The antioxidant ergothioneine alleviates cisplatin-induced hearing loss through the Nrf2 pathway.

AIMS: Cisplatin (CDDP) is a commonly used chemotherapeutic agent for treating head and neck tumors. However, there is high incidence of ototoxicity in patients treated with CDDP, which may be caused by the excessive reactive oxygen species generation (ROS) in the inner ear. Many studies have demonstrated the strong antioxidant effects of ergothioneine (EGT). Therefore, we assumed that EGT could also attenuate CIHL as well. However, the protective effect and mechanism of EGT on CIHL have not been elucidated as so far. In this study, we investigated whether EGT could treat CIHL and the mechanism. RESULTS: In our study, we confirmed the protective effect of EGT on preventing cisplatin induced toxicity both in vitro and in vivo. The auditory brainstem response (ABR) threshold shift in the EGT + CDDP treatment mice was 30 dB less than that in the CDDP treatment mice. EGT suppressed production of ROS and pro-apoptotic proteins both in tissue and cells. By silencing Nrf2, we confirmed that EGT protected against CIHL via the Nrf2 pathway. We also found that SLC22A4 (OCTN1), an important molecule involved in transporting EGT, was expressed in the cochlea. INNOVATION: Our results revealed the role of EGT in the prevention of CIHL by activating Nrf2/HO-1/NQO-1 pathway, and broadened a new perspective therapeutic target of EGT. CONCLUSION: EGT decreased ROS production and promoted the expression of antioxidative enzymes to maintain redox homeostasis in sensory hair cells (HCs). Overall, our results indicated that EGT may serve as a novel treatment drug to attenuate CIHL.

Hesperidin activates Nrf2 to protect cochlear hair cells from cisplatin-induced damage.

Cisplatin is widely employed in clinical oncology as an anticancer chemotherapy drug in clinical practice and is known for its severe ototoxic side effects. Prior research indicates that the accumulation of reactive oxygen species (ROS) plays a pivotal role in cisplatin's inner ear toxicity. Hesperidin is a flavanone glycoside extracted from citrus fruits that has anti-inflammatory and antioxidant effects. Nonetheless, the specific pharmacological actions of hesperidin in alleviating cisplatin-induced ototoxicity remain elusive. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is a critical mediator of the cellular oxidative stress response, is influenced by hesperidin. Activation of Nrf2 was shown to have a protective effect against cisplatin-induced ototoxicity. The potential of hesperidin to stimulate Nrf2 in attenuating cisplatin's adverse effects on the inner ear warrants further investigation. This study employs both in vivo and in vitro models of cisplatin ototoxicity to explore this possibility. Our results reveal that hesperidin mitigates cisplatin-induced ototoxicity by activating the Nrf2/NQO1 pathway in sensory hair cells, thereby reducing ROS accumulation, preventing hair cell apoptosis, and alleviating hearing loss.

CFTR potentiator ivacaftor protects against noise-induced hair cell loss by increasing Nrf2 and reducing oxidative stress.

Over-production of reactive oxygen species (ROS) in the inner ear can be triggered by a variety of pathological events identified in animal models after traumatic noise exposure. Our previous research found that inhibition of the AMP-activated protein kinase alpha subunit (AMPKα) protects against noise-induced cochlear hair cell loss and hearing loss by reducing ROS accumulation. However, the molecular pathway through which AMPKα exerts its antioxidative effect is still unclear. In this study, we have investigated a potential target of AMPKα and ROS, cystic fibrosis transmembrane conductance regulator (CFTR), and the protective effect against noise-induced hair cell loss of an FDA-approved CFTR potentiator, ivacaftor, in FVB/NJ mice, mouse explant cultures, and HEI-OC1 cells. We found that noise exposure increases phosphorylation of CFTR at serine 737 (p-CFTR, S737), which reduces wildtype CFTR function, resulting in oxidative stress in cochlear sensory hair cells. Pretreatment with a single dose of ivacaftor maintains CFTR function by preventing noise-increased p-CFTR (S737). Furthermore, ivacaftor treatment increases nuclear factor E2-related factor 2 (Nrf2) expression, diminishes ROS formation, and attenuates noise-induced hair cell loss and hearing loss. Additionally, inhibition of noise-induced AMPKα activation by compound C also diminishes p-CFTR (S737) expression. In line with these in-vivo results, administration of hydrogen peroxide to cochlear explants or HEI-OC1 cells increases p-CFTR (S737) expression and induces sensory hair cell or HEI-OC1 cell damage, while application of ivacaftor halts these effects. Although ivacaftor increases Nrf2 expression and reduces ROS accumulation, cotreatment with ML385, an Nrf2 inhibitor, abolishes the protective effects of ivacaftor against hydrogen-peroxide-induced HEI-OC1 cell death. Our results indicate that noise-induced sensory hair cell damage is associated with p-CFTR. Ivacaftor has potential for treatment of noise-induced hearing loss by maintaining CFTR function and increasing Nrf2 expression for support of redox homeostasis in sensory hair cells.

Serum metabolomics analysis revealed metabolic disorders in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is by now the second of the most prevalent neurodegenerative diseases in the world, and its incidence is increasing rapidly as the global population ages, with 14.2 million PD patients expected worldwide by 2040. METHODS: We gathered a completion of 45 serum samples, including 15 of healthy controls and 30 from the PD group. We used non-targeted metabolomics analysis based on liquid chromatography-mass spectrometry to identify the molecular changes in PD patients, and conducted bioinformatics analysis on this basis to explore the possible pathogenesis of PD. RESULTS: We found significant metabolomics changes in the levels of 30 metabolites in PD patients compared with healthy controls. CONCLUSION: Lipids and lipid-like molecules accounted for the majority of the 30 differentially expressed metabolites. Also, pathway enrichment analysis showed significant enrichment in sphingolipid metabolic pathway. These assessments can improve our perception on the underlying mechanism of PD as well as facilitate a better targeting on therapeutic interventions.

Age-related hearing loss accelerates the decline in fast speech comprehension and the decompensation of cortical network connections.

Patients with age-related hearing loss face hearing difficulties in daily life. The causes of age-related hearing loss are complex and include changes in peripheral hearing, central processing, and cognitive-related abilities. Furthermore, the factors by which aging relates to hearing loss via changes in auditory processing ability are still unclear. In this cross-sectional study, we evaluated 27 older adults (over 60 years old) with age-related hearing loss, 21 older adults (over 60 years old) with normal hearing, and 30 younger subjects (18-30 years old) with normal hearing. We used the outcome of the upper-threshold test, including the time-compressed threshold and the speech recognition threshold in noisy conditions, as a behavioral indicator of auditory processing ability. We also used electroencephalography to identify presbycusis-related abnormalities in the brain while the participants were in a spontaneous resting state. The time-compressed threshold and speech recognition threshold data indicated significant differences among the groups. In patients with age-related hearing loss, information masking (babble noise) had a greater effect than energy masking (speech-shaped noise) on processing difficulties. In terms of resting-state electroencephalography signals, we observed enhanced frontal lobe (Brodmann's area, BA11) activation in the older adults with normal hearing compared with the younger participants with normal hearing, and greater activation in the parietal (BA7) and occipital (BA19) lobes in the individuals with age-related hearing loss compared with the younger adults. Our functional connection analysis suggested that compared with younger people, the older adults with normal hearing exhibited enhanced connections among networks, including the default mode network, sensorimotor network, cingulo-opercular network, occipital network, and frontoparietal network. These results suggest that both normal aging and the development of age-related hearing loss have a negative effect on advanced auditory processing capabilities and that hearing loss accelerates the decline in speech comprehension, especially in speech competition situations. Older adults with normal hearing may have increased compensatory attentional resource recruitment represented by the top-down active listening mechanism, while those with age-related hearing loss exhibit decompensation of network connections involving multisensory integration.

Efficacy of Tailor-Made Notched Music Training Versus Tinnitus Retraining Therapy in Adults With Chronic Subjective Tinnitus: A Randomized Controlled Clinical Trial.

OBJECTIVES: Chronic subjective tinnitus can have a serious effect on daily life, even causing serious psychological disorders. Currently there are no specific effective solutions or cures. Tailor-made notched music training (TMNMT) is a recently proposed sound therapy that has simpler processes and a higher compliance rate than tinnitus retraining therapy (TRT), a widely used treatment for chronic subjective tinnitus. This study explores the therapeutic effect of TMNMT in comparison to TRT to highlight its clinical value. DESIGN: The study was a randomized controlled, single-blinded clinical trial. One hundred twenty eligible participants were randomly assigned to receive TMNMT (n = 60) or TRT (n = 60) for 3 mo with concurrent follow-up. It should be noted that the duration of sound treatment in TRT was modified to 2 hr per day for better feasibility in practice. The primary outcome was mean change in tinnitus handicap inventory (THI) measured at baseline ( T0 ), 1 mo ( T1 ) and 3 mo ( T2 ) after intervention. Change in visual analog scale (VAS) was measured as a secondary outcome. A comparison of therapeutic effectiveness between TMNMT and TRT was evaluated by repeated measure analysis of variance. RESULTS: One hundred and twelve (93%) of participants took part in the study, of which 64 were men and 48 women. Mean (SD) age was 42.80 (12.91) years. Fifty-eight were allocated to receive TMNMT and 54 to receive TRT. The between-group difference in primary outcome was -6.90 points (95% confidence interval [CI], -13.53 to -0.27) at T1 and -6.17 points (95% CI, -13.04 to 0.71) at T2 . These results closely reached to clinical significance of tinnitus-related effective relief. For the secondary outcome, the mean value in the TMNMT group was 0.83 points (95% CI, 0.12 to 1.54), significantly lower than the mean value of the TRT group. The differences in THI and VAS between the two groups were statistically significant after intervention. Further analysis showed that age and baseline THI and VAS scores were associated with change in THI and VAS scores after interventions. CONCLUSIONS: Both TMNMT and TRT were able to alleviate chronic subjective tinnitus effectively after a 3 month intervention. When the two forms of therapy were compared TMNMT appeared to be more effective and consequently potentially superior to TRT for reducing tinnitus loudness and functional and emotional disturbance associated with chronic subjective tinnitus.

Dietary ß-carotene and vitamin A and risk of Parkinson disease: A protocol for systematic review and meta-analysis.

BACKGROUND: The beneficial effects of dietary ß-carotene and vitamin A on Parkinson disease (PD) have been confirmed, but some studies have yielded questionable results. Therefore, this meta-analysis investigated the effect of dietary ß-carotene and vitamin A on the risk of PD. METHODS: The following databases were searched for relevant paper: PubMed, Embase, Medline, Scopus, Cochrane Library, CNKI, Wanfang Med online, and Weipu databases for the relevant paper from 1990 to March 28, 2022. The studies included were as follows: ß-carotene and vitamin A intake was measured using scientifically recognized approaches, such as food frequency questionnaire (FFQ); evaluation of odds ratios using OR, RR, or HR; ß-carotene and vitamin A intake for three or more quantitative categories; and PD diagnosed by a neurologist or hospital records. RESULTS: This study included 11 studies (four cohort studies, six case-control studies, and one cross-sectional study). The high ß-carotene intake was associated with a significantly lower chance of developing PD than low ß-carotene intake (pooled OR = 0.83, 95%CI = 0.74-0.94). Whereas the risk of advancement of PD was not significantly distinctive among the highest and lowest vitamin A intake (pooled OR = 1.08, 95%CI = 0.91-1.29). CONCLUSIONS: Dietary ß-carotene intake may have a protective effect against PD, whereas dietary vitamin A does not appear to have the same effect. More relevant studies are needed to include into meta-analysis in the further, as the recall bias and selection bias in retrospective and cross-sectional studies cause misclassifications in the assessment of nutrient intake.

Tinnitus Affects Endogenous But Not Exogenous Auditory Attention Orienting.

PURPOSE: Previous studies have demonstrated that people with tinnitus show attention dysfunctions. In this study, we investigated the influence of tinnitus on attention orienting, especially whether the ability of attention orienting could be modulated by the degree of tinnitus. METHOD: Fifty-nine and 54 unilateral tinnitus participants were included in Experiment 1 and Experiment 2, respectively. All participants reported subjective tinnitus for at least 3 months and were divided into a mild tinnitus group (Tinnitus Handicap Inventory [THI] < 37) or a moderate to severe tinnitus group (THI ≥ 37) according to the THI score. An auditory exogenous attention task and an auditory endogenous attention task were adopted. In the exogenous task, a target sound following a cue sound was presented on either the left or right side. Participants were required to discriminate whether the target was pure tone or white noise. In the endogenous task, participants were required to pay attention to the stimuli on one side and judge the pitch of a target sound. Mixed-design analyses of variance were conducted for the mean reaction times and accuracy across the experimental conditions. RESULTS: Our results showed that in the endogenous attention task, compared with the mild tinnitus group, moderate to severe tinnitus participants had better performance for stimuli presented on the tinnitus side but not on the nontinnitus side. In contrast, in the exogenous attention task, no differences were found between mild and moderate to severe tinnitus groups. CONCLUSION: The results suggest that the degree of tinnitus influences the performance of auditory endogenous attention but not auditory exogenous attention orienting.

A Deep Learning Approach to Predict Conductive Hearing Loss in Patients With Otitis Media With Effusion Using Otoscopic Images.

Importance: Otitis media with effusion (OME) is one of the most common causes of acquired conductive hearing loss (CHL). Persistent hearing loss is associated with poor childhood speech and language development and other adverse consequence. However, to obtain accurate and reliable hearing thresholds largely requires a high degree of cooperation from the patients. Objective: To predict CHL from otoscopic images using deep learning (DL) techniques and a logistic regression model based on tympanic membrane features. Design, Setting, and Participants: A retrospective diagnostic/prognostic study was conducted using 2790 otoscopic images obtained from multiple centers between January 2015 and November 2020. Participants were aged between 4 and 89 years. Of 1239 participants, there were 209 ears from children and adolescents (aged 4-18 years [16.87%]), 804 ears from adults (aged 18-60 years [64.89%]), and 226 ears from older people (aged >60 years, [18.24%]). Overall, 679 ears (54.8%) were from men. The 2790 otoscopic images were randomly assigned into a training set (2232 [80%]), and validation set (558 [20%]). The DL model was developed to predict an average air-bone gap greater than 10 dB. A logistic regression model was also developed based on otoscopic features. Main Outcomes and Measures: The performance of the DL model in predicting CHL was measured using the area under the receiver operating curve (AUC), accuracy, and F1 score (a measure of the quality of a classifier, which is the harmonic mean of precision and recall; a higher F1 score means better performance). In addition, these evaluation parameters were compared to results obtained from the logistic regression model and predictions made by three otologists. Results: The performance of the DL model in predicting CHL showed the AUC of 0.74, accuracy of 81%, and F1 score of 0.89. This was better than the results from the logistic regression model (ie, AUC of 0.60, accuracy of 76%, and F1 score of 0.82), and much improved on the performance of the 3 otologists; accuracy of 16%, 30%, 39%, and F1 scores of 0.09, 0.18, and 0.25, respectively. Furthermore, the DL model took 2.5 seconds to predict from 205 otoscopic images, whereas the 3 otologists spent 633 seconds, 645 seconds, and 692 seconds, respectively. Conclusions and Relevance: The model in this diagnostic/prognostic study provided greater accuracy in prediction of CHL in ears with OME than those obtained from the logistic regression model and otologists. This indicates great potential for the use of artificial intelligence tools to facilitate CHL evaluation when CHL is unable to be measured.

A New Method Combining Pattern Prediction and Preference Prediction for Next Basket Recommendation.

Market basket prediction, which is the basis of product recommendation systems, is the concept of predicting what customers will buy in the next shopping basket based on analysis of their historical shopping records. Although product recommendation systems develop rapidly and have good performance in practice, state-of-the-art algorithms still have plenty of room for improvement. In this paper, we propose a new algorithm combining pattern prediction and preference prediction. In pattern prediction, sequential rules, periodic patterns and association rules are mined and probability models are established based on their statistical characteristics, e.g., the distribution of periods of a periodic pattern, to make a more precise prediction. Products that have a higher probability will have priority to be recommended. If the quantity of recommended products is insufficient, then we make a preference prediction to select more products. Preference prediction is based on the frequency and tendency of products that appear in customers' individual shopping records, where tendency is a new concept to reflect the evolution of customers' shopping preferences. Experiments show that our algorithm outperforms those of the baseline methods and state-of-the-art methods on three of four real-world transaction sequence datasets.

Ubisol Coenzyme Q10 promotes mitochondrial biogenesis in HT22 cells challenged by glutamate.

Glutamate-induced excitotoxicity is a well-recognized cause of neuronal cell death. Nutritional supplementation with Coenzyme Q10 (CoQ10) has been previously demonstrated to serve neuro-protective effects against glutamate-induced excitotoxicity. The aim of the present study was to determine whether the protective effect of CoQ10 against glutamate toxicity could be attributed to stimulating mitochondrial biogenesis. Mouse hippocampal neuronal HT22 cells were incubated with glutamate with or without ubisol Q10. The results revealed that glutamate significantly decreased levels of mitochondrial biogenesis related proteins, including peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α and nuclear respiratory factor (NRF)2. Additionally, glutamate reduced mitochondrial biogenesis, as determined using a mitochondrial biogenesis kit. Pretreatment with CoQ10 prevented decreases in phosphorylated (p)-Akt, p-cAMP response element-binding protein, PGC-1α, NRF2 and mitochondrial transcription factor A, increasing mitochondrial biogenesis. Taken together, the results described a novel mechanism of CoQ10-induced neuroprotection and indicated a central role for mitochondrial biogenesis in protecting against glutamate-induced excitotoxicity.

Reversal of alopecia areata, osteoporosis follow treatment with activation of Tgr5 in mice.

BACKGROUND: Alopecia areata is an autoimmune hair loss disease with infiltration of pro-inflammatory cells into hair follicles. The role of Tgr5 in dermatitis has attracted considerable attention. The present study aimed to investigate the effect of Tgr5 in the development of Alopecia areata. METHODS: The study utilized a comparison control group design with four groups of wild-type group, wild-type+INT777 group, Tgr5-/- group, and Tgr5-/-+INT777 group. The mice were treated with INT777 (30 mg/kg/day) or the carrier solution (DMSO) intraperitoneally for 7 weeks, and the back skin was collected and analyzed by histology and immunohistochemistry staining. The lumbar vertebrae 4 has also been analyzed by DXA and Micro-CT. RESULTS: Tgr5-/- mice displayed the decreasingly significant in hair area and length, skin thickness, and the ratio of anagen and telogen, collagen, and mast cell number and loss the bone mass than WT group. After treating with INT777, the appearance of alopecia areata and bone microstructure has improved. Immunohistochemistry and qPCR analysis showed that activation of Tgr5 can down-regulate the express of JAK1, STAT3, IL-6, TNF-α, and VEGF. CONCLUSION: These findings indicate that activation of Tgr5 mediated amelioration of alopecia areata and osteoporosis by down-regulated JAK1-STAT3 signaling pathway.

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.

Mitochondrial dysfunction contributes to Rapamycin-induced apoptosis of Human Glioblastoma Cells - A synergistic effect with Temozolomide.

Mammalian target of rapamycin (mTOR) is upregulated in a high percentage of glioblastomas. While a well-known mTOR inhibitor, rapamycin, has been shown to reduce glioblastoma survival, the role of mitochondria in achieving this therapeutic effect is less well known. Here, we examined mitochondrial dysfunction mechanisms that occur with the suppression of mTOR signaling. We found that, along with increased apoptosis, and a reduction in transformative potential, rapamycin treatment significantly affected mitochondrial health. Specifically, increased production of reactive oxygen species (ROS), depolarization of the mitochondrial membrane potential (MMP), and altered mitochondrial dynamics were observed. Furthermore, we verified the therapeutic potential of rapamycin-induced mitochondrial dysfunction through co-treatment with temzolomide (TMZ), the current standard of care for glioblastoma. Together these results demonstrate that the mitochondria remain a promising target for therapeutic intervention against human glioblastoma and that TMZ and rapamycin have a synergistic effect in suppressing glioblastoma viability, enhancing ROS production, and depolarizing MMP.

Suppression of NLRP3 Inflammasome, Pyroptosis, and Cell Death by NIM811 in Rotenone-Exposed Cells as an in vitro Model of Parkinson's Disease.

BACKGROUND: Parkinson's disease (PD) is characterized by the selective death of dopaminergic neurons in the substantia nigra. Recently, NLRP3 inflammasome and pyroptosis were found to be associated with PD. Cyclosporine A (CsA), an immunosuppressant, reduces neuronal death in PD. However, CsA could hardly pass through the blood-brain barrier (BBB) and high dose is associated with severe side effects and toxicity. N-methyl-4-isoleucine-cyclosporine (NIM811) is a CsA derivate that can pass through the BBB. However, little is known about its effect on PD. OBJECTIVE: The objectives of this study were to explore the mechanism of rotenone-induced cell damage and to examine the protective effects of NIM811 on the neurotoxicity of a Parkinson-like in vitro model induced by rotenone. METHODS: Murine hippocampal HT22 cells were cultured with the mitochondrial complex I inhibitor rotenone, a widely used pesticide that has been used for many years as a tool to induce a PD model in vitro and in vivo and proven to be reproducible. NIM811 was added to the culture media 3 h prior to the rotenone incubation. Cell viability was determined by resazurin assay, reactive oxygen species (ROS) production by dihydroethidine (DHE), and mitochondrial membrane potential by tetramethyl rhodamine methyl ester (TMRM). TUNEL and caspase-1 immunofluorescent double staining was used to detect pyroptosis. NLRP3, caspase-1, pro-caspase-1, GSDMD, and interleukin-18 (IL-18) were measured using Western blotting after 24 h of rotenone incubation. The reactivity of interleukin-1ß (IL-1ß) was determined by ELISA. RESULTS: Our results demonstrated that rotenone caused more than 40% of cell death, increased ROS production, and reduced mitochondrial membrane potential, while NIM811 reversed these alterations. Immunofluorescent double staining showed that rotenone increased the percentage of caspase-1 and TUNEL double-labelled cells, an indication of pyroptosis, after 24 h of incubation. The protein expression of NLRP3, caspase-1, pro-caspase-1, GSDMD, IL-18, and IL-1ß was significantly increased after 24 h of rotenone incubation. NIM811 suppressed rotenone-induced pyroptosis and downregulated the protein expression of NLRP3, caspase-1, pro-caspase-1, GSDMD, IL-1ß, and IL-18. CONCLUSION: These results provide evidence that rotenone activates the NLRP3 inflammomere and induces pyroptosis. NIM811 protects the cell from rotenone-induced damage and inhibits NLRP3 inflammasome and pyroptosis. NIM811 might serve as a potential therapeutic drug in the treatment of PD.

Autoimmune glial fibrillary acidic protein astrocytopathy mimics infectious meningitis: Two case reports.

BACKGROUND: Autoimmune glial fibrillary acidic protein astrocytopathy (A-GFAP-A) has been recently characterized as a novel autoimmune central nervous system (CNS) disorder with GFAP antibody as the biomarker. However, nonspecific symptoms of A-GFAP-A contribute to misdiagnosis. CASE PRESENTATION: The patients presented with initial symptoms of fever, headache, and nuchal rigidity. Case 1 exhibited mild signs of irritability, active tendon reflexes, and dysuria; case 2 had transient loss of consciousness. Cerebrospinal fluid (CSF) revealed lymphocytosis, elevated protein level, and decreased glucose level. Magnetic resonance imaging (MRI) revealed radial gadolinium enhancement perpendicular to the lateral ventricle. Viral meningitis or tubercular meningitis was suspected. However, their inflammatory and pathogenic indicators showed no abnormal changes, and empirical antibiotic and antiviral drugs did not result in remarkable recovery. Subsequently, cases were detected with a strongly positive expression of GFAP antibody in CSF and the symptoms improved dramatically after high-dose methylprednisolone pulse treatment. CONCLUSION: A-GFAP-A with meningitis-like symptoms could initially masquerade as intracranial infection, and prompt detection of GFAP antibody is essential for differentiation.

Aberrant Functional and Causal Connectivity in Acute Tinnitus With Sensorineural Hearing Loss.

PURPOSE: The neural bases in acute tinnitus remains largely undetected. The objective of this study was to identify the alteration of the brain network involved in patients with acute tinnitus and hearing loss. METHODS: Acute tinnitus patients (n = 24) with hearing loss and age-, sex-, education-matched healthy controls (n = 21) participated in the current study and underwent resting-state functional magnetic resonance imaging (fMRI) scanning. Regional homogeneity and amplitude of low-frequency fluctuation were used to investigate the local spontaneous neural activity and functional connectivity (FC), and Granger causality analysis (GCA) was used to analyze the undirected and directed connectivity of brain regions. RESULTS: Compared with healthy subjects, acute tinnitus patients had a general reduction in FC between auditory and non-auditory brain regions. Based on FC analysis, the superior temporal gyrus (STG) revealed reduced undirected connectivity with non-auditory brain regions including the amygdala (AMYG), nucleus accumbens (NAc), the cerebellum, and postcentral gyrus (PoCG). Using the GCA algorithm, increased effective connectivity from the right AMYG to the right STG, and reduced connectivity from the right PoCG to the left NAc was observed in acute tinnitus patients with hearing loss. The pure-tone threshold was positively correlated with FC between the AMYG and STG, and negatively correlated with FC between the left NAc and the right PoCG. In addition, a negative association between the GCA value from the right PoCG to the left NAc and the THI scores was observed. CONCLUSION: Acute tinnitus patients have aberrant FC strength and causal connectivity in both the auditory and non-auditory cortex, especially in the STG, AMYG, and NAc. The current findings will provide a new perspective for understanding the neuropathophysiological mechanism in acute tinnitus.

Inhibition of Brain Area and Functional Connectivity in Idiopathic Sudden Sensorineural Hearing Loss With Tinnitus, Based on Resting-State EEG.

This study aimed to identify the mechanism behind idiopathic sudden sensorineural hearing loss (ISSNHL) in patients with tinnitus by investigating aberrant activity in areas of the brain and functional connectivity. High-density electroencephalography (EEG) was used to investigate central nervous changes in 25 ISSNHL subjects and 27 healthy controls. ISSNHL subjects had significantly reduced activity in the left frontal lobe at the alpha 2 frequency band compared with controls. Linear lagged connectivity and lagged coherence analysis showed significantly reduced functional connectivity between the temporal gyrus and supramarginal gyrus at the gamma 2 frequency band in the ISSNHL group. Additionally, a significantly reduced functional connectivity was found between the central cingulate gyrus and frontal lobe under lagged phase synchronization analysis. These results strongly indicate inhibition of brain area activity and change in functional connectivity in ISSNHL with tinnitus patients.

Influence of Audiovisual Training on Horizontal Sound Localization and Its Related ERP Response.

The objective was to investigate the influence of audiovisual training on horizontal sound localization and the underlying neurological mechanisms using a combination of psychoacoustic and electrophysiological (i.e., event-related potential, ERP) measurements on sound localization. Audiovisual stimuli were used in the training group, whilst the control group was trained using auditory stimuli only. Training sessions were undertaken once per day for three consecutive days. Sound localization accuracy was evaluated daily after training, using psychoacoustic tests. ERP responses were measured on the first and last day of tasks. Sound localization was significantly improved in the audiovisual training group when compared to the control group. Moreover, a significantly greater reduction in front-back confusion ratio for both trained and untrained angles was found between pre- and post-test in the audiovisual training group. ERP measurement showed a decrease in N1 amplitude and an increase in P2 amplitude in both groups. However, changes in late components were only found in the audiovisual training group, with an increase in P400 amplitude and decrease in N500 amplitude. These results suggest that the interactive effect of audiovisual localization training is likely to be mediated at a relatively late cognitive processing stage.