Findings: Despite differences in the mechanisms of tinnitus induction, the structural changes initiated from the cochlea and continued to cortex reflect the extent of the affected regions in the creation, development, and preservation of tinnitus. Conclusion: Animal models (exposed to noise or ototoxic drugs such as salicylate) are ideal tools for studying tinnitus and understanding the details of its propagation and unknown mecha­nisms.