Revisiting the Cochlear and Central Mechanisms of Tinnitus and Therapeutic Approaches

Abstract

This short review aims at revisiting some of the putative mechanisms of tinnitus. Cochlear-type tinnitus is suggested to result from aberrant activity generated before or at the cochlear nerve level. It is proposed that outer hair cells, through their role in regulating the endocochlear potential, can contribute to the enhancement of cochlear spontaneous activity. This hypothesis is attractive as it provides a possible explanation for cochlear tinnitus of different aetiologies, such as tinnitus produced by acute noise trauma, intense low-frequency sounds, middle-ear dysfunction or temporomandibular joint disorders. Other mechanisms, namely an excitatory drift in the operating point of the inner hair cells and activation of NMDA receptors, are also briefly reported. Central-type tinnitus is supposed to result from aberrant activity generated in auditory centres, i.e. in these patients, the tinnitus-related activity does not pre-exist in the cochlear nerve. A reduction in cochlear activity due to hearing loss is suggested to produce tinnitus-related plastic changes, namely cortical reorganisation, thalamic neuron hyperpolarisation, facilitation of non-auditory inputs and/or increase in central gain. These central changes can be associated with abnormal patterns of spontaneous activity in the auditory pathway, i.e. hyperactivity, hypersynchrony and/or oscillating activity. Therapeutic approaches aimed at reducing cochlear activity and/or tinnitus-related central changes are discussed.

Factor Analysis of Low-Frequency Repetitive Transcranial Magnetic Stimulation to the Temporoparietal Junction for Tinnitus

“…Tinnitus can occur constantly or intermittently in one or both ears or centrally in the head and can be perceived as coming from within the head. There is convincing evidence from functional imaging and neurophysiological studies that central mechanisms are responsible for most cases of tinnitus [4–6], which may be caused by (1) changes in the firing pattern of neurons in the central auditory system, (2) changes in burst firing and neural synchrony, and (3) cortical tonotopic map reorganization [7]. All of the above may occur due to alterations in neuronal activity in the brain cortex, which suggests promising treatment strategies for tinnitus.…”

Tinnitus in patients with hearing loss due to mitochondrial DNA pathogenic variants

“…Tinnitus may arise as a consequence of cochlear hair cells injury or damage of the auditory pathway [6, 32, 33] but the molecular mechanism leading to tinnitus development is largely unknown. Changes in the structure of mtDNA due to occurrence of pathogenic variants may lead to dysfunction of mitochondria [34–36].…”

Evidence and evidence gaps in tinnitus therapy

“…Thus, tinnitus corresponds to a primary functional loss of mainly external hair cells of the inner ear as described recently by Noreña [8] in a review article. However, mostly enhancement mechanisms in the auricular system are responsible for the perception of tinnitus that enhance this frequency via cortical reactions and priming or reduction of lateral inhibition or increase of base frequencies so that the impression is dominant.…”

“…The ear noise will then be suppressed simply by habituation processes. The basic knowledge about the significance of the chronic tinnitus and its assessment as a disease still remains that the actual persistence of tinnitus and consequently the developing distress are only due to cortical plasticity [8], [34]. Even if originally a hearing damage, especially damage of the external hair cells of the inner ear is present, the processing in the auricular system and the interconnection with emotional and evaluation qualities in the auricular system that are basic for the significance and the pathology of this ear noise.…”