Mechanisms Flashcards
What are some challenges in understanding tinnitus mechanisms?
Assessment limitations
Limitations of animal models (cannot tell us if they have tinnitus, do not have the emotional aspect)
Complexity of the auditory system
Historically, what structure was tinnitus thought to arise from?
The peripheral auditory system
What are challenges to ear-based theories (peripheral tinnitus)?
Many patients exhibit normal hearing sensitivity
Degree of hearing loss does not consistently correlate with the severity of tinnitus
Surgical section of the auditory nerve does not eliminate tinnitus in every case
What theory of site of tinnitus preferred?
Central origin
Tinnitus perception is a brain issue
There is an underlying cause that begins the process, but it’s the brains reaction to some change the creates the continued neurological response
What are the different levels/systems that tinnitus is proposed to be involved with?
Peripheral auditory system
Central auditory system
Somatosensory system
Limbic and autonomic nervous systems
(could be all of these contributing at the same time, could be at each level)
What were the proposed three subtypes of tinnitus that were proposed by norena (2015)?
Cochlear tinnitus
Peripheral-dependent central tinnitus (happening central but it depends on the peripheral - both are involved)
Peripheral-independent central tinnitus (just central)
What are the tinnitus mechanisms that are associated with the cochlea?
Cellular mechanisms
Discordant damage of IHC and OHCs (damage is not uniform – some have damage more than others)
Tectorial membrane displacement
Neurotransmitters and their receptors
Synaptopathy
What are the cellular mechanisms that can be involved in tinnitus? (all would lead to hearing loss, and possibly tinnitus)
Loss of OHC electromotility (decreases boost)
Loss of synapses between IHCs and spiral ganglion neurons (synaptopathy)
Damage to the stereociliary bundle
Rupture of the basilar membrane
Death of OHCs or IHCs
*All lead to decreased neural output up to the brain
What is edge theory (contrast theory)?
Tinnitus is induced by increased spontaneous activity in the edge area (an area that represents a transition from normal OHCs on the apical side of a lesion to OHCs toward the basal side that are missing or altered)
What is discordant damage of IHCs and OHCs?
Noise and ototoxicity leads to imbalance of cilia damage (IHC and OHC loss at areas of major damage)
Leads to imbalance of nerve fibers that are stimulated (type 1 and 2)
Leads to altered higher brain centers
Tinnitus
Could be combined with the edge theory (increased spontaneous activity in the transition areas between damaged and undamaged areas)
What are the limitations for discordant damage of IHC and OHCs?
Not uniform
If the damage is uniform, there should not be imbalance
Doesn’t account for those with tinnitus and a flat profound loss
Can changes in the position of the tectorial membrane trigger acute tinnitus following intense noise exposure?
Yes
Can result from tectorial membrane detachment, increased pressure in the scala media, and degeneration of OHCs or stereocilia
In damaged regions, the tectorial membrane may sag onto IHC cilia, causing depolarization and increased cochlear activity, contributing to tinnitus perception
What two processes does noise exposure damage in OHCs?
Intracellular calcium levels
Biochemical changes in the structural proteins of OHCs
What are glutamate (excit) and GABA (inhib) mediated by? (receptors)
AMPA (Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)
NMDA (N-methyl-D-aspartate)
What is the process of the AMPA receptors?
Noise exposure
Excessive glutamate release (by IHCs)
AMPA receptor overactivation (due to excessive release)
Excessive calcium influx
Nerve cell damage
Disrupted auditory signal transmission
Tinnitus perception
What is the process for NMDA receptors?
Glutamate overstimulation (caused from noise)
NMDA receptor activation
Excessive calcium influx
Disrupted neural activity
Enhanced spontaneous firing
Auditory nerve hyperactivity
Tinnitus perception
*very similar to the AMPA receptors
What is cochlear synaptopathy as it relates to tinnitus?
Hidden hearing loss arises from irreversible damage to synapses between IHCs and cochlear nerve fibers, causing tinnitus, hyperacusis, and difficulty hearing in noise
Noise-induced excitotoxicity causes excessive glutamate release from IHC synapses, leading to dendrite swelling, partial disconnection of IHCs from afferent neurons, and resulting in hearing loss and tinnitus
Could show up in speech in noise tests
Synaptic repair can restore hearing, but incomplete recovery may result in persistent tinnitus
What are central mechanisms for tinnitus triggered by?
Reduced cochlear activity, but cochlear damage is not always necessary
Suggests that noise or music induced tinnitus results from abnormal brain activity due to reduced auditory input from hearing loss
What two functional changes does auditory deprivation cause?
Imbalance between inhibition and excitation - cochlear pathologies reduce inhibition more than excitation, leading to increased neuronal activity and the perception of sound without external stimuli
Activation of neuronal plasticity - lack of sensory input promotes neuroplasticity, causing changes that can be temporary or long-lasting
What is the inhibitory gating mechanism?
A system that blocks the tinnitus signal from reaching the auditory cortex
If compromised, the tinnitus signal is not inhibited at the thalamic level and is relayed to the auditory cortex (resulting in tinnitus)
What are the consequences of inhibitory gating mechanism?
Intermittent tinnitus may result from temporary malfunctions of this gating mechanism
Chronic tinnitus may result from prolonged malfunctions of the gating mechanism, leading to reorganization of the auditory cortex
Is abnormal auditory cortex activation linked with reorganization of cortical tonotopic maps?
Yes
Maladaptive plasticity
The extent of reorganization is correlated with the occurrence and severity of tinnitus in both patients and model animals
According to the auditory plasticity theory, can damage to the cochlea lead to increased spontaneous firing rate of neurons in several auditory structures?
Yes
Such as the DCN, IC, and the primary and secondary auditory cortex
Evidence suggests that DCN is the initial site where tinnitus originates before affecting higher areas
To offset reduced input from cochlear damage, the central auditory system increases its gain (central gain)
This compensation leads to hyperactivity in the CN, IC, and auditory cortex, manifesting as tinnitus and hyperacusis
Has tinnitus been proposed as a hypersynchrony disorder?
Yes
This synchronization may be initiated by increased neural activity and reorganization of cortical frequency maps
Focused on the timing of these spontaneous activities, less on the quantity
If the spontaneous activities are going at the same time, they are going to be heard
