Research's Attempt to Objectively Assess Tinnitus

Sensory and Cognitive Components of Auditory Processing in Individuals With Tinnitus

Purpose
The main purpose of the study is to explore the auditory selective attention abilities (using event-related potentials) and the neuronal oscillatory activity in the default mode network sites (using electroencephalogram [EEG]) in individuals with tinnitus.

Method
Auditory selective attention was measured using P300, and the resting state EEG was assessed using the default mode function analysis. Ten individuals with continuous and bothersome tinnitus along with 10 age- and gender-matched control participants underwent event-related potential testing and 5 min of EEG recording (at wakeful rest).

Results
Individuals with tinnitus were observed to have larger N1 and P3 amplitudes along with prolonged P3 latency. The default mode function analysis revealed no significant oscillatory differences between the groups.

Conclusion
The current study shows changes in both the early sensory and late cognitive components of auditory processing. The change in the P3 component is suggestive of selective auditory attention deficit, and the sensory component (N1) suggests an altered bottom-up processing in individuals with tinnitus.

Source: https://pubs.asha.org/doi/abs/10.1044/2019_AJA-19-0011
 
Morphological Neuroimaging Biomarkers for Tinnitus: Evidence Obtained by Applying Machine Learning

According to previous studies, many neuroanatomical alterations have been detected in patients with tinnitus. However, the results of these studies have been inconsistent. The objective of this study was to explore the cortical/subcortical morphological neuroimaging biomarkers that may characterize idiopathic tinnitus using machine learning methods. Forty-six patients with idiopathic tinnitus and fifty-six healthy subjects were included in this study. For each subject, the gray matter volume of 61 brain regions was extracted as an original feature pool. From this feature pool, a hybrid feature selection algorithm combining the -score and sequential forward floating selection (SFFS) methods was performed to select features. Then, the selected features were used to train a support vector machine (SVM) model. The area under the curve (AUC) and accuracy were used to assess the performance of the classification model. As a result, a combination of 13 cortical/subcortical brain regions was found to have the highest classification accuracy for effectively differentiating patients with tinnitus from healthy subjects. These brain regions include the bilateral hypothalamus, right insula, bilateral superior temporal gyrus, left rostral middle frontal gyrus, bilateral inferior temporal gyrus, right inferior parietal lobule, right transverse temporal gyrus, right middle temporal gyrus, right cingulate gyrus, and left superior frontal gyrus. The accuracy in the training and test datasets was 80.49% and 80.00%, respectively, and the AUC was 0.8586. To the best of our knowledge, this is the first study to elucidate brain morphological changes in patients with tinnitus by applying an SVM classifier. This study provides validated cortical/subcortical morphological neuroimaging biomarkers to differentiate patients with tinnitus from healthy subjects and contributes to the understanding of neuroanatomical alterations in patients with tinnitus.

Full article: https://www.hindawi.com/journals/np/2019/1712342/
 
Corticostriatal functional connectivity of bothersome tinnitus in single-sided deafness

Abstract
Subjective tinnitus is an auditory phantom perceptual disorder without an objective biomarker. Bothersome tinnitus in single-sided deafness (SSD) is particularly challenging to treat because the deaf ear can no longer be stimulated by acoustic means. We contrasted an SSD cohort with bothersome tinnitus (TIN; N = 15) against an SSD cohort with no or non-bothersome tinnitus (NO TIN; N = 15) using resting-state functional magnetic resonance imaging (fMRI). All study participants had normal hearing in one ear and severe or profound hearing loss in the other. We evaluated corticostriatal functional connectivity differences by placing seeds in the caudate nucleus and Heschl's Gyrus (HG) of both hemispheres. The TIN cohort showed increased functional connectivity between the left caudate and left HG, and left and right HG and the left caudate. Within the TIN cohort, functional connectivity between the right caudate and cuneus was correlated with the Tinnitus Functional Index (TFI) relaxation subscale. And, functional connectivity between the right caudate and superior lateral occipital cortex, and the right caudate and anterior supramarginal gyrus were correlated with the TFI control subscale. These findings support a striatal gating model of tinnitus and suggest tinnitus biomarkers to monitor treatment response and to target specific brain areas for innovative neuromodulation therapies.

Full article: https://www.nature.com/articles/s41598-019-56127-1
 
Exposure to sodium salicylate disrupts VGLUT3 expression in cochlear inner hair cells and contributes to tinnitus.

Abstract
To examine whether exposure to sodium salicylate disrupts expression of vesicular glutamate transporter 3 (VGLUT3) and whether the alteration in expression corresponds to increased risk for tinnitus. Rats were treated with saline (control) or sodium salicylate (treated) Rats were examined for tinnitus by monitoring gap-pre-pulse inhibition of the acoustic startle reflex (GPIAS). Auditory brainstem response (ABR) was applied to evaluate hearing function after treatment. Rats were sacrificed after injection to obtain the cochlea, cochlear nucleus (CN), and inferior colliculus (IC) for examination of VGLUT3 expression. No significant differences in hearing thresholds between groups were identified (p>0.05). Tinnitus in sodium salicylate-treated rats was confirmed by GPIAS. VGLUT3 encoded by solute carrier family 17 members 8 (SLC17a8) expression was significantly increased in inner hair cells (IHCs) of the cochlea in treated animals, compared with controls (p<0.01). No significant differences in VGLUT3 expression between groups were found for the cochlear nucleus (CN) or IC (p>0.05). Exposure to sodium salicylate may disrupt SLC17a8 expression in IHCs, leading to alterations that correspond to tinnitus in rats. However, the CN and IC are unaffected by exposure to sodium salicylate, suggesting that enhancement of VGLUT3 expression in IHCs may contribute to the pathogenesis of tinnitus.

Source: https://www.ncbi.nlm.nih.gov/pubmed/31852197
 
OK it is just a case study, but it relates a new tool: Diffusion Tensor Tractography
and a specific etiology of tinnitus: auditory radiation.

Diagnosis of Tinnitus Due to Auditory Radiation Injury Following Whiplash Injury: A Case Study
 

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Altered functional connectivity of the thalamus in tinnitus patients is correlated with symptom alleviation after sound therapy

Abstract
Altered functional connectivity (FC) of the thalamus has been proven to be an important finding in tinnitus patients. Tinnitus can be effectively desensitized by sound therapy. However, it is still unclear whether and how sound therapy affects the FC of the thalamus. Resting-state functional magnetic resonance imaging data and anatomical data were longitudinally collected from 25 idiopathic tinnitus patients before and after 12 weeks of sound therapy by using adjusted narrow band noise and from 25 matched healthy controls at the same time interval without any intervention. The FC of bilateral thalami were analyzed by setting the left and right thalamus as the regions of interest. Significant main effect of group on the FC of the thalamus were found mainly in the key components of the default mode network, limbic network, salience network, cognitive control network, auditory network and occipital region. FC values between the thalamus, inferior frontal gyrus (IFG), and anterior cingulate cortex (ACC) featured higher values in the tinnitus group at baseline compared to the healthy controls and restoration in tinnitus patients after treatment. Decreased Tinnitus Handicap Inventory (THI) scores and decreased FC values between the right thalamus and right IFG were positively correlated (r = 0.476, P = 0.016). Abnormal FC of the thalamus is associated with multiple brain networks. Sound therapy has a normalizing effect on the enhanced FC of the thalamus-IFG and thalamus-ACC, representing decreased tinnitus attention control and less involvement of the noise-canceling system.

Source: https://link.springer.com/article/10.1007/s11682-019-00218-0
 
A 7 Tesla fMRI investigation of human tinnitus percept in cortical and subcortical auditory areas

Highlights

UHF-fMRI is used to study frequency-specific processing in tinnitus patients
Control patients are hearing-loss matched to tinnitus patients
MGB and auditory cortex display reduced frequency selectivity with tinnitus
Thalamocortical and cortico-cortical connectivity is reduced with tinnitus
Relevance of UHF-fMRI for investigating subcortical auditory regions in tinnitus

Abstract

Tinnitus is a clinical condition defined by hearing a sound in the absence of an objective source. Early experiments in animal models have suggested that tinnitus stems from an alteration of processing in the auditory system. However, translating these results to humans has proven challenging. One limiting factor has been the insufficient spatial resolution of non-invasive measurement techniques to investigate responses in subcortical auditory nuclei, like the inferior colliculus and the medial geniculate body (MGB). Here we employed ultra-high field functional magnetic resonance imaging (UHF-fMRI) at 7 Tesla to investigate the frequency-specific processing in sub-cortical and cortical regions in a cohort of six tinnitus patients and six hearing loss matched controls. We used task-based fMRI to perform tonotopic mapping and compared the magnitude and tuning of frequency-specific responses between the two groups. Additionally, we used resting-state fMRI to investigate the functional connectivity. Our results indicate frequency-unspecific reductions in the selectivity of frequency tuning that start at the level of the MGB and continue in the auditory cortex, as well as reduced thalamocortical and cortico-cortical connectivity with tinnitus. These findings suggest that tinnitus may be associated with reduced inhibition in the auditory pathway, potentially leading to increased neural noise and reduced functional connectivity. Moreover, these results indicate the relevance of high spatial resolution UHF-fMRI for the investigation of the role of sub-cortical auditory regions in tinnitus.

Keywords
Tinnitus
Ultra-high field MRI
Tonotopic maps
Auditory pathway
Resting-state connectivity

Full article: https://www.sciencedirect.com/science/article/pii/S221315822030005X

It is a good thing that better tools (more than the typical 3 tesla MRI) are used to investigate tinnitus.
It reminds me this project that we (french people) heard last summer:
http://www.cea.fr/english/Pages/News/Iseult-MRI-Magnet-Record.aspx
Maybe I will contact them to ask if tinnitus is included in their future investigations.
 
Abnormal Spontaneous Neural Activity of the Central Auditory System Changes the Functional Connectivity in the Tinnitus Brain: A Resting-State Functional MRI Study

Objective
An abnormal state of the central auditory system (CAS) likely plays a large role in the occurrence of phantom sound of tinnitus. Various tinnitus studies using resting-state functional MRI (RS-fMRI) have reported aberrant spontaneous brain activity in the non-auditory system and altered functional connectivity between the CAS and non-auditory system. This study aimed to investigate abnormal functional connections between the aberrant spontaneous activity in the CAS and the whole brain in tinnitus patients, compared to healthy controls (HC) using RS-fMRI.

Materials and Methods
RS-fMRI from 16 right-ear tinnitus patients with normal hearing (TNHs) and 15 HC individuals was collected, and the time series were extracted from different clusters of a CAS template, supplied by the Anatomy Toolbox of the Statistical Parametric Mapping software. These data were used to derive the smoothed mean amplitude of low-frequency fluctuation (smALFF) values and calculate the relationship between such values and the corresponding clinical data. In addition, clusters in the CAS identified by the smALFF maps were set as seed regions for calculating and comparing the brain-wide connectivity between TNH and HC.

Results
We identified the different clusters located in the left higher auditory cortex (HAC) and the right inferior colliculus (IC) from the smALFF maps that contained increased (HAC) and decreased (IC) activity when the TNH group was compared to the HC group, respectively. The value of increased smALFF cluster in the HAC was positively correlated with the tinnitus score, but the decreased smALFF cluster in the IC was not correlated with any clinical characters of tinnitus. The TNH group displayed increased connectivity, compared to the HC group, in brain regions that encompassed the left IC, bilateral Heschl gyrus, bilateral supplementary motor area, right insula, bilateral superior temporal gyrus, right middle temporal gyrus, left hippocampus, left amygdala, and right supramarginal gyrus.

Conclusion
Tinnitus may be linked to abnormal spontaneous activity in the HAC, which can arise from the neural plasticity induced from the increased functional connectivity between the auditory network, cerebellum, and limbic system.

Keywords: tinnitus, resting-state functional magnetic resonance imaging, amplitude of low-frequency fluctuation, auditory cortex, auditory pathway, spontaneous neural synchrony

Full article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6932986/
 
Exposure to sodium salicylate disrupts VGLUT3 expression in cochlear inner hair cells and contributes to tinnitus.
This article that you posted above is very interesting.

I have posted most of this before. When I first developed tinnitus and hyperacusis from ear syringing about ten ago, I had to retire. Sometime before walking out the door for the last time, a clinical scientist that examined rare disease by blood analysis said to me, all patients that have a high level of sodium salicylate also have tinnitus. Some also have high B12 or D3. He also said that it's not a lack of vitamins other than magnesium, it's too much of a vitamin taken and that's always a problem for those where it stores and is not processed. His thought was, always get your blood examined with complete profiles every few years and always when receiving tinnitus.
 
This article that you posted above is very interesting.

I have posted most of this before. When I first developed tinnitus and hyperacusis from ear syringing about ten ago, I had to retire. Sometime before walking out the door for the last time, a clinical scientist that examined rare disease by blood analysis said to me, all patients that have a high level of sodium salicylate also have tinnitus. Some also have high B12 or D3. He also said that it's not a lack of vitamins other than magnesium, it's too much of a vitamin taken and that's always a problem for those where it stores and is not processed. His thought was, always get your blood examined with complete profiles every few years and always when receiving tinnitus.
But I thought we were supposed to take B12 like candy? Too much of a a water soluble vitamin would just come out in the urine, wouldn't it?
 
Age-related change of auditory functional connectivity in Human Connectome Project data and tinnitus patients

Abstract

Background: We reported that tinnitus patients showed reduced levels of auditory functional connectivity (FC) in comparison with normal hearing control subjects, and that we succeeded in objective diagnosis of tinnitus with 86% sensitivity and 74% specificity by focusing only on auditory-related FC. However, the age-related change of auditory FC is not clarified. In this study, we examine age-related change of the auditory FC using the database of Human Connectome Project (HCP) and compared with our database of tinnitus patients.

Method: From the HCP database HCP Lifespan Pilot project, we studied five age groups, 8 to 9 years old, 14 to 15, 25 to 35, 45 to 55, and 65 to 75. We also applied our tinnitus patients' resting-state functional magnetic resonance imaging (fMRI) database, which is divided into three generations; 20 to 40 years old, 40 to 60, and 60 to 80 to compare with the HCP database. The resting state fMRI analyses were performed using the CONN toolbox version 18. As auditory-related regions, Heschl's gyrus, planum temporale, planum polare, operculum, insular cortex, and superior temporal gyrus were set as the regions of interest from our previous reports.

Result: Auditory FC is strongest among adolescents and reduces with age. But the auditory FC of tinnitus patients were significantly less than those of HCP data in each generation.

Conclusion: Although auditory FC decreases with age, tinnitus patients have less auditory FC compared with age-matched controls. The age-matched cutoff values are necessary for an objective diagnosis of tinnitus with resting state fMRI.

KEYWORDS auditory functional connectivity, resting state functional magnetic resonance imaging, tinnitus

Full article see attached file
 

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Evaluation of Tinnitus and Hearing Loss in the Adult

Abstract:
Tinnitus and hearing loss in the adult can have profound effects on the quality of life. The imaging workup for tinnitus and hearing loss in adults follows otoscopic exam and audiometry testing. CT and MR imaging have different and often complementary roles in the evaluation of tinnitus and hearing loss depending on the clinical scenario and the suspected underlying cause. Imaging can often identify the cause and evaluate the extent of disease for surgical planning. This article discusses anatomy, imaging technique, and diseases that cause tinnitus and hearing loss with a mass and without a mass.

Source: https://link.springer.com/chapter/10.1007/978-3-030-38490-6_15

These parts of this article are interesting (good state of art):
15.5 Tinnitus and Hearing Loss without a Mass
15.6 Tinnitus and Hearing Loss with a Mass
 
Regional homogeneity and functional connectivity in resting-state brain activity intinnitus patients

Subjective tinnitus is characterized by the perception of sound in the absence of any external auditory stimuli. This perceived sound may be related to altered intrinsic neural activity generated along the central auditory pathway. This retrospective study was designed to investigate regional homogeneityand functional connectivity in the resting-state brain activity of patients withtinnitus. We recruited tinnitus patients with normal hearing or mild hearing loss (n = 17) and age-matched healthy controls (n = 20), and examined regional homogeneity and functional connectivity in resting-state brain activity using resting-state functional magnetic resonance imaging data. The present study protocol was approved by the Institutional Review Board on Experimental Ethics at Sun Yat-sen University, China (approval No. SYSEC-KY-KS-2019-083). Compared with normal controls, patients with tinnitus had significantly decreased regional homogeneity in the anterior lobe of the cerebellum and increased homogeneity in the inferior frontal gyrus (P < 0.05 corrected at a cluster-level). In addition, tinnitus patients showed enhanced functional connectivity between the inferior frontal gyrus and the ventral striatum and midbrain, as well as increased connectivity between the cerebellum and ventromedial prefrontal cortex (P < 0.05 corrected at a cluster-level). We also found decreased connectivity between the cerebellum and the anterior insula compared with controls (P < 0.05 corrected at a cluster-level). Abnormal connectivity in non-auditory brain structures, particularly those related to emotion processing, may be associated with tinnitus persistence.

Copyright © 2020 The Chinese Medical Association. Published by Wolters Kluwer Health, Inc.

Source: https://journals.lww.com/jbioxresea...eneity_and_functional_connectivity.99952.aspx
 
It is about Zwicker Tone

Investigating functional changes in the brain to intermittently induced auditory illusions and its relevance to chronic tinnitus

Abstract

Several studies have demonstrated the neural correlates of chronic tinnitus. However, we still do not understand what happens in the acute phase. Past studies have established Zwicker tone (ZT) illusions as a good human model for acute tinnitus. ZT illusions are perceived following the presentation of a notched noise stimulus, that is, broadband noise with a narrow band-stop filter (notch). In the current study, we compared the neural correlates of the reliable perception of a ZT illusion to that which is not. We observed changes in evoked and total theta power in wide-spread regions of the brain particularly in the temporal-parietal junction, pregenual anterior cingulate cortex/ventromedial prefrontal cortex (pgACC/vmPFC), parahippocampus during perception of the ZT illusion. Furthermore, we observe that increased theta power significantly predicts a gradual positive change in the intensity of the ZT illusion. Such changes may suggest a malfunction of the sensory gating system that enables habituation to redundant stimuli and suppresses hyperactivity. It could also suggest a successful retrieval of the memory of the missing frequencies, resulting in their conscious perception indicating the role of higher-order processing in the mechanism of action of ZT illusions. To establish a more concrete relationship between ZT illusion and chronic tinnitus, future longitudinal studies following up a much larger sample of participants who reliably perceive a ZT illusion to see if they develop tinnitus at a later stage is essential. This could inform us if the ZT illusion may be a precursor to chronic tinnitus.

KEYWORDS ERP, sLORETA, time–frequency decomposition, Zwicker tone
 

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So does it mean that tinnitus is an incomplete hearing loss process?

Cortical Tonotopic Map Changes in Humans are Larger in Hearing Loss than in additional Tinnitus

Abstract
Neural plasticity due to hearing loss results in tonotopic map changes. Several studies have suggested a relation between hearing-loss-induced tonotopic reorganization and tinnitus. This large functional magnetic resonance imaging (fMRI) study on humans intended to clarify the relations between hearing loss, tinnitus and tonotopic reorganization. To determine the differential effect of hearing loss and tinnitus, both male and female participants with bilateral high frequency hearing loss, with and without tinnitus, and a control group were included. In a total of 90 participants, bilateral cortical responses to sound stimulation were measured with loudness matched pure-tone stimuli (0.25 - 8 kHz). In the bilateral auditory cortices, the high frequency sound-evoked activation level was higher in both hearing-impaired participant groups, compared to the control group. This was most prominent in the hearing loss group without tinnitus. Similarly, the tonotopic maps for the hearing loss without tinnitus group were significantly different from the controls, whereas the maps of those with tinnitus were not. These results show that higher response amplitudes and map reorganization are a characteristic of hearing loss, not of tinnitus. Both tonotopic maps and response amplitudes of tinnitus participants appear intermediate to the controls and hearing loss without tinnitus group. This observation suggests a connection between tinnitus and an incomplete form of central compensation to hearing loss, rather than excessive adaptation. One implication of this may be that treatments for tinnitus shift their focus towards enhancing the cortical plasticity on track, instead of reversing it.

Significance Statement: Tinnitus, a common and potentially devastating condition, is the presence of a 'phantom' sound that often accompanies hearing loss. Hearing loss is known to induce plastic changes in cortical and sub-cortical areas. Although plasticity is a valuable trait that allows the human brain to rewire and recover from injury and sensory deprivation, it can lead to tinnitus as an unwanted side effect. In this large fMRI study, we provide evidence that tinnitus is related to a more conservative form of reorganization than in hearing loss without tinnitus. This result contrasts with the previous notion that tinnitus is related to excessive reorganization. As a consequence, treatments for tinnitus may need to enhance the cortical plasticity, rather than reversing it.

Source: https://www.jneurosci.org/content/early/2020/03/13/JNEUROSCI.2083-19.2020.abstract
 
New Automatic and Robust Measures to Evaluate Hearing Loss and Tinnitus in Preclinical Models

Abstract

During this collaboration between CILcare and KeenEye Technologies, a full pipeline has been designed to automatically classify and quantify the number of hair cells in 3D cochlea images. This project introduced many challenges with regard to specific pre- and post-data processing and an adaptive model for 3D object detection. The model has been trained using transfer learning with mini batch images keeping the context information around the different types of cells. This new automatic counting method performed 10 times faster than humans, with on average 3.5 min to analyze one fragment image. The algorithm gave performance metrics of 90% for precision and 70% for sensitivity. While the precision value is good, additional work is needed to increase the overall sensitivity and reduce its variance. In addition, an objective quantification method to detect tinnitus on rats was developed in collaboration between CILcare and Charles Coulomb Laboratory (L2C-BioNanoNMRI team). Tinnitus, a phantom auditory sensation, which occurs in the absence of an external sound stimulus, is generated presumably within the auditory brain. Here we focus on the inferior colliculus (IC), a midbrain structure that integrates auditory information from both ears as well as information from other sensory systems. Some studies reveal neural hyperactivity in the IC after salicylate drug administration. In this study, we present an innovative manganese-enhanced magnetic resonance imaging (MEMRI) analysis method called ∆R2/R2. This quantitative method detects1H NMR relaxation rate changes in the absence or presence of tinnitus. The ∆R2/R2 method generates relevant data comparable to those obtained with the signal-to-noise ratio (SNR) and signal intensity ratio (SIR) methods when manganese is administered by the transtympanic or intraperitoneal route. A major advantage of the ∆R2/R2 method is that it is automatic, robust, and reveals quantitative markers compared to qualitative methods like SNR and SIR.

Keywords
Cochleogram Automated method Rat Hearing loss Tinnitus MEMRI

Source: https://link.springer.com/chapter/10.1007/978-3-030-40413-0_7
See also:
https://keeneye.ai/
https://www.cilcare.com/
 
So does it mean that tinnitus is an incomplete hearing loss process?

Cortical Tonotopic Map Changes in Humans are Larger in Hearing Loss than in additional Tinnitus

Abstract
Neural plasticity due to hearing loss results in tonotopic map changes. Several studies have suggested a relation between hearing-loss-induced tonotopic reorganization and tinnitus. This large functional magnetic resonance imaging (fMRI) study on humans intended to clarify the relations between hearing loss, tinnitus and tonotopic reorganization. To determine the differential effect of hearing loss and tinnitus, both male and female participants with bilateral high frequency hearing loss, with and without tinnitus, and a control group were included. In a total of 90 participants, bilateral cortical responses to sound stimulation were measured with loudness matched pure-tone stimuli (0.25 - 8 kHz). In the bilateral auditory cortices, the high frequency sound-evoked activation level was higher in both hearing-impaired participant groups, compared to the control group. This was most prominent in the hearing loss group without tinnitus. Similarly, the tonotopic maps for the hearing loss without tinnitus group were significantly different from the controls, whereas the maps of those with tinnitus were not. These results show that higher response amplitudes and map reorganization are a characteristic of hearing loss, not of tinnitus. Both tonotopic maps and response amplitudes of tinnitus participants appear intermediate to the controls and hearing loss without tinnitus group. This observation suggests a connection between tinnitus and an incomplete form of central compensation to hearing loss, rather than excessive adaptation. One implication of this may be that treatments for tinnitus shift their focus towards enhancing the cortical plasticity on track, instead of reversing it.

Significance Statement: Tinnitus, a common and potentially devastating condition, is the presence of a 'phantom' sound that often accompanies hearing loss. Hearing loss is known to induce plastic changes in cortical and sub-cortical areas. Although plasticity is a valuable trait that allows the human brain to rewire and recover from injury and sensory deprivation, it can lead to tinnitus as an unwanted side effect. In this large fMRI study, we provide evidence that tinnitus is related to a more conservative form of reorganization than in hearing loss without tinnitus. This result contrasts with the previous notion that tinnitus is related to excessive reorganization. As a consequence, treatments for tinnitus may need to enhance the cortical plasticity, rather than reversing it.

Source: https://www.jneurosci.org/content/early/2020/03/13/JNEUROSCI.2083-19.2020.abstract
Wouldn't that explain why Neuromodulation actually works, as in enhancing cortical plasticity?
 
Global resting-state functional connectivity of neural oscillations in tinnitus with and without hearing loss

Abstract

This study examined global resting-state functional connectivity of neural oscillations in individuals with chronic tinnitus and normal and impaired hearing. We tested the hypothesis that distinct neural oscillatory networks are engaged in tinnitus with and without hearing loss. In both tinnitus groups, with and without hearing loss, we identified multiple frequency band-dependent regions of increased and decreased global functional connectivity. We also found that the auditory domain of tinnitus severity, assayed by the Tinnitus Functional Index, was associated with global functional connectivity in both auditory and nonauditory regions. These findings provide candidate biomarkers to target and monitor treatments for tinnitus with and without hearing loss.

Full article: see attached file.
 

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Aberrant expression of Nav1.6 in the cochlear nucleus correlates with salicylate-induced tinnitus in rats


Highlights
Acute and chronic administrations of salicylate produce tinnitus-like behavior in rats.

Decreased number of inhibitory neurons and increased number of excitatory neurons in the CN are correlated with tinnitus.

Percentage of co-localization of Nav1.6 and inhibitory neurons decreases in the AVCN and DCN during tinnitus.

Percentage of co-localization of Nav1.6 and fusiform cells increases in the DCN during tinnitus.

Abstract

Hyperactivity in cochlear nucleus (CN) is one of the major neural correlates for tinnitus induction, yet the molecular factors that participate in the neuronal hyperexcitability remain unclear. The present study showed that acute and chronic administrations of salicylate were both capable of inducing reversible tinnitus in rats. The number of GAD 65/67-immunoreactive neurons in the AVCN and DCN was decreased, while the number of VGLUT 1/2-immunoreactive neurons in the AVCN and DCN was increased when rats were experiencing tinnitus, providing evidence for excitatory-inhibitory imbalance in CN is correlated with tinnitus. Interestingly, the expression level of Nav1.6, an important subtype of voltage-gated sodium channels was significantly increased in the DCN and AVCN of rats experiencing tinnitus, the up-regulation of Nav1.6 was returned to normal level following the disappearance of tinnitus. Double-labeling experiments revealed that Nav1.6 expression was down-regulated in the GAD 65/67-positive neurons in the DCN and AVCN of rats experiencing tinnitus. Notably, the percentage of co-localization of Nav1.6 and NeuN-labeling fusiform neurons was markedly increased in the DCN during tinnitus. These findings uncover the tinnitus-associated alteration in Nav1.6, a potential key contributor that can lead to hyperexcitability in CN and contribute to salicylate-induced tinnitus.

Keywords
Tinnitus
Salicylate
Cochlear nucleus
Neuronal hyperexcitability
Nav1.6

Source: https://www.sciencedirect.com/science/article/abs/pii/S0006291X20306148
 
Acoustic trauma induced the alteration of the activity balance of excitatory and inhibitory neurons in the inferior colliculus of mice

Highlights

Acoustic trauma inversed the balance of excitatory and inhibitory activities in IC.
Glutamatergic neurons increased the spontaneous firings by acoustic trauma.
GABAergic neurons did not change the spontaneous firings by acoustic trauma.
Bursting events increased in the glutamatergic neurons by acoustic trauma.
Spike shapes of both cell types were changed by acoustic trauma.

Abstract

We examined the effect of acoustic trauma on the spontaneous activities of the glutamatergic and GABAergic neurons in the inferior colliculus (IC) of mice. Optogenetics was used to identify the neuron type. In control animals, the spontaneous firing rate was higher in GABAergic neurons than in glutamatergic neurons. However, in the animals with acoustic trauma, the balance of spontaneous activities between glutamatergic and GABAergic neurons was inverted. The spontaneous firing rate was enhanced in glutamatergic neurons only, with bursting episodes occurring frequently. Moreover, the spike shapes of GABAergic and glutamatergic neurons were modified differently in both cell types. These results suggested that the acoustic trauma induced plastic changes in the neuronal circuits in the IC and altered the balance of the activities of excitatory and inhibitory neurons. This aberrant excitatory–inhibitory balance in the IC might underpin tinnitus perception.

Source: https://www.sciencedirect.com/science/article/pii/S0378595520300484
 
Screenshot 2020-05-02 at 08.50.45.png
 
Binaural Interaction in Tinnitus Patients

Abstract

The auditory brainstem response (ABR) is a commonly used objective clinical measure for hearing evaluation. It can be also used to draw conclusions about the functioning of distinct stages of the auditory pathway including the binaural processing stages using the binaural interaction component (BIC) of the ABR.

Objective:

To study binaural processing in normal hearing subjects complaining of tinnitus.

Methods:

Sixty cases with bilateral normal peripheral hearing were included in this work, divided into 2 groups, i.e., group 1 (comprised of 30 healthy subjects representing the control group) and group 2 (comprised of 30 subjects with tinnitus representing the study group). All of the subjects were submitted to a basic audiological evaluation (including pure tone audiometry, speech audiometry, and immittancemetry) and ABR audiometry recorded in monaural and then binaural conditions.

Results:

In monaural recording, the tinnitus group showed significantly delayed latencies of waves I, III, and V in addition to significantly reduced wave I and III amplitudes when compared with the controls. Similar significant findings were found when binaural ABR responses were compared between both groups. Comparing BIC between both groups showed significant earlier BIC for latencies of waves I and V in the control group, while the BIC for amplitudes showed similar results in both groups.

Conclusions:

These finding suggest the presence of binaural processing deficits in tinnitus patients at different levels along the ascending auditory pathway.

Source: https://www.karger.com/Article/Abstract/507274
 
Sensory and Cognitive Components of Auditory Processing in Individuals With Tinnitus

Purpose
The main purpose of the study is to explore the auditory selective attention abilities (using event-related potentials) and the neuronal oscillatory activity in the default mode network sites (using electroencephalogram [EEG]) in individuals with tinnitus.

Method
Auditory selective attention was measured using P300, and the resting state EEG was assessed using the default mode function analysis. Ten individuals with continuous and bothersome tinnitus along with 10 age- and gender-matched control participants underwent event-related potential testing and 5 min of EEG recording (at wakeful rest).

Results
Individuals with tinnitus were observed to have larger N1 and P3 amplitudes along with prolonged P3 latency. The default mode function analysis revealed no significant oscillatory differences between the groups.

Conclusion
The current study shows changes in both the early sensory and late cognitive components of auditory processing. The change in the P3 component is suggestive of selective auditory attention deficit, and the sensory component (N1) suggests an altered bottom-up processing in individuals with tinnitus.

Source: https://pubs.asha.org/doi/abs/10.1044/2019_AJA-19-0011
This one sounds interesting, but I only read the abstract, not the full text...

Does "latency" mean the speed at which sound is driven to the brain?
 
Mean platelet volume and neutrophil to lymphocyte ratio in patients with tinnitus: a case-control study

Abstract
Introduction
Different theories have been proposed on the etiology of tinnitus, including metabolic and audiologic causes. We suggest that mean platelet volume and neutrophil to lymphocyte ratio levels change in tinnitus, indicating microcirculatory disturbance and inflammatory process in the etiopathogenesis of tinnitus.

Objectives
We aimed to evaluate the mean platelet volume and neutrophil to lymphocyte ratio in patients with tinnitus in comparison to healthy controls.

Methods
Retrospective case-control study. Two-hundred and eighty-seven patients aged 18–59 years and diagnosed with tinnitus in the Ear, Nose, and Throat Clinic between December 2014 and May 2017 (patient group) and 275 healthy individuals who applied for a hearing screening within the same time period (control group). Demographics, concomitant diseases, laboratory results, and audiometric data were recorded. Mean platelet volume and neutrophil to lymphocyte ratio were the outcome measures. Patients with hearing loss due to presbycusis or another reasons, and patients with anatomical disorders in the external and middle ear were excluded from the study by using physical examinations, pure audio audiometry results and radiological imaging. The upper age limit was set at 59 to exclude presbycusis patients.

Results
The ratio of female patients was higher in patient group than control group (58.5%, n = 168 vs. 49.4%, n = 127; respectively; p = 0.033). The mean age of patient group was significantly higher than those of control group (44.89 ± 10.96 years and 38.37 ± 10.65 years, respectively; p = 0.001). The percentage of subjects with high mean platelet volume level was significantly higher in patient group than control group (9.4%, n = 27, and 3.1%, n = 8 respectively; p = 0.008). The mean neutrophil to lymphocyte ratio was higher in patients with tinnitus than control group (1.95 ± 1.02 and 1.67 ± 0.57, p = 0.012). A neutrophil to lymphocyte ratio level of 2.17 and above is associated with 1.991 times higher risk of tinnitus (odds ratio = 1.99, 95% confidence interval 1.31–3.02).

Conclusion
High mean platelet volume and neutrophil to lymphocyte ratio values are associated with idiopathic tinnitus, suggesting the role of vascular pathologies in etiology of tinnitus. Tinnitus may be a sign of underlying systemic or local disorders. Therefore, patients with tinnitus should undergo detailed evaluation including hematological indices.

Source: https://www.sciencedirect.com/science/article/pii/S1808869420300641
 
Differences in Clinical Characteristics and Brain Activity between Patients with Low- and High-Frequency Tinnitus

This study was aimed at delineating and comparing differences in clinical characteristics and brain activity between patients with low- and high-frequency tinnitus (LFT and HFT, respectively) using high-density electroencephalography (EEG). This study enrolled 3217 patients with subjective tinnitus who were divided into LFT ( Hz) and HFT (≥4000 Hz) groups. Data regarding medical history, Tinnitus Handicap Inventory, tinnitus matching, and hearing threshold were collected from all patients. Twenty tinnitus patients and 20 volunteers were subjected to 256-channel EEG, and neurophysiological differences were evaluated using standardized low-resolution brain electromagnetic tomography (sLORETA) source-localized EEG recordings. Significant differences in sex (), age (), laterality (), intensity (), tinnitus type (), persistent tinnitus (), average threshold (), and hearing loss () were observed between LFT and HFT groups. The tinnitus pitch only appeared to be correlated with the threshold of the worst hearing loss in the HFT group. Compared with the controls, the LFT group exhibited increased gamma power (), predominantly in the posterior cingulate cortex (PCC, BA31), whereas the HFT group had significantly decreased alpha1 power () in the angular gyrus (BA39) and auditory association cortex (BA22). Higher gamma linear connectivity between right BA39 and right BA41 was observed in the HFT group relative to controls (, ). Significant changes associated with increased gamma in the LFT group and decreased alpha1 in the HFT group indicate that tinnitus pitch is crucial for matching between the tinnitus and control groups. Differences of band frequency energy in brain activity levels may contribute to the clinical characteristics and internal tinnitus "spectrum" differences.

Full article: https://www.hindawi.com/journals/np/2020/5285362/
 
Analysis of cerebellum with magnetic resonance 3D T1 sequence in individuals with chronic subjective tinnitus

Abstract

Tinnitus is a symptom in which the patient can hear ringing, buzzing and similar sounds in the ear for 3 months longer. In our study, we aimed to analyse the cerebellum volume and cerebellum connections in patients with chronic tinnitus using VolBrain program. A total number of 10 patients and 10 otherwise healthy peoples records were then enrolled. Volumetric analysis was performed with automated segmentation of the cerebellum and its lobules, using magnetic resonance imaging (MRI). The mean volumes of 10 cerebellar volume were compared between the tinnitus and control groups. Quadrangular lobular portion of the cerebellum, the flocculonodular part and the volume of the central cerebellar lobule were decreased in the tinnitus group. White and grey matter decreased and the amygdala size was increased. We found statistically important volumetric changes in our study. VolBrain can be used in the future for analysing, diagnosis and treatment tinnitus patients. We recommend to use this practical, free of charge and easy programme to analyse for tinnitus patients. This may provide us with practical and useful information about the disease. In patients with tinnitus, the volume loss was 17.48% in the quadrangular lobe, 21% in the central lobule, and 9.33% in the total cerebellum volume.

Source: https://link.springer.com/article/10.1007/s13760-020-01451-x
 
Electrophysiological correlates of focused attention on low- and high-distressed tinnitus

Objectives

The study aimed at determining the EEG correlates of concentration on either low or high-distressed tinnitus.

Methods
Sixty-seven patients (36 women, mean age = 50.34 ± 12.94 years) with chronic tinnitus were assigned to either a high (HD) or low (LD) tinnitus-related distress group based on THI results. All participants took part in the EEG study comprising two 3–4 min blocks of focusing on either tinnitus (Tinnitus Focus Condition, TFC) or the sensations from one's own body (Body Focus Condition, BFC). The absolute power and current density of 8 frequency bands in 7 clusters were compared between conditions and groups.

Results
The most pronounced differences were found in the HD patients in the TFC, relative to the BFC, i.e. reduced power of frontally distributed low alpha (8–10 Hz) and posterior high alpha (10–12 Hz) as well as lower current density of 8–10 Hz rhythm over the right frontal/anterior cingulate cortex and higher middle beta (15–18 Hz) density in the precuneus. The HD, relative to LD patients, in both conditions, exhibited increased low beta (12–15 Hz) power over the left middle area and greater higher beta (15–25 Hz) power in the left posterior region.

Conclusions
The present study contrasted bioelectrical activity, acquired when concentrating on tinnitus with EEG data collected whilst patients focused on their body. Decreased alpha power and current density in the frontal/cingulate cortex when listening to bothersome tinnitus might reflect greater cortical arousal whereas increased beta power and density in the precuneus/posterior cingulate activity in this condition could be indicative for elevated tension or augmented cognitive/emotional processing of tinnitus sound. Enhanced beta rhythm in patients with high versus low tinnitus distress, observed independently of the study condition, may be due to greater self-focused attention or more active processing of sensations derived from the own body.

Full article: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0236521
 

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