Mechanisms of tinnitus generation Carol A. Bauer Current Opinion in Otolaryngology & Head and Neck Surgery 2004,12:413 – 417 R1 石堅

Introduction Tinnitus: auditory sensation without external stimulus. 6~20%, (1~3% interferes with daily life) Theories of tinnitus pathophysiology aberrant peripheral neural activity central neural sources central dysfunction + peripheral source of abnormal input More than one physiologic mechanism

Peripheral sources of tinnitus Hair cell damage  stereocilia decoupling from tectorial membrane  noise ↑ from molecular motion within the hair cells  tinnitus Baseline deviation from random activity of auditory nerve in the absence of stimulation High-rate pulsatile electrical stimulation to the cochlea  suppression of tinnitus (5/11) Loss of tonic random afferent input  loss of inhibition within brainstem auditory structures

Central sources of tinnitus Complete eighth nerve section: normal Peripheral injury  central changes acute (acoustic trauma) / slowly progressive hearing loss. Inhibition ↓ / excitation ↑ : dorsal cochlear nucleus, inferior colliculus Complex change in glutamatergic transmitter release in ipsilateral cochlear nucleus after noise exposure. Initially: damaged hair cells, neural fibers degenerated  acute ↑ in glutamatergic release 2 weeks later: glutamatergic release ↓ and uptake ↓ 90 days later: long-term ↑ of residual glutamatergic synapses

Plasticity and tinnitus Neural plasticity: long-term alterations in central neural function after peripheral sensory receptor damage Bidirectional information modulation within auditory pathway: corticofugal / corticopetal projections between auditory cortex and brainstem nuclei Disturbing tinnitus: fail to develop the normal habituation in response to a repetitive non- informative sound. Auditory enrichment or sound therapy: long- term exposure to low-level (15 dB SPL) sound

Plasticity and tinnitus Tinnitus ≒ maladaptive cortical reorganization (ex: phantom limb pain) Magnetoencephalography: subjective tinnitus loudness / frequency  primary auditory cortex. Psychophysical training with frequency discrimination task  plastic changes in cortical representation of a range of frequencies Exposure to continuous low-level background sound (auditory enhancement)  shift in loudness judgments

Somatosensory / vascular factors Electrical excitation of median nerve  somatosensory system  modulate the characteristics and loudness of tinnitus. PET imaging: orofacial maneuvers (jaw clenching)  changes in blood flow in temporal lobe / hippocampus  modulation of tinnitus loudness. Injury to head / neck  brainstem somatosensory nuclei  inappropriate excitation of auditory pathway (dorsal cochlear nucleus)  craniocervical tinnitus

Somatosensory / vascular factors Cochlear implants: isometric movements of head, neck, or jaw muscles  50~80% change in tinnitus loudness Trigeminal ganglion  excitatory and inhibitory projections  synapse within ventral and dorsal cochlear nucleus Stimulate trigeminal ganglion  2-deoxyglucose uptake ↑ in ipsilateral and contralateral lateral lemniscus and inferior colliculus Guinea pig: capsaicin  trigeminal control of cochlear blood flow Capsaicin: agonist of type 1 vanilloid receptor (VR-1), nonselective cation channel in small- to medium- diameter primary afferents in the somatosensory system.

Somatosensory / vascular factors Immunoreactive fibers: trigeminal origin. electrical stimulation of trigeminal ganglion  plasma extravasation from cochlear vessels. inflammatory conditions exacerbate tinnitus. Spiral and vestibular ganglia of rats: VR-1 and 5-lipoxygenase. tinnitus generation by aspirin and nonsteroidal ototoxicity.

Conclusion Tinnitus appears to be significantly affected in complex ways by somatosensory, limbic, and motor influences. Effective treatments will certainly emerge from these new areas of research.