Exam 1 (Tinnitus Mechanisms) Flashcards
Challenges to Understanding Mechanisms of Tinnitus
Assessment limitations
Limitations of animal mode
Complexity of the auditory system
hard to understand what causes a person to perceive it because there is difficulty in accurately diagnosing tinnitus in humans (no objective tests to show there actually is tinnitus), in animals you can look at so many things but a limitation because they cannot talk they don’t know, and lastly we know auditory system is complex and redundant (ipsi and contra and certain lesions have a greater impact on things than others etc)
Theories of peripheral mechanisms
cellular mechanisms
edge theory
discordant damage of IHC and OHCs
tectorial membrane displacement
NTs and their receptors
synaptopathy
describe cellular mechanisms of Theories of peripheral mechanisms:
cochlear damage can involve
Loss of OHC electromotility - cochlear amplifiers, affect our sensory ability to hear really soft sounds
Loss of synapses between IHCs and spiral ganglion neurons (synaptopathy) -
Damage to the stereociliary bundle
Rupture of the basilar membrane - affects everything, fluid can mix (toxic)
Death of OHCs or IHCs
aka contrast theory
edge theory
what is the edge theory
Tinnitus is induced by increased spontaneous activity in the edge area
what is the edge area in the edge theory
Area representing a transition from normal OHCs on the apical side of a lesion to OHCs toward the basal side that are missing or altered
Region between the damage and healthy area of increased spontaneous activity
Area of transition: more IHCs are functional and OHC is the damage so the extra work done by the IHC is hyperactivity
true
describe discordant damage of iHC or OHCs of Theories of peripheral mechanisms:
noise & ototoxicity leads to imbalance of stereocilia damage (IHC & OHC loss), which causes nerve fiber imbalance (type I and II) causing altered higher brain centers that leads to tinnitus
if there is noise or ototoxicity, it can lead to cochlear damage, which can cause HL in HFs (4-6 kHz) and this suggests leading to an imbalance of IHC & OHCs (IHCs are more resilient to damage than OHCs - in areas of max damage both are damaged and those with less damaged there will be damaged OHCs but healthy IHCs)
end result is that the imbalance is carried out to the brain so it is perceived as tinnitus
limitations to the discordant damage of iHC & OHCs
it is based on the imbalance between healthy and unhealthy structure making it not uniform and leading to hyperactivity
Profound HL - means there is max damage of loss & if it is a uniform loss then there shouldn’t be any increased activity
what happens to damage of OHCs in the two fundamental processes of the OHC
Intracellular calcium levels
Biochemical changes in the structural proteins of OHCs
messenger, helps to transmit impulses between the nerve and cells
NT
excitatory NT
glutamate
inhibitory NT
GABA
what are examples of nTs in the AS
Glutamate (excitatory) and GABA (inhibitory)
what mediates the NTs in the auditory system (glutamate & GABA)
AMPA - (Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)
NMDA (N-methyl-D-aspartate)
what leads to tinnitus in NT & receptors
When this balance is messed up between excitatory and inhibitory, leads to spontaneous activity; how NT bind to AMPA & NMDA leads to spontaneous activity
Tectorial membrane displacement for theories of peripheral mechanisms
there is hyperactivity but is related to detachment of ™ causing sagging causing IHC to depolarize and this chronic depolarization is hyperactivity heard by the brain
Tectorial membrane position changes can trigger acute tinnitus following intense noise exposure and can result from
Tectorial membrane detachment
Shouldn’t normally touch the IHCs but when detachment occurs it causes it to sag over them and depolarize them
This leads to depolarization, then hyperactivity and then is heard as tinnitus by the brain
Tectorial membrane position changes can trigger acute tinnitus following intense noise exposure and can result from
tectorial membrane detachment
increased pressure in the scala media
degeneration of oHCs or stereocilia
NT & receptors in peripheral mechanism of tinnitus
Since there is overstimulation there is a massive amount of glutamate not usually produced
When calcium channels open at the bottom, calcium channels dump more in the cell than normal
Calcium comes from perilyphm that is rich in this
This causes glutamate to dump more than the normal amount at the synaptic cleft causing it to accumulate and overwhelm the reuptake mechanisms (doesn’t clear as fast as normal) causing it to stay at the cleft and leads to overstimulation of the receptors
hair cells stimulate, releases excess glutamate that the cell doesn’t usually need resulting in excess calcium to stay at the synaptic cleft and over stimulates the receptors which damages the level of the nerve fibers as well as damage inside the hair cells resulting in nerve loss and hair cell loss through apoptosis
what would an increase in glutamate do in AMPA receptors?
Damage (noise exposure), causes excessive glutamate released by the IHCs leading to overactiviation of the AMPA receptor, this results in excessive calcium influx (more than normal and too much causes nerve cell damage - makes an enzyme that kills the cell) and in turn disrupts the auditory signal that goes to the brain resulting in the perception of tinnitus
what would an increase in glutamate do in NMDA receptors
There is damage, glutamate is overstimulated causing overactivation at the NMDA receptor, leads to excessive calcium influx, which disrupts the neural activity, this leads to an enhanced spontaneous firing and hyperactivity of the auditory nerve leading to tinnitus perception
synaptopathy
involves damage specifically to the synapses without necessarily affecting the hair cells or causing immediate, measurable hearing loss on standard audiograms.
hidden hearing loss
what is HHL
irreversible damage to synapses between iHCs and the cochlear nerve fibers - causes tinnitus, hyperacusis & issues hearing in noise
f
Noise induced excitotoxicity causes excessive glutamate release from IHC synapses leading to
swelling of dendrite, partial disconnection of IHCs from afferent neurons and results in hearing loss and tinnitus
Synaptic repair can restore hearing but incomplete recovery can result in persistent tinnitus
true
3 subtypes of tinnitus
cochlear tinnitus
peripheral-dependent central tinnitus
peripheral-independent central tinnitus
describe cochlear tinnitus
origin/source is the cochlea
cochlear damage
HL is present
innitus originates directly from within the cochlea itself, often due to damage or dysfunction in the hair cells or supporting structures (hair cell damage, spontaneous OHC activity, ototoxicity, NIHL, etc.)
describe peripheral-dependent central tinnitus
happening somewhere in the central system and dependent on the periphery; originates from peripheral hearing damage and can lead to central auditory system dysfunction
spontaneous activity (hyperactivity) in cochlea feeds the central mech perceiving tinnitus
peripheral and central systems are involved but central depends on input of the peripheral
describe peripheral-independent central tinnitus
happening somewhere in the central system and doesn’t depend on the peripheral; generated and maintained by central auditory system without peripheral damage
if you dissect nerve it won’t stop the tinnitus
no input from the cochlea
Difference between cochlear & peripheral-dependent tinnitus
Cochlear - tinnitus originates directly from within the cochlea itself, often due to damage or dysfunction in the hair cells or supporting structures (hair cell damage, spontaneous OHC activity, ototoxicity, NIHL, etc.)
Location: limited to peripheral as & no involvement from maladaptive plasticity or changes in CANS
Peripheral dependent - tinnitus is initially triggered by peripheral damage in the cochlea or auditory nerve, it becomes maintained and amplified by central auditory structures.
Tinnitus here happens with reduced auditory input, central auditory plasticity or ongoing central maintenance
Initially triggered in periphery but shifts to CANS & linked to hyperactivity and plasticity in the brain
what are the theories of central mechanisms
auditory deprivation
inhibitory gating mechanism
Maladaptive plasticity
Hyperactivity and hypersynchrony
Neural crosstalk
MOC dysfunction and the use of OAEs to assess its integrity
describe two functional changes auditory deprivation causes in relation to theories of central origin
Imbalance between excitatory and inhibitory: cochlear pathologies reduce inhibition more than excitation leading to increased neural activity and perception of sound with no external stimulus
Activation of neural plasticity: lack of sensory input promotes neuroplasticity and causes changes that can be temporary or long-lasting
noise cancellation system
inhibitory gating mechanism
what does inhibitory gating mechanism
do
System that blocks tinnitus signal from reaching the auditory cortex
what happens when IGM is compromised
Compromised system leads to the tinnitus signal not being inhibited at the thalamic level and is relayed to the auditory cortex resulting in the perceived tinnitus
Consequences in IGM
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.
what is maladaptive plasticity
Changes in the brain’s structure or function that leads to negative consequences or dysfunction and results in persistent symptoms or worsens a condition instead of improving it
what in maladaptive plasticity leads to tinnitus perception
abnormal auditory cortex activation is linked with reorganization of cortical tonotopic maps.
The extent to which reorganization occurs is related to the occurrence and severity of tinnitus
Auditory plasticity theory
damage to the cochlea can lead to an increase in spontaneous firing rate of neurons in several auditory structures (dorsal cochlear nucleus, inferior colliculus, & primary and secondary auditory cortex
CANS increases its central gain to offset the reduced input from the cochlear damage
true
Evidence shows _______ is initial site where tinnitus originates before it affects higher areas
DCN
what is central gain
brain’s ability to amplify or enhance signals in the central nervous system, often in response to a reduction in sensory input. This increase in “gain” is a form of neural plasticity that makes the brain more sensitive to certain signals, especially when incoming sensory information is lacking or diminished
leads to hyperactivity in the CN, IC, & auditory cortex that manifests as tinnitus & hyperacusis
central gain compensation
Proposed as a ________ disorder
hypersynchrony
what is hypersynchrony
This is where groups of neurons fire together in a highly synchronized manner - usually abnormal
Synchronization might be initiated by increased neural activity and reorganization of cortical frequency maps
quantity of the neurons firing
hyperactivity
timing of activity of neurons firing
hypersynchrony
what is crosstalk
artificial connections
when does crosstalk happen
These form between auditory nerve fibers when the auditory nerve fibers are intact but other cranial nerves are damaged
what are the causes of neural crosstalk
nerve compression or demyelination can lead to ephaptic coupling to allow signals to spread throughout the nerve causing crosstalk
what is the impact and results of neural crosstalk
Impact: the artificial connections lead to synchronized firing of auditory neurons which mimicks the neural patterns of actual sounds
Results: brain interprets these patterns as sounds and results in tinnitus
what does the medial efferent system? the job?
reduces and controls the electromotility of the OHCs and if nothing does then they will remain hyperactive leading to
OHCs are the source of OAEs and dysfunction hre doesn’t inhibit with reduced input and leads to hyperactive OHCs
always heard by the cortex and interpreted as tinnitus
hyperactivity
what is the MOC dysfunction theory
Plays a potential role in tinnitus
Reduction in the neural efferent input to the OHCs can result in an increase in gain of the cochlear amplifier which can lead to an enhancement of spontaneous activity in the auditory nerve or other plastic readjustments in the central auditory system
relationship between tinnitus & dysfunction of the efferent auditory system has been investigated by measuring the suppression of OAEs
true
Contralateral OAE suppression
OAEs are measured in the presence of white noise presented to the contralateral ear
Suppression value is calculated as the difference between values obtained in the presence and absence of the noise
in a normal system, how does the inhibition of the efferent system affect the OAEs? what difference do you see with suppression?
reduced amplitude
there is no dysfunction here
in a dysfunctional system, how does this affect the OAEs?
there will be no reduction in the amplitude
Suppression effect of ______ indicates integrity of the MOC system
.5-1.0
Changes in the cochlea can be detected by this test before it shows on the audio
contra oae suppression
PTs with tinnitus show reduced or no OAE suppression - suggests dysfunction of the efferent auditory system
true
Somatosensor
complex sensory network that allows our brain to perceive and interpret sensations from the body
only nonauditory sensory system appearing to be related to tinnitus
SSS
triggers for tinnitus in the somatosensory system
emporomandibular joint syndrome or whiplash
Anything related to the head and neck
what are the mechanisms of somatosensory tinnitus
Disinhibition of the ipsilateral DCN
Crosstalk
explain the disinhibition of the ipsilateral DCN
Somatosensory stimuli disinhibit the ipsilateral CN leading to excitatory neuronal activity within the auditory pathway that results in tinnitus
should disinhibit the CN and if there is damage that causes this to not happen results in increased excitatory input because there is less inhibition and more excitation (more hyperactivity) which is perceived as tinnitus
explain crosscheck mechanism in sss
Pain signals sent by the cochlea might be interpreted as tinnitus by the CNS
Abnormal crosstalk happens as nerves from the head and neck converge near the auditory brain regions influencing the tinnitus perception
limbic system function
Involved in our behavioral and emotional responses - feeding, reproduction, caring for our young, and fight or flight responses
what structures are in the limbic system
hypothalamus, thalamus, hippocampus, & amygdala
role of the hypothalamus
homeostasis- creates & controls hormones, regulates body temp, thirst, emotions & appetite
role of the thalamus
regulates sleep cycles, every sensory function besides smell, thalamic nucleus that includes vision, hearing, and touch - somatosensor
role of the amygdala
emotions - fear, pleasure, anxiety, anger
role of the hippocampus
memory conversion
turns short term into long term
what do the structures of the limbic system do
overall has these for emotions, emotional behavior, memory, motivation etc
what is the limbic systems role in tinnitus
Mediates the emotional response to tinnitus
Those with strong emotional responses often show enhanced sympathetic nervous system activity - fight or flight response
When it is heard there is a reaction and the reaction is controlled by this system and it can make it worse which explains why some cannot ignore it while others can
Those with strong emotional responses often show
enhanced sympathetic nervous system activity - fight or flight response
When it is heard there is a reaction and the reaction is controlled by this system and it can make it worse which explains why some cannot ignore it while others can
how can the limbic system make tinnitus worse
Anatomical or physiological abnormalities in the limbic system - leads to emotional reaction to the tinnitus
if there is any lesion or damage, limbic system will not block the tinnitus signal meaning that all of it reaches the cortex and perceived causing it to be loud and clear
when will we hear tinnitus with issues with the limbic system
The limbic system should block the tinnitus system because it deals with emotions so it should suppress this and when it isn;t functioning is when we hear the tinnitus
Imaging functional and structural results in tinnitus PTs
Dysregulation between limbic & auditory systems
Increased connectivity between limbic and auditory (mostly A1 & emotion and cognition areas)
Greater brain connectivity between auditory and limbic areas = more distress levels
Patients who are more concerned with tinnitus and more severe reactions to it show
more connectivity between the auditory and limbic areas
Greater brain connectivity between auditory and limbic areas =
more distress levels
Collectively these areas contribute to “distress circuit” that is activated by real or phantom stimuli with hearing, vision, pain, and other sensations
connectivity between limbic and auditory (mostly A1 & emotion and cognition areas)
