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  • Review Article
  • Published:

Maladaptive plasticity in tinnitus — triggers, mechanisms and treatment

Nature Reviews Neurology volume 12, pages 150–160 (2016)Cite this article

Subjects

Key Points

  • Tinnitus is prevalent in up to 15% of the world population

  • Tinnitus is linked to hearing loss: loss of input from the cochlea to central auditory pathways triggers plastic neural changes that result in increased spontaneous activity and synchrony in affected regions

  • Neurons in nonauditory regions are also affected by tinnitus

  • Although tinnitus is often linked to noise exposure, tinnitus does not always occur after noise damage in humans or animal models

  • An understanding of the neural mechanisms of tinnitus is essential for developing effective treatments

Abstract

Tinnitus is a phantom auditory sensation that reduces quality of life for millions of people worldwide, and for which there is no medical cure. Most cases of tinnitus are associated with hearing loss caused by ageing or noise exposure. Exposure to loud recreational sound is common among the young, and this group are at increasing risk of developing tinnitus. Head or neck injuries can also trigger the development of tinnitus, as altered somatosensory input can affect auditory pathways and lead to tinnitus or modulate its intensity. Emotional and attentional state could be involved in the development and maintenance of tinnitus via top-down mechanisms. Thus, military personnel in combat are particularly at risk owing to combined risk factors (hearing loss, somatosensory system disturbances and emotional stress). Animal model studies have identified tinnitus-associated neural changes that commence at the cochlear nucleus and extend to the auditory cortex and other brain regions. Maladaptive neural plasticity seems to underlie these changes: it results in increased spontaneous firing rates and synchrony among neurons in central auditory structures, possibly generating the phantom percept. This Review highlights the links between animal and human studies, and discusses several therapeutic approaches that have been developed to target the neuroplastic changes underlying tinnitus.

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Figure 1: Assessment of tinnitus in animals with GPIAS.
Figure 2: Simplified representation of auditory and nonauditory pathways in tinnitus.
Figure 3: Mechanisms of tinnitus initiation in the dorsal cochlear nucleus.
Figure 4: Mechanisms that contribute to increased StDP, SFR and synchrony in the DCN.

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Acknowledgements

The authors have received funding from the Tinnitus Research Initiative. S.E.S. has received funding from the NIH (grants NIHR01-DC004825, NIH P30-DC05188). L.E.R. has received funding from the Natural Sciences and Engineering Research Council of Canada and the Canadian Institutes of Health Research and the American Tinnitus Association. B.L. has received funding from the European Commission (TINNET COST Action BM 1306). We thank Calvin Wu and Amarins Heeringa for excellent assistance with graphics.

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Authors and Affiliations

  1. Department of Otolaryngology, Molecular and Integrative Physiology, Biomedical Engineering, University of Michigan, 1150 W Medical Center Drive, Michigan, 48104, USA

    Susan E. Shore

  2. Department of Psychology, Neuroscience, and Behavior, McMaster University, 1280 Main Street West, Hamilton, L8S 4K1, Ontario, Canada

    Larry E. Roberts

  3. Department of Psychiatry and Psychotherapy and Interdisciplinary Tinnitus Clinic, University of Regensburg, Universitätsstr. 84, D-93053, Regensburg, Germany

    Berthold Langguth

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  1. Susan E. Shore
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  2. Larry E. Roberts
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  3. Berthold Langguth
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All authors researched literature for the article, provided substantial contributions to discussion of content and wrote, reviewed and edited the manuscript.

Corresponding author

Correspondence to Susan E. Shore.

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Competing interests

B.L. has received honoraria for speaking and consultancy from ANM, AstraZeneca, Autifony, Gerson Lehrman Group, Lundbeck, McKinsey, Merz, Magventure, Novartis, Neuromod Devices, Pfizer and Servier, grants and research support from AstraZeneca, Cerbomed, Deymed, Magventure, Sivantos and Otonomy, and travel and accommodation payments from Lilly, Servier and Pfizer. B.L. holds patents for the use of neuronavigation for transcranial magnetic stimulation and for the use of cyclobenzaprine for tinnitus treatment. The other authors declare no competing interests.

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Glossary

Auditory nerve

The nerve that innervates cochlear hair cells and has a central projection to the cochlear nucleus.

Suprathreshold hearing

Hearing at levels above the measuring threshold.

Hidden hearing loss

Hearing loss that is not detectible by conventional auditory threshold testing and which reflects deficits in suprathreshold hearing.

Auditory brainstem response

Volume-conducted far field potentials reflecting synchronous activation of brainstem structures beginning with the cochlear nucleus and ending at the inferior colliculus.

dB hearing level

Decibels hearing level; dB relative to the quietest sound at a given frequency that a young individual with normal hearing is able to hear.

Tonotopicity

Frequency-specific organization at the auditory system.

Spike-timing-dependent plasticity

Spike-timing-dependent strengthening or weakening of synaptic transmission measured in vitro.

Stimulus-timing-dependent plasticity

The macroscopic equivalent of spike-timing-dependent plasticity, measured in vivo.

Hebbian plasticity

The strengthening of synaptic transmission when presynaptic activation precedes postsynaptic activation.

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Shore, S., Roberts, L. & Langguth, B. Maladaptive plasticity in tinnitus — triggers, mechanisms and treatment. Nat Rev Neurol 12, 150–160 (2016). https://doi.org/10.1038/nrneurol.2016.12

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