Materiały źródłowe

• #1 Etiology and Pathophysiology of Tinnitus: A Systematic Review

  https://www.tinnitusjournal.com/articles/etiology-and-pathophysiology-of-tinnitus–a-systematic-review-16383.html

  Introduction: Prevalence of tinnitus range from 7.1% to 14.6% (National Center for Health Statistics, 2016), but the mechanisms responsible for the development of this abnormal sensory state remain poorly understood. […] Multiple pathophysiology were identified, including inner ear pathology, auditory nerve synchronisation, central nervous system anomalies and limbic and autonomous nervous system problems. […] The results indicate a high level of heterogeneity between the studies for all the assessed areas. […] Establishment of a direct causal link between tinnitus and these etiologies and pathophysiology remains elusive. […] The pathophysiology of subjective tinnitus is poorly understood so are the neuroplastic changes in central auditory structures that take place when brain is deprived of its normal input by pathology in the cochlea.

• #2 :: JCN :: Journal of Clinical Neurology

  https://www.thejcn.com/DOIx.php?id=10.3988/jcn.2021.17.1.1

  Tinnitus can be attributable to hearing loss, somatosensory system dysfunction, or auditory cortex dysfunction, with hearing loss being the most common cause and serious underlying pathologies being rare. […] The earliest speculations regarding the site of tinnitus generation described a cochlear origin. This view has shifted over time to tinnitus originating in the central auditory system rather than to mechanisms in the peripheral auditory system such as due to cochlear damage; that is, abnormal auditory signals activate neural plasticity within central auditory structures and manifest as tinnitus. […] However, it turns out that the pathophysiology of tinnitus is not limited to the auditory system, with the somatosensory system also provoking or modulating tinnitus, and the limbic system being necessary for its maintenance.

• #3 Tinnitus – Wikipedia

  https://en.wikipedia.org/wiki/Tinnitus

  Tinnitus may be caused by increased neural activity in the auditory brainstem, where the brain processes sounds, causing some auditory nerve cells to become overexcited. The basis of this theory is that many with tinnitus also have hearing loss. […] Three reviews in 2016 emphasized the large range and possible combinations of pathologies involved in tinnitus, which result in a great variety of symptoms and specifically adapted therapies. […] Some tinnitus may be caused by neuroplastic changes in the central auditory pathway. In this theory, the disturbance of sensory input caused by hearing loss results in such changes as a homeostatic response of neurons in the central auditory system, causing tinnitus. […] The most common cause of tinnitus is hearing loss. Hearing loss may have many different causes, but among those with tinnitus, the major cause is cochlear injury.

• #4 Pathophysiology and Treatment of Tinnitus: An Elusive Disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3918281/

  Tinnitus has been associated with a variety of risk factors, including prolonged noise exposure (22% of cases), head/neck injury (17% of cases) and infections (10% of cases) [13]. The most recent pathophysiologic theory suggests that the central nervous system is the source or generator of tinnitus [14]. Positron emission tomography (PET) scanning and functional magnetic resonance imaging (fMRI) studies indicate that a loss of cochlear input to neurons in the central auditory system (such as occurs in cochlear hair cell damage or a lesion of the vestibulocochlear nerve) can result in abnormal neural activity in the auditory cortex [15]. This activity is linked to the perception of tinnitus. […] Recent improvements in neuro-otometry have confirmed the complex pathophysiologic mechanisms involved in tinnitus, elucidating sites in which these processes take place [1719]. It is now known that approximately 24% of cases occur as a result of abnormalities within the otoacoustic periphery (i.e. inner ear and the vestibulocochlear nerve), 35% originate from the acoustic pathways and 41% have their cause within supratentorial structures [6]. A decrease in inhibition and/or increase in excitation may lead to an excitatory-inhibitory imbalance causing neuronal hyperexcitability in these regions and lead to the perception of tinnitus [20]. However, neuronal excitability can be modulated by different neurotransmitters and neuromodulators that act on voltage- or ligand-gated channels, thus providing potential pharmacologic targets [20].

• #5 Pathophysiology and Treatment of Tinnitus: An Elusive Disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3918281/

  Tinnitus has been associated with a variety of risk factors, including prolonged noise exposure (22% of cases), head/neck injury (17% of cases) and infections (10% of cases) [13]. The most recent pathophysiologic theory suggests that the central nervous system is the source or generator of tinnitus [14]. Positron emission tomography (PET) scanning and functional magnetic resonance imaging (fMRI) studies indicate that a loss of cochlear input to neurons in the central auditory system (such as occurs in cochlear hair cell damage or a lesion of the vestibulocochlear nerve) can result in abnormal neural activity in the auditory cortex [15]. This activity is linked to the perception of tinnitus. […] Recent improvements in neuro-otometry have confirmed the complex pathophysiologic mechanisms involved in tinnitus, elucidating sites in which these processes take place [1719]. It is now known that approximately 24% of cases occur as a result of abnormalities within the otoacoustic periphery (i.e. inner ear and the vestibulocochlear nerve), 35% originate from the acoustic pathways and 41% have their cause within supratentorial structures [6]. A decrease in inhibition and/or increase in excitation may lead to an excitatory-inhibitory imbalance causing neuronal hyperexcitability in these regions and lead to the perception of tinnitus [20]. However, neuronal excitability can be modulated by different neurotransmitters and neuromodulators that act on voltage- or ligand-gated channels, thus providing potential pharmacologic targets [20].

• #6 Pathophysiology and Treatment of Tinnitus: An Elusive Disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3918281/

  Tinnitus has been associated with a variety of risk factors, including prolonged noise exposure (22% of cases), head/neck injury (17% of cases) and infections (10% of cases) [13]. The most recent pathophysiologic theory suggests that the central nervous system is the source or generator of tinnitus [14]. Positron emission tomography (PET) scanning and functional magnetic resonance imaging (fMRI) studies indicate that a loss of cochlear input to neurons in the central auditory system (such as occurs in cochlear hair cell damage or a lesion of the vestibulocochlear nerve) can result in abnormal neural activity in the auditory cortex [15]. This activity is linked to the perception of tinnitus. […] Recent improvements in neuro-otometry have confirmed the complex pathophysiologic mechanisms involved in tinnitus, elucidating sites in which these processes take place [1719]. It is now known that approximately 24% of cases occur as a result of abnormalities within the otoacoustic periphery (i.e. inner ear and the vestibulocochlear nerve), 35% originate from the acoustic pathways and 41% have their cause within supratentorial structures [6]. A decrease in inhibition and/or increase in excitation may lead to an excitatory-inhibitory imbalance causing neuronal hyperexcitability in these regions and lead to the perception of tinnitus [20]. However, neuronal excitability can be modulated by different neurotransmitters and neuromodulators that act on voltage- or ligand-gated channels, thus providing potential pharmacologic targets [20].

• #7 Pathophysiology and Treatment of Tinnitus: An Elusive Disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3918281/

  Tinnitus has been associated with a variety of risk factors, including prolonged noise exposure (22% of cases), head/neck injury (17% of cases) and infections (10% of cases) [13]. The most recent pathophysiologic theory suggests that the central nervous system is the source or generator of tinnitus [14]. Positron emission tomography (PET) scanning and functional magnetic resonance imaging (fMRI) studies indicate that a loss of cochlear input to neurons in the central auditory system (such as occurs in cochlear hair cell damage or a lesion of the vestibulocochlear nerve) can result in abnormal neural activity in the auditory cortex [15]. This activity is linked to the perception of tinnitus. […] Recent improvements in neuro-otometry have confirmed the complex pathophysiologic mechanisms involved in tinnitus, elucidating sites in which these processes take place [1719]. It is now known that approximately 24% of cases occur as a result of abnormalities within the otoacoustic periphery (i.e. inner ear and the vestibulocochlear nerve), 35% originate from the acoustic pathways and 41% have their cause within supratentorial structures [6]. A decrease in inhibition and/or increase in excitation may lead to an excitatory-inhibitory imbalance causing neuronal hyperexcitability in these regions and lead to the perception of tinnitus [20]. However, neuronal excitability can be modulated by different neurotransmitters and neuromodulators that act on voltage- or ligand-gated channels, thus providing potential pharmacologic targets [20].

• #8 KoreaMed Synapse

  https://synapse.koreamed.org/articles/1044299

  Sensorineural tinnitus can be expressed as tonal sound, narrow band sound or white noise. […] A recent study revealed that tinnitus is a consequence of neuroplastic alterations in the central auditory pathway as well as somatosensory change. […] The exact mechanism of subjective tinnitus is obscure. […] The hypothesis of maladaptive neural plasticity seems to explain those changes of increased spontaneous firing rates and synchrony among neurons in central auditory structures and non-auditory brain networks, possibly generating the phantom percept analogue to phantom limb sensation. […] The neurophysiological model has been widely accepted in this field and habituation strategy to both tinnitus signal and the reaction against tinnitus has been developed as a Tinnitus Retraining Therapy. […] The complex interaction between peripheral auditory pathways, central auditory pathway and non-auditory region of the limbic, somatosensory and autonomic system, might contribute to the generation and persistence of tinnitus.

• #9 Tinnitus – Wikipedia

  https://en.wikipedia.org/wiki/Tinnitus

  Tinnitus may be caused by increased neural activity in the auditory brainstem, where the brain processes sounds, causing some auditory nerve cells to become overexcited. The basis of this theory is that many with tinnitus also have hearing loss. […] Three reviews in 2016 emphasized the large range and possible combinations of pathologies involved in tinnitus, which result in a great variety of symptoms and specifically adapted therapies. […] Some tinnitus may be caused by neuroplastic changes in the central auditory pathway. In this theory, the disturbance of sensory input caused by hearing loss results in such changes as a homeostatic response of neurons in the central auditory system, causing tinnitus. […] The most common cause of tinnitus is hearing loss. Hearing loss may have many different causes, but among those with tinnitus, the major cause is cochlear injury.

• #10 Tinnitus – Wikipedia

  https://en.wikipedia.org/wiki/Tinnitus

  Tinnitus may be caused by increased neural activity in the auditory brainstem, where the brain processes sounds, causing some auditory nerve cells to become overexcited. The basis of this theory is that many with tinnitus also have hearing loss. […] Three reviews in 2016 emphasized the large range and possible combinations of pathologies involved in tinnitus, which result in a great variety of symptoms and specifically adapted therapies. […] Some tinnitus may be caused by neuroplastic changes in the central auditory pathway. In this theory, the disturbance of sensory input caused by hearing loss results in such changes as a homeostatic response of neurons in the central auditory system, causing tinnitus. […] The most common cause of tinnitus is hearing loss. Hearing loss may have many different causes, but among those with tinnitus, the major cause is cochlear injury.

• #11 Ringing Ears: The Neuroscience of Tinnitus | Journal of Neuroscience

  https://www.jneurosci.org/content/30/45/14972

  One consequence of high-frequency hearing loss revealed by animal models is that cortical neurons in the hearing loss region begin to respond preferentially to sound frequencies at the edge of normal hearing, such that edge frequencies come to be overrepresented in the cortical tonotopic map. […] This reorganization of the tonotopic map, which has been detected in human tinnitus sufferers by neuromagnetic brain imaging, may occur when neurons that receive diminished thalamocortical input begin to respond to input from their unaffected neighbors via lateral connections on their apical dendrites. […] Together, these findings suggest that what neurons do in the hearing loss region causes tinnitus, and stopping what they do suppresses it. […] Damage to the cochlea induced by traumatizing sound, ototoxic agents, or other means increases the spontaneous firing rate (SFR) of neurons in several auditory structures including the dorsal cochlear nucleus (DCN) and ventral cochlear nucleus (VCN).

• #12 Tinnitus: Practice Essentials, Philosophy, Classification, Pathophysiology, and Quantification, Evaluation: History, Physical, and Laboratory

  https://emedicine.medscape.com/article/856916-overview

  Clinically, subjective tinnitus is the perception of sound in the absence of auditory stimulation. In terms of neurophysiology, tinnitus is the consequence of the brains response to input deprivation from the auditory periphery. […] When a region of the cochlea is damaged, the subcortical and cortical projections adjust to this chronic lack of output (plasticity), and the tonotopic organization is altered. In the auditory cortex, the region that corresponds to the area of cochlear damage is termed the lesion projection zone (LPZ). After cochlear damage, neurons in the LPZ show 2 important changes: an increase in the spontaneous firing rate and an increase in the frequency representation of the neurons that border the region of damage (the so-called lesion edge frequencies). […] These findings are explained in terms of a) the loss of central inhibition on the regions that are damaged and b) cortical plasticity of the neighboring regions of the cortex that are still active. Hence, tinnitus neurophysiology is related to detrimental cortical adaptation to input deprivation from the sensory periphery. […] Additional data from animal and human studies have suggested that tinnitus may be associated with neuronal hyperactivity at different levels of the central auditory pathways, including the dorsal cochlear nucleus, the inferior colliculus, auditory cortex, and the striatum.

• #13 Ringing Ears: The Neuroscience of Tinnitus | Journal of Neuroscience

  https://www.jneurosci.org/content/30/45/14972

  One consequence of high-frequency hearing loss revealed by animal models is that cortical neurons in the hearing loss region begin to respond preferentially to sound frequencies at the edge of normal hearing, such that edge frequencies come to be overrepresented in the cortical tonotopic map. […] This reorganization of the tonotopic map, which has been detected in human tinnitus sufferers by neuromagnetic brain imaging, may occur when neurons that receive diminished thalamocortical input begin to respond to input from their unaffected neighbors via lateral connections on their apical dendrites. […] Together, these findings suggest that what neurons do in the hearing loss region causes tinnitus, and stopping what they do suppresses it. […] Damage to the cochlea induced by traumatizing sound, ototoxic agents, or other means increases the spontaneous firing rate (SFR) of neurons in several auditory structures including the dorsal cochlear nucleus (DCN) and ventral cochlear nucleus (VCN).

• #14 KoreaMed Synapse

  https://synapse.koreamed.org/articles/1044299

  Sensorineural tinnitus can be expressed as tonal sound, narrow band sound or white noise. […] A recent study revealed that tinnitus is a consequence of neuroplastic alterations in the central auditory pathway as well as somatosensory change. […] The exact mechanism of subjective tinnitus is obscure. […] The hypothesis of maladaptive neural plasticity seems to explain those changes of increased spontaneous firing rates and synchrony among neurons in central auditory structures and non-auditory brain networks, possibly generating the phantom percept analogue to phantom limb sensation. […] The neurophysiological model has been widely accepted in this field and habituation strategy to both tinnitus signal and the reaction against tinnitus has been developed as a Tinnitus Retraining Therapy. […] The complex interaction between peripheral auditory pathways, central auditory pathway and non-auditory region of the limbic, somatosensory and autonomic system, might contribute to the generation and persistence of tinnitus.

• #15 Ringing Ears: The Neuroscience of Tinnitus | Journal of Neuroscience

  https://www.jneurosci.org/content/30/45/14972

  One consequence of high-frequency hearing loss revealed by animal models is that cortical neurons in the hearing loss region begin to respond preferentially to sound frequencies at the edge of normal hearing, such that edge frequencies come to be overrepresented in the cortical tonotopic map. […] This reorganization of the tonotopic map, which has been detected in human tinnitus sufferers by neuromagnetic brain imaging, may occur when neurons that receive diminished thalamocortical input begin to respond to input from their unaffected neighbors via lateral connections on their apical dendrites. […] Together, these findings suggest that what neurons do in the hearing loss region causes tinnitus, and stopping what they do suppresses it. […] Damage to the cochlea induced by traumatizing sound, ototoxic agents, or other means increases the spontaneous firing rate (SFR) of neurons in several auditory structures including the dorsal cochlear nucleus (DCN) and ventral cochlear nucleus (VCN).

• #16 Ringing Ears: The Neuroscience of Tinnitus | Journal of Neuroscience

  https://www.jneurosci.org/content/30/45/14972

  One consequence of high-frequency hearing loss revealed by animal models is that cortical neurons in the hearing loss region begin to respond preferentially to sound frequencies at the edge of normal hearing, such that edge frequencies come to be overrepresented in the cortical tonotopic map. […] This reorganization of the tonotopic map, which has been detected in human tinnitus sufferers by neuromagnetic brain imaging, may occur when neurons that receive diminished thalamocortical input begin to respond to input from their unaffected neighbors via lateral connections on their apical dendrites. […] Together, these findings suggest that what neurons do in the hearing loss region causes tinnitus, and stopping what they do suppresses it. […] Damage to the cochlea induced by traumatizing sound, ototoxic agents, or other means increases the spontaneous firing rate (SFR) of neurons in several auditory structures including the dorsal cochlear nucleus (DCN) and ventral cochlear nucleus (VCN).

• #17 Tinnitus: Summary of Current Understanding of the Pathophysiology Mechanisms in different Ear Diseases

  https://www.tinnitusjournal.com/articles/tinnitus-summary-of-current-understanding-of-the-pathophysiology-mechanisms-in-different-ear-diseases-21074.html

  Neural plasticity has been explained as the reason behind generation of subjective tinnitus. […] Many theories are available in literature to explain neuroplasticity mechanism which includes. […] Peripheral auditory system related hypothesis to explain subjective tinnitus origin: Spontaneous Otoacoustic Emissions mechanism (SOE) theory: Kemp discussed this hypothesis in an article published in 1981. These are acoustic signals generated by normal cochlear Outer Hair Cells (OHC), which is propagated to external canal. This hypothesis is the reason behind abnormal sound perception in patients with: […] Dorsal Cochlear Nucleus: has been proposed as site for generation of tinnitus particular after exposure to intense noise and chemotherapeutic drugs like cisplatin. Ototoxicity and intense noise damages outer hair cells in cochlea. Inadequate OHCs and IHCs sensory supply led to overactivity by dorsal cochlear nucleus in brainstem after neuroplasticity changes.

• #18 Etiology and Pathophysiology of Tinnitus: A Systematic Review

  https://www.tinnitusjournal.com/articles/etiology-and-pathophysiology-of-tinnitus–a-systematic-review-16383.html

  Cochlear-type tinnitus is suggested to result from aberrant activity generated at the cochlear nerve level. […] A reduction in cochlear activity produces tinnitus-related plastic changes, namely cortical reorganisation, thalamic neuron hyperpolarisation, facilitation of nonauditory limbic inputs and increase in central gain. […] The Dorsal Cochlear Nucleus (DCN) has been implicated as a possible site for the generation of tinnitus-related signals owing to its tendency to become hyperactive following exposure to tinnitus-inducing agents such as intense sound and cisplatin. […] Tinnitus might be generated in the temporal lobe in the auditory association cortex and inferior colliculus on low-frequency fluctuations of fMRI confirms that chronic tinnitus patients have aberrant significant increased spontaneous neuronal activity within the right middle temporal gyrus (MTG), right superior frontal gyrus (SFG) and right angular gyrus. […] The involvement of limbic and autonomic nervous system could explain why some people suffer from tinnitus while others do not.

• #19 Etiology and Pathophysiology of Tinnitus: A Systematic Review

  https://www.tinnitusjournal.com/articles/etiology-and-pathophysiology-of-tinnitus–a-systematic-review-16383.html

  Cochlear-type tinnitus is suggested to result from aberrant activity generated at the cochlear nerve level. […] A reduction in cochlear activity produces tinnitus-related plastic changes, namely cortical reorganisation, thalamic neuron hyperpolarisation, facilitation of nonauditory limbic inputs and increase in central gain. […] The Dorsal Cochlear Nucleus (DCN) has been implicated as a possible site for the generation of tinnitus-related signals owing to its tendency to become hyperactive following exposure to tinnitus-inducing agents such as intense sound and cisplatin. […] Tinnitus might be generated in the temporal lobe in the auditory association cortex and inferior colliculus on low-frequency fluctuations of fMRI confirms that chronic tinnitus patients have aberrant significant increased spontaneous neuronal activity within the right middle temporal gyrus (MTG), right superior frontal gyrus (SFG) and right angular gyrus. […] The involvement of limbic and autonomic nervous system could explain why some people suffer from tinnitus while others do not.

• #20 Tinnitus: Summary of Current Understanding of the Pathophysiology Mechanisms in different Ear Diseases

  https://www.tinnitusjournal.com/articles/tinnitus-summary-of-current-understanding-of-the-pathophysiology-mechanisms-in-different-ear-diseases-21074.html

  Neural plasticity has been explained as the reason behind generation of subjective tinnitus. […] Many theories are available in literature to explain neuroplasticity mechanism which includes. […] Peripheral auditory system related hypothesis to explain subjective tinnitus origin: Spontaneous Otoacoustic Emissions mechanism (SOE) theory: Kemp discussed this hypothesis in an article published in 1981. These are acoustic signals generated by normal cochlear Outer Hair Cells (OHC), which is propagated to external canal. This hypothesis is the reason behind abnormal sound perception in patients with: […] Dorsal Cochlear Nucleus: has been proposed as site for generation of tinnitus particular after exposure to intense noise and chemotherapeutic drugs like cisplatin. Ototoxicity and intense noise damages outer hair cells in cochlea. Inadequate OHCs and IHCs sensory supply led to overactivity by dorsal cochlear nucleus in brainstem after neuroplasticity changes.

• #21 Ringing Ears: The Neuroscience of Tinnitus | Journal of Neuroscience

  https://www.jneurosci.org/content/30/45/14972

  Increased SFRs in fusiform cells in the DCN and pyramidal cells in the auditory cortex may reflect a shift in the balance of excitation and inhibition in cortical networks as powerful inhibitory regulation is diminished by deafferentation of central auditory structures. […] Chronic tinnitus appears to be dependent on changes taking place at more than one level of the auditory system. […] One mechanism for the increased SFR could be a reduction in inhibitory inputs to the fusiform cells, or changes in glycine receptors unmasking the excitability of the fusiform cells. […] Another mechanism, however, could be an increase in excitatory inputs to the CN from the somatosensory system after noise damage. […] Increased SFRs in DCN principal cells have been observed following noise-induced cochlear damage and have been proposed as correlates of tinnitus in animal behavioral models. […] The upregulation of glutamatergic somatosensory innervation of both granule and magnocellular cells in the CN could account for the increase in SFR in DCN fusiform cells after cochlear damage.

• #22 Current and Emerging Therapies for Chronic Subjective Tinnitus

  https://www.mdpi.com/2077-0383/12/20/6555

  Animal models of tinnitus—primarily achieved via loud sound and/or ototoxic agents following operant or reflexive conditioning to silence—have played a valuable role in understanding the pathophysiology of tinnitus. Through these models, neuronal hyperactivity and hyporeactivity, neuronal gain and synchrony, and tonotopic reorganization in the brain have been associated with tinnitus symptoms. Persistent dysfunctional neuronal activity in the ventral cochlear nucleus, inferior colliculus, medial geniculate body, and auditory cortex are thereby proposed to be responsible for tinnitus maintenance. […] In turn, these alterations in activity have been attributed to changes in glycinergic, GABAergic, glutaminergic, and cholinergic systems. For example, dorsal cochlear nucleus hyperexcitability is possibly due to a reduction in potassium transport via KCNQ channels.

• #23 Current and Emerging Therapies for Chronic Subjective Tinnitus

  https://www.mdpi.com/2077-0383/12/20/6555

  Animal models of tinnitus—primarily achieved via loud sound and/or ototoxic agents following operant or reflexive conditioning to silence—have played a valuable role in understanding the pathophysiology of tinnitus. Through these models, neuronal hyperactivity and hyporeactivity, neuronal gain and synchrony, and tonotopic reorganization in the brain have been associated with tinnitus symptoms. Persistent dysfunctional neuronal activity in the ventral cochlear nucleus, inferior colliculus, medial geniculate body, and auditory cortex are thereby proposed to be responsible for tinnitus maintenance. […] In turn, these alterations in activity have been attributed to changes in glycinergic, GABAergic, glutaminergic, and cholinergic systems. For example, dorsal cochlear nucleus hyperexcitability is possibly due to a reduction in potassium transport via KCNQ channels.

• #24 Scientists find mechanism that causes noise-induced tinnitus and drug that can prevent it | ScienceDaily

  https://www.sciencedaily.com/releases/2013/05/130527153701.htm

  An epilepsy drug shows promise in an animal model at preventing tinnitus from developing after exposure to loud noise, according to a new study. […] The findings reveal for the first time the reason the chronic and sometimes debilitating condition occurs. […] The team focused on an area of the brain that is home to an important auditory center called the dorsal cochlear nucleus (DCN). […] From previous research in a mouse model, they knew that tinnitus is associated with hyperactivity of DCN cells — they fire impulses even when there is no actual sound to perceive. […] „We found that mice with tinnitus have hyperactive DCN cells because of a reduction in KCNQ potassium channel activity,” Dr. Tzounopoulos said. […] „Tinnitus is a channelopathy, and these KCNQ channels represent a novel target for developing drugs that block the induction of tinnitus in humans.”

• #25 Scientists find mechanism that causes noise-induced tinnitus and drug that can prevent it

  https://medicalxpress.com/news/2013-05-scientists-mechanism-noise-induced-tinnitus-drug.html

  Scientists find mechanism that causes noise-induced tinnitus and drug that can prevent it. An epilepsy drug shows promise in an animal model at preventing tinnitus from developing after exposure to loud noise, according to a new study by researchers at the University of Pittsburgh School of Medicine. The findings, reported this week in the early online version of the Proceedings of the National Academy of Sciences, reveal for the first time the reason the chronic and sometimes debilitating condition occurs. […] The team focused on an area of the brain that is home to an important auditory center called the dorsal cochlear nucleus (DCN). From previous research in a mouse model, they knew that tinnitus is associated with hyperactivity of DCN cells—they fire impulses even when there is no actual sound to perceive.

• #26 Scientists find mechanism that causes noise-induced tinnitus and drug that can prevent it

  https://medicalxpress.com/news/2013-05-scientists-mechanism-noise-induced-tinnitus-drug.html

  „We found that mice with tinnitus have hyperactive DCN cells because of a reduction in KCNQ potassium channel activity,” Dr. Tzounopoulos said. „These KCNQ channels act as effective 'brakes’ that reduce excitability or activity of neuronal cells.” […] „This is an important finding that links the biophysical properties of a potassium channel with the perception of a phantom sound,” Dr. Tzounopoulos said. „Tinnitus is a channelopathy, and these KCNQ channels represent a novel target for developing drugs that block the induction of tinnitus in humans.”

• #27 Tinnitus – Wikipedia

  https://en.wikipedia.org/wiki/Tinnitus

  Tinnitus may be caused by increased neural activity in the auditory brainstem, where the brain processes sounds, causing some auditory nerve cells to become overexcited. The basis of this theory is that many with tinnitus also have hearing loss. […] Three reviews in 2016 emphasized the large range and possible combinations of pathologies involved in tinnitus, which result in a great variety of symptoms and specifically adapted therapies. […] Some tinnitus may be caused by neuroplastic changes in the central auditory pathway. In this theory, the disturbance of sensory input caused by hearing loss results in such changes as a homeostatic response of neurons in the central auditory system, causing tinnitus. […] The most common cause of tinnitus is hearing loss. Hearing loss may have many different causes, but among those with tinnitus, the major cause is cochlear injury.

• #28 Current and Emerging Therapies for Chronic Subjective Tinnitus

  https://www.mdpi.com/2077-0383/12/20/6555

  There is a current consensus that the origin of subjective tinnitus is cochlear dysfunction that provokes an aberrant central neuroplastic response. Jastreboff’s neurophysiological model of tinnitus proposes that cochlear damage is the ‘ignition’ event leading to altered activity in the limbic, autonomic, and reticular systems that promote chronic tinnitus. Cochlear damage can include loss of outer hair cells (OHCs) and inner hair cells (IHC), loss of synapses between IHC and type 1 spiral ganglion neurons (synaptopathy), or mechanical damage to hair cells’ stereocilia or the cochlea’s basilar membrane. […] It was previously believed that tinnitus could occur without cochlear damage; however, it is now evident that this damage may occur before hearing loss becomes clinically apparent. For example, tinnitus patients both with and without hearing loss have been shown to have significantly different OHC function than normal subjects (as measured with distortion product otoacoustic emission (DPOAE)), suggestive of OHC loss or damage that has not yet impacted audiometric thresholds. Indeed, hearing loss was undetectable in rats treated with an ototoxic drug (styrene) until >33% of OHCs were lost. Additionally, the acoustic characteristics of tinnitus perception often correspond to the region of hearing loss (i.e., high-pitched tinnitus with high-frequency hearing loss).

• #29 Current and Emerging Therapies for Chronic Subjective Tinnitus

  https://www.mdpi.com/2077-0383/12/20/6555

  There is a current consensus that the origin of subjective tinnitus is cochlear dysfunction that provokes an aberrant central neuroplastic response. Jastreboff’s neurophysiological model of tinnitus proposes that cochlear damage is the ‘ignition’ event leading to altered activity in the limbic, autonomic, and reticular systems that promote chronic tinnitus. Cochlear damage can include loss of outer hair cells (OHCs) and inner hair cells (IHC), loss of synapses between IHC and type 1 spiral ganglion neurons (synaptopathy), or mechanical damage to hair cells’ stereocilia or the cochlea’s basilar membrane. […] It was previously believed that tinnitus could occur without cochlear damage; however, it is now evident that this damage may occur before hearing loss becomes clinically apparent. For example, tinnitus patients both with and without hearing loss have been shown to have significantly different OHC function than normal subjects (as measured with distortion product otoacoustic emission (DPOAE)), suggestive of OHC loss or damage that has not yet impacted audiometric thresholds. Indeed, hearing loss was undetectable in rats treated with an ototoxic drug (styrene) until >33% of OHCs were lost. Additionally, the acoustic characteristics of tinnitus perception often correspond to the region of hearing loss (i.e., high-pitched tinnitus with high-frequency hearing loss).

• #30 Current and Emerging Therapies for Chronic Subjective Tinnitus

  https://www.mdpi.com/2077-0383/12/20/6555

  There is a current consensus that the origin of subjective tinnitus is cochlear dysfunction that provokes an aberrant central neuroplastic response. Jastreboff’s neurophysiological model of tinnitus proposes that cochlear damage is the ‘ignition’ event leading to altered activity in the limbic, autonomic, and reticular systems that promote chronic tinnitus. Cochlear damage can include loss of outer hair cells (OHCs) and inner hair cells (IHC), loss of synapses between IHC and type 1 spiral ganglion neurons (synaptopathy), or mechanical damage to hair cells’ stereocilia or the cochlea’s basilar membrane. […] It was previously believed that tinnitus could occur without cochlear damage; however, it is now evident that this damage may occur before hearing loss becomes clinically apparent. For example, tinnitus patients both with and without hearing loss have been shown to have significantly different OHC function than normal subjects (as measured with distortion product otoacoustic emission (DPOAE)), suggestive of OHC loss or damage that has not yet impacted audiometric thresholds. Indeed, hearing loss was undetectable in rats treated with an ototoxic drug (styrene) until >33% of OHCs were lost. Additionally, the acoustic characteristics of tinnitus perception often correspond to the region of hearing loss (i.e., high-pitched tinnitus with high-frequency hearing loss).

• #31 Current and Emerging Therapies for Chronic Subjective Tinnitus

  https://www.mdpi.com/2077-0383/12/20/6555

  There is a current consensus that the origin of subjective tinnitus is cochlear dysfunction that provokes an aberrant central neuroplastic response. Jastreboff’s neurophysiological model of tinnitus proposes that cochlear damage is the ‘ignition’ event leading to altered activity in the limbic, autonomic, and reticular systems that promote chronic tinnitus. Cochlear damage can include loss of outer hair cells (OHCs) and inner hair cells (IHC), loss of synapses between IHC and type 1 spiral ganglion neurons (synaptopathy), or mechanical damage to hair cells’ stereocilia or the cochlea’s basilar membrane. […] It was previously believed that tinnitus could occur without cochlear damage; however, it is now evident that this damage may occur before hearing loss becomes clinically apparent. For example, tinnitus patients both with and without hearing loss have been shown to have significantly different OHC function than normal subjects (as measured with distortion product otoacoustic emission (DPOAE)), suggestive of OHC loss or damage that has not yet impacted audiometric thresholds. Indeed, hearing loss was undetectable in rats treated with an ototoxic drug (styrene) until >33% of OHCs were lost. Additionally, the acoustic characteristics of tinnitus perception often correspond to the region of hearing loss (i.e., high-pitched tinnitus with high-frequency hearing loss).

• #32 :: JCN :: Journal of Clinical Neurology

  https://www.thejcn.com/DOIx.php?id=10.3988/jcn.2021.17.1.1

  The present model assigns a more-central role to limbic and paralimbic structures in and around the subcallosal area, where they participate in a self-regulating gating process that can prevent the tinnitus signal from being perceived. […] The term cause refers to biological or structural changes, while etiology refers only to the events associated with tinnitus onset, and not to the underlying mechanisms. […] The three main locations where tinnitus is initiated are the peripheral auditory system, somatosensory system, and auditory cortex. […] Lesions involving the dorsal cochlear nucleus, inferior colliculus, and thalamus may also cause tinnitus. […] The most common cause of tinnitus is noise-induced hearing loss, followed by changes in the central auditory pathway. […] Tinnitus may be provoked or modulated by stimulation from the somatosensorial system.

• #33 Identification of a Neurocognitive Mechanism Underpinning Awareness of Chronic Tinnitus | Scientific Reports

  https://www.nature.com/articles/s41598-017-15574-4

  Tinnitus (ringing in the ears) is a common auditory sensation that can become a chronic debilitating health condition with pervasive effects on health and wellbeing, substantive economic burden, and no known cure. […] Here we investigate if impaired functioning of the cognitive control network that directs attentional focus is a mechanism erroneously maintaining the tinnitus sensation. […] Our findings indicate that in addition to auditory dysfunction, altered interactions between non-auditory neurocognitive networks maintain chronic tinnitus awareness, revealing new avenues for the identification of effective treatments. […] Investigations of the neural correlates of chronic tinnitus have indicated involvement of non-auditory regions, including the prefrontal, anterior cingulate and insula cortices, the amygdala, and the hippocampal formation.

• #34 Current and Emerging Therapies for Chronic Subjective Tinnitus

  https://www.mdpi.com/2077-0383/12/20/6555

  Additionally, non-auditory pathways play a critical role in the maintenance and affective response to tinnitus. Correspondingly, tinnitus is known to be co-morbid with depression and anxiety, and intracochlear-glucocorticoid-mediated glutamate release may be a link between psychological stressors and tinnitus. The frontostriatal gating theory posits that the nucleus accumbens and ventromedial prefrontal cortex are important in the affective response to tinnitus. Perception of tinnitus demands attentional resource, and accordingly patients with tinnitus have been shown to have poorer selective attention on auditory tasks. […] There is growing interest in potential genetic contributions to tinnitus risk. Twin studies have estimated the heritability of tinnitus at 40–60%, although several candidate gene studies have failed to find such an association. However, a recent (2020) large-scale, genome-wide association study (GWAS) in the UK Biobank and United States Million Veteran Program identified six genome-wide loci and 27 candidate genes associated with self-reported tinnitus among >170,000 people of European ancestry. The estimated heritability was modest at 6%, but significant. This contrasts somewhat with the results of a prior GWAS that did not identify any significant candidate genes and estimated a lower heritability of 3.2%, which could be attributed to its comparatively much smaller population.

• #35 Special Issue “New Insights into Pathophysiology, Diagnosis and Treatment of Tinnitus”

  https://www.mdpi.com/2076-3425/12/10/1330

  Tinnitus can be defined as a sound arising exclusively within one’s own neural auditory system, without an external or internal sound that generates it. […] Despite many articles being published on its pathophysiology, diagnosis, and treatment, the precise generation, measurement, and remedy of tinnitus remains to be completely elucidated. […] The perception of tinnitus is due to plastic attempts of the neural auditory system to compensate for a diminished sensory input. […] Functional imaging and electrophysiological measurements suggest that tinnitus is produced by increased neural synchrony (hypersynchrony), reorganization of the tonotopic map, and increased spontaneous firing rate (hyperactivity) of the auditory system. […] A comprehensive understanding of the pathophysiology of tinnitus is still challenging for clinical practice. Recent theories on the tinnitus mechanism are mainly focused on the anomalous activity of the central auditory system. Al-Rawashdeh et al. proposed an outstanding mechanism of tinnitus, based on the quantum tunnelling of ion model. The energy barrier of the gate is decreased by the risk factors of tinnitus promoting neuron demyelination and enhancing the quantum tunnelling of calcium, potassium, and sodium ions through the closed voltage-gated channels.

• #36 Tinnitus – Ear, Nose, and Throat Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/ear-nose-and-throat-disorders/approach-to-the-patient-with-ear-problems/tinnitus

  Subjective tinnitus is thought to be caused by abnormal neuronal activity in the auditory cortex. This activity results when input from the auditory pathway (cochlea, auditory nerve, brain stem nuclei, auditory cortex) is disrupted or altered in some manner. This disruption may cause loss of suppression of intrinsic cortical activity and perhaps creation of new neural connections. Some believe the phenomenon is similar to the development of phantom limb pain after amputation. […] Objective tinnitus represents actual noise generated by physiologic phenomena occurring near the middle ear that can be heard by the clinician. Usually the noise is pulsatile and comes from blood vessels, either normal vessels in conditions of increased or turbulent flow (eg, caused by atherosclerosis) or abnormal vessels (eg, in tumors or vascular malformations). […] Continuous tinnitus is usually subjective (except perhaps for that caused by a venous hum, which may be identified by presence of a bruit and often by a change in tinnitus with head rotation or jugular vein compression).

• #37 Tinnitus – Ear, Nose, and Throat Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/ear-nose-and-throat-disorders/approach-to-the-patient-with-ear-problems/tinnitus

  Subjective tinnitus is thought to be caused by abnormal neuronal activity in the auditory cortex. This activity results when input from the auditory pathway (cochlea, auditory nerve, brain stem nuclei, auditory cortex) is disrupted or altered in some manner. This disruption may cause loss of suppression of intrinsic cortical activity and perhaps creation of new neural connections. Some believe the phenomenon is similar to the development of phantom limb pain after amputation. […] Objective tinnitus represents actual noise generated by physiologic phenomena occurring near the middle ear that can be heard by the clinician. Usually the noise is pulsatile and comes from blood vessels, either normal vessels in conditions of increased or turbulent flow (eg, caused by atherosclerosis) or abnormal vessels (eg, in tumors or vascular malformations). […] Continuous tinnitus is usually subjective (except perhaps for that caused by a venous hum, which may be identified by presence of a bruit and often by a change in tinnitus with head rotation or jugular vein compression).

• #38 Tinnitus – Ear, Nose, and Throat Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/ear-nose-and-throat-disorders/approach-to-the-patient-with-ear-problems/tinnitus

  Subjective tinnitus is thought to be caused by abnormal neuronal activity in the auditory cortex. This activity results when input from the auditory pathway (cochlea, auditory nerve, brain stem nuclei, auditory cortex) is disrupted or altered in some manner. This disruption may cause loss of suppression of intrinsic cortical activity and perhaps creation of new neural connections. Some believe the phenomenon is similar to the development of phantom limb pain after amputation. […] Objective tinnitus represents actual noise generated by physiologic phenomena occurring near the middle ear that can be heard by the clinician. Usually the noise is pulsatile and comes from blood vessels, either normal vessels in conditions of increased or turbulent flow (eg, caused by atherosclerosis) or abnormal vessels (eg, in tumors or vascular malformations). […] Continuous tinnitus is usually subjective (except perhaps for that caused by a venous hum, which may be identified by presence of a bruit and often by a change in tinnitus with head rotation or jugular vein compression).

• #39 Tinnitus – Ear, Nose, and Throat Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/ear-nose-and-throat-disorders/approach-to-the-patient-with-ear-problems/tinnitus

  Subjective tinnitus is thought to be caused by abnormal neuronal activity in the auditory cortex. This activity results when input from the auditory pathway (cochlea, auditory nerve, brain stem nuclei, auditory cortex) is disrupted or altered in some manner. This disruption may cause loss of suppression of intrinsic cortical activity and perhaps creation of new neural connections. Some believe the phenomenon is similar to the development of phantom limb pain after amputation. […] Objective tinnitus represents actual noise generated by physiologic phenomena occurring near the middle ear that can be heard by the clinician. Usually the noise is pulsatile and comes from blood vessels, either normal vessels in conditions of increased or turbulent flow (eg, caused by atherosclerosis) or abnormal vessels (eg, in tumors or vascular malformations). […] Continuous tinnitus is usually subjective (except perhaps for that caused by a venous hum, which may be identified by presence of a bruit and often by a change in tinnitus with head rotation or jugular vein compression).

• #40 The Mechanism of Pulsatile Tinnitus and Treatment | SpringerLink

  https://link.springer.com/chapter/10.1007/978-981-16-4269-2_6

  Pulsatile tinnitus (PT), a common otology symptom, is synchronous with patients heartbeat. PT is generally objective, induced by cranial vascular sound, and its mechanism is a biomechanical problem. Multiple etiologies and treatments were proposed in clinical studies, but without quantitative analysis in view of biomechanics. In this chapter, both numerical and experimental models were developed for quantification of generation, propagation and reception of PT sound in view of biomechanics. Based on these models, two commonly reported etiologies were analyzed, including sigmoid sinus cortical plate dehiscence/thinness and hyperpneumatization of temporal bone air cells. It is indicated in results that dehiscence of sigmoid sinus cortical plate would directly induce PT, while thinness would not. Normal pneumatization temporal bone cavity would amplify PT sound mostly, but the pneumatization grade would not be the direct etiology of PT. Based on the findings, we propose that PT patients with sigmoid sinus cortical plate dehiscence undergo plate resurfacing surgery, while the patients with thinness should not receive resurfacing surgery. For patients with only hyperpneumatization shown in radiology data, other etiologies should be searched and considered. […] Tian S, Fan X, Wang Y, Liu Z, Wang L (2019) An in vitro experimental study on the relationship between pulsatile tinnitus and the dehiscence/thinness of sigmoid sinus cortical plate. J Biomech 84:197203.

• #41 The Mechanism of Pulsatile Tinnitus and Treatment | SpringerLink

  https://link.springer.com/chapter/10.1007/978-981-16-4269-2_6

  Pulsatile tinnitus (PT), a common otology symptom, is synchronous with patients heartbeat. PT is generally objective, induced by cranial vascular sound, and its mechanism is a biomechanical problem. Multiple etiologies and treatments were proposed in clinical studies, but without quantitative analysis in view of biomechanics. In this chapter, both numerical and experimental models were developed for quantification of generation, propagation and reception of PT sound in view of biomechanics. Based on these models, two commonly reported etiologies were analyzed, including sigmoid sinus cortical plate dehiscence/thinness and hyperpneumatization of temporal bone air cells. It is indicated in results that dehiscence of sigmoid sinus cortical plate would directly induce PT, while thinness would not. Normal pneumatization temporal bone cavity would amplify PT sound mostly, but the pneumatization grade would not be the direct etiology of PT. Based on the findings, we propose that PT patients with sigmoid sinus cortical plate dehiscence undergo plate resurfacing surgery, while the patients with thinness should not receive resurfacing surgery. For patients with only hyperpneumatization shown in radiology data, other etiologies should be searched and considered. […] Tian S, Fan X, Wang Y, Liu Z, Wang L (2019) An in vitro experimental study on the relationship between pulsatile tinnitus and the dehiscence/thinness of sigmoid sinus cortical plate. J Biomech 84:197203.

• #42 Torrents of torment: turbulence as a mechanism of pulsatile tinnitus secondary to venous stenosis revealed by high-fidelity computational fluid dynamics | Journal of NeuroInterventional Surgery

  https://jnis.bmj.com/content/13/8/732

  Pulsatile tinnitus (PT) is a debilitating condition that can be caused by a vascular abnormality, such as an arterial or venous lesion. […] Despite reports of successful treatments of PT related to these venous lesions, much controversy still exists regarding the role of these vascular lesions (especially venous lesions) in the etiology of PT. […] For the first time, turbulence generated distal to a venous stenosis is shown to be a cause of PT. High-fidelity CFD may be useful for identifying patients with such torrents of flow, to help guide treatment decision-making. […] We demonstrated that the giant arachnoid granulation resulted in narrowing of the sinus lumen, causing turbulent-like flow that caused the PT, possibly as a result of resonance through the temporal bone to the auditory structures.

• #43 Torrents of torment: turbulence as a mechanism of pulsatile tinnitus secondary to venous stenosis revealed by high-fidelity computational fluid dynamics | Journal of NeuroInterventional Surgery

  https://jnis.bmj.com/content/13/8/732

  Pulsatile tinnitus (PT) is a debilitating condition that can be caused by a vascular abnormality, such as an arterial or venous lesion. […] Despite reports of successful treatments of PT related to these venous lesions, much controversy still exists regarding the role of these vascular lesions (especially venous lesions) in the etiology of PT. […] For the first time, turbulence generated distal to a venous stenosis is shown to be a cause of PT. High-fidelity CFD may be useful for identifying patients with such torrents of flow, to help guide treatment decision-making. […] We demonstrated that the giant arachnoid granulation resulted in narrowing of the sinus lumen, causing turbulent-like flow that caused the PT, possibly as a result of resonance through the temporal bone to the auditory structures.

• #44 Reactive Tinnitus: The Definitive Guide | NeuroMed Tinnitus Clinic

  https://neuromedcare.com/what-is-reactive-tinnitus/

  Reactive tinnitus is a subtype of tinnitus characterized by an abnormal increase in tinnitus loudness, intensity, or character in response to specific auditory triggers. […] The Central Sensitization (CS) theory suggests that, similar to chronic pain or migraine, reactive-type tinnitus may worsen progressively due to an increased sensitivity within the central nervous system. […] A key component of CS is the wind-up phenomenon, where repeated stimulation causes bigger reaction from the brain. […] This is precisely what we see in tinnitus that is reactive; low or moderate sounds encountered throughout the day create a winding effect, progressively worsening the tinnitus reactivity with each incremental sound stimulus. […] Reactive tinnitus shares features with chronic pain and migraine, such as exaggerated brain responses to sensory input.

• #45 Reactive Tinnitus: The Definitive Guide | NeuroMed Tinnitus Clinic

  https://neuromedcare.com/what-is-reactive-tinnitus/

  Reactive tinnitus is a subtype of tinnitus characterized by an abnormal increase in tinnitus loudness, intensity, or character in response to specific auditory triggers. […] The Central Sensitization (CS) theory suggests that, similar to chronic pain or migraine, reactive-type tinnitus may worsen progressively due to an increased sensitivity within the central nervous system. […] A key component of CS is the wind-up phenomenon, where repeated stimulation causes bigger reaction from the brain. […] This is precisely what we see in tinnitus that is reactive; low or moderate sounds encountered throughout the day create a winding effect, progressively worsening the tinnitus reactivity with each incremental sound stimulus. […] Reactive tinnitus shares features with chronic pain and migraine, such as exaggerated brain responses to sensory input.

• #46 Reactive Tinnitus: The Definitive Guide | NeuroMed Tinnitus Clinic

  https://neuromedcare.com/what-is-reactive-tinnitus/

  Reactive tinnitus is a subtype of tinnitus characterized by an abnormal increase in tinnitus loudness, intensity, or character in response to specific auditory triggers. […] The Central Sensitization (CS) theory suggests that, similar to chronic pain or migraine, reactive-type tinnitus may worsen progressively due to an increased sensitivity within the central nervous system. […] A key component of CS is the wind-up phenomenon, where repeated stimulation causes bigger reaction from the brain. […] This is precisely what we see in tinnitus that is reactive; low or moderate sounds encountered throughout the day create a winding effect, progressively worsening the tinnitus reactivity with each incremental sound stimulus. […] Reactive tinnitus shares features with chronic pain and migraine, such as exaggerated brain responses to sensory input.

• #47 Pathophysiology and Treatment of Tinnitus: An Elusive Disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3918281/

  Tinnitus has been associated with a variety of risk factors, including prolonged noise exposure (22% of cases), head/neck injury (17% of cases) and infections (10% of cases) [13]. The most recent pathophysiologic theory suggests that the central nervous system is the source or generator of tinnitus [14]. Positron emission tomography (PET) scanning and functional magnetic resonance imaging (fMRI) studies indicate that a loss of cochlear input to neurons in the central auditory system (such as occurs in cochlear hair cell damage or a lesion of the vestibulocochlear nerve) can result in abnormal neural activity in the auditory cortex [15]. This activity is linked to the perception of tinnitus. […] Recent improvements in neuro-otometry have confirmed the complex pathophysiologic mechanisms involved in tinnitus, elucidating sites in which these processes take place [1719]. It is now known that approximately 24% of cases occur as a result of abnormalities within the otoacoustic periphery (i.e. inner ear and the vestibulocochlear nerve), 35% originate from the acoustic pathways and 41% have their cause within supratentorial structures [6]. A decrease in inhibition and/or increase in excitation may lead to an excitatory-inhibitory imbalance causing neuronal hyperexcitability in these regions and lead to the perception of tinnitus [20]. However, neuronal excitability can be modulated by different neurotransmitters and neuromodulators that act on voltage- or ligand-gated channels, thus providing potential pharmacologic targets [20].

• #48 Tinnitus – Wikipedia

  https://en.wikipedia.org/wiki/Tinnitus

  Tinnitus may be caused by increased neural activity in the auditory brainstem, where the brain processes sounds, causing some auditory nerve cells to become overexcited. The basis of this theory is that many with tinnitus also have hearing loss. […] Three reviews in 2016 emphasized the large range and possible combinations of pathologies involved in tinnitus, which result in a great variety of symptoms and specifically adapted therapies. […] Some tinnitus may be caused by neuroplastic changes in the central auditory pathway. In this theory, the disturbance of sensory input caused by hearing loss results in such changes as a homeostatic response of neurons in the central auditory system, causing tinnitus. […] The most common cause of tinnitus is hearing loss. Hearing loss may have many different causes, but among those with tinnitus, the major cause is cochlear injury.

• #49 Tinnitus – Wikipedia

  https://en.wikipedia.org/wiki/Tinnitus

  Ototoxic drugs also may cause subjective tinnitus, as they may cause hearing loss, or increase the damage done by exposure to loud noise. […] Tinnitus can also occur from the discontinuation of therapeutic doses of benzodiazepines. It can sometimes be a protracted symptom of benzodiazepine withdrawal and may persist for many months. […] In 2020, information about clinical trials indicated that bimodal neuromodulation may reduce the symptoms of tinnitus. It is a noninvasive technique that involves applying an electrical stimulus to the tongue while also administering sounds. […] Some evidence supports neuromodulation techniques such as transcranial magnetic stimulation, transcranial direct current stimulation, and neurofeedback.

• #50 Tinnitus – Wikipedia

  https://en.wikipedia.org/wiki/Tinnitus

  Ototoxic drugs also may cause subjective tinnitus, as they may cause hearing loss, or increase the damage done by exposure to loud noise. […] Tinnitus can also occur from the discontinuation of therapeutic doses of benzodiazepines. It can sometimes be a protracted symptom of benzodiazepine withdrawal and may persist for many months. […] In 2020, information about clinical trials indicated that bimodal neuromodulation may reduce the symptoms of tinnitus. It is a noninvasive technique that involves applying an electrical stimulus to the tongue while also administering sounds. […] Some evidence supports neuromodulation techniques such as transcranial magnetic stimulation, transcranial direct current stimulation, and neurofeedback.

• #51 :: JCN :: Journal of Clinical Neurology

  https://www.thejcn.com/DOIx.php?id=10.3988/jcn.2021.17.1.1

  Tinnitus can be attributable to hearing loss, somatosensory system dysfunction, or auditory cortex dysfunction, with hearing loss being the most common cause and serious underlying pathologies being rare. […] The earliest speculations regarding the site of tinnitus generation described a cochlear origin. This view has shifted over time to tinnitus originating in the central auditory system rather than to mechanisms in the peripheral auditory system such as due to cochlear damage; that is, abnormal auditory signals activate neural plasticity within central auditory structures and manifest as tinnitus. […] However, it turns out that the pathophysiology of tinnitus is not limited to the auditory system, with the somatosensory system also provoking or modulating tinnitus, and the limbic system being necessary for its maintenance.

• #52 :: JCN :: Journal of Clinical Neurology

  https://www.thejcn.com/DOIx.php?id=10.3988/jcn.2021.17.1.1

  Tinnitus can be attributable to hearing loss, somatosensory system dysfunction, or auditory cortex dysfunction, with hearing loss being the most common cause and serious underlying pathologies being rare. […] The earliest speculations regarding the site of tinnitus generation described a cochlear origin. This view has shifted over time to tinnitus originating in the central auditory system rather than to mechanisms in the peripheral auditory system such as due to cochlear damage; that is, abnormal auditory signals activate neural plasticity within central auditory structures and manifest as tinnitus. […] However, it turns out that the pathophysiology of tinnitus is not limited to the auditory system, with the somatosensory system also provoking or modulating tinnitus, and the limbic system being necessary for its maintenance.

• #53 TMJD and Tinnitus: What About Pathogenesis? | The Hearing Review

  https://hearingreview.com/hearing-loss/tinnitus/tmjd-and-tinnitus-what-about-pathogenesis

  Like many hearing care providers, we frequently see patients who present non-otic tinnitus and temporomandibular joint disorders (TMJD). […] Among this group, there are many patients who have non-otic tinnitus without any detectable ear/nerve disorder or without any temporal relationship between such disorders and tinnitus. […] Additionally, tinnitus is significantly more prevalent in the TMJD patients than in the healthy-patients control groups and sometimes the TMJD treatment ameliorates otologic symptoms. […] Nevertheless, few solid theories have been reported in the literature regarding the TMJD-tinnitus association. […] Recently, the central neural basis of TMJD-related tinnitus has been speculated. According to Vass, trigeminal nerve irritation induced by the TMJD can disturb the normal inner-ear vascular tone causing some otologic disturbances such as tinnitus.

• #54 TMJD and Tinnitus: What About Pathogenesis? | The Hearing Review

  https://hearingreview.com/hearing-loss/tinnitus/tmjd-and-tinnitus-what-about-pathogenesis

  According to the central neural theories proposed by Levine and Henry, the authors recently proposed The Double Hit Hypothesis. This proposes that TMJD could irritate the auriculo-temporal nerve (ATN), triggering a somatosensory pathway-induced disinhibition of the dorsal cochlear nucleus (DCN) activity in the auditory pathway. […] Serotonin exerts major modulatory effects on sensory systems, and 5-HT dysfunction is implicated in a number of clinically-relevant conditions, including anxiety and the generation and chronicization of tinnitus. […] A genetically serotoninergic reduction could promote plastic changes underlying tinnitus that might be described as tinnitus memory circuits through diminished filtering of incoming signals. […] According to our hypothesis, a TMJD-tinnitus management needs a double hit strategy under the umbrella of a multidisciplinary team: 1) Treatment for TMJD; 2) In selected patients, complementary therapies could be aimed at decreasing the activation of tinnitus memory circuits, modulating the serotoninergic neurotransmission. […] More than 70 years after it was first described, every facet of the TMJD-tinnitus continues to evoke controversy. Any contribution to understand the pathogenesis of the controversial association between TMJD and tinnitus is to be welcomed.

• #55 Patogenesis of tinnitus in patients with post-COVID sy…

  https://otolaryngologypl.com/seo/article/01.3001.0053.8645/en?language=en

  Tinnitus in patients suffering from post-COVID syndrome may be related to prolonged conduction of nerve impulses within the brainstem auditory pathway. […] The pathogenesis behind the development of tinnitus in the post-COVID syndrome remains unclear. One speculated mechanism suggests that tinnitus develops as a result of brainstem disorders of inflammatory character related to oxidative stress, which stimulates the synthesis of proinflammatory cytokines, including interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α). […] Statistically significant differences demonstrated between the examined subgroups suggest that the development of tinnitus in patients with post-COVID syndrome originates in the central nervous system. […] The available databases do not contain any scientific reports comparing the results of brainstem auditory evoked potential tests in terms of tinnitus development in patients after SARS-CoV-2 infection.

• #56 Patogenesis of tinnitus in patients with post-COVID sy…

  https://otolaryngologypl.com/seo/article/01.3001.0053.8645/en?language=en

  Tinnitus in patients suffering from post-COVID syndrome may be related to prolonged conduction of nerve impulses within the brainstem auditory pathway. […] The pathogenesis behind the development of tinnitus in the post-COVID syndrome remains unclear. One speculated mechanism suggests that tinnitus develops as a result of brainstem disorders of inflammatory character related to oxidative stress, which stimulates the synthesis of proinflammatory cytokines, including interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α). […] Statistically significant differences demonstrated between the examined subgroups suggest that the development of tinnitus in patients with post-COVID syndrome originates in the central nervous system. […] The available databases do not contain any scientific reports comparing the results of brainstem auditory evoked potential tests in terms of tinnitus development in patients after SARS-CoV-2 infection.

• #57 Pathophysiology and Treatment of Tinnitus: An Elusive Disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3918281/

  Tinnitus has been associated with a variety of risk factors, including prolonged noise exposure (22% of cases), head/neck injury (17% of cases) and infections (10% of cases) [13]. The most recent pathophysiologic theory suggests that the central nervous system is the source or generator of tinnitus [14]. Positron emission tomography (PET) scanning and functional magnetic resonance imaging (fMRI) studies indicate that a loss of cochlear input to neurons in the central auditory system (such as occurs in cochlear hair cell damage or a lesion of the vestibulocochlear nerve) can result in abnormal neural activity in the auditory cortex [15]. This activity is linked to the perception of tinnitus. […] Recent improvements in neuro-otometry have confirmed the complex pathophysiologic mechanisms involved in tinnitus, elucidating sites in which these processes take place [1719]. It is now known that approximately 24% of cases occur as a result of abnormalities within the otoacoustic periphery (i.e. inner ear and the vestibulocochlear nerve), 35% originate from the acoustic pathways and 41% have their cause within supratentorial structures [6]. A decrease in inhibition and/or increase in excitation may lead to an excitatory-inhibitory imbalance causing neuronal hyperexcitability in these regions and lead to the perception of tinnitus [20]. However, neuronal excitability can be modulated by different neurotransmitters and neuromodulators that act on voltage- or ligand-gated channels, thus providing potential pharmacologic targets [20].

• #58 TMJD and Tinnitus: What About Pathogenesis? | The Hearing Review

  https://hearingreview.com/hearing-loss/tinnitus/tmjd-and-tinnitus-what-about-pathogenesis

  According to the central neural theories proposed by Levine and Henry, the authors recently proposed The Double Hit Hypothesis. This proposes that TMJD could irritate the auriculo-temporal nerve (ATN), triggering a somatosensory pathway-induced disinhibition of the dorsal cochlear nucleus (DCN) activity in the auditory pathway. […] Serotonin exerts major modulatory effects on sensory systems, and 5-HT dysfunction is implicated in a number of clinically-relevant conditions, including anxiety and the generation and chronicization of tinnitus. […] A genetically serotoninergic reduction could promote plastic changes underlying tinnitus that might be described as tinnitus memory circuits through diminished filtering of incoming signals. […] According to our hypothesis, a TMJD-tinnitus management needs a double hit strategy under the umbrella of a multidisciplinary team: 1) Treatment for TMJD; 2) In selected patients, complementary therapies could be aimed at decreasing the activation of tinnitus memory circuits, modulating the serotoninergic neurotransmission. […] More than 70 years after it was first described, every facet of the TMJD-tinnitus continues to evoke controversy. Any contribution to understand the pathogenesis of the controversial association between TMJD and tinnitus is to be welcomed.

• #59 TMJD and Tinnitus: What About Pathogenesis? | The Hearing Review

  https://hearingreview.com/hearing-loss/tinnitus/tmjd-and-tinnitus-what-about-pathogenesis

  According to the central neural theories proposed by Levine and Henry, the authors recently proposed The Double Hit Hypothesis. This proposes that TMJD could irritate the auriculo-temporal nerve (ATN), triggering a somatosensory pathway-induced disinhibition of the dorsal cochlear nucleus (DCN) activity in the auditory pathway. […] Serotonin exerts major modulatory effects on sensory systems, and 5-HT dysfunction is implicated in a number of clinically-relevant conditions, including anxiety and the generation and chronicization of tinnitus. […] A genetically serotoninergic reduction could promote plastic changes underlying tinnitus that might be described as tinnitus memory circuits through diminished filtering of incoming signals. […] According to our hypothesis, a TMJD-tinnitus management needs a double hit strategy under the umbrella of a multidisciplinary team: 1) Treatment for TMJD; 2) In selected patients, complementary therapies could be aimed at decreasing the activation of tinnitus memory circuits, modulating the serotoninergic neurotransmission. […] More than 70 years after it was first described, every facet of the TMJD-tinnitus continues to evoke controversy. Any contribution to understand the pathogenesis of the controversial association between TMJD and tinnitus is to be welcomed.

• #60 Tinnitus – Wikipedia

  https://en.wikipedia.org/wiki/Tinnitus

  Ototoxic drugs also may cause subjective tinnitus, as they may cause hearing loss, or increase the damage done by exposure to loud noise. […] Tinnitus can also occur from the discontinuation of therapeutic doses of benzodiazepines. It can sometimes be a protracted symptom of benzodiazepine withdrawal and may persist for many months. […] In 2020, information about clinical trials indicated that bimodal neuromodulation may reduce the symptoms of tinnitus. It is a noninvasive technique that involves applying an electrical stimulus to the tongue while also administering sounds. […] Some evidence supports neuromodulation techniques such as transcranial magnetic stimulation, transcranial direct current stimulation, and neurofeedback.

• #61 Tinnitus – Wikipedia

  https://en.wikipedia.org/wiki/Tinnitus

  Ototoxic drugs also may cause subjective tinnitus, as they may cause hearing loss, or increase the damage done by exposure to loud noise. […] Tinnitus can also occur from the discontinuation of therapeutic doses of benzodiazepines. It can sometimes be a protracted symptom of benzodiazepine withdrawal and may persist for many months. […] In 2020, information about clinical trials indicated that bimodal neuromodulation may reduce the symptoms of tinnitus. It is a noninvasive technique that involves applying an electrical stimulus to the tongue while also administering sounds. […] Some evidence supports neuromodulation techniques such as transcranial magnetic stimulation, transcranial direct current stimulation, and neurofeedback.

• #62 Identification of a Neurocognitive Mechanism Underpinning Awareness of Chronic Tinnitus | Scientific Reports

  https://www.nature.com/articles/s41598-017-15574-4

  Tinnitus (ringing in the ears) is a common auditory sensation that can become a chronic debilitating health condition with pervasive effects on health and wellbeing, substantive economic burden, and no known cure. […] Here we investigate if impaired functioning of the cognitive control network that directs attentional focus is a mechanism erroneously maintaining the tinnitus sensation. […] Our findings indicate that in addition to auditory dysfunction, altered interactions between non-auditory neurocognitive networks maintain chronic tinnitus awareness, revealing new avenues for the identification of effective treatments. […] Investigations of the neural correlates of chronic tinnitus have indicated involvement of non-auditory regions, including the prefrontal, anterior cingulate and insula cortices, the amygdala, and the hippocampal formation.

• #63 Identification of a Neurocognitive Mechanism Underpinning Awareness of Chronic Tinnitus | Scientific Reports

  https://www.nature.com/articles/s41598-017-15574-4

  This has led to the idea of a tinnitus network, typically characterized by altered auditory processing that generates the tinnitus sensation, which becomes associated with heightened attention and emotions (prefrontal cortex, anterior cingulate, insula, amygdala), consolidating memory of the sound (hippocampal region). […] Based on behavioral evidence, we have recently shown that psychological markers of attention-switching, namely cognitive and emotional control, are impaired in chronic tinnitus suggesting reduced cognitive control may constitute a core mechanism that maintains the awareness of tinnitus, rather than being a down-stream effect. […] Attention-switching is underpinned by efficient interactions between large-scale neurocognitive networks that facilitate processing of relevant stimuli, and inhibit goal-irrelevant stimuli.

• #64 Transcranial direct current stimulation for the treatment of tinnitus: a review of clinical trials and mechanisms of action | BMC Neuroscience | Full Text

  https://bmcneurosci.biomedcentral.com/articles/10.1186/s12868-018-0467-3

  Tinnitus is the perception of sound in the absence of any external acoustic stimulation. […] The present study aims to review the recent advances in applications of tDCS for tinnitus treatment. In addition, the clinical efficacy and main mechanisms of action of tDCS on suppressing tinnitus are discussed. […] Neuroimaging, neuroelectrophysiologic, and neuroanatomic studies have shown that maladaptive plastic changes in different auditory and non-auditory cerebral regions and abnormal neural activities of specific cortical regions might be the main etiology of tinnitus. […] Tinnitus perception is an integrated output of a large and complicated brain network comprising of different subnetworks with overlapping functions. […] Neurobiological and neuroimaging findings have shown that abnormal activities of the non-auditory regions associated with cognitive and attentional functions as well as limbic processes probably contribute to the unpleasant and distressing aspects of tinnitus.

• #65 Transcranial direct current stimulation for the treatment of tinnitus: a review of clinical trials and mechanisms of action | BMC Neuroscience | Full Text

  https://bmcneurosci.biomedcentral.com/articles/10.1186/s12868-018-0467-3

  Tinnitus is the perception of sound in the absence of any external acoustic stimulation. […] The present study aims to review the recent advances in applications of tDCS for tinnitus treatment. In addition, the clinical efficacy and main mechanisms of action of tDCS on suppressing tinnitus are discussed. […] Neuroimaging, neuroelectrophysiologic, and neuroanatomic studies have shown that maladaptive plastic changes in different auditory and non-auditory cerebral regions and abnormal neural activities of specific cortical regions might be the main etiology of tinnitus. […] Tinnitus perception is an integrated output of a large and complicated brain network comprising of different subnetworks with overlapping functions. […] Neurobiological and neuroimaging findings have shown that abnormal activities of the non-auditory regions associated with cognitive and attentional functions as well as limbic processes probably contribute to the unpleasant and distressing aspects of tinnitus.

• #66 Etiology and Pathophysiology of Tinnitus: A Systematic Review

  https://www.tinnitusjournal.com/articles/etiology-and-pathophysiology-of-tinnitus–a-systematic-review-16383.html

  Cochlear-type tinnitus is suggested to result from aberrant activity generated at the cochlear nerve level. […] A reduction in cochlear activity produces tinnitus-related plastic changes, namely cortical reorganisation, thalamic neuron hyperpolarisation, facilitation of nonauditory limbic inputs and increase in central gain. […] The Dorsal Cochlear Nucleus (DCN) has been implicated as a possible site for the generation of tinnitus-related signals owing to its tendency to become hyperactive following exposure to tinnitus-inducing agents such as intense sound and cisplatin. […] Tinnitus might be generated in the temporal lobe in the auditory association cortex and inferior colliculus on low-frequency fluctuations of fMRI confirms that chronic tinnitus patients have aberrant significant increased spontaneous neuronal activity within the right middle temporal gyrus (MTG), right superior frontal gyrus (SFG) and right angular gyrus. […] The involvement of limbic and autonomic nervous system could explain why some people suffer from tinnitus while others do not.

• #67 KoreaMed Synapse

  https://synapse.koreamed.org/articles/1044299

  Sensorineural tinnitus can be expressed as tonal sound, narrow band sound or white noise. […] A recent study revealed that tinnitus is a consequence of neuroplastic alterations in the central auditory pathway as well as somatosensory change. […] The exact mechanism of subjective tinnitus is obscure. […] The hypothesis of maladaptive neural plasticity seems to explain those changes of increased spontaneous firing rates and synchrony among neurons in central auditory structures and non-auditory brain networks, possibly generating the phantom percept analogue to phantom limb sensation. […] The neurophysiological model has been widely accepted in this field and habituation strategy to both tinnitus signal and the reaction against tinnitus has been developed as a Tinnitus Retraining Therapy. […] The complex interaction between peripheral auditory pathways, central auditory pathway and non-auditory region of the limbic, somatosensory and autonomic system, might contribute to the generation and persistence of tinnitus.

• #68 KoreaMed Synapse

  https://synapse.koreamed.org/articles/1044299

  Sensorineural tinnitus can be expressed as tonal sound, narrow band sound or white noise. […] A recent study revealed that tinnitus is a consequence of neuroplastic alterations in the central auditory pathway as well as somatosensory change. […] The exact mechanism of subjective tinnitus is obscure. […] The hypothesis of maladaptive neural plasticity seems to explain those changes of increased spontaneous firing rates and synchrony among neurons in central auditory structures and non-auditory brain networks, possibly generating the phantom percept analogue to phantom limb sensation. […] The neurophysiological model has been widely accepted in this field and habituation strategy to both tinnitus signal and the reaction against tinnitus has been developed as a Tinnitus Retraining Therapy. […] The complex interaction between peripheral auditory pathways, central auditory pathway and non-auditory region of the limbic, somatosensory and autonomic system, might contribute to the generation and persistence of tinnitus.

• #69 Tinnitus: Practice Essentials, Philosophy, Classification, Pathophysiology, and Quantification, Evaluation: History, Physical, and Laboratory

  https://emedicine.medscape.com/article/856916-overview

  Clinically, subjective tinnitus is the perception of sound in the absence of auditory stimulation. In terms of neurophysiology, tinnitus is the consequence of the brains response to input deprivation from the auditory periphery. […] When a region of the cochlea is damaged, the subcortical and cortical projections adjust to this chronic lack of output (plasticity), and the tonotopic organization is altered. In the auditory cortex, the region that corresponds to the area of cochlear damage is termed the lesion projection zone (LPZ). After cochlear damage, neurons in the LPZ show 2 important changes: an increase in the spontaneous firing rate and an increase in the frequency representation of the neurons that border the region of damage (the so-called lesion edge frequencies). […] These findings are explained in terms of a) the loss of central inhibition on the regions that are damaged and b) cortical plasticity of the neighboring regions of the cortex that are still active. Hence, tinnitus neurophysiology is related to detrimental cortical adaptation to input deprivation from the sensory periphery. […] Additional data from animal and human studies have suggested that tinnitus may be associated with neuronal hyperactivity at different levels of the central auditory pathways, including the dorsal cochlear nucleus, the inferior colliculus, auditory cortex, and the striatum.

• #70 Brain Inflammation Identified as Potential Target to Treat Tinnitus | University of Arizona News

  https://news.arizona.edu/news/brain-inflammation-identified-potential-target-treat-tinnitus

  Shaowen Bao, associate professor of physiology at the University of Arizona College of Medicine Tucson, and his colleagues are closing in on potential treatments for tinnitus by connecting brain inflammation to the condition. […] Their research showed mice with noise-induced hearing loss (under anesthesia) had elevated levels of molecules called proinflammatory cytokines and the activation of non-neuronal cells called microglia, two defining features of neuroinflammatory responses, in the primary auditory cortex in the brain. […] The research also showed that the cytokine tumor necrosis factor alpha (TNF-), a cell signaling protein (cytokine) involved in systemic inflammation, is necessary for noise-induced neuroinflammation, tinnitus and synaptic imbalance (an altered pattern of signaling between neurons).

• #71 Brain Inflammation Identified as Potential Target to Treat Tinnitus | University of Arizona News

  https://news.arizona.edu/news/brain-inflammation-identified-potential-target-treat-tinnitus

  Shaowen Bao, associate professor of physiology at the University of Arizona College of Medicine Tucson, and his colleagues are closing in on potential treatments for tinnitus by connecting brain inflammation to the condition. […] Their research showed mice with noise-induced hearing loss (under anesthesia) had elevated levels of molecules called proinflammatory cytokines and the activation of non-neuronal cells called microglia, two defining features of neuroinflammatory responses, in the primary auditory cortex in the brain. […] The research also showed that the cytokine tumor necrosis factor alpha (TNF-), a cell signaling protein (cytokine) involved in systemic inflammation, is necessary for noise-induced neuroinflammation, tinnitus and synaptic imbalance (an altered pattern of signaling between neurons).

• #72 Brain Inflammation Identified as Potential Target to Treat Tinnitus | University of Arizona News

  https://news.arizona.edu/news/brain-inflammation-identified-potential-target-treat-tinnitus

  Shaowen Bao, associate professor of physiology at the University of Arizona College of Medicine Tucson, and his colleagues are closing in on potential treatments for tinnitus by connecting brain inflammation to the condition. […] Their research showed mice with noise-induced hearing loss (under anesthesia) had elevated levels of molecules called proinflammatory cytokines and the activation of non-neuronal cells called microglia, two defining features of neuroinflammatory responses, in the primary auditory cortex in the brain. […] The research also showed that the cytokine tumor necrosis factor alpha (TNF-), a cell signaling protein (cytokine) involved in systemic inflammation, is necessary for noise-induced neuroinflammation, tinnitus and synaptic imbalance (an altered pattern of signaling between neurons).

• #73 Brain Inflammation Identified as Potential Target to Treat Tinnitus | University of Arizona News

  https://news.arizona.edu/news/brain-inflammation-identified-potential-target-treat-tinnitus

  The findings suggest that neuroinflammation may be a therapeutic target for treating tinnitus and other hearing loss-related disorders. […] We have more work to do to confirm the mechanism that is causally linked to tinnitus and determine if the results translate to humans,” Bao cautioned. „While promising, we still have a long way to go from research to patient care.

• #74 A role of sleep in tinnitus identified for the first time — Department of Physiology, Anatomy and Genetics (DPAG)

  https://www.dpag.ox.ac.uk/news/a-role-of-sleep-in-tinnitus-identified-for-the-first-time

  Phantom percepts, such as subjective tinnitus, are driven by fundamental changes in spontaneous brain activity. […] In conclusion, they propose a fundamental relationship between natural brain dynamics and the expression and pathogenesis of tinnitus. […] Tinnitus related activity in the brain during sleep may cause local wakefulness and hinder the brain from entering global, restorative sleep. […] However, precisely what happens in the brain as tinnitus develops and progresses is currently unclear. […] They have thus proposed a fundamental interaction between the phantom percepts caused by tinnitus-aberrant brain activity and natural brain state dynamics. […] These findings have important implications for tinnitus research, diagnostics and potential therapeutic interventions. […] Tinnitus activity might be reduced during intense NREM sleep.

• #75 A role of sleep in tinnitus identified for the first time — Department of Physiology, Anatomy and Genetics (DPAG)

  https://www.dpag.ox.ac.uk/news/a-role-of-sleep-in-tinnitus-identified-for-the-first-time

  Phantom percepts, such as subjective tinnitus, are driven by fundamental changes in spontaneous brain activity. […] In conclusion, they propose a fundamental relationship between natural brain dynamics and the expression and pathogenesis of tinnitus. […] Tinnitus related activity in the brain during sleep may cause local wakefulness and hinder the brain from entering global, restorative sleep. […] However, precisely what happens in the brain as tinnitus develops and progresses is currently unclear. […] They have thus proposed a fundamental interaction between the phantom percepts caused by tinnitus-aberrant brain activity and natural brain state dynamics. […] These findings have important implications for tinnitus research, diagnostics and potential therapeutic interventions. […] Tinnitus activity might be reduced during intense NREM sleep.

• #76 A role of sleep in tinnitus identified for the first time — Department of Physiology, Anatomy and Genetics (DPAG)

  https://www.dpag.ox.ac.uk/news/a-role-of-sleep-in-tinnitus-identified-for-the-first-time

  Phantom percepts, such as subjective tinnitus, are driven by fundamental changes in spontaneous brain activity. […] In conclusion, they propose a fundamental relationship between natural brain dynamics and the expression and pathogenesis of tinnitus. […] Tinnitus related activity in the brain during sleep may cause local wakefulness and hinder the brain from entering global, restorative sleep. […] However, precisely what happens in the brain as tinnitus develops and progresses is currently unclear. […] They have thus proposed a fundamental interaction between the phantom percepts caused by tinnitus-aberrant brain activity and natural brain state dynamics. […] These findings have important implications for tinnitus research, diagnostics and potential therapeutic interventions. […] Tinnitus activity might be reduced during intense NREM sleep.

• #77 A role of sleep in tinnitus identified for the first time — Department of Physiology, Anatomy and Genetics (DPAG)

  https://www.dpag.ox.ac.uk/news/a-role-of-sleep-in-tinnitus-identified-for-the-first-time

  Phantom percepts, such as subjective tinnitus, are driven by fundamental changes in spontaneous brain activity. […] In conclusion, they propose a fundamental relationship between natural brain dynamics and the expression and pathogenesis of tinnitus. […] Tinnitus related activity in the brain during sleep may cause local wakefulness and hinder the brain from entering global, restorative sleep. […] However, precisely what happens in the brain as tinnitus develops and progresses is currently unclear. […] They have thus proposed a fundamental interaction between the phantom percepts caused by tinnitus-aberrant brain activity and natural brain state dynamics. […] These findings have important implications for tinnitus research, diagnostics and potential therapeutic interventions. […] Tinnitus activity might be reduced during intense NREM sleep.

• #78 Current and Emerging Therapies for Chronic Subjective Tinnitus

  https://www.mdpi.com/2077-0383/12/20/6555

  Additionally, non-auditory pathways play a critical role in the maintenance and affective response to tinnitus. Correspondingly, tinnitus is known to be co-morbid with depression and anxiety, and intracochlear-glucocorticoid-mediated glutamate release may be a link between psychological stressors and tinnitus. The frontostriatal gating theory posits that the nucleus accumbens and ventromedial prefrontal cortex are important in the affective response to tinnitus. Perception of tinnitus demands attentional resource, and accordingly patients with tinnitus have been shown to have poorer selective attention on auditory tasks. […] There is growing interest in potential genetic contributions to tinnitus risk. Twin studies have estimated the heritability of tinnitus at 40–60%, although several candidate gene studies have failed to find such an association. However, a recent (2020) large-scale, genome-wide association study (GWAS) in the UK Biobank and United States Million Veteran Program identified six genome-wide loci and 27 candidate genes associated with self-reported tinnitus among >170,000 people of European ancestry. The estimated heritability was modest at 6%, but significant. This contrasts somewhat with the results of a prior GWAS that did not identify any significant candidate genes and estimated a lower heritability of 3.2%, which could be attributed to its comparatively much smaller population.

• #79 Current and Emerging Therapies for Chronic Subjective Tinnitus

  https://www.mdpi.com/2077-0383/12/20/6555

  Additionally, non-auditory pathways play a critical role in the maintenance and affective response to tinnitus. Correspondingly, tinnitus is known to be co-morbid with depression and anxiety, and intracochlear-glucocorticoid-mediated glutamate release may be a link between psychological stressors and tinnitus. The frontostriatal gating theory posits that the nucleus accumbens and ventromedial prefrontal cortex are important in the affective response to tinnitus. Perception of tinnitus demands attentional resource, and accordingly patients with tinnitus have been shown to have poorer selective attention on auditory tasks. […] There is growing interest in potential genetic contributions to tinnitus risk. Twin studies have estimated the heritability of tinnitus at 40–60%, although several candidate gene studies have failed to find such an association. However, a recent (2020) large-scale, genome-wide association study (GWAS) in the UK Biobank and United States Million Veteran Program identified six genome-wide loci and 27 candidate genes associated with self-reported tinnitus among >170,000 people of European ancestry. The estimated heritability was modest at 6%, but significant. This contrasts somewhat with the results of a prior GWAS that did not identify any significant candidate genes and estimated a lower heritability of 3.2%, which could be attributed to its comparatively much smaller population.

• #80 Current and Emerging Therapies for Chronic Subjective Tinnitus

  https://www.mdpi.com/2077-0383/12/20/6555

  Additionally, non-auditory pathways play a critical role in the maintenance and affective response to tinnitus. Correspondingly, tinnitus is known to be co-morbid with depression and anxiety, and intracochlear-glucocorticoid-mediated glutamate release may be a link between psychological stressors and tinnitus. The frontostriatal gating theory posits that the nucleus accumbens and ventromedial prefrontal cortex are important in the affective response to tinnitus. Perception of tinnitus demands attentional resource, and accordingly patients with tinnitus have been shown to have poorer selective attention on auditory tasks. […] There is growing interest in potential genetic contributions to tinnitus risk. Twin studies have estimated the heritability of tinnitus at 40–60%, although several candidate gene studies have failed to find such an association. However, a recent (2020) large-scale, genome-wide association study (GWAS) in the UK Biobank and United States Million Veteran Program identified six genome-wide loci and 27 candidate genes associated with self-reported tinnitus among >170,000 people of European ancestry. The estimated heritability was modest at 6%, but significant. This contrasts somewhat with the results of a prior GWAS that did not identify any significant candidate genes and estimated a lower heritability of 3.2%, which could be attributed to its comparatively much smaller population.

• #81 Pathophysiology and Treatment of Tinnitus: An Elusive Disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3918281/

  Though there have been advances in the understanding of the pathophysiology of this condition, the treatment modalities are still aimed at lessening the awareness of tinnitus and its impact on quality of life rather than attaining a definitive cure. Currently, no drug is available that has demonstrated replicable, long-term reduction of tinnitus impact in excess of placebo effects. Medical therapy has been limited in efficacy and consistency and more research needs to be conducted into non-medical treatment modalities such as TRT, cognitive behavioral therapy and masking. As a result, tinnitus remains a chronic, often debilitating condition for a significant number of patients. However, the development of molecular, biochemical and imaging techniques are offering increasing insights into the underlying causes of tinnitus and for the development of new potential targets for treatment.

• #82 Pathophysiology and Treatment of Tinnitus: An Elusive Disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3918281/

  Though there have been advances in the understanding of the pathophysiology of this condition, the treatment modalities are still aimed at lessening the awareness of tinnitus and its impact on quality of life rather than attaining a definitive cure. Currently, no drug is available that has demonstrated replicable, long-term reduction of tinnitus impact in excess of placebo effects. Medical therapy has been limited in efficacy and consistency and more research needs to be conducted into non-medical treatment modalities such as TRT, cognitive behavioral therapy and masking. As a result, tinnitus remains a chronic, often debilitating condition for a significant number of patients. However, the development of molecular, biochemical and imaging techniques are offering increasing insights into the underlying causes of tinnitus and for the development of new potential targets for treatment.

• #83 Severe Tinnitus: A Brain Disorder Beyond the Ringing Sound | AAO-HNS Bulletin

  https://bulletin.entnet.org/clinical-patient-care/article/22934209/severe-tinnitus-a-brain-disorder-beyond-the-ringing-sound

  This new understanding of tinnitus as a manifestation of CS represents an evolution of Jastreboffs original neurophysiological model. Although Jastreboff emphasized the auditory systems interaction with limbic and attentional networks, the CS framework expands this to include systemic neuroinflammatory processes, dysregulated sensory gating, and maladaptive plasticity across the CNS. […] Understanding tinnitus through the lens of central sensitization provides a comprehensive framework for addressing its underlying mechanisms, offering a pathway toward more effective, multimodal treatment strategies.

• #84 KoreaMed Synapse

  https://synapse.koreamed.org/articles/1044299

  Tinnitus represents a phantom auditory sensation without an external sound source. […] Considering the heterogeneity of tinnitus, a single theory or a hypothesis cannot sufficiently explain the mechanism of tinnitus. […] Degeneration of outer hair cell in the peripheral auditory system is known to be associated with tinnitus, while auditory plasticity theory, upregulation of excitation of central auditory structures explains the role of the central auditory pathway in the generation of tinnitus. […] In addition, somatosensory and limbic autonomic nervous systems are also deeply involved with the pathogenesis of tinnitus. […] Understanding of the mechanism of the tinnitus generation might be the cornerstone in the development of tinnitus treatment. […] Although a number of theories for the etiology of tinnitus were proposed, a single theory or a hypothesis could not explain the mechanism due to the diverse nature of tinnitus.

• #85 Transcranial direct current stimulation for the treatment of tinnitus: a review of clinical trials and mechanisms of action | BMC Neuroscience | Full Text

  https://bmcneurosci.biomedcentral.com/articles/10.1186/s12868-018-0467-3

  Structural and functional abnormalities in dorsolateral prefrontal cortex (DLPFC) and auditory cortex (AC) are associated with tinnitus. […] Therefore, in development of any treatment modality for tinnitus, this disorder should be considered as a complex and heterogamous condition involving a large network consisting of multiple overlapping brain networks. […] Considering the engagements of AC and DLPFC in the tinnitus perception, these regions may be good targets for any therapeutic intervention for tinnitus. […] The general hypothesis in application of tDCS for treatment of tinnitus like other neuropsychiatric disorders is that anodal tDCS increases the neural excitability, whereas cathodal tDCS decreases it. […] The main approach in choosing the target site and electrode placement in tDCS applications in different neuropsychiatric disorders is modulating the impaired region(s) of the brain to alter the activities or functions of the region(s) towards normal conditions.

• #86 Current and Emerging Therapies for Chronic Subjective Tinnitus

  https://www.mdpi.com/2077-0383/12/20/6555

  Following cochlear damage, the according reduction in auditory nerve output is proposed to initiate a neurobiological signaling cascade resulting in hyperactivity in the central auditory system encoding for tinnitus. Thus, it is possible that the loss of cochlear afferent activity liberates involuntary, internally generated percepts in the brain, similar to the neural mechanism for phantom limb pain. This would explain the common clinical finding that tinnitus persists even after destruction of the auditory nerve via, for example, surgery for vestibular schwannoma. […] This theory is further bolstered by the high rate of acquired hearing loss in tinnitus patients (~90%), the rarity of tinnitus among the congenitally deaf, and that tinnitus is often suppressed by cochlear implants which functionally replace cochlear nerve output. This mechanism for tinnitus is clinically relevant because treatment at the peripheral site (e.g., sound masking at the cochlea) may not correct alterations of activity in the central auditory pathway responsible for tinnitus persistence. However, restoring cochlear input via hearing-aid-mediated sound therapy can be effective in improving patients’ subjective experience of tinnitus, and approximately 80% of patients with chronic tinnitus reported improvement in tinnitus annoyance and loudness in a questionnaire-based study in Japan.

• #87 KoreaMed Synapse

  https://synapse.koreamed.org/articles/1044299

  Sensorineural tinnitus can be expressed as tonal sound, narrow band sound or white noise. […] A recent study revealed that tinnitus is a consequence of neuroplastic alterations in the central auditory pathway as well as somatosensory change. […] The exact mechanism of subjective tinnitus is obscure. […] The hypothesis of maladaptive neural plasticity seems to explain those changes of increased spontaneous firing rates and synchrony among neurons in central auditory structures and non-auditory brain networks, possibly generating the phantom percept analogue to phantom limb sensation. […] The neurophysiological model has been widely accepted in this field and habituation strategy to both tinnitus signal and the reaction against tinnitus has been developed as a Tinnitus Retraining Therapy. […] The complex interaction between peripheral auditory pathways, central auditory pathway and non-auditory region of the limbic, somatosensory and autonomic system, might contribute to the generation and persistence of tinnitus.

• #88 Scientists find mechanism that causes noise-induced tinnitus and drug that can prevent it

  https://medicalxpress.com/news/2013-05-scientists-mechanism-noise-induced-tinnitus-drug.html

  „We found that mice with tinnitus have hyperactive DCN cells because of a reduction in KCNQ potassium channel activity,” Dr. Tzounopoulos said. „These KCNQ channels act as effective 'brakes’ that reduce excitability or activity of neuronal cells.” […] „This is an important finding that links the biophysical properties of a potassium channel with the perception of a phantom sound,” Dr. Tzounopoulos said. „Tinnitus is a channelopathy, and these KCNQ channels represent a novel target for developing drugs that block the induction of tinnitus in humans.”

• #89 Transcranial direct current stimulation for the treatment of tinnitus: a review of clinical trials and mechanisms of action | BMC Neuroscience | Full Text

  https://bmcneurosci.biomedcentral.com/articles/10.1186/s12868-018-0467-3

  The first hypothesis is based on the disturbing theory of an ongoing neural activity associated with tinnitus. It is hypothesized that tDCS disturbs the abnormal ongoing neural activity induced by tinnitus. […] The second hypothesis is changing the maladaptive plasticity of tinnitus through repeated sessions of tDCS. […] Therefore, in the treatment of tinnitus with tDCS, the main idea is modulating the abnormal excitability in the auditory pathways and maladaptive plasticity in auditory and limbic cortexes through applying single or repeated sessions of tDCS. […] The clinical trials conducted so far have shown that single and repeated sessions of tDCS applied over DLPFC or AC may induce transient and long lasting therapeutic effects in tinnitus patients. […] Some evidence showed that the tDCS effects on tinnitus symptoms are probably induced through modulations of a large neural network comprising of pregenual anterior cingulate cortex, parahippocampal area, and right primary AC in resting-state spontaneous brain activity.

• #90 Pathophysiology and Treatment of Tinnitus: An Elusive Disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3918281/

  Though there have been advances in the understanding of the pathophysiology of this condition, the treatment modalities are still aimed at lessening the awareness of tinnitus and its impact on quality of life rather than attaining a definitive cure. Currently, no drug is available that has demonstrated replicable, long-term reduction of tinnitus impact in excess of placebo effects. Medical therapy has been limited in efficacy and consistency and more research needs to be conducted into non-medical treatment modalities such as TRT, cognitive behavioral therapy and masking. As a result, tinnitus remains a chronic, often debilitating condition for a significant number of patients. However, the development of molecular, biochemical and imaging techniques are offering increasing insights into the underlying causes of tinnitus and for the development of new potential targets for treatment.

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