What's the buzz? The neuroscience and the treatment of tinnitus.

Tinnitus is a pervasive public health issue that affects ∼15% of the United States population. Similar estimates have also been shown on a global scale, with similar prevalence found in Europe, Asia, and Africa. The severity of tinnitus is heterogeneous, ranging from mildly bothersome to extremely disruptive. In the United States, ∼10-20% of individuals who experience tinnitus report symptoms that severely reduce their quality of life. Due to the huge personal and societal burden, in the last 20 yr a concerted effort on basic and clinical research has significantly advanced our understanding and treatment of this disorder. Yet, neither full understanding, nor cure exists. We know that tinnitus is the persistent involuntary phantom percept of internally generated nonverbal indistinct noises and tones, which in most cases is initiated by acquired hearing loss and maintained only when this loss is coupled with distinct neuronal changes in auditory and extra-auditory brain networks. Yet, the exact mechanisms and patterns of neural activity that are necessary and sufficient for the perceptual generation and maintenance of tinnitus remain incompletely understood. Combinations of animal model and human research will be essential in filling these gaps. Nevertheless, the existing progress in investigating the neurophysiological mechanisms has improved current treatment and highlighted novel targets for drug development and clinical trials. The aim of this review is to thoroughly discuss the current state of human and animal tinnitus research, outline current challenges, and highlight new and exciting research opportunities.

Tinnitus classification based on resting-state functional connectivity using a convolutional neural network architecture.

OBJECTIVES: Many studies have investigated aberrant functional connectivity (FC) using resting-state functional MRI (rs-fMRI) in subjective tinnitus patients. However, no studies have verified the efficacy of resting-state FC as a diagnostic imaging marker. We established a convolutional neural network (CNN) model based on rs-fMRI FC to distinguish tinnitus patients from healthy controls, providing guidance and fast diagnostic tools for the clinical diagnosis of subjective tinnitus. METHODS: A CNN architecture was trained on rs-fMRI data from 100 tinnitus patients and 100 healthy controls using an asymmetric convolutional layer. Additionally, a traditional machine learning model and a transfer learning model were included for comparison with the CNN, and each of the three models was tested on three different brain atlases. RESULTS: Of the three models, the CNN model outperformed the other two models with the highest area under the curve, especially on the Dos_160 atlas (AUC = 0.944). Meanwhile, the model with the best classification performance highlights the crucial role of the default mode network, salience network, and sensorimotor network in distinguishing between normal controls and patients with subjective tinnitus. CONCLUSION: Our CNN model could appropriately tackle the diagnosis of tinnitus patients using rs-fMRI and confirmed the diagnostic value of FC as measured by rs-fMRI.

Switching tinnitus on or off: An initial investigation into the role of the pregenual and rostral to dorsal anterior cingulate cortices.

Research indicates that hearing loss significantly contributes to tinnitus, but it alone does not fully explain its occurrence, as many people with hearing loss do not experience tinnitus. To identify a secondary factor for tinnitus generation, we examined a unique dataset of individuals with intermittent chronic tinnitus, who experience fluctuating periods of tinnitus. EEGs of healthy controls were compared to EEGs of participants who reported perceiving tinnitus on certain days, but no tinnitus on other days.. The EEG data revealed that tinnitus onset is associated with increased theta activity in the pregenual anterior cingulate cortex and decreased theta functional connectivity between the pregenual anterior cingulate cortex and the auditory cortex. Additionally, there is increased alpha effective connectivity from the dorsal anterior cingulate cortex to the pregenual anterior cingulate cortex. When tinnitus is not perceived, differences from healthy controls include increased alpha activity in the pregenual anterior cingulate cortex and heightened alpha connectivity between the pregenual anterior cingulate cortex and auditory cortex. This suggests that tinnitus is triggered by a switch involving increased theta activity in the pregenual anterior cingulate cortex and decreased theta connectivity between the pregenual anterior cingulate cortex and auditory cortex, leading to increased theta-gamma cross-frequency coupling, which correlates with tinnitus loudness. Increased alpha activity in the dorsal anterior cingulate cortex correlates with distress. Conversely, increased alpha activity in the pregenual anterior cingulate cortex can transiently suppress the phantom sound by enhancing theta connectivity to the auditory cortex. This mechanism parallels chronic neuropathic pain and suggests potential treatments for tinnitus by promoting alpha activity in the pregenual anterior cingulate cortex and reducing alpha activity in the dorsal anterior cingulate cortex through pharmacological or neuromodulatory approaches.

Phantom perception as a Bayesian inference problem: a pilot study.

Tinnitus is the perception of a continuous sound in the absence of an external source. Although the role of the auditory system is well investigated, there is a gap in how multisensory signals are integrated to produce a single percept in tinnitus. Here, we train participants to learn a new sensory environment by associating a cue with a target signal that varies in perceptual threshold. In the test phase, we present only the cue to see whether the person perceives an illusion of the target signal. We perform two separate experiments to observe the behavioral and electrophysiological responses to the learning and test phases in 1) healthy young adults and 2) people with continuous subjective tinnitus and matched control subjects. We observed that in both parts of the study the percentage of false alarms was negatively correlated with the 75% detection threshold. Additionally, the perception of an illusion goes together with increased evoked response potential in frontal regions of the brain. Furthermore, in patients with tinnitus, we observe no significant difference in behavioral or evoked response in the auditory paradigm, whereas patients with tinnitus were more likely to report false alarms along with increased evoked activity during the learning and test phases in the visual paradigm. This emphasizes the importance of integrity of sensory pathways in multisensory integration and how this process may be disrupted in people with tinnitus. Furthermore, the present study also presents preliminary data supporting evidence that tinnitus patients may be building stronger perceptual models, which needs future studies with a larger population to provide concrete evidence on.NEW & NOTEWORTHY Tinnitus is the continuous phantom perception of a ringing in the ears. Recently, it has been suggested that tinnitus may be a maladaptive inference of the brain to auditory anomalies, whether they are detected or undetected by an audiogram. The present study presents empirical evidence for this hypothesis by inducing an illusion in a sensory domain that is damaged (auditory) and one that is intact (visual). It also presents novel information about how people with tinnitus process multisensory stimuli in the audio-visual domain.

Amygdala structural and functional reorganization as an indicator of affective dysfunction in patients with tinnitus.

The aim of this study was to systematically investigate structural and functional alterations in amygdala subregions using multimodal magnetic resonance imaging (MRI) in patients with tinnitus with or without affective dysfunction. Sixty patients with persistent tinnitus and 40 healthy controls (HCs) were recruited. Based on a questionnaire assessment, 26 and 34 patients were categorized into the tinnitus patients with affective dysfunction (TPAD) and tinnitus patients without affective dysfunction (TPWAD) groups, respectively. MRI-based measurements of gray matter volume, fractional anisotropy (FA), fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity (ReHo), degree centrality (DC), and functional connectivity (FC) were conducted within 14 amygdala subregions for intergroup comparisons. Associations between the MRI properties and clinical characteristics were estimated via partial correlation analyses. Compared with that of the HCs, the TPAD and TPWAD groups exhibited significant structural and functional changes, including white matter integrity (WMI), fALFF, ReHo, DC, and FC alterations, with more pronounced WMI changes in the TPAD group, predominantly within the left auxiliary basal or basomedial nucleus (AB/BM), right central nucleus, right lateral nuclei (dorsal portion), and left lateral nuclei (ventral portion containing basolateral portions). Moreover, the TPAD group exhibited decreased FC between the left AB/BM and left middle occipital gyrus and right superior frontal gyrus (SFG), left basal nucleus and right SFG, and right lateral nuclei (intermediate portion) and right SFG. In combination, these amygdalar alterations exhibited a sensitivity of 65.4% and specificity of 96.9% in predicting affective dysfunction in patients with tinnitus. Although similar structural and functional amygdala remodeling were observed in the TPAD and TPWAD groups, the changes were more pronounced in the TPAD group. These changes mainly involved alterations in functionality and white matter microstructure in various amygdala subregions; in combination, these changes could serve as an imaging-based predictor of emotional disorders in patients with tinnitus.

The potassium channels: Neurobiology and pharmacology of tinnitus.

Tinnitus is a widespread public health issue that imposes a significant social burden. The occurrence and maintenance of tinnitus have been shown to be associated with abnormal neuronal activity in the auditory pathway. Based on this view, neurobiological and pharmacological developments in tinnitus focus on ion channels and synaptic neurotransmitter receptors in neurons in the auditory pathway. With major breakthroughs in the pathophysiology and research methodology of tinnitus in recent years, the role of the largest family of ion channels, potassium ion channels, in modulating the excitability of neurons involved in tinnitus has been increasingly demonstrated. More and more potassium channels involved in the neural mechanism of tinnitus have been discovered, and corresponding drugs have been developed. In this article, we review animal (mouse, rat, hamster, and guinea-pig), human, and genetic studies on the different potassium channels involved in tinnitus, analyze the limitations of current clinical research on potassium channels, and propose future prospects. The aim of this review is to promote the understanding of the role of potassium ion channels in tinnitus and to advance the development of drugs targeting potassium ion channels for tinnitus.

Tinnitus is associated with increased extracellular matrix density in the auditory cortex of Mongolian gerbils.

Most scientists agree that subjective tinnitus is the pathological result of an interaction of damage to the peripheral auditory system and central neuroplastic adaptations. Here we investigate such tinnitus related adaptations in the primary auditory cortex (AC) 7 and 13 days after noise trauma induction of tinnitus by quantifying the density of the extracellular matrix (ECM) in the AC of Mongolian gerbils (Meriones unguiculatus). The ECM density has been shown to be relevant for neuroplastic processes and synaptic stability within the cortex. We utilized a mild monaural acoustic noise trauma in overall 22 gerbils to induce tinnitus and a sham exposure in 16 control (C) animals. Tinnitus was assessed by a behavioral response paradigm. Animals were separated for a presence (T) or absence (NT) of a tinnitus percept by a behavioral task. The ECM density 7 and 13 days after trauma was quantified using immunofluorescence luminance of Wisteria floribunda lectin-fluoresceine-5-isothiocyanate (WFA-FITC) on histological slices of the primary AC, relative to the non-auditory brainstem as a reference area. At both timepoints, we found that the WFA-FITC luminance of the AC of NT animals was not significantly different from that of C animals. However, we found a significant increase of luminance in T animals' ACs compared to NT or C animals' cortices. This effect was found exclusively on the AC side contralateral to the trauma ear. These results point to a hemisphere specific process of stabilization of synaptic connections in primary AC, which may be involved in the chronic manifestation of tinnitus.

Prevalence and characteristics of visual snow syndrome in a cohort of young Italian adults.

BACKGROUND: Visual snow (VS) and visual snow syndrome (VSS) are becoming increasingly recognized. However, their prevalence worldwide is unknown. This study aimed to investigate lifetime prevalence and describe the clinical characteristics of VS and VSS in a representative population sample from Italy. METHODS: This cross-sectional study was conducted among students attending different faculties in three universities in the central and southern regions of Italy. Eligible participants completed a self-administered questionnaire. In patients fulfilling possible criteria for VS/VSS, the diagnosis was validated by an on-site visit conducted by experienced neurologists and neuro-ophthalmologists that included optical coherence tomography angiography (OCTA). RESULTS: A total of 750 participants completed the study. Seven (0.9%) reported symptoms compatible with VS (mean age 24.8 ± 3.85 years). Among the seven patients, five (0.7%) also met the phenomenological and temporal criteria for VSS. Neuroimaging and ophthalmological examinations showed normal results upon review or during the on-site visit including OCTA. For the five patients with full VSS, the other visual symptoms reported were enhanced entoptic phenomenon (n = 5), photophobia (n = 5), palinopsia (n = 1), and nyctalopia (n = 4). In four of the seven patients (57%) reporting VS symptoms, there was a concomitant diagnosis of migraine with aura, and in one (14%) migraine without aura. All patients (n = 7) reported tinnitus. Six of the seven (85.7%) patients with VS/VSS had never used specific treatments for the condition. None of the seven patients had received a previous diagnosis of VS/VSS. CONCLUSIONS: The prevalence in Italy of VSS is around 1%. However, there is a limited tendency for affected individuals to seek medical attention, leading to a low rate of diagnosis and treatment.

Predictive coding and stochastic resonance as fundamental principles of auditory phantom perception.

Mechanistic insight is achieved only when experiments are employed to test formal or computational models. Furthermore, in analogy to lesion studies, phantom perception may serve as a vehicle to understand the fundamental processing principles underlying healthy auditory perception. With a special focus on tinnitus-as the prime example of auditory phantom perception-we review recent work at the intersection of artificial intelligence, psychology and neuroscience. In particular, we discuss why everyone with tinnitus suffers from (at least hidden) hearing loss, but not everyone with hearing loss suffers from tinnitus. We argue that intrinsic neural noise is generated and amplified along the auditory pathway as a compensatory mechanism to restore normal hearing based on adaptive stochastic resonance. The neural noise increase can then be misinterpreted as auditory input and perceived as tinnitus. This mechanism can be formalized in the Bayesian brain framework, where the percept (posterior) assimilates a prior prediction (brain's expectations) and likelihood (bottom-up neural signal). A higher mean and lower variance (i.e. enhanced precision) of the likelihood shifts the posterior, evincing a misinterpretation of sensory evidence, which may be further confounded by plastic changes in the brain that underwrite prior predictions. Hence, two fundamental processing principles provide the most explanatory power for the emergence of auditory phantom perceptions: predictive coding as a top-down and adaptive stochastic resonance as a complementary bottom-up mechanism. We conclude that both principles also play a crucial role in healthy auditory perception. Finally, in the context of neuroscience-inspired artificial intelligence, both processing principles may serve to improve contemporary machine learning techniques.

Analysis of Loudness Discomfort Level Tests in Tinnitus Patients.

INTRODUCTION: We aimed to investigate the clinical significance of the loudness discomfort level (LDL) test in tinnitus patients and its relationship with pure-tone audiometry, tinnitogram, and questionnaires. METHODS: We retrospectively reviewed the medical records of 320 tinnitus patients who visited a tertiary university hospital's tinnitus clinic and completed LDL tests between March 2020 and December 2022. Epidemiological data and psychoacoustic test results were collected. RESULTS: The LDL showed no significant differences between frequencies for both ears. The mean LDL did not correlate with mean pure-tone average or hearing thresholds at each frequency. The hearing loss group had a higher LDL at 8 kHz compared to the normal hearing group (p < 0.01). Objective sound intolerance was found in a quarter, correlating with subjective hyperacusis, anxiety, and depression. Weak negative correlations were found between most of questionnaire's scores and LDL on the left side. Tinnitus loudness weak negatively correlated with LDL at most frequencies, except 8 kHz. DISCUSSION/CONCLUSION: Our findings suggest a notable association between LDL levels and emotional factors in tinnitus patients, rather than with auditory thresholds. While lateralized differences in LDL responses were observed, specifically on the left side, these preliminary results do not confirm a causal link and thus do not warrant changes to current clinical testing protocols without further research.

Sudden Hearing Loss before, during, and after the Pandemic: Investigating COVID-19 Illness and Vaccine-Related Symptoms.

INTRODUCTION: Accumulating reports suggest an increase in sudden sensorineural hearing loss during the COVID-19 pandemic and vaccination periods. However, clear evidence is lacking. The goal of this study was to determine if sudden sensorineural hearing loss is associated with COVID-19 illness or its vaccine. METHODS: Retrospective chart review of 50 randomly selected patients from three, 6-month time periods: "pre-pandemic," "early pandemic," and "late pandemic." Group comparisons were performed for demographics, comorbid conditions, audiologic history, audiometric data, speech reception thresholds, and word recognition. RESULTS: One hundred 50 patients were included in this study. A mean difference was observed in that the relative percentage of sensorineural hearing loss (SNHL) cases increased over time, corresponding to a relative decrease in conductive hearing loss cases. However, this change was not explained by proportional changes in sudden SNHL. Patients in the early pandemic time period were more likely to report tinnitus. Otherwise, the patient groups did not differ on demographic variables, hearing health history, hearing loss presentation, pure tone averages, speech reception thresholds, or word recognition performance. CONCLUSIONS: Proportion of patients with sudden sensorineural hearing loss did not change over time from the pre-pandemic period to the early or late pandemic phases. Despite a randomized sample, these findings do not support the hypothesis that COVID-19 illness or vaccine is associated with sudden sensorineural hearing loss.

Reduced Intra- and Inter-Network Functional Connectivity Identified in Patients with Tinnitus with and without Hearing Loss.

INTRODUCTION: The aim of the study was to investigate differences in the intra- and inter-network functional connectivity (FC) of the brain using resting-state functional magnetic resonance imaging (rs-fMRI) in patients with tinnitus, with (T + H) or without hearing loss (T). METHODS: We performed rs-fMRI on 82 participants (21 T, 32 T + H, and 29 healthy controls). An independent component analysis (ICA) was performed to obtain the resting-state networks (RSNs) and calculate the differences in FC. Moreover, we investigated the relationships between networks using functional network connectivity analysis. RESULTS: We identified nine major RSNs, including the auditory network; default mode network; executive control network (ECN), including the right frontoparietal network and left frontoparietal network (LFPN); somatomotor network (SMN); dorsal attention network; ventral attention network; salience network (SN); and visual network (VN). These RSNs were extracted in all groups using ICA. Compared with that in the control group, we observed reduced FC between the LFPN and VN in the T group and between the LFPN and SN in the T + H group. The inter-network connectivity analysis revealed decreased network interactions in the SMN (IC 22)-ECN (IC 2), SMN (IC 22)-VN (IC 8), and VN (IC 14)-SN (IC 3) connections in the T + H group, compared with the healthy control group. Furthermore, we observed significantly decreased network interactions in the SMN (IC 22)-VN (IC 8) in the T group. CONCLUSIONS: Our results indicated abnormalities within the brain networks of the T and T + H groups, including the SMN, ECN, and VN, compared with the control group. Furthermore, both T and T + H groups demonstrated reduced FC between the LFPN, VN, and SMN. There were no significant differences between the T and the T + H groups. Furthermore, we observed reduced FC between the right olfactory cortex and the orbital part of the right middle frontal gyrus, right precentral gyrus, left dorsolateral superior frontal gyrus, and right triangular part of the inferior frontal gyrus within the T and T + H groups. Thus, disruptions in brain regions responsible for attention, stimulus monitoring, and auditory orientation contribute to tinnitus generation.

Changes in temporal lobe activation during a sound stimulation task in patients with sensorineural tinnitus: a multi-channel near-infrared spectroscopy study.

BACKGROUND: The subjective sign of a serious pandemic in human work and life is mathematical neural tinnitus. fNIRS (functional near-infrared spectroscopy) is a new non-invasive brain imaging technology for studying the neurological activity of the human cerebral cortex. It is based on neural coupling effects. This research uses the fNIRS approach to detect differences in the neurological activity of the cerebral skin in the sound stimulation mission in order to better discriminate between the sensational neurological tinnitus. METHODS: In the fNIRS brain imaging method, 14 sensorineural tinnitus sufferers and 14 healthy controls listened to varied noise and quiet for fNIRS data collection. Linear fitting was employed in MATLAB to eliminate slow drifts during preprocessing and event-related design analysis. The false discovery rate (FDR) procedure was applied in IBM SPSS Statistics 26.0 to control the false positive rate in multiple comparison analyses. RESULTS: When the ill group and the healthy control group were stimulated by pink noise, there was a significant difference in blood oxygen concentration (P < 0.05), and the healthy control group exhibited a high activation, according to the fNIRS measurement data. The blood oxygen concentration level in the patient group was dramatically enhanced after one month of acupuncture therapy under the identical stimulation task settings, and it was favorably connected with the levels of THI and TEQ scales. CONCLUSIONS: Using sensorineural tinnitus illness as an example, fNIRS technology has the potential to disclose future pathological study on subjective diseases throughout time. Other clinical disorders involving the temporal lobe and adjacent brain areas may also be examined, in addition to tinnitus-related brain alterations.

The out-of-pocket expenses of people with tinnitus in Europe.

BACKGROUND: Despite the high frequency of tinnitus and its impact on wellbeing, little is known about its economic burden and no data to our knowledge are available on out-of-pocket (OOP) expenses. METHODS: In 2022 a survey was conducted on OOP costs of tinnitus. We enrolled 679 participants with slight, moderate and severe tinnitus in Italy, United Kingdom, Netherlands, Germany and Spain. We estimated annual OOP expenses for tinnitus-related healthcare visits, treatments, medications and alternative medicine practices. Prevalence of tinnitus in the general population, obtained from a representative survey we conducted in Europe in 2017-2018, was used to generalise costs for people with any tinnitus at the national level. RESULTS: OOP expenses were 368€ (95% confidence intervals (CI), 78€-690€), 728€ (95% CI, 316€-1,288€), and 1,492€ (95% CI, 760€-2,688€) for slight, moderate, and severe tinnitus, respectively, with annual expenditure of 565€ for people with any tinnitus: 209€ for healthcare visits, 93€ for treatments, 16€ for drugs, 64€ for hearing supporting systems and 183€ for acupuncture, homeopathy and osteopathy. Individuals with slight, moderate, and severe tinnitus expressed a willingness to invest 1.6, 4.3, and 7.0 times their monthly income, respectively, to achieve complete relief from tinnitus. CONCLUSIONS: This study offers for the first time insights into the OOP expenses incurred by individuals with tinnitus. OOP expenses exhibited substantial variations based on severity status, accounting for more than 17 thousand million€ in the countries considered. In terms of financial burden, these findings align tinnitus to the recognised leading disabilities, including back pain and migraine.

Patient-reported measures of tinnitus for individuals with neurofibromatosis type 2-related schwannomatosis: Recommendations for clinical trials.

BACKGROUND: Neurofibromatosis type 2-related schwannomatosis is a genetic disease characterized by the development of bilateral vestibular schwannomas, ependymomas, meningiomas, and cataracts. Mild to profound hearing loss and tinnitus are common symptoms reported by individuals with neurofibromatosis type 2. While tinnitus is known to have a significant and negative impact on the quality of life of individuals from the general population, the impact on individuals with neurofibromatosis type 2 is unknown. Consensus regarding the selection of suitable patient-reported outcome measures for assessment could advance further research into tinnitus in neurofibromatosis type 2 patients. The purpose of this work is to achieve a consensus recommendation by the Response Evaluation in Neurofibromatosis and Schwannomatosis International Collaboration for patient-reported outcome measures used to evaluate quality of life in the domain of tinnitus for neurofibromatosis type 2 clinical trials. METHODS: The Response Evaluation in Neurofibromatosis and Schwannomatosis Patient-Reported Outcomes Communication Subgroup systematically evaluated patient-reported outcome measures of quality of life in the domain of tinnitus for individuals with neurofibromatosis type 2 using previously published Response Evaluation in Neurofibromatosis and Schwannomatosis rating procedures. Of the 19 identified patient-reported outcome measures, 3 measures were excluded because they were not validated as an outcome measure or could not have been used as a single outcome measure for a clinical trial. Sixteen published patient-reported outcome measures for the domain of tinnitus were scored and compared on their participant characteristics, item content, psychometric properties, and feasibility for use in clinical trials. RESULTS: The Tinnitus Functional Index was identified as the most highly rated measure for the assessment of tinnitus in populations with neurofibromatosis type 2, due to strengths in the areas of item content, psychometric properties, feasibility, and available scores. DISCUSSION: Response Evaluation in Neurofibromatosis and Schwannomatosis currently recommends the Tinnitus Functional Index for the assessment of tinnitus in neurofibromatosis type 2 clinical trials.

Exploring the interplay of depression, sleep quality, and hearing in tinnitus-related handicap: insights from polysomnography and pure-tone audiometry.

BACKGROUND: Tinnitus affects approximately 740 million adults globally, involving hearing, emotion, and sleep systems. However, studies using polysomnography and pure-tone audiometry (PTA) are limited. We aimed to assess the correlation between tinnitus and hearing, sleep quality, characteristics, and depression using polysomnography and PTA. METHODS: In this cross-sectional study, we divided participants into tinnitus and non-tinnitus groups. We included 100 outpatients (65 with tinnitus, 35 without) from a medical center in Taiwan, who underwent polysomnography and completed rating scales including the Patient Health Questionnaire-9 (PHQ-9), Chinese version of the Pittsburgh Sleep Quality Index (PSQI), and Chinese-Mandarin version of the Tinnitus Handicap Inventory (THI-CM). We analyzed correlations, conducted group comparisons, assessed factors related to THI-CM scores, constructed ROC curves to predict depression in the tinnitus group, and performed multinomial and logistic regression to explore associations. RESULTS: Descriptive statistics identified a cohort with mean age 53.9 ± 12.80 years, 63% exhibited PHQ-9 scores ≥ 10, and 66% had Apnea-Hypopnea Index (AHI) > 5. The ratio of rapid eye movement and deep sleep to stage 1 + 2 sleep was relatively low and non-significant. Likewise, leg movements was higher in the tinnitus group but not statistically significant. In the tinnitus group, 63.08% had depression, and 81.54% had AHI > 5. Univariate logistic regression linked tinnitus to AHI > 5 (Odds ratio (OR) 2.67, p = 0.026) and male sex (OR 2.49, p = 0.034). A moderate positive correlation was found between the THI-CM score and PHQ-9 score (rs = 0.50, p < 0.001). Further adjustment for obstructive sleep apnea showed associations between PHQ-9 (total score) or depression and THI-CM Grade 3-5 (OR = 1.28; OR = 8.68). Single- and multifactor regression analyses highlighted significant associations of PSQI scores > 13 (OR 7.06, p = 0.018) and THI-CM scores > 47 (OR 7.43, p = 0.002) with depression. CONCLUSIONS: Our study recruited tinnitus participants with slight or mild hearing loss and mild tinnitus handicap. Depression was identified as a predominant factor in tinnitus-related handicap. The mild tinnitus handicap in tinnitus participants may explain the lack of significant differences in depression, sleep quality, and polysomnographic sleep characteristics between tinnitus and non-tinnitus groups. Further extensive and prospective studies are needed to elucidate the complex links among depression, sleep, and tinnitus.

A peripherally acting µ-opioid receptor antagonist for treating opioid-associated tinnitus: A case report.

BACKGROUND: The use of opioids occasionally causes tinnitus. However, there is a paucity of data regarding the use of peripherally acting µ-opioid receptor antagonists for opioid-associated tinnitus in patients with cancer. ACTUAL CASE: A 74-year-old male with pancreatic cancer complained of abdominal pain. Two days after initiating oxycodone therapy, the patient experienced tinnitus during body movements. Although peripheral tinnitus disappeared after discontinuing oxycodone, it reappeared with hydromorphone or tapentadol administration. POSSIBLE COURSES OF ACTION: Drug cessation is a preferred intervention for drug-induced tinnitus; however, the cessation of opioids may not be feasible in patients with cancer who are already taking opioids. FORMULATION OF A PLAN: Based on the presumed mechanism of peripheral tinnitus, the use of peripherally acting µ-opioid receptor antagonists was planned, and 200 µg/day of naldemedine was prescribed for tinnitus relief. OUTCOME: Tinnitus disappeared immediately after initiating naldemedine, and the pain was well-controlled. The effect was preserved after increasing or switching opioids. LESSONS: The use of peripherally acting µ-opioid receptor antagonists may be an option to treat opioid-associated tinnitus without compromising the analgesic effects. VIEW: Further clinical data regarding the secondary effect of peripherally acting µ-opioid receptor antagonists on opioid-associated complications other than constipation are required.

Tinnitus update: what can be done for the ringing?

Physicians will frequently encounter patients who report tinnitus. Tinnitus is a symptom whereby there is the perception of sound or sounds in the ear or head in the absence of an external source of sound. Most individuals experiencing tinnitus will have a neutral reaction to the percept, but in a small proportion of patients, tinnitus can be a debilitating symptom. When it causes burden, patients can be affected in multiple different facets of life, including impairment in sleep, hearing cognition and psychological and psychiatric well-being, often resulting in high healthcare utilisation and societal costs. Hence, chronic, disabling tinnitus is a complex condition with multifactorial causes and multiple perpetuating biopsychosocial factors. Despite efforts to increase knowledge about its pathophysiology and research into treatments, little impact on real-world clinical practice has been seen. There are no proven effective pharmacological treatments or complementary medicines specifically for chronic, disabling tinnitus. Despite this, there is a role for treating this condition through a multidisciplinary approach specifically targeting comorbid active psychiatric conditions, using hearing aids in appropriate clinical settings such as in those with a coassociated confirmed hearing loss, and specialised cognitive behavioural therapy for patients reporting bothersome tinnitus. Cognitive behavioural therapy remains the most valuable evidence-based intervention in this regard. This narrative review attempts to summarise the current understanding in terms of pathophysiology, assessment and treatment of tinnitus for the internal physician who may encounter patients with disabling, chronic tinnitus.

Pulsatile Tinnitus: Differential Diagnosis and Approach to Management.

PURPOSE OF REVIEW: The purpose of this review is to provide an updated approach to the evaluation and management of pulsatile tinnitus (PT), an uncommon but often treatable subtype of tinnitus. RECENT FINDINGS: Secondary PT can be due to either vascular or non-vascular etiologies, including, but not limited to: neoplasm, arteriovenous malformation or fistula, idiopathic intracranial hypertension, dural venous sinus stenosis, otoacoustic etiologies (e.g., otosclerosis, patulous eustachian tube) and bony defects (e.g., superior semicircular canal dehiscence). Computed tomography (CT) and magnetic resonance imaging (MRI) imaging have comparable diagnostic yield, though each may be more sensitive to specific etiologies. If initial vascular imaging is negative and a vascular etiology is strongly suspected, digital subtraction angiography (DSA) may further aid in the diagnosis. Many vascular etiologies of PT can be managed endovascularly, often leading to PT improvement or resolution. Notably, venous sinus stenting is an emerging therapy for PT secondary to idiopathic intracranial hypertension with venous sinus stenosis. Careful history and physical exam can help establish the differential diagnosis for PT and guide subsequent evaluation and management. Additional studies on the efficacy and long-term outcome of venous sinus stenting for venous stenosis are warranted.

Beyond Vertigo: Vestibular, Aural, and Perceptual Symptoms in Vestibular Migraine.

PURPOSE: To review the vestibular, aural, and perceptual symptoms of vestibular migraine (VM) that may present alongside vertigo. RECENT FINDINGS: Increased research attention to the wide spectrum of symptoms presenting in VM patients has improved understanding of this disorder, with recent identification of five different VM phenotypes. Research into the clinical overlap between VM and other chronic vestibular syndromes such as persistent postural-perceptual dizziness and mal-de-debarquement syndrome reveals a range of vestibular symptoms and hints at pathophysiological connections between migraine and vestibular dysfunction. Studies of migraine treatment for hearing loss suggest patients presenting with aural symptoms may have an underlying diagnosis of migraine and deserve a trial of migraine preventives. Research into the neurologic basis of the perceptual disorder Alice in Wonderland syndrome has revealed brain areas that are likely involved and may help explain its prevalence in VM patients. VM is a sensory processing disorder that presents with more than just vertigo. Understanding the range of potential symptoms improves diagnosis and treatment for migraine patients whose diagnosis may be missed when only the symptoms identified in the diagnostic criteria are considered.