Feasibility and Safety of High-Definition Infraslow Pink Noise Stimulation for Treating Chronic Tinnitus-A Randomized Placebo-Controlled Trial.

INTRODUCTION: Tinnitus has been linked to activity and connectivity changes in the auditory cortex (AC), parahippocampus (PHC), and posterior cingulate cortex (PCC). Although previous studies have targeted these areas individually, no study has yet modulated them simultaneously. Furthermore, novel stimulation designs may be superior to traditional alternating or direct current stimulation. This pilot study investigated the feasibility and safety of a novel brain stimulation technique (high-definition transcranial infraslow pink noise stimulation [HD-tIPNS]) for treating chronic tinnitus targeting the AC, PHC, and PCC. MATERIALS AND METHODS: A pilot, double-blind, randomized two-arm placebo-controlled parallel trial was conducted, with clinical outcomes collected at baseline, three days, and ten days after treatment. Participants with chronic tinnitus (n = 20) received 12 sessions (three per week for four weeks) of either HD-tIPNS or acti-sham stimulation. Primary outcomes included feasibility, safety, and resting-state electroencephalography (rsEEG) measures, and secondary outcomes included tinnitus and quality of life questionnaires. Feasibility, safety, and secondary measures were assessed using descriptive statistics. rsEEG was analyzed using standard low-resolution electromagnetic brain tomography. RESULTS: No long-term adverse events were reported. Mild side effects included headache and dizziness, indicating the safety of this stimulation. Participants were rapidly recruited and adhered to the study protocol with minimal difficulty. Drop-out rate was 13%, and the treatment approach was acceptable to participants, supporting the feasibility of the protocol. Tinnitus measures were similar between HD-tIPNS and acti-sham stimulation. rsEEG analyses revealed decreased beta-1 activity in PCC ten days after treatment for acti-sham. The HD-tIPNS group showed decreased beta-1 activity in inferior parietal lobule three days after treatment. Increased functional connectivity in the beta-1 frequency between left and right PHC was found in the HD-tIPNS group compared with the acti-sham group, three days after treatment. CONCLUSIONS: In conclusion, the novel approach is safe and feasible and revealed EEG changes unsupported by clinical benefit. Further research is essential to evaluate the potential of this multifocal network stimulation approach. CLINICAL TRIAL REGISTRATION: This study was registered with the Australia New Zealand Clinical Trial Registry (Registry number: ACTRN12621000151831; Universal Trial Number: U1111-1261-6945).

Tinnitus, sound intolerance, and mental health: the role of long-term occupational noise exposure.

PURPOSE: Whereas chronic noise exposure (CNE) is a known risk factor for tinnitus, little is known about how a history of CNE impacts tinnitus characteristics and its comorbid symptoms. METHODS: Seventy-five participants with chronic tinnitus (59m/16f, 22-78 years, 48 with sensory-neural hearing loss, and 27 with a normal audiogram) including 43 individuals with (Tin-CNE group) and 32 without (Tin group) a history of long-term occupational noise exposure were studied. Tinnitus characteristics were rated by a visual analog scale, and tinnitus comorbid symptoms were scored using self-assessment questionnaires. RESULTS: The Tin-CNE group showed reduced uncomfortable loudness level (ULL), sound tolerance, and quality of life (QoL), and increased tinnitus loudness, tinnitus handicap, anxiety, depression, insomnia severity, and tinnitus annoyance scores compared to the Tin group. Higher tinnitus loudness and a lower anxiety score were observed in participants with hearing loss relative to those without. Using a stepwise regression model also showed that tinnitus-related characteristics, hyperacusis, and tinnitus comorbid symptoms enhance one another. CONCLUSIONS: The findings were in support of accumulative evidence indicating the adverse auditory and non-auditory effects of CNE, including exacerbated sound intolerance and tinnitus-related psychiatric symptoms. The results also showed that tinnitus alone can affect mental health regardless of hearing loss.

A Prospective Study of the Effect of Tinnitus Sound Matching Degree on the Efficacy of Customized Sound Therapy in Patients with Chronic Tinnitus.

OBJECTIVES: The aim of this study was to explore and compare the customized sound therapy effect between tinnitus sound matching and nonmatching patients in tinnitus customized sound therapy and therapy-related influencing factors. METHODS: This prospective study investigated a total of 100 patients with unilateral chronic tinnitus who received customized sound therapy. The participants were dichotomously divided into matching (group A) and nonmatching (group B) groups after 4 stages of tinnitus matching via the tinnitus assistant app (provided by Sound Ocean Company, SuZhou, China). Each group consists of 50 participants. Before and 6 months after the treatment, Hospital Anxiety and Depression Scale (HADS), tinnitus handicap inventory (THI), and tinnitus loudness Visual Analog Scale (VAS) were used to evaluate the customized sound therapy effect and explore other related influencing factors. RESULTS: (1) The HADS-A, HADS-D, THI, and VAS scores of 2 groups were both significantly decreased after treatment. (2) The HADS-A and THI scores improved markedly in group A than that in group B, which could be related to the hearing loss of the tinnitus side ear before treatment; the lighter the degree of hearing loss, the better the improvement. No statistically significant differences were detected in HADS-D and VAS scores between the 2 groups, and also, these were not related to the degree of hearing loss. The differences in age, gender, and tinnitus duration did not show any statistically significant effect on the improvement of the 2 groups. CONCLUSIONS: Both tinnitus sound matching and nonmatching of the customized sound therapy brought a significant effect to tinnitus participants. Our study also suggests that THI and HADS-A scores of those with tinnitus matching participants improved markedly as compared to those of nonmatching participants, and the customized sound therapy effect is negatively correlated with the severity of hearing loss.

Alterations of brain activity and functional connectivity in transition from acute to chronic tinnitus.

The objective of this study was to investigate alterations to brain activity and functional connectivity in patients with tinnitus, exploring neural features in the transition from acute to chronic phantom perception. Twenty-four patients with acute tinnitus, 23 patients with chronic tinnitus, and 32 healthy controls were recruited. High-density electroencephalography (EEG) was used to explore changes in brain areas and functional connectivity in different groups. When compared with healthy subjects, acute tinnitus patients had a significant reduction in superior frontal cortex activity across all frequency bands, whereas chronic tinnitus patients had a significant reduction in the superior frontal cortex at beta 3 and gamma frequency bands as well as a significant increase in the inferior frontal cortex at delta-band and superior temporal cortex at alpha 1 frequency band. When compared to the chronic tinnitus group, the acute tinnitus group activity was significantly increased in the middle frontal and parietal gyrus at the gamma-band. Functional connectivity analysis showed that the chronic tinnitus group had increased connections between the parahippocampus gyrus, posterior cingulate cortex, and precuneus when compared with the healthy group. Alterations of local brain activity and connections between the parahippocampus gyrus and other nonauditory areas appeared in the transition from acute to chronic tinnitus. This indicates that the appearance and development of tinnitus is a dynamic process involving aberrant local neural activity and abnormal connectivity in multifunctional brain networks.

Investigation on chronic tinnitus efficacy of combination of non-repetitive preferred music and educational counseling: a preliminary study.

PURPOSE: To improve the efficacy of music therapy on tinnitus relief, specific music that was not repetitively played and satisfies individualized preference was developed. The aim of this study was to investigate effects of combination of the specific music and educational counseling on tinnitus relief in short term. METHODS: Sixty patients suffering from chronic tinnitus were included. The non-randomized controlled study was designed with two intervention groups: educational counseling (EC, which included a 1-h individualized instruction) and preferred music therapy [PMT, which included EC plus 15, 30-min preferred music sessions (PMS)]. Three assessments-the Chinese-Mandarin version of Tinnitus Handicap Inventory (THI-CM), Tinnitus Evaluation Questionnaire (TEQ), and Visual Analogue Scale (VAS) were administered before and 1, 2, 3 weeks after initiation of treatment to evaluate the efficacy. RESULTS: Twenty-six patients in PMT group attained a clinically meaningful improvement in THI compared to 15 in the EC group, though both groups achieved a statistically relevant reduction in the 3 assessments. CONCLUSION: The PMT had a positive impact on chronic tinnitus and related distress in a short term. It outperformed the separate EC, which is an appropriate treatment option in clinic. Therefore, it presents a possible complement to the therapeutic spectrum in chronic tinnitus. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900022624. Registered on 19 April 2019.

Aberrant cerebral blood flow in tinnitus patients with migraine: a perfusion functional MRI study.

PURPOSE: Migraine is often accompanied with chronic tinnitus that will affect the cerebral blood flow (CBF) and exacerbate the tinnitus distress. However, the potential relationship between migraine and tinnitus remains unclear. This study will investigate whether aberrant CBF patterns exist in migraine patients with tinnitus and examine the influence of migraine on CBF alterations in chronic tinnitus. MATERIALS AND METHODS: Participants included chronic tinnitus patients (n = 45) and non-tinnitus controls (n = 50), matched for age, sex, education, and hearing thresholds. CBF images were collected and analyzed using arterial spin labeling (ASL) perfusion functional magnetic resonance imaging (fMRI). Regions with major CBF differences between tinnitus patients and non-tinnitus controls were first detected. The effects of migraine on tinnitus for CBF alterations were further examined. Correlation analyses illustrated the association between CBF values and tinnitus severity as well as between CBF and severity of migraine. RESULTS: Compared with non-tinnitus controls, chronic tinnitus patients without migraine exhibited decreased CBF, primarily in right superior temporal gyrus (STG), bilateral middle frontal gyrus (MFG), and left superior frontal gyrus (SFG); decreased CBF in these regions was correlated with tinnitus distress. There was a significant effect of migraine on tinnitus for CBF in right STG and MFG. Moreover, the severity of migraine correlated negatively with CBF in tinnitus patients. CONCLUSIONS: Chronic tinnitus patients exhibited reduced CBF in the auditory and prefrontal cortex. Migraine may facilitate a CBF decrease in the setting of tinnitus, which may underlie the neuropathological mechanisms of chronic tinnitus comorbid with migraine.

Repetitive transcranial magnetic stimulation on chronic tinnitus: a systematic review and meta-analysis.

BACKGROUND: Although the clinical efficacy and safety of repetitive transcranial magnetic stimulation (rTMS) in the treatment of chronic tinnitus have been frequently examined, the results remain contradictory. Therefore, we performed a systematic review and meta-analysed clinical trials examining the effects of rTMS to evaluate its clinical efficacy and safety. METHODS: Studies of rTMS for chronic tinnitus were retrieved from PubMed, Embase, and Cochrane Library through April 2020. Review Manager 5.3 software was employed for data synthesis, and Stata 13.0 software was used for analyses of publication bias and sensitivity. RESULTS: Twenty-nine randomized studies involving 1228 chronic tinnitus patients were included. Compared with sham-rTMS, rTMS exhibited significant improvements in the tinnitus handicap inventory (THI) scores at 1 week (mean difference [MD]: - 7.92, 95% confidence interval [CI]: - 14.18, - 1.66), 1 month (MD: -8.52, 95% CI: - 12.49, - 4.55), and 6 months (MD: -6.53, 95% CI: - 11.406, - 1.66) post intervention; there were significant mean changes in THI scores at 1 month (MD: -14.86, 95% CI: - 21.42, - 8.29) and 6 months (MD: -16.37, 95% CI: - 20.64, - 12.11) post intervention, and the tinnitus questionnaire (TQ) score at 1 week post intervention (MD: -8.54, 95% CI: - 15.56, - 1.52). Nonsignificant efficacy of rTMS was found regarding the THI score 2 weeks post intervention (MD: -1.51, 95% CI: - 13.42, - 10.40); the mean change in TQ scores 1 month post intervention (MD: -3.67, 95% CI: - 8.56, 1.22); TQ scores 1 (MD: -8.97, 95% CI: - 20.41, 2.48) and 6 months (MD: -7.02, 95% CI: - 18.18, 4.13) post intervention; and adverse events (odds ratios [OR]: 1.11, 95% CI: 0.51, 2.42). Egger's and Begg's tests indicated no publication bias (P = 0.925). CONCLUSION: This meta-analysis demonstrated that rTMS is effective for chronic tinnitus; however, its safety needs more validation. Restrained by the insufficient number of included studies and the small sample size, more large randomized double-blind multi-centre trials are needed for further verification.

Chronic tinnitus and BDNF/GDNF CpG promoter methylations: a case-control study.

Brain-derived neurotrophic factor (BDNF) and Glial-derived neurotrophic factor (GDNF) are neurotrophic factors that play key roles in the auditory pathway. While the relationship between serum levels and polymorphisms of BDNF/GDNF and chronic tinnitus is emphasized in the literature, there is no study showing the link between the promoter methylations of these genes and tinnitus. For this purpose, the relationship between chronic tinnitus and peripheral blood derived BDNF/GDNF promoter methylations was investigated to identify their role in the pathophysiology of tinnitus. In this case-control study, we examined the possible effects of BDNF/GDNF methylations in the blood samples of patients with tinnitus complaints for more than 3 months. Sixty tinnitus subjects between the ages of 18-55 and 50 healthy control subjects in the same age group who were free of any otorhinolaryngology and systemic disease were selected for examination. Methylation of total 12 CpG sites in BDNF and GDNF promoter regions were determined by the bisulfite-pyrosequencing method. Statistically significant differences were detected between BDNF CpG6 and GDNF CpG3-5-6 methylation ratios in the comparison of control group and the chronic tinnitus patients (P = 0.002, 0.0005, 0.00003, and 0.0029, respectively). To our knowledge, this is the first study in the literature investigating the relationship between chronic tinnitus and peripheral blood derived BDNF/GDNF promoter methylations. It is believed that the current results might be supported by investigating the relationships between BDNF/GDNF methylations and genotypes in future research using higher sample sizes.

A proof-of-concept study on the combination of repetitive transcranial magnetic stimulation and relaxation techniques in chronic tinnitus.

Interference of ongoing neuronal activity and brain stimulation motivated this study to combine repetitive transcranial magnetic stimulation (rTMS) and relaxation techniques in tinnitus patients. Forty-two patients were enrolled in this one-arm proof-of-concept study to receive ten sessions of rTMS applied to the left dorsolateral prefrontal cortex and temporo-parietal cortex. During stimulation, patients listened to five different kinds of relaxation audios. Variables of interest were tinnitus questionnaires, tinnitus numeric rating scales, depressivity, and quality of life. Results were compared to results of historical control groups having received the same rTMS protocol (active control) and sham treatment (placebo) without relaxation techniques. Thirty-eight patients completed the treatment, drop-out rates and adverse events were low. Responder rates (reduction in tinnitus questionnaire (TQ) score ≥5 points 10 weeks after treatment) were 44.7 % in the study, 27.8 % in the active control group, and 21.7 % in the placebo group, differing between groups on a near significant level. For the tinnitus handicap inventory (THI), the main effect of group was not significant. However, linear mixed model analyses showed that the relaxation/rTMS group differed significantly from the active control group showing steeper negative THI trend for the relaxation/rTMS group indicating better amelioration over the course of the trial. Deepness of relaxation during rTMS and selection of active relaxation vs. passive listening to music predicted larger TQ. All remaining secondary outcomes turned out non-significant. This combined treatment proved to be a safe, feasible and promising approach to enhance rTMS treatment effects in chronic tinnitus.

Relationship Between Chronic Tinnitus and Glial Cell Line-Derived Neurotrophic Factor Gene rs3812047, rs1110149, and rs884344 Polymorphisms in a Turkish Population.

Glial cell line-derived neurotrophic factor (GDNF) plays a key role in early development of central auditory pathway and the inner ear. However, the auditory pathway studies of GDNF gene polymorphisms are scarce in the literature, and the studies especially associated with tinnitus are limited. Our study aimed to identify whether GDNF gene polymorphisms play any roles in the pathophysiology of tinnitus by investigating the relationship between tinnitus and GDNF polymorphisms. A total of 52 patients with chronic tinnitus and ages ranging from 18 to 55 were admitted to the Ear-Nose-Throat outpatient clinic of Celal Bayar University Medical Faculty Hospital of Manisa, Turkey and constituted the study group. Another 42 patients of the same age range, without tinnitus symptoms and lacking any systemic disease, were also admitted to the clinic and formed the control group. The tympanometric, audiological, and psychoacoustic assessments of the subjects were performed. Deoxyribonucleic acid samples obtained using venous blood taken for routine inspections were used to investigate GDNF gene polymorphisms (rs884344, rs3812047, and rs1110149) by polymerase chain reaction-based restriction fragment length polymorphism method. No correlation could be detected between GDNF rs884344 and rs3812047 polymorphisms and subjects with tinnitus (p > 0.05). Heterozygosity was significantly lower for GDNF rs1110149 polymorphism in tinnitus subjects compared to the controls (p < 0.05). However, the allele frequencies for all 3 polymorphisms were not significantly different between tinnitus and control groups (p > 0.05). Failure to detect correlations between tinnitus and GDNF gene polymorphisms suggests this may be due to the fact that the GDNF gene has a variable expression pattern in different tissues and pathologies. Therefore, the study should be improved and its scope should be expanded by including a larger group of patients and different tissues to investigate the expression pattern of GDNF.

Associations between tinnitus and body composition: a cross-sectional study.

The relationship between tinnitus and body composition in specific regions has not been extensively investigated. This study aimed to identify associations between tinnitus and body composition. Individuals with data on physical and otological examination findings, and bioelectrical impedance analysis were included from the ninth Korea National Health and Nutritional Examination Survey. They were divided into a tinnitus group and a non-tinnitus group. Participants with tinnitus were further classified into acute or chronic tinnitus group. The tinnitus group showed significantly higher body fat percentages in each region (arms: P = 0.014; legs: P = 0.029; trunk: P = 0.008; whole body: P = 0.010) and waist circumference (P = 0.007) than the non-tinnitus group, and exhibited lower leg muscle percentage (P = 0.038), total body fluid percentage (P = 0.010), and intracellular fluid percentage (P = 0.009) than the non-tinnitus group in men. Furthermore, men with chronic tinnitus showed a significantly higher trunk fat percentage (P = 0.015) and waist circumference (P = 0.043), and lower intracellular fluid percentage (P = 0.042) than their counterparts without tinnitus. No significant differences in body composition were observed among the groups in the female population. In men, body composition may be associated with tinnitus.

Customized Music Therapy Combined With the Counseling and Follow-Up System: Stratified Results for Tinnitus Efficacy.

Objective: Chronic subjective tinnitus is a worldwide intractable problem. In our previous studies, customized music therapy combined with a follow-up system can reduce tinnitus perception and improve anxiety/depression. This study aims to explore which characteristics of tinnitus patients are more likely to benefit from our therapy. Study Design: This study included 1031 patients with chronic subjective tinnitus, all of whom completed customized music therapy with the follow-up system. Population demographics, tinnitus characteristics, and tinnitus-related scales at pretherapy and posttherapy were collected. Setting: Huadong Hospital affiliated Fudan University, Department of Otorhinolaryngology-Head & Neck Surgery from 2018 to 2022. Methods: A paired t test and the one-way analysis of variance were utilized to the overall efficacy and stratified difference based on tinnitus duration/age/tinnitus frequency. Results: There were significant statistical differences in the Tinnitus Handicap Inventory (THI), Tinnitus Loudness Visual Analog Scale (VAS), and Hospital Anxiety and Depression Scale (HADS)-A/D scores between pretherapy and 3 months posttherapy. THI and HADS (A/D) scores decreased the most in the 1-year duration tinnitus group. The most significant decrease in THI and VAS scores was observed in the 31- to 50-year-old tinnitus group. Patients with high-frequency tinnitus and extended high-frequency tinnitus had greater decreases generally than those with low-frequency tinnitus though no significance. Conclusion: Group with severe and prolonged tinnitus, shorter duration of tinnitus onset, and 31 to 50 years old benefit more from our therapy. Therefore, standardized personalized music and consulting and follow-up systems while promoting early treatment can reduce tinnitus and its comorbidities.

Non-invasive treatments improve patient outcomes in chronic tinnitus: a systematic review and network meta-analysis.

OBJECTIVE: To investigate the relative effectiveness of various Non-Invasive Treatment Techniques (NITs) in chronic tinnitus management. METHODS: We searched PubMed, Embase and Cochrane Library databases from the time of data construction to December 31, 2022. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, NITs were evaluated, including Aacceptance and commitment therapy (A), Cognitive behavioral therapy (C), Sound therapy (S), Transcranial magnetic stimulation (T), Electrical stimulation therapy (E), Virtual reality therapy (V), tinnitus Retraining therapy (R), general psychotherapy (D), and Placebo (P). The outcome indicators included the Tinnitus Handicap Inventory (THI), Tinnitus Questionnaire (TQ), Hospital Anxiety and Depression Scale-anxiety-Depression (HADS-D), Insomnia Severity Index (ISI), Visual Analogue Scales-Loudness (VAS-L), and Visual Analogue Scales-Distress (VAS-D). Statistical analysis was performed using Stata 14.0 for NMA. RESULTS: This systematic review and meta-analysis included 22 randomized controlled trials comprising 2,354 patients. The treatment effects varied on each scale. For THI, S (86.9%) was the most effective, whereas P (6.5%) was the worst. For TQ, C (89.5%) was the most effective, whereas D (25.4%) was the worst. For HADS-D, A (82.4%) was the most effective, whereas D (9.47%) was the worst. For ISI, A (83.2%) was the most effective, whereas R (20.6%) was the worst. For VAS-L, S (73.5%) was the most effective, whereas E (18.9%) was the worst. For VAS-D, C (84.7%) was the most effective, whereas P (18.1%) was the worst. CONCLUSIONS: The combination of acoustics and cognitive behavioral therapy may be an effectively treat patients with chronic tinnitus. LEVEL OF EVIDENCE: How common is the problem? Level 2. Is this diagnostic or monitoring test accurate? (Diagnosis) Level 1. What will happen if we do not add a therapy? (Prognosis) Level 1. Does this intervention help? (Treatment Benefits) Level 1. What are the COMMON harms? (Treatment Harms) Level 1. What are the RARE harms? (Treatment Harms) Level 1. Is this (early detection) test worthwhile? (Screening) Level 1I.

Individuals with Tinnitus Report More Positive Experiences following Internet-Based Cognitive Behavioral Therapy.

BACKGROUND: This study aimed to examine whether individuals with chronic tinnitus report more positive experiences following internet-based cognitive behavioral therapy (CBT). METHODS: A mixed-methods design was used, nested in clinical trials evaluating internet interventions for tinnitus. Participants (n = 164) completed online questionnaires (both structured and open-ended) providing demographic information as well as health variables (e.g., tinnitus distress, anxiety, depression, insomnia). An open-ended question listing positive effects or outcomes related to having tinnitus was also included. Responses to the open-ended questions were analyzed using qualitative content analysis. RESULTS: Of the 164 eligible participants, 32.3% (n = 53) provided at least 1 positive experience both at pre- and post-intervention, with 9.1% (n = 19) providing positive experiences only at pre-intervention, 49 (29.9%) providing positive experiences only at post-intervention, and 28.7% (n = 47) of the participants did not provide any positive experiences on either measurement occasion. Significantly more positive experiences were reported following the intervention in the overall sample (p < 0.0001, paired sample t-test). In addition, participants who reported positive experiences in both pre- and post-intervention also reported more positive experiences following intervention (p = 0.008, paired sample t-test). CONCLUSIONS: Internet-based CBT can help individuals with tinnitus to think more positively by changing unhelpful thought patterns. Open-ended questions can supplement structured questionnaires to measure treatment outcomes.

Health-Related Quality of Life in Subjective, Chronic Tinnitus Patients: A Scoping Review.

PURPOSE: This scoping review aims to assess whether the severity or distress of subjective tinnitus is negatively associated or correlated with the level of health-related quality of life (HRQoL). A second objective is to examine whether tinnitus patients score differently on HRQoL questionnaires in comparison to subjects without tinnitus and whether HRQoL differs between specific subgroups of tinnitus. METHODS: This scoping review adheres to the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines (PRISMA guidelines): the statement and extension for scoping reviews (PRISMA-ScR). The following databases were consulted (on the 20th of October 2023): PubMed, Cochrane Library, Web of Science, and Scopus. The search string was composed of the terms tinnitus, HRQoL, and synonyms. A double-blinded screening for eligibility was performed, first on the title and abstract and subsequently on the full-text articles. Studies were considered eligible if they looked at HRQoL questionnaire results for adult patients (> 18 years) reporting chronic (> 3 months), subjective tinnitus as a primary complaint. RESULTS: In total, 37 studies with a total sample size of 33,900 participants were included in this scoping review, with some studies answering multiple study objectives. Seventeen studies demonstrated the presence of a significant negative correlation between tinnitus-related distress and HRQoL. Two studies indicated that HRQoL is mediated by tinnitus-related distress. Eighteen studies found that, in general, patients with tinnitus scored significantly lower on HRQoL questionnaires in comparison to subjects without tinnitus. Nineteen studies demonstrated that subgroups of patients with more severe tinnitus complaints or specific additional complaints scored worse on HRQoL questionnaires. CONCLUSION: Based on the current literature, chronic subjective tinnitus-related distress has a significant impact on health-related quality of life. In addition, subjects without tinnitus generally score significantly higher on HRQoL questionnaires than patients with tinnitus. The heterogeneity in outcome measures between studies precludes meta-analysis. Increased homogeneity in the choice of HRQoL questionnaires would make a comparison between studies possible, which would give valuable information on both a clinical and an economic level, guiding future tinnitus treatment. REGISTRATION: The protocol for the scoping review is registered at Open Science Framework: https://doi.org/10.17605/OSF.IO/F5S9C .

Glymphatic system dysfunction associated with cognitive impairment in chronic tinnitus patients.

Background: The glymphatic system has been regarded as a pivotal factor in the pathogenesis of neurodegenerative diseases. Given the heightened risk of cognitive impairment in chronic tinnitus patients, the possible alterations of the glymphatic system in tinnitus patients remain elusive. This study was designed to evaluate glymphatic dysfunction in chronic tinnitus patients using the diffusion tensor imaging (DTI) along the perivascular space (DTI-ALPS) approach. Methods: Fifty chronic tinnitus patients and 50 age, sex, and education-matched healthy controls (HCs) with normal hearing thresholds were recruited. The DTI-ALPS was calculated from each group. We investigated the differences in the DTI-ALPS index between the tinnitus patients and HCs. The relationships between the DTI-ALPS index and specific cognitive performance were further assessed. Results: There were significant differences in the DTI-ALPS index between the two groups. The DTI-ALPS index was significantly lower in the tinnitus group than in HCs group (p < 0.01). In addition, the Dyyproj index was significantly higher in the tinnitus group than in the HC group (p < 0.01). In chronic tinnitus patients, the decreased DTI-ALPS index was negatively associated with worse TMT-B scores (r = -0.309, p = 0.039). Moreover, the increased Dyyproj index was negatively correlated with the reduced AVLT performances (r = -0.413, p = 0.005). Conclusion: In this current study, glymphatic system activity in chronic tinnitus was investigated for the first time using DTI-ALPS index. Significant decrease in glymphatic system function was detected in chronic tinnitus, which correlated well with the specific cognitive performance. The current study may provide pivotal imaging markers for chronic tinnitus with cognitive impairment.

Lipid parameters and depression in patients with chronic tinnitus: A cross-sectional observation.

BACKGROUND: Pathophysiological theories assume importance of metabolic abnormalities in patients with major depression - and possibly chronic tinnitus. Although chronic tinnitus frequently correlates with depression, links between high-density lipoprotein (HDL) and depression are uninvestigated. METHODS: Two-hundred patients with chronic tinnitus (Mage = 55; 51% female) were examined. Serum levels of total cholesterol (TC), triglycerides (TGs), HDL, low-density lipoprotein cholesterol (LDL), non-HDL, as well as LDL/HDL and TC/HDL ratios were analysed. Questionnaires included depression subscales of the ICD-10 Symptom Rating, the Hospital Anxiety and Depression Scale (HADS_D), and the Berlin Mood Questionnaire (BSF). Multivariate analyses of covariance and linear regression models - which controlled age, tinnitus-related distress and perceived stress - investigated between-subgroup differences (p < 0.05) and linear associations between HDL indices and depression (p < 0.01). RESULTS: HDL levels did not differ for tinnitus-symptom durations, smoking and alcohol use levels, statin or antihypertensive drug use, and body-mass indices. Relative to non-to-mildly depressed patients with chronic tinnitus, patients with moderate-to-severe depression (n = 45; 23%) had significantly lower HDL levels (d = -0.35) and higher LDL/HDL (d = 0.39) and TC/HDL ratios (d = 0.40). Across participants, HDL-levels were negatively associated with depression as measured by the HADS_D and BSF_indifference scales. CONCLUSIONS: In keeping with general depression research, low serum HDL levels correlate with depressive symptomatology in patients with chronic tinnitus. This association may be influenced by proximal (e.g. modulations of HPA-axis activity) or distal factors (e.g. maladaptive coping behaviours) - both of which should be conceptualized within psychological stimulus-processing frameworks.

Personality Traits and Tinnitus Distress: Results Based on Patients with Tinnitus in China.

Background: Due to the socio-cultural differences between China and other countries, which may affect the development of an individual's personality and behavior, it is necessary to explore the relationship between personality traits and tinnitus distress in the context of China's socio-cultural background. Methods: The Tinnitus Handicap Inventory and the Eysenck Personality Questionnaire Short Scale Chinese version were used to explore the influence of personality traits on tinnitus distress in Chinese patients with tinnitus. Results: The results were not entirely consistent with previous studies from other countries. First, extroversion was significantly higher in patients with bothersome tinnitus, both in acute and chronic conditions. Second, the personality traits that affected the patients with bothersome tinnitus were different in different conditions. Finally, the tridimensional personality structure, high psychoticism / normal extroversion / normal neuroticism, was significantly higher in people with bothersome tinnitus. Furthermore, the difference became more obvious with a prolonged disease course. Conclusions: This study suggested that the relationship between personality traits and tinnitus distress in Chinese patients with tinnitus was not the same as in other countries. "High psychoticism / normal extroversion / normal neuroticism" may be a risk factor for chronic bothersome tinnitus in China.

Evaluation of chronic idiopathic tinnitus and its psychosocial triggers.

BACKGROUND: The tinnitus susceptibility patterns in relation to different psychological and life stressors are unknown in different cultures. AIM: To determine the comorbid psychosocial factors and behaviors associated with tinnitus and the predictors for the increase in its severity. METHODS: Participants were 230 adults (males = 70; females = 160; mean age = 38.6 ± 3.3). They underwent audiograms, speech discrimination and masking testing, and neuropsychiatric evaluation. Measures used for assessment included tinnitus handicap inventory, depression anxiety stress scale 21 (DASS-21), perceived stress scale (PSS), and insomnia severity index (ISI). RESULTS: Patients had mean duration of tinnitus of 11.5 ± 2.5 mo. They had intact hearing perception at 250-8000 Hz and 95 (41.3%) had aggravation of tinnitus loudness by masking noise. Decompensated tinnitus was reported in 77% (n = 177). The majority had clinically significant insomnia (81.3%), somatic symptoms (75%) other than tinnitus and perceived moderate (46.1%) and high (44.3%) stress to tinnitus. The severe/extremely severe symptoms of depression, anxiety and stress were reported in 17.4%, 35.7% and 44.3%, respectively. Patients with decom-pensated type had significantly higher scores for ISI (P = 0.001) and DASS-21 (depression = 0.02, anxiety = 0.01, stress = 0.001) compared to those with compensated tinnitus. Psychiatric interviewing showed that 35.7% had non-specific anxiety disorder, 17.4% had major depression, and 19.6% fulfilled the criteria of somatization disorder. Multivariate analysis showed that the only independent predictors for tinnitus severity were the duration of tinnitus [odd ratios (OR) = 0.832, 95%CI: 0.640-1.158; P = 0.001] and PSS (OR = 0.835, 95%CI: 0.540-1.125; P = 0.001) scores. CONCLUSION: To the best of our knowledge, this is the first study in our culture to evaluate the causal relationship between psychological factors and tinnitus onset, severity and persistence. Tinnitus could be the earliest and dominant somatic symptom induced by life stressors and psychological vulnerabilities. Therefore, multidisciplinary consultation (psychologists, psychiatrists, and neurologists) is important to acknowledge among the audiologists and otolaryngologists who primarily consult patients.

Acupuncture for chronic tinnitus: A CARE-compliant case report.

INTRODUCTION: Tinnitus is a sound hallucination characterised by buzzing and hissing in the ear or brain of a patient in the absence of an externally available sound source. It could be perceived as one or more sounds and can last for a certain period of time. OBJECTIVE: We aimed to report the successful treatment of tinnitus using acupuncture. METHOD: A patient diagnosed with chronic tinnitus had buzzing sounds in both ears for over 4 years. Acupuncture treatment was administered a total of five times. GV20 (Baihui), EX-HN1 (Sishencong), GV24 (Shenting), CV12 (Zhongwan), CV10 (Xiawan), CV6 (Qihai), CV4 (Guanyuan), and other bilateral acupuncture points, including GB13 (Benshen), SI19 (Tinggong), GB2 (Tinghui), SJ17 (Yifeng), KI19 (Yindu), and KI17 (Shangqu), were selected as acupuncture points. RESULTS: Tinnitus was successfully resolved, and THI scores decreased. CONCLUSIONS: Acupuncture is a potential alternative treatment for chronic tinnitus.