Functional Connectivity Alterations and Molecular Characterization of the Anterior Cingulate Cortex in Tinnitus Pathology without Hearing Loss.

Compared with individuals with hearing loss, tinnitus patients without hearing loss have more psychological or emotional problems. Tinnitus is closely associated to abnormal metabolism and function of the limbic system, a key brain region for emotion experience, but the underlying molecular mechanism remains unknown. Using whole-brain microvasculature dynamics imaging, the anterior cingulate cortex (ACC) is identified as a key brain region of limbic system involve in the onset of salicylate-induced tinnitus in mice. In the tinnitus group, there is enhanced purine metabolism, oxidative phosphorylation, and a distinct pattern of phosphorylation in glutamatergic synaptic pathway according to the metabolome profiles, quantitative proteomic, and phosphoproteomic data of mice ACC tissue. Electroencephalogram in tinnitus patients with normal hearing thresholds show that the functional connectivity between pregenual anterior cingulate cortex and the primary auditory cortex is significantly increased for high-gamma frequency band, which is positively correlated with the serum glutamate level. These findings indicate that ACC plays an important role in the pathophysiology of tinnitus by interacting with the primary auditory cortex and provide potential molecular targets in the ACC for tinnitus treatment.

Multimodal quantitative magnetic resonance imaging of the thalamus in tinnitus patients with different outcomes after sound therapy.

AIMS: This study systematically investigated structural and functional alterations in the thalamus and its subregions using multimodal magnetic resonance imaging (MRI) and examined its clinical relevance in tinnitus patients with different outcomes after sound therapy (narrowband noise). METHODS: In total, 60 patients with persistent tinnitus and 57 healthy controls (HCs) were recruited. Based on treatment efficacy, 28 patients were categorized into the effective group and 32 into the ineffective group. Five MRI measurements of the thalamus and its seven subregions, including gray matter volume, fractional anisotropy, fractional amplitude of low-frequency fluctuation, and functional connectivity (FC), were obtained for each participant and compared between the groups. RESULTS: Patients in both the groups exhibited widespread functional and diffusion abnormalities in the whole thalamus and several subregions, with more obvious changes observed in the effective group. All tinnitus patients had abnormal FC compared with the HCs; FC differences between the two patient groups were only observed in the striatal network, auditory-related cortex, and the core area of the limbic system. We combined the multimodal quantitative thalamic alterations and used it as an imaging indicator to evaluate prognosis before sound therapy and achieved a sensitivity of 71.9% and a specificity of 85.7%. CONCLUSION: Similar patterns of thalamic alterations were identified in tinnitus patients with different outcomes, with more obvious changes observed in the effective group. Our findings support the tinnitus generation hypothesis of frontostriatal gating system dysfunction. A combination of multimodal quantitative thalamic properties may be used as indicators to predict tinnitus prognosis before sound therapy.

Differences in Hearing, Balance, and Quality-of-Life Outcomes in Petroclival Versus Nonpetroclival Posterior Fossa Meningiomas.

OBJECTIVE: To compare hearing, tinnitus, balance, and quality-of-life treatment outcomes of petroclival meningioma and nonpetroclival cerebellopontine angle meningioma cohorts. STUDY DESIGN: A retrospective cohort study of 60 patients with posterior fossa meningiomas, 25 petroclival and 35 nonpetroclival, who were treated at a single tertiary care center between 2000 and 2020. INTERVENTION: A survey battery that included the Hearing Effort of the Tumor Ear, Speech and Spatial Qualities of Hearing, Tinnitus Functional Index, Dizziness Handicap Inventory (DHI), and Short Form Health Survey. Petroclival and nonpetroclival cohorts were matched for tumor size and demographic features. MAIN OUTCOME MEASURES: Differences between groups in hearing, balance outcomes, and quality of life and patient factors that influence posttreatment quality of life. RESULTS: Petroclival meningioma patients reported poorer audiovestibular outcomes with a higher rate of deafness in the tumor ear (36.0% versus 8.6%, p = 0.032) and lower functional hearing by the Hearing Effort of the Tumor Ear, Speech and Spatial Qualities of Hearing (76.6 [6.1] versus 82.0 [4.4], p < 0.001). Current dizziness rate was higher (48.0% versus 23.5%, p = 0.05), with more severe dizziness by DHI (18.4 [4.8] versus 5.7 [2.2], p < 0.001). Both cohorts had similar high quality of life and low tinnitus severity indices. Quality-of-life Short Form Health Survey predictors were tumor size ( p = 0.012) and DHI ( p = 0.005) in multivariable analysis. CONCLUSIONS: Hearing and dizziness treatment outcomes of petroclival meningioma are poorer relative to other posterior fossa meningiomas. Despite audiovestibular outcome distinctions, the overall posttreatment quality of life was high for both petroclival and nonpetroclival meningioma.

Protective Effect of Resveratrol in an Experimental Model of Salicylate-Induced Tinnitus.

To date, the effect of resveratrol on tinnitus has not been reported. The attenuative effects of resveratrol (RSV) on a salicylate-induced tinnitus model were evaluated by in vitro and in vivo experiments. The gene expression of the activity-regulated cytoskeleton-associated protein (ARC), tumor necrosis factor-alpha (TNFα), and NMDA receptor subunit 2B (NR2B) in SH-SY5Y cells was examined using qPCR. Phosphorylated cAMP response element-binding protein (p-CREB), apoptosis markers, and reactive oxygen species (ROS) were evaluated by in vitro experiments. The in vivo experiment evaluated the gap-prepulse inhibition of the acoustic startle reflex (GPIAS) and auditory brainstem response (ABR) level. The NR2B expression in the auditory cortex (AC) was determined by immunohistochemistry. RSV significantly reduced the salicylate-induced expression of NR2B, ARC, and TNFα in neuronal cells; the GPIAS and ABR thresholds altered by salicylate in rats were recovered close to their normal range. RSV also reduced the salicylate-induced NR2B overexpression of the AC. These results confirmed that resveratrol exerted an attenuative effect on salicylate-induced tinnitus and may have a therapeutic potential.

Tinnitus Triggered by a Cerebellopontine Arachnoid Cyst in an Adolescent.

BACKGROUND Tinnitus can be a symptom of a wide range of disorders. The identification and treatment of the underlying condition is essential for management of tinnitus in children. Tinnitus can occur with medical conditions other than sensorineural hearing loss. Cerebellopontine arachnoid cysts are rare and can cause tinnitus and hearing loss in adults. Tinnitus caused by an arachnoid cyst has not been reported in an adolescent. We report clinical and radiological features of a teenager with bothersome tinnitus caused by an arachnoid cyst. CASE REPORT A 14-year-old girl with unilateral tinnitus for 10 months presented to the Pediatric Otolaryngology Clinic. The loudness and duration of tinnitus had progressed gradually. Turning the head to the right induced right otalgia and tinnitus. The patient denied hearing loss, vertigo, exposure to loud noise, feeling of fullness in ear, otorrhea, facial weakness, numbness, dysphagia, changes in smell or taste, and problems with the jaw or temporomandibular joint. The focused neurological examination and head and neck examination were within normal limits. The patient had normal hearing on audiometry. T1-weighted, T2-spin-echo, T2-FLAIR, and diffusion-weighted magnetic resonance imaging sequences were obtained, revealing a right cerebellopontine angle arachnoid cyst. After arachnoid cyst marsupialization, the patient's tinnitus and otalgia resolved. CONCLUSIONS This case highlights the importance of suspecting identifiable nonauditory system disorders as causes of tinnitus in children. Thorough analysis of clinical findings and timely use of imaging is critical to prevent delay in diagnosis and treatment of children with bothersome tinnitus caused by rare medical conditions.

Altered Amplitude of Low-Frequency Fluctuations and Degree Centrality in Patients with Acute Subjective Tinnitus: A Resting-State Functional Magnetic Resonance Imaging Study.

BACKGROUND: The difference in spontaneous brain activity between acute subjective tinnitus patients (with or without hearing loss) and control participants was explored using the amplitude of low-frequency fluctuations and degree centrality methods through resting-state functional magnetic resonance imaging. The study aimed to provide an objective basis for clinical diagnosis and pathogenesis of patients with acute subjective tinnitus. METHODS: Fourteen acute subjective tinnitus (AST) patients with hearing loss (AST-HL), 6 AST patients with no hearing loss (AST-NHL), and 14 healthy controls (HCs) with age, sex, and education status matched were recruited for this study. Resting-state functional magnetic resonance imaging (fMRI) examinations were performed in a resting state and the amplitude of low-frequency fluctuations (ALFF) and degree centrality (DC) values of each group were acquired. Statistical analysis was performed to assess the ALFF and DC values of different brain areas of the participants (AST-HL and AST-NHL were compared with HCs, but AST-HL and AST-NHL were not). RESULTS: Patients with acute subjective tinnitus and hearing loss showed a significantly increased amplitude of low-frequency fluctuation values in the left middle temporal gyrus and bilateral frontal gyrus/marginal lobe/cingulate gyrus but a decreased amplitude of low-frequency fluctuations values in the bilateral superior temporal gyrus/anterior cerebellar lobe in comparison with healthy controls. The amplitude of low-frequency fluctuation values of patients with acute subjective tinnitus and hearing loss in the right posterior lobe of the cerebellum, bilateral temporal gyrus, bilateral lenticular nucleus, bilateral frontal gyrus, right inferior occipital gyrus, were higher, but were significantly lower in the bilateral anterior lobe of cerebellum/superior temporal gyrus and left posterior cerebellar lobe as compared with those of healthy controls. Degree centrality values in the healthy controls group were increased in the right superior marginal gyrus and decreased in the right thalamus in patients with acute subjective tinnitus and hearing loss, while patients with acute subjective tinnitus with no hearing loss presented significantly higher degree centrality values in the left frontal lobe and lower degree centrality values in the left center rear return. CONCLUSIONS: Aberrant amplitude of low-frequency fluctuations and values exist in various brain regions, indicating abnormal spontaneous brain activity in both acute subjective tinnitus and hearing loss and acute subjective tinnitus no hearing loss patients. The pathogenesis of acute subjective tinnitus may be related to abnormalities in both the auditory cortex and nonauditory cortex. These findings provide more evidence to help clarify the neuronal symptoms of acute subjective tinnitus patients.

Brain herniation (encephalocele) into arachnoid granulations: prevalence and association with pulsatile tinnitus and idiopathic intracranial hypertension.

PURPOSE: Brain herniation into arachnoid granulations (BHAG) of the dural venous sinuses is a recently described finding of uncertain etiology. The purpose of this study was to investigate the prevalence of BHAG in a cohort of patients with pulsatile tinnitus (PT) and to clarify the physiologic and clinical implications of these lesions. METHODS: The imaging and charts of consecutive PT patients were retrospectively reviewed. All patients were examined with MRI including pre- and post-contrast T1- and T2-weighted sequences. Images were reviewed separately by three blinded neuroradiologists to identify the presence of BHAG. Their location, signal intensity, size, presence of arachnoid granulation, and associated dural venous sinus stenosis were documented. Clinical records were further reviewed for idiopathic intracranial hypertension, history of prior lumbar puncture, and opening pressure. RESULTS: Two hundred sixty-two consecutive PT patients over a 4-year period met inclusion criteria. PT patients with BHAG were significantly more likely to have idiopathic intracranial hypertension than PT patients without BHAG (OR 4.2, CI 1.5-12, p = 0.006). Sixteen out of 262 (6%) patients were found to have 18 BHAG. Eleven out of 16 (69%) patients had unilateral temporal or occipital lobe herniations located in the transverse sinus or the transverse-sigmoid junction. Three out of 16 (19%) patients had unilateral cerebellar herniations and 2/16 (13%) patients had bilateral BHAG. CONCLUSION: In patients with PT, BHAG is a prevalent MRI finding that is strongly associated with the clinical diagnosis of IIH. The pathogenesis of BHAG remains uncertain, but recognition should prompt comprehensive evaluation for IIH.

Distinct brain structural-functional network topological coupling explains different outcomes in tinnitus patients treated with sound therapy.

Topological properties, which serve as the core of the neural network, and their couplings can reflect different therapeutic effects in tinnitus patients. We hypothesized that tinnitus patients with different outcomes after sound therapy (narrowband noise) would have distinct brain network topological alterations. Diffusion tensor imaging and resting-state functional magnetic resonance imaging (fMRI) were prospectively performed in 60 patients with idiopathic tinnitus and 57 healthy controls (HCs). Graph-theoretical network analyses of structural connectivity (SC), functional connectivity (FC), and SC and FC coupling were performed. Associations between clinical performance and graph-theoretical features were also analyzed. Treatment was effective (effective group; EG) in 28 patients and ineffective (ineffective group; IG) in 32 patients. For FC, the patients in the EG showed higher local efficiency than patients in the IG. For SC, patients in both the EG and IG displayed lower normalized characteristic path length, characteristic path length, and global efficiency than the HCs. More importantly, patients in the IG had higher coupling than the HCs, whereas there was no difference in coupling between patients in the EG and HCs. Additionally, there were significant associations between the SC features and clinical performance in patients in the EG. Our findings demonstrate that tinnitus patients exhibited significant brain network topological alterations, especially in the structural brain network. More importantly, patients who demonstrated different curative effects showed distinct SC-FC topological coupling properties. SC-FC coupling could be an indicator that could be used to predict prognoses in patients with idiopathic tinnitus before sound therapy.

Topological features of limbic dysfunction in chronicity of tinnitus with intact hearing: New hypothesis for 'noise-cancellation' mechanism.

PURPOSE: The reorganization of the limbic regions extend to general cognitive network is believed to exist in the chronicity of tinnitus with particular 'hubs' contributing to a 'noise-cancellation' mechanism. To test this hypothesis, we investigated the topological brain network of tinnitus in different periods. METHODS: Resting-state functional magnetic resonance imaging were obtained from 32 patients with acute tinnitus, 41 patients with chronic tinnitus and 60 age- and gender- matched healthy controls (HC). The topological features of their brain networks were explored using graph theory analysis. RESULTS: Common small-world attributes were compared between the three groups, all showed a significantly increased values in Cp, Lp, λ (all p < 0.05). Significantly increased nodal centralities in the left superior frontal gyrus and the right precuneus, significantly decreased nodal centralities in the right inferior temporal gyrus were observed for acute tinnitus patients compared to HC. While for chronic tinnitus patients, there were significant increased nodal centralities in the left hippocampus, amygdala, and temporal pole, but decreased nodal centralities in the right inferior temporal gyrus. Additionally, significant higher nodal centralities were found in bilateral medial superior frontal gyrus for acute tinnitus patients compared to chronic tinnitus patients. Besides, alterations in rich-club organization were found in acute tinnitus patients and chronic tinnitus patients compared with HC, with increased functional connections among rich-club nodes and peripheral nodes in patients with tinnitus. CONCLUSIONS: Brain network topological properties altered across prefrontal-limbic-subcortical regions in tinnitus. The existed hubs in tinnitus might indicate an emotional and cognitive burden in 'noise-cancellation' mechanism.

Association between tinnitus and depressive symptoms in the South Korean population.

In this study, we aimed to examine the association between tinnitus and depressive symptoms in middle-aged and elderly South Korean population. The participants were selected from among those who participated in the 2014, 2016, and 2018 Korea National Health and Nutrition Examination Surveys. The incidence and severity of tinnitus was assessed using a self-reported questionnaire, while depressive symptoms were evaluated using self-reported Patient Health Questionnaire-9. Multiple logistic regression was performed to examine the association between tinnitus and depressive symptoms. Overall, 10 979 (4821 men and 6158 women) participants were enrolled in the study. Regardless of sex, individuals who reported having tinnitus were more likely to have depressive symptoms than those without tinnitus (men: odds ratio 1.53, 95% confidence interval 1.01-2.32; women: odds ratio 1.78, 95% confidence interval 1.35-2.35). In severe cases of tinnitus, women were more likely to have depressive symptoms (odds ratio 7.18, 95% confidence interval 3.71-13.87) compared to men. This study revealed a significant association between tinnitus and depressive symptoms among the middle-aged and elderly South Korean population.

Migraine and Cochlear Symptoms.

Migraine is one of the most common and highest burdens of disease. As a primary cerebral dysfunction illness, migraine might exhibit other system-related symptoms, including vestibular and cochlear symptoms. With the publication of the diagnostic criteria of vestibular migraine, the link between migraine and vestibular symptoms became clear. However, the relationship between migraine and cochlear symptoms is far from straightforward. Therefore, we focus on the correlation between migraine and deafness, sudden sensorineural hearing loss, acute tinnitus, and chronic tinnitus to better understand the relationship between migraine and cochlear symptoms.

The role of vitamin D in subjective tinnitus-A case-control study.

Regarding the high prevalence of vitamin D (25(OH)D) deficiency in the population and its possible association with ear diseases, we aimed to investigate the 25(OH)Dserum level in patients with subjective, nonpulsating tinnitus and its effect on tinnitus severity. The study included 201 tinnitus patients and 99 controls. Patient clinical information, including tinnitus characteristics and severity according to Tinnitus Handicap Inventory (THI), loudness assessed by Visual Analogue Scale (VAS), audiometry, and the blood level of vitamin D, was recorded. The level of 25(OH)D in tinnitus patients was significantly decreased compared with the controls (19.86 ± 7.53 and 27.43 ± 8.85 ng/ml, respectively; P value < 0.0001). More patients in the tinnitus group were deficient in vitamin D, compared with the controls (50.7% vs. 22.2% respectively, p < 0.0001). Tinnitus patients with a lower serum level of 25(OH)D (≤15 ng/dl) were significantly younger, had a higher degree of tinnitus severity measured with THI and VAS scales, had higher triglyceride and TSH levels, and a lower HDL level compared with individuals who had higher 25(OH)D level (>15 ng/dl). There was a strong correlation between the 25(OH)D level and THI. Our findings suggest that a large proportion of tinnitus patients suffers from vitamin D deficiency and that the vitamin D level correlates with tinnitus impact. We recommend a vitamin D assessment for all tinnitus patients.

Evidence of Tinnitus Development Due to Stress: An Experimental Study in Rats.

OBJECTIVES/HYPOTHESIS: Tinnitus can develop due to, or be aggravated by, stress in a rat model. To investigate stress as a possible causal factor in the development of tinnitus, we designed an animal study that included tinnitus behavior and excitatory/inhibitory neurotransmitter expression after noise exposure as well as restraint stress. STUDY DESIGN: An experimental animal study. METHODS: Wistar rats were grouped according to single or double exposure to noise and restraint stress. The noise exposure (NE) group was subjected to 110 dB sound pressure level (SPL) of 16 kHz narrow-band noise (NBN) for 1 hour, and the restraint stress (RS) group was restrained for 1 hour with or without noise exposure. Gap prepulse inhibition of the acoustic startle (GPIAS) reflex was measured at an NBN of 16 kHz to investigate tinnitus development. Various immunohistopathologic and molecular biologic studies were undertaken to evaluate possible mechanisms of tinnitus development after noise and/or restraint stress. RESULTS: The RS-only group showed a reduced GPIAS response, which is a reliable sign of tinnitus development. In the double-stimulus groups, more tinnitus-development signs of reduced GPIAS responses were observed. The expression of γ-aminobutyric acid A receptor α1 (GABAAR α1) in the hippocampus decreased in the NE│RS group. Increased N-methyl-d-aspartate receptor1 intensities in the NE│RS group and decreased GABAAR α1 intensities in the RS and NE│RS groups were observed in the CA3 region of the hippocampus. CONCLUSIONS: Tinnitus appeared to develop after stress alone in this animal study. An imbalance in excitatory and inhibitory neurotransmitters in the hippocampus may be related to the development of tinnitus after acute NE and/or stress. LEVEL OF EVIDENCE: NA Laryngoscope, 131:2332-2340, 2021.

Role of microRNA­375­3p­mediated regulation in tinnitus development.

Changes in the dorsal cochlear nucleus (DCN) following exposure to noise play an important role in the development of tinnitus. As the development of several diseases is known to be associated with microRNAs (miRNAs/miRs), the aim of the present study was to identify the miRNAs that may be implicated in pathogenic changes in the DCN, resulting in tinnitus. A previously developed tinnitus animal model was used for this study. The study consisted of four stages, including identification of candidate miRNAs involved in tinnitus development using miRNA microarray analysis, validation of miRNA expression using reverse transcription­quantitative PCR (RT­qPCR), evaluation of the effects of candidate miRNA overexpression on tinnitus development through injection of a candidate miRNA mimic or mimic negative control, and target prediction of candidate miRNAs using mRNA microarray analysis and western blotting. The miRNA microarray and RT­qPCR analyses revealed that miR­375­3p expression was significantly reduced in the tinnitus group compared with that in the non­tinnitus group. Additionally, miR­375­3p overexpression via injection of miR­375­3p mimic reduced the proportion of animals with persistent tinnitus. Based on mRNA microarray and western blot analyses, connective tissue growth factor (CTGF) was identified as a potential target for miR­375­3p. Thus, it was inferred that CTGF downregulation by miR­375­3p may weaken with the decrease in miRNA expression, and the increased pro­apoptotic activity of CTGF may result in more severe neuronal damage, contributing to tinnitus development. These findings are expected to contribute significantly to the development of a novel therapeutic approach to tinnitus, thereby bringing about a significant breakthrough in the treatment of this potentially debilitating condition.

Cortical and subcortical gray matter changes in patients with chronic tinnitus sustaining after vestibular schwannoma surgery.

Tinnitus is attributed to partial sensory deafferentation resulting in a central maladaptive neuroplasticity. Unfortunately, the agent of deafferentation is usually unknown or irreversible. In patients with unilateral vestibular schwannoma (VS), however, the auditory nerve is affected by a benign tumor. Hence, removal of the tumor can cease the tinnitus. In turn, sustaining complaints after surgery indicate cortical neuroplasticity. The present study is a cross sectional study which aims to track cortical structural changes by surface-based morphometry in 46 VS patients with sustained (i.e. centralized) or ceased (i.e. peripheral) tinnitus after surgery. A volumetric analysis of cortical and subcortical gray matter (GM) anatomy was performed on preoperative high-resolution MRI and related to the presence of hearing impairment, pre- and/or postoperative tinnitus. Patients with sustained (i.e. chronic) tinnitus showed an increased GM volume of the bilateral caudate nucleus, the contralateral superior colliculus, the middle frontal and middle temporal gyrus, the fusiform gyrus as well as the ipsilateral pars orbitalis when compared to those patients in whom tinnitus ceased postoperatively. Chronic tinnitus in VS patients is associated with characteristic structural changes in frontal, temporal and subcortical areas. Notably, a significant GM change of the caudate nucleus was detected providing further support for the striatal gaiting model of tinnitus.

Neuroanatomic Volume Differences in Tinnitus and Hearing Loss.

OBJECTIVES: To investigate neuroanatomic volume differences in tinnitus and hearing loss. STUDY DESIGN: Cross-sectional. METHODS: Sixteen regions of interest (ROIs) in adults (43 male, 29 female) were examined using 3Tesla structural magnetic resonance imaging in four cohorts: 1) tinnitus with moderate hearing loss (N = 31), 2) moderate hearing loss only (N = 15), 3) tinnitus with normal hearing (N = 17), and 4) normal hearing only (N = 13). ROI volumes were corrected for brain size, age, and sex variations. Analysis of covariance (ANCOVA) and post hoc Tukey's test were used to isolate the effects of tinnitus and hearing loss on volume differences. Effect sizes were calculated as the fraction of total variance (η2 ) in ANCOVA models and percent of mean volume difference relative to mean total volume. RESULTS: The four cohort ANCOVA revealed tinnitus and hearing loss cohorts to have increased volume in the corona radiata (η2  = 0.192; P = .0018) and decreased volume in the nucleus accumbens (η2  = 0.252; P < .0001), caudate nucleus (η2  = 0.188; P = .002), and inferior fronto-occipital fasciculus (η2  = 0.250; P = .0001). Tinnitus with normal hearing showed decreased volume in the nucleus accumbens (22.0%; P = .001) and inferior fronto-occipital fasciculus (18.1%; P = .002), and hearing loss only showed increased volume in the corona radiata (10.7%; P = .01) and decreased volume in the nucleus accumbens (22.1%; P = .001), caudate nucleus (16.1%; P = .004), and inferior fronto-occipital fasciculus (18.3%; P = .003). CONCLUSION: Tinnitus and hearing loss have overlapping effects on neurovolumetric alterations, especially impacting the nucleus accumbens and inferior fronto-occipital fasciculus. Neurovolumetric studies on tinnitus or hearing loss can be more complete by accounting for those two clinical dimensions separately and jointly. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:1863-1868, 2021.

Macrostructural Changes of the Acoustic Radiation in Humans with Hearing Loss and Tinnitus Revealed with Fixel-Based Analysis.

Age-related hearing loss is the most prevalent sensory impairment in the older adult population and is related to noise-induced damage or age-related deterioration of the peripheral auditory system. Hearing loss may affect the central auditory pathway in the brain, which is a continuation of the peripheral auditory system located in the ear. A debilitating symptom that frequently co-occurs with hearing loss is tinnitus. Strikingly, investigations into the impact of acquired hearing loss, with and without tinnitus, on the human central auditory pathway are sparse. This study used diffusion-weighted imaging (DWI) to investigate changes in the largest central auditory tract, the acoustic radiation, related to hearing loss and tinnitus. Participants with hearing loss, with and without tinnitus, and a control group were included. Both conventional diffusion tensor analysis and higher-order fixel-based analysis were applied. The fixel-based analysis was used as a novel framework providing insight into the axonal density and macrostructural morphologic changes of the acoustic radiation in hearing loss and tinnitus. The results show tinnitus-related atrophy of the left acoustic radiation near the medial geniculate body. This finding may reflect a decrease in myelination of the auditory pathway, instigated by more profound peripheral deafferentation or reflecting a preexisting marker of tinnitus vulnerability. Furthermore, age was negatively correlated with the axonal density in the bilateral acoustic radiation. This loss of fiber density with age may contribute to poorer speech understanding observed in older adults.SIGNIFICANCE STATEMENT Age-related hearing loss is the most prevalent sensory impairment in the older adult population. Older individuals are subject to the cumulative effects of aging and noise exposure on the auditory system. A debilitating symptom that frequently co-occurs with hearing loss is tinnitus: the perception of a phantom sound. In this large DWI-study, we provide evidence that in hearing loss, the additional presence of tinnitus is related to degradation of the acoustic radiation. Additionally, older age was related to axonal loss in the acoustic radiation. It appears that older adults have the aggravating circumstances of age, hearing loss, and tinnitus on central auditory processing, which may partly be because of the observed deterioration of the acoustic radiation with age.

Genome-wide association study suggests that variation at the RCOR1 locus is associated with tinnitus in UK Biobank.

Tinnitus is a prevalent condition in which perception of sound occurs without an external stimulus. It is often associated with pre-existing hearing loss or noise-induced damage to the auditory system. In some individuals it occurs frequently or even continuously and leads to considerable distress and difficulty sleeping. There is little knowledge of the molecular mechanisms involved in tinnitus which has hindered the development of treatments. Evidence suggests that tinnitus has a heritable component although previous genetic studies have not established specific risk factors. From a total of 172,608 UK Biobank participants who answered questions on tinnitus we performed a case-control genome-wide association study for self-reported tinnitus. Final sample size used in association analysis was N = 91,424. Three variants in close proximity to the RCOR1 gene reached genome wide significance: rs4906228 (p = 1.7E-08), rs4900545 (p = 1.8E-08) and 14:103042287_CT_C (p = 3.50E-08). RCOR1 encodes REST Corepressor 1, a component of a co-repressor complex involved in repressing neuronal gene expression in non-neuronal cells. Eleven other independent genetic loci reached a suggestive significance threshold of p < 1E-06.

Middle-ear or mastoid granulation pathology associated with retraction of the pars flaccida and low-pitched tinnitus.

OBJECTIVE: This study aimed to evaluate the clinical features and outcomes of patients with middle-ear granulation pathologies associated with attic retractions. METHOD: The clinical records of adult patients with middle-ear granulation pathologies and attic retractions confirmed via computed tomography and surgical exploration between January 2012 and January 2019 were retrospectively reviewed. RESULTS: A total of 59 patients were included. Endoscopic examination showed a normal pars tensa but retraction of the pars flaccida in all patients. No granulation tissue or debris were observed. Low-pitched tinnitus was the principal complaint of 55 patients (100 per cent), followed by ear fullness (14 patients, 23.7 per cent). Of the 59 patients, 52 patients (88.1 per cent) underwent canal wall up mastoidectomy and 7 patients (11.9 per cent) underwent endoscopic endaural atticoantrotomy. No ossicular chain destruction was evident. All patients were followed up for 12 months. Tinnitus disappeared completely in 48 patients (81.4 per cent), improved significantly in 9 patients (15.3 per cent) and improved mildly in 2 patients (3.3 per cent). CONCLUSION: A granulation tissue pathology should be considered when a patient complains of low-pitched tinnitus and exhibits retraction of the pars flaccida. Computed tomography and surgical exploration should be scheduled.

The progression of chronic tinnitus over the years.

Little is known about the trajectory of tinnitus over time. This study addressed (1) how often tinnitus remitted in patients with chronic tinnitus; (2) how subjective reported tinnitus characteristics, such as loudness, laterality, and type and measures of burden, such as tinnitus distress, depression, and quality of life, changes over time; (3) how often tinnitus-specific treatments were undertaken and the prevalence of comorbidities, (4) if the number of treatments and comorbidities were associated to changes in tinnitus distress over time. Data from 388 patients with chronic tinnitus who visited a tertiary tinnitus clinic between 2012 and 2017 were interrogated via a mail survey in 2018. Tinnitus characteristics were measured with the Tinnitus Sample Case History Questionnaire and numeric rating scales; tinnitus distress with Tinnitus Handicap Inventory (THI) and the Tinnitus Questionnaire (TQ), depression with the Major Depression Inventory and Quality of life with the World Health Organisation Quality of Life BREF at both time points and the clinical global impression scale. Comorbidities experienced and undertaken treatments were assessed with an in-house survey. Three participants (0.8% of the sample) reported tinnitus remission between both assessments. A decrease in the THI and TQ, and numeric ratings for tinnitus severity, annoyance, unpleasantness, and discomfort was observed, but no differences in tinnitus characteristics, depression, quality of life or overall health status. 64% presented at least one comorbidity, and 88% sought at least on tinnitus-specific treatment. Common comorbidities were psychological and sleeping problems, and the most common interventions were going to the dentist, taking medications, and wearing hearing aids. Our results suggest that full remission of tinnitus is a rare condition, that tinnitus distress on average decreases over time, and that tinnitus characteristics, quality of life, and depression tend to remain unaltered. The high number of interventions and comorbidities displayed minimal association to the changes in tinnitus distress, highlighting the substantial and durable burden of tinnitus sufferers.