Effects of sound source localization of masking sound on perception level of simulated tinnitus.

Tinnitus therapies have been combined with the use of varieties of sound/noise. For masking external sounds, location of the masker in space is important; however, effects of the spatial location of the masker on tinnitus are less understood. We aimed to test whether a masking sound location would affect the perception level of simulated tinnitus. The 4 kHz simulated tinnitus was induced in the right ear of healthy volunteers through an open-type earphone. White noise was presented to the right ear using a single-sided headphone or a speaker positioned on the right side at a distance of 1.8 m for masking the simulated tinnitus. In other sessions, monaurally recorded noise localized within the head (inside-head noise) or binaurally recorded noise localized outside the head (outside-head noise) was separately presented from a dual-sided headphone. The noise presented from a distant speaker and the outside-head noise masked the simulated tinnitus in 71.1% and 77.1% of measurements at a lower intensity compared to the noise beside the ear and the inside-head noise, respectively. In conclusion, spatial information regarding the masking noise may play a role in reducing the perception level of simulated tinnitus. Binaurally recorded sounds may be beneficial for an acoustic therapy of tinnitus.

Direct Relay Pathways from Lemniscal Auditory Thalamus to Secondary Auditory Field in Mice.

Tonotopy is an essential functional organization in the mammalian auditory cortex, and its source in the primary auditory cortex (A1) is the incoming frequency-related topographical projections from the ventral division of the medial geniculate body (MGv). However, circuits that relay this functional organization to higher-order regions such as the secondary auditory field (A2) have yet to be identified. Here, we discovered a new pathway that projects directly from MGv to A2 in mice. Tonotopy was established in A2 even when primary fields including A1 were removed, which indicates that tonotopy in A2 can be established solely by thalamic input. Moreover, the structural nature of differing thalamocortical connections was consistent with the functional organization of the target regions in the auditory cortex. Retrograde tracing revealed that the region of MGv input to a local area in A2 was broader than the region of MGv input to A1. Consistent with this anatomy, two-photon calcium imaging revealed that neuronal responses in the thalamocortical recipient layer of A2 showed wider bandwidth and greater heterogeneity of the best frequency distribution than those of A1. The current study demonstrates a new thalamocortical pathway that relays frequency information to A2 on the basis of the MGv compartmentalization.

Reliability and validity of the Japanese version of the Glasgow Edinburgh Throat Scale (GETS-J): Use for a symptom scale of globus sensation.

OBJECTIVE: Globus sensation, a feeling of lump or something stuck in the throat, could be caused by structural, functional, and psychogenic diseases. Due to a possible multifactorial nature of the disease, neither diagnosing test battery nor standard treatment for globus sensation has been established. Therefore, a questionnaire to accurately identify globus patients and evaluate the severity of the disease is desired. Glasgow Edinburgh Throat Scale (GETS) is a 10-item questionnaire about the throat symptoms consisting of three subscales relating to dysphagia, globus sensation, and pain/swelling in the throat. It was reported that globus patients marked high scores specifically for the globus scale among three scales, indicating that GETS can be used as a valid symptom scale for globus sensation. Aims of this study were to translate GETS into Japanese and to test its reliability and validity. METHODS: Fifty-five patients complaining of globus sensation without abnormal endoscopic and CT findings were enrolled into the study. They were asked to answer the questions of GETS translated into Japanese (GETS-J). Reliability (internal consistency) of the questionnaire was tested using Cronbach's coefficient alpha. To test the validity, principal components analysis was used to identify the factorial structure of the questionnaire and GETS-J data were compared with those reported in the original GETS. Contribution of psychiatric comorbidities to globus sensation was also investigated by examining the correlation between Hospital Anxiety and Depression Scale (HADS) and GETS-J. RESULTS: Reliability of the questionnaire examined by the Cronbach's coefficient alpha was satisfactory and all higher than 0.75. Principal components analysis identified following three questions as the globus scale: Q1, Feeling something stuck in the throat; Q5, Throat closing off; Q9, Want to swallow all the time. Somatic distress, i.e., patients' reaction to throat symptoms, was significantly correlated with globus scale (r=0.680). Anxiety component of HADS was significantly correlated with somatic distress but not with globus scale. These results were consistent with those of the original GETS except for the replacement of Q3 (discomfort/irritation in the throat) to Q5 (throat closing off) for globus scale in GETS-J. CONCLUSION: Translation of GETS into Japanese showed high reliability and validity, suggesting that translation and cross-cultural adaptation were not problematic. High correlation of globus scale of GETS-J with somatic distress indicated that GETS-J could be a useful questionnaire to identify the globus patients and evaluate the severity of the disease. Anxiety may complicate the somatic distress in patients with globus sensation.

Risk Factors of Recurrence in Pediatric Congenital Cholesteatoma.

OBJECTIVE: To examine the risk factors of recurrence in pediatric congenital cholesteatoma. STUDY DESIGN: Retrospective chart review. SETTING: University hospital. PATIENTS: Sixty-seven patients having tympanic type of congenital cholesteatoma under 15-years old at surgery. INTERVENTIONS: Canal wall-up tympanomastoidectomy (n = 30) or transcanal atticotomy/tympanoplasty (n = 37) was performed depending on cholesteatoma extension, 16 of which were followed by second-look surgery. Preoperative computed tomography (CT) before second-look surgery or follow-up CT was performed to detect residual recurrence 1 year after the surgery. Cholesteatoma found at the second surgery was also included in the recurrence. All patients had no recurrent cholesteatoma at the last follow-up (median, 61 mo after surgery). MAIN OUTCOME MEASURES: Possible predictive factors were compared between the groups. RESULTS: Residual cholesteatoma and retraction cholesteatoma occurred in 21 and 6%, respectively. There was no significant difference in age, sex, and type of cholesteatoma (open or closed) between the groups; however, Potsic stage and status of stapes involvement were more advanced in the residual cholesteatoma group. All residual lesions could be detected by follow-up CT or by second-look surgery. All of four retraction cholesteatoma patients were male, young at the surgery and in stage IV. CONCLUSION: Recurrence mostly occurred as residual cholesteatoma, suggesting that CT is recommended as a follow-up tool for congenital cholesteatoma. Advanced lesions had the risk of residual cholesteatoma, suggesting that complete removal of epithelium is important. Although rare, young advanced-stage patients had risk of retraction cholesteatoma and therefore normal mucosa should be preserved as much as possible for these patients.

Bone Density Development of the Temporal Bone Assessed by Computed Tomography.

HYPOTHESIS: The temporal bone shows regional differences in bone development. BACKGROUND: The spreading pattern of acute mastoiditis shows age-related differences. In infants, it spreads laterally and causes retroauricular swelling, whereas in older children, it tends to spread medially and causes intracranial complications. We hypothesized that bone maturation may influence the spreading pattern of acute mastoiditis. METHODS: Eighty participants with normal hearing, aged 3 months to 42 years, participated in this study. Computed tomography (CT) values (Hounsfield unit [HU]) in various regions of the temporal bone, such as the otic capsule (OC), lateral surface of the mastoid cavity (LS), posterior cranial fossa (PCF), and middle cranial fossa (MCF), were measured as markers of bone density. Bone density development curves, wherein CT values were plotted against age, were created for each region. The age at which the CT value exceeded 1000 HU, which is used as an indicator of bone maturation, was calculated from the development curves and compared between the regions. RESULTS: The OC showed mature bone at birth, whereas the LS, PCF, and MCF showed rapid maturation in early childhood. However, there were significant regional differences in the ages of maturation: 1.7, 3.9, and 10.8 years for the LS, PCF, and MCF, respectively. CONCLUSION: To our knowledge, this is the first report to show regional differences in the maturation of temporal bone, which could partly account for the differences in the spreading pattern of acute mastoiditis in individuals of different ages.

Corrigendum: Reconsidering Tonotopic Maps in the Auditory Cortex and Lemniscal Auditory Thalamus in Mice.

[This corrects the article on p. 14 in vol. 11, PMID: 28293178.].

Creating an Optimal 3D Printed Model for Temporal Bone Dissection Training.

OBJECTIVE: Making a 3-dimensional (3D) temporal bone model is simple using a plaster powder bed and an inkjet printer. However, it is difficult to reproduce air-containing spaces and precise middle ear structures. The objective of this study was to overcome these problems and create a temporal bone model that would be useful both as a training tool and for preoperative simulation. METHODS: Drainage holes were made to remove excess materials from air-containing spaces, ossicle ligaments were manually changed to bony structures, and small and/or soft tissue structures were colored differently while designing the 3D models. The outcomes were evaluated by 3 procedures: macroscopic and endoscopic inspection of the model, comparison of computed tomography (CT) images of the model to the original CT, and assessment of tactile sensation and reproducibility by 20 surgeons performing surgery on the model. RESULTS: Macroscopic and endoscopic inspection, CT images, and assessment by surgeons were in agreement in terms of reproducibility of model structures. Most structures could be reproduced, but the stapes, tympanic sinus, and mastoid air cells were unsatisfactory. Perioperative tactile sensation of the model was excellent. CONCLUSIONS: Although this model still does not embody perfect reproducibility, it proved sufficiently practical for use in surgical training.

Reconsidering Tonotopic Maps in the Auditory Cortex and Lemniscal Auditory Thalamus in Mice.

The auditory thalamus and auditory cortex (AC) are pivotal structures in the central auditory system. However, the thalamocortical mechanisms of processing sounds are largely unknown. Investigation of this process benefits greatly from the use of mice because the mouse is a powerful animal model in which various experimental techniques, especially genetic tools, can be applied. However, the use of mice has been limited in auditory research, and thus even basic anatomical knowledge of the mouse central auditory system has not been sufficiently collected. Recently, optical imaging combined with morphological analyses has enabled the elucidation of detailed anatomical properties of the mouse auditory system. These techniques have uncovered fine AC maps with multiple frequency-organized regions, each of which receives point-to-point thalamocortical projections from different origins inside the lemniscal auditory thalamus, the ventral division of the medial geniculate body (MGv). This precise anatomy now provides a platform for physiological research. In this mini review article, we summarize these recent achievements that will facilitate physiological investigations in the mouse auditory system.

Vestibular Involvement in Patients With Otitis Media With Antineutrophil Cytoplasmic Antibody-associated Vasculitis.

OBJECTIVE: Otitis media (OM) with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (OMAAV) is a novel concept of ear disease that is characterized by progressive mixed or sensorineural hearing loss with occasional systemic involvement. Considering the accumulating knowledge about the characteristics of and treatment for auditory dysfunction in OMAAV, the objective of this study was to investigate the vestibular function and symptoms of patients with OMAAV. STUDY DESIGN: Retrospective chart review. SETTING: University hospital. PATIENTS: Thirty-one OMAAV patients met criteria proposed by the OMAAV study group in Japan. MAIN OUTCOME MEASURES: Clinical characteristics and vestibular tests. RESULTS: Eleven of 31 OMAAV patients had vestibular symptoms; 3 patients had acute vertigo attack with sudden hearing loss and 8 patients had chronic dizziness. Episodic vertigo was not seen in any of the patients. Three patients who received a less intensive therapy without immunosuppressive agents developed intractable persistent dizziness. All symptomatic patients and six of the nine OMAAV patients without vestibular symptoms showed unilateral or bilateral caloric weakness; therefore, vestibular involvement was present in 84% of OMAAV patients. Gain of vestibulo-ocular reflex was reduced in symptomatic patients. The eye-tracking test and optokinetic nystagmus revealed no evidence of central dysfunction. CONCLUSION: Vestibular dysfunction was seen in 84% of OMAAV patients. One-third of OMAAV patients showed vestibular symptoms such as acute vertigo attack or chronic dizziness, which are of peripheral origin. One-third of the symptomatic patients developed intractable dizziness. Initial intensive treatment by combination therapy with steroid and immunosuppressive agents may be essential for preventing the development of intractable dizziness.

[A Case of the Relapsing Polychondritis Limited to the Trachea].

A 62-year-old woman, who had dysesthesia in the throat, and polyposia the previous year, was admitted in a coma because of respiratory failure. Computed tomography scans demonstrated dilatation of the esophagus and stenosis of the trachea. After emergency intubation, extubation was not possible due to a collapsed trachea, so we performed a tracheostomy. The tracheoscopy from the stoma showed an esophagus-like trachea due to disappearance of the tracheal cartilage and the straight pattern on the membranous portion, and the lumen deformed with coughing. With the continuous dyspnea episode, the patient was diagnosed as having tracheomalacia. Anti-type II collagen antibody and pathological findings of the trachea led us to the diagnosis of Relapsing Polychondritis.

De novo mutation in X-linked hearing loss-associated POU3F4 in a sporadic case of congenital hearing loss.

OBJECTIVES: In this report, we present a male patient with no family history of hearing loss, in whom we identified a novel de novo mutation in the POU3F4 gene. METHODS: One hundred ninety-four (194) Japanese subjects from unrelated and nonconsanguineous families were enrolled in this study. We used targeted genomic enrichment and massively parallel sequencing of all known nonsyndromic hearing loss genes for identifying the genetic causes of hearing loss. RESULTS: A novel de novo frameshift mutation of POU3F4 to c.727_728insA (p.N244KfsX26) was identified. The patient was a 7-year-old male with congenital progressive hearing loss and inner ear deformity. Although the patient had received a cochlear implant, auditory skills were still limited. The patient also exhibited developmental delays similar to those previously associated with POU3F4 mutation. CONCLUSION: This is the first report of a mutation in POU3F4 causing hearing loss in a Japanese patient without a family history of hearing loss. This study underscores the importance of comprehensive genetic testing of patients with hearing loss for providing accurate prognostic information and guiding the optimal management of patient rehabilitation.

Auditory cortical areas activated by slow frequency-modulated sounds in mice.

Species-specific vocalizations in mice have frequency-modulated (FM) components slower than the lower limit of FM direction selectivity in the core region of the mouse auditory cortex. To identify cortical areas selective to slow frequency modulation, we investigated tonal responses in the mouse auditory cortex using transcranial flavoprotein fluorescence imaging. For differentiating responses to frequency modulation from those to stimuli at constant frequencies, we focused on transient fluorescence changes after direction reversal of temporally repeated and superimposed FM sweeps. We found that the ultrasonic field (UF) in the belt cortical region selectively responded to the direction reversal. The dorsoposterior field (DP) also responded weakly to the reversal. Regarding the responses in UF, no apparent tonotopic map was found, and the right UF responses were significantly larger in amplitude than the left UF responses. The half-max latency in responses to FM sweeps was shorter in UF compared with that in the primary auditory cortex (A1) or anterior auditory field (AAF). Tracer injection experiments in the functionally identified UF and DP confirmed that these two areas receive afferent inputs from the dorsal part of the medial geniculate nucleus (MG). Calcium imaging of UF neurons stained with fura-2 were performed using a two-photon microscope, and the presence of UF neurons that were selective to both direction and direction reversal of slow frequency modulation was demonstrated. These results strongly suggest a role for UF, and possibly DP, as cortical areas specialized for processing slow frequency modulation in mice.

Cortical depression in the mouse auditory cortex after sound discrimination learning.

Cortical responses after sound discrimination learning were investigated using transcranial flavoprotein fluorescence imaging in mice. Water-deprived mice were trained to discriminate between rewarded (S+) and unrewarded (S-) sound stimuli. After the learning, they were anesthetized, and cortical responses to S+ and S- were recorded in the right auditory cortex. When a pure tone (PT) at 10 kHz and a 10 kHz amplitude-modulated (AM) sound were used as S+ and S-, the cortical responses to S- using AM were significantly depressed but those to S- using PT were not. The cortical responses to S+ showed no significant change. Upward frequency-modulated sounds from 5 kHz to 40 kHz (FM upward arrow) and downward frequency-modulated sounds from 40 kHz to 5 kHz (FM downward arrow) were also used as S+ and S-. Cortical responses to S- using FM[upward arrow] and FM[downward arrow] were significantly depressed after learning, while those to S+ were unchanged. No significant change of cortical responses to S- using FMs was observed in the left auditory cortex after learning. The learning-induced depression of S- using FMs was most clearly observed in the medial part of the tonotopic band to 40 kHz in the right primary auditory cortex, which might be involved in processing FM sounds.

Transcranial flavoprotein fluorescence imaging of mouse cortical activity and plasticity.

Endogenous fluorescence signals derived from mitochondria reflect activity-dependent changes in brain metabolism and may be exploited in functional brain imaging. Endogenous flavoprotein fluorescence imaging in mice is especially important because many genetically manipulated strains of mice are available and the transparent skull of mice allows transcranial fluorescence imaging of cortical activities. In the primary sensory areas of mice, cortical activities and experience-dependent plasticity have been investigated using transcranial fluorescence imaging. Furthermore, differential imaging, based on stimulus specificity of cortical areas, distinguished activities in higher visual areas around the primary visual cortex from those in primary visual cortex. The combination of transcranial fluorescence imaging with the suppression of cortical activities using photobleaching of flavoproteins is expected to aid in elucidating the roles of sensory cortices including higher areas in mice.

Transcranial photo-inactivation of neural activities in the mouse auditory cortex.

Flavoprotein fluorescence in the brain is intimately coupled with neuronal aerobic energy metabolism. If flavoproteins are photobleached, neural activities may be affected owing to dysfunction in aerobic energy metabolism in mitochondria. We tested this possibility in cortical slices from mice, and found that exposure to blue light (lambda = 475 nm) derived from a 20 mW diode laser for 50 min suppresses trans-synaptic components of field potentials. This finding formed the basis of a transcranial photo-inactivation technique, that was used to investigate auditory signal transmission between the anterior auditory field (AAF) and the primary auditory cortex (AI) in anesthetized mice. Cortical responses in AAF and AI, elicited by 5 kHz tonal stimuli, were visualized using transcranial flavoprotein fluorescence imaging. After determining responsive areas in AAF and AI, the auditory cortex was exposed to the blue diode laser via the intact skull, while either AAF or AI was protected with a piece of carbon paper. Although the photo-inactivation of AI had no significant effect on the fluorescence responses in AAF, the photo-inactivation of AAF significantly reduced the fluorescence responses in AI, indicating the presence of auditory signal transmission from AAF to AI.

Transcranial fluorescence imaging of auditory cortical plasticity regulated by acoustic environments in mice.

Functional brain imaging using endogenous fluorescence of mitochondrial flavoprotein is useful for investigating mouse cortical activities via the intact skull, which is thin and sufficiently transparent in mice. We applied this method to investigate auditory cortical plasticity regulated by acoustic environments. Normal mice of the C57BL/6 strain, reared in various acoustic environments for at least 4 weeks after birth, were anaesthetized with urethane (1.7 g/kg, i.p.). Auditory cortical images of endogenous green fluorescence in blue light were recorded by a cooled CCD camera via the intact skull. Cortical responses elicited by tonal stimuli (5, 10 and 20 kHz) exhibited mirror-symmetrical tonotopic maps in the primary auditory cortex (AI) and anterior auditory field (AAF). Depression of auditory cortical responses regarding response duration was observed in sound-deprived mice compared with naïve mice reared in a normal acoustic environment. When mice were exposed to an environmental tonal stimulus at 10 kHz for more than 4 weeks after birth, the cortical responses were potentiated in a frequency-specific manner in respect to peak amplitude of the responses in AI, but not for the size of the responsive areas. Changes in AAF were less clear than those in AI. To determine the modified synapses by acoustic environments, neural responses in cortical slices were investigated with endogenous fluorescence imaging. The vertical thickness of responsive areas after supragranular electrical stimulation was significantly reduced in the slices obtained from sound-deprived mice. These results suggest that acoustic environments regulate the development of vertical intracortical circuits in the mouse auditory cortex.