Ventral cochlear nucleus bushy cells encode hyperacusis in guinea pigs.

Psychophysical studies characterize hyperacusis as increased loudness growth over a wide-frequency range, decreased tolerance to loud sounds and reduced behavioral reaction time latencies to high-intensity sounds. While commonly associated with hearing loss, hyperacusis can also occur without hearing loss, implicating the central nervous system in the generation of hyperacusis. Previous studies suggest that ventral cochlear nucleus bushy cells may be putative neural contributors to hyperacusis. Compared to other ventral cochlear nucleus output neurons, bushy cells show high firing rates as well as lower and less variable first-spike latencies at suprathreshold intensities. Following cochlear damage, bushy cells show increased spontaneous firing rates across a wide-frequency range, suggesting that they might also show increased sound-evoked responses and reduced latencies to higher-intensity sounds. However, no studies have examined bushy cells in relationship to hyperacusis. Herein, we test the hypothesis that bushy cells may contribute to the neural basis of hyperacusis by employing noise-overexposure and single-unit electrophysiology. We find that bushy cells exhibit hyperacusis-like neural firing patterns, which are comprised of enhanced sound-driven firing rates, reduced first-spike latencies and wideband increases in excitability.

Altered neuronal activity in the auditory brainstem following sound stimulation in thalidomide-induced autism model rats.

Auditory hypersensitivity in autism is frequently observed in clinics. Dysfunction in the auditory brainstem has been suspected. We have established autism model rats using prenatal thalidomide exposure. Here we investigated whether abnormal response occurs in the brainstem following sound stimulus in autism model rats. Autism model rats were prepared by prenatal exposure to thalidomide on embryonic days 9 and 10 in pregnant rats. Then, the animals were exposed to 16-kHz pure tone auditory stimulus and c-Fos immunostaining was performed to examine the neuronal activity on postnatal day 49 to 51. Following sound stimulus, increased number of c-Fos-positive neurons was observed in the medial nucleus of the trapezoid body of autism model rats compared with the control rats. These results suggest that prenatal thalidomide might cause altered processing of auditory stimulus, leading to the characteristics of auditory hypersensitivity in autism.

An item response theory based integrated model of headache, nausea, photophobia, and phonophobia in migraine patients.

This study developed an integrated model of severity scores of migraine headache and the incidence of nausea, photophobia, and phonophobia to predict the natural time course of migraine symptoms, which are likely to occur by a common disease progression mechanism. Data were acquired from two phase 3 clinical trials conducted during the development of eletriptan. Only the placebo arm was used for analysis. A conventional proportional odds model was compared with an item response theory (IRT) based approach. Results suggested that the IRT based approach led to a better model fit, successfully revealing the difference in relief rates among different symptoms, which was the fastest in phonophobia and the slowest in headache. Simulation with the developed model suggested that using headache scores at 4 h post-dose attained greatest statistical power, yielding sample size of 100 per arm given drug effect of 40%, as compared to that of 200 per arm when 2 h post-dose scores were used as in the original eletriptan protocol. This work demonstrated the usefulness of an IRT based model as applied to analyzing multidimensional migraine symptoms and designing clinical trials. Our model can be similarly applied to analyzing other multiple endpoints sharing a common underlying mechanism.

Hyperacoustic hypoacusis: A new pontine syndrome-Case report.

We herein report a unique case of a lateral pontine demyelinating lesion presenting with unilateral sensorineural hearing loss and paradoxical ipsilateral hyperacusis. The association of unilateral hearing loss and ipsilateral hyperacusis is a rare manifestation of a central nervous system lesion. The paradoxical combination of these symptoms strongly suggests pontine dysfunction and prompts urgent neurological evaluation.

Clinical Interventions for Hyperacusis in Adults: A Scoping Review to Assess the Current Position and Determine Priorities for Research.

BACKGROUND: There is no universally accepted definition for hyperacusis, but in general it is characterised by decreased sound tolerance to ordinary environmental sounds. Despite hyperacusis being prevalent and having significant clinical implications, much remains unknown about current management strategies. PURPOSE: To establish the current position of research on hyperacusis and identify research gaps to direct future research. DESIGN AND SAMPLE: Using an established methodological framework, electronic and manual searches of databases and journals identified 43 records that met our inclusion criteria. Incorporating content and thematic analysis approaches, the definitions of hyperacusis, management strategies, and outcome measures were catalogued. RESULTS: Only 67% of the studies provided a definition of hyperacusis, such as "reduced tolerance" or "oversensitivity to sound." Assessments and outcome measures included Loudness Discomfort Levels, the Hyperacusis Questionnaire, and Tinnitus Retraining Therapy (TRT) interview. Management strategies reported were Cognitive Behavioural Therapy, TRT, devices, pharmacological therapy, and surgery. CONCLUSIONS: Management strategies were typically evaluated in patients reporting hyperacusis as a secondary complaint or as part of a symptom set. As such the outcomes reported only provided an indication of their effectiveness for hyperacusis. Randomised Controlled Trials are needed to evaluate the effectiveness of management strategies for patients experiencing hyperacusis.

Mechanism of auditory hypersensitivity in human autism using autism model rats.

BACKGROUND: Auditory hypersensitivity is one of the major complications in autism spectrum disorder. The aim of this study was to investigate whether the auditory brain center is affected in autism model rats. METHODS: Autism model rats were prepared by prenatal exposure to thalidomide on embryonic day 9 and 10 in pregnant rats. The superior olivary complex (SOC), a complex of auditory nuclei, was immunostained with anti-calbindin d28k antibody at postnatal day 50. RESULTS: In autism model rats, SOC immunoreactivity was markedly decreased. Strength of immunostaining of SOC auditory fibers was also weak in autism model rats. Surprisingly, the size of the medial nucleus of trapezoid body, a nucleus exerting inhibitory function in SOC, was significantly decreased in autism model rats. CONCLUSIONS: Auditory hypersensitivity may be, in part, due to impairment of inhibitory processing by the auditory brain center.

Tinnitus and hyperacusis involve hyperactivity and enhanced connectivity in auditory-limbic-arousal-cerebellar network.

Hearing loss often triggers an inescapable buzz (tinnitus) and causes everyday sounds to become intolerably loud (hyperacusis), but exactly where and how this occurs in the brain is unknown. To identify the neural substrate for these debilitating disorders, we induced both tinnitus and hyperacusis with an ototoxic drug (salicylate) and used behavioral, electrophysiological, and functional magnetic resonance imaging (fMRI) techniques to identify the tinnitus-hyperacusis network. Salicylate depressed the neural output of the cochlea, but vigorously amplified sound-evoked neural responses in the amygdala, medial geniculate, and auditory cortex. Resting-state fMRI revealed hyperactivity in an auditory network composed of inferior colliculus, medial geniculate, and auditory cortex with side branches to cerebellum, amygdala, and reticular formation. Functional connectivity revealed enhanced coupling within the auditory network and segments of the auditory network and cerebellum, reticular formation, amygdala, and hippocampus. A testable model accounting for distress, arousal, and gating of tinnitus and hyperacusis is proposed.

Hyperacusis following unilateral damage to the insular cortex: a three-case report.

The insula is a multisensory area involved in various brain functions, including central auditory processing. However, its specific role in auditory function remains unclear. Here we report three cases of persistent hypersensitivity to auditory stimuli following damage to the insular cortex, using behavioral and neurophysiological measures. Two patients who complained of auditory disturbance since they suffered an isolated unilateral insular stroke, and one epileptic patient who underwent right insular resection for control of drug-resistant seizures, were involved in this study. These patients, all young adult women, were tested for auditory function more than one year after brain injury, and were compared to 10 healthy control participants matched for age, sex, and education. The assessment included pure-tone detection and speech detection in quiet, loudness discomfort levels, random gap detection, recognition of frequency and duration patterns, binaural separation, dichotic listening, as well as late-latency auditory event-related potentials (ERPs). Each patient showed mild or moderate hyperacusis, as revealed by decreased loudness discomfort levels, which was more important on the side of lesion in two cases. Tests of temporal processing also revealed impairments, in concordance with previous findings. ERPs of two patients were characterised by increased amplitude of the P3b component elicited during a two-tone auditory oddball detection task. This study is the first to report cases of persistent hyperacusis following damage to the insular cortex, and suggests that the insula is involved in modulating the perceived intensity of the incoming auditory stimuli during late-stage processing.

Bell's palsy: symptoms preceding and accompanying the facial paresis.

This individual prospective cohort study aims to report and analyze the symptoms preceding and accompanying the facial paresis in Bell's palsy (BP). Two hundred sixty-nine patients affected by BP with a maximum delay of 48 hours from the onset were enrolled in the study. The evolution of the facial paresis expressed as House-Brackmann grade in the first 10 days and its correlation with symptoms were analyzed. At the onset, 136 patients presented postauricular pain, 114 were affected by dry eye, and 94 reported dysgeusia. Dry mouth was present in 54 patients (19.7%), facial pain, hyperlacrimation, aural fullness, and hyperacusis represented a smaller percentage of the reported symptoms. After 10 days, 39.9% of the group had a severe paresis while 10.2% reached a complete recovery. Dry mouth at the onset was correlated with severe grade of palsy and was prognostic for poor recovery in the early period. These outcomes lead to the deduction that the nervus intermedius plays an important role in the presentation of the BP and it might be responsible for most of the accompanying symptomatology of the paresis. Our findings could be of important interest to early address a BP patient to further examinations and subsequent therapy.

Simultaneous, unilateral plugging of superior and posterior semicircular canal dehiscences to treat debilitating hyperacusis.

OBJECTIVE: To describe a case of bilateral superior and posterior semicircular canal dehiscences, and the use of a unilateral transmastoid approach to address both right-sided defects simultaneously. CASE REPORT: In a patient with right-sided hyperacusis, bilateral dehiscence of both the superior and the posterior semicircular canals was identified, located adjacent to the common crus, together with a right-sided, anterosuperiorly positioned sigmoid sinus and a high-riding jugular bulb. Results for audiography and cervical vestibular evoked myogenic potential testing were consistent with right-sided semicircular canal dehiscence. At surgery, a right-sided transmastoid approach provided access to plug both defects simultaneously, following posterior mobilisation of the sigmoid sinus. The patient's hyperacusis was completely resolved, with a 10-30 dB improvement in his right ear air conduction hearing, without decrement in bone conduction. CONCLUSION: In properly selected patients, a transmastoid approach can be used to effectively manage superior semicircular canal dehiscence and posterior semicircular canal dehiscence simultaneously. Pre-operative computed tomography is recommended to evaluate the dehiscence sites and to identify complicating vascular anatomy.

Hyperacusis-associated pathological resting-state brain oscillations in the tinnitus brain: a hyperresponsiveness network with paradoxically inactive auditory cortex.

Although hyperacusis, a hyperresponsiveness to non-noxious auditory stimuli, is a sound-evoked symptom, possible resting-state pathologic oscillations in hyperacusis brain have never been explored. By comparing 17 tinnitus participants with hyperacusis (T+H+) and 17 without hyperacusis (T+H-), we aimed to explore characteristic resting-state cortical activity of hyperacusis. The T+H+ and T+H- groups, strictly matched for all tinnitus sound characteristics to exclude tinnitus-related cortical changes, were compared using resting-state electroencephalography source-localized activity complemented by functional connectivity analyses. Correlation analysis revealed that hyperacusis questionnaire score was positively correlated with the orbitofrontal cortex (OFC) beta power, the right auditory cortex (AC) alpha1 power, and the dorsal anterior cingulate cortex (dACC) beta1 power. Compared to the T+H- group, the T+H+ group demonstrated increased beta power in the dACC and OFC, and increased alpha power in the right AC. Region of interest analyses including 17 normal controls further confirmed that these differences originated solely from relatively increased power of the T+H+ group, not from a relative power decrease of the T+H- group. Also, the T+H+ group showed increased connectivity between the OFC/dACC and the AC as compared to the T+H- group. The beta power increase in the OFC/dACC may indicate increased resting-state vigilance in tinnitus patients with hyperacusis. In addition, increased alpha power in the AC may reflect an adaptive top-down inhibition against sound stimuli probably mediated by the increased beta power of the OFC. The OFC/dACC, also frequently found to be activated in analogous diseases such as allodynia/hyperalgesia, may compose a hyperresponsiveness network.

15th Yahya Cohen Memorial Lecture - the relationship between the air-bone gap and the size of superior semicircular canal dehiscence.

INTRODUCTION: This study aimed to examine the relationship between the air-bone gap (ABG) and the size of the superior semicircular canal dehiscence (SSCD) as measured on a computed tomography (CT) scan. MATERIALS AND METHODS: The study design was a case series with chart review. Twenty-three patients (28 ears) from a tertiary referral centre were diagnosed with SSCD. The size of the dehiscence on CT scans and the ABG on pure-tone audiometry were recorded. RESULTS: The size of the dehiscence ranged from 1.0 to 6.0 mm (mean, 3.5 ± 1.6 mm). Six ears with a dehiscence measuring less than 3.0 mm did not have an ABG (0 dB). The remaining 18 ears showed an average ABG at 500, 1000, and 2000 Hz (AvABG(500-2000)) ranging from 3.3 to 27.0 dB (mean, 11.6 ± 5.7 dB). The analysis of the relationship between the dehiscence size and AvABG(500-2000) revealed a correlation of R(2) = 0.828 (P <0.001, quadratic fit) and R(2) = 0.780 (P <0.001, linear fi t). Therefore, the larger the dehiscence, the larger the ABG at lower frequencies on pure-tone audiometry. CONCLUSION: In SSCD patients, an ABG is consistently shown at the low frequency when the dehiscence is larger than 3 mm. The size of the average ABG correlates with the size of the dehiscence. These findings highlight the effect of the dehiscence size on conductive hearing loss in SSCD and contribute to a better understanding of the symptomatology of patients with SSCD.

Acoustic injury and TRPV1 expression in the cochlear spiral ganglion.

Acoustic trauma not only produces temporary and permanent hearing loss but is a common cause of chronic tinnitus. Recent work indicated a possible role for the transient receptor potential channel vanilloid subfamily type 1 (TRPV1) in modulating the effects of cochlear injury. In our research, we investigated the effects of acoustic damage on TRPV1 expression in spiral ganglion neurons of adult rats. After exposing them unilaterally to noise, we extracted cochleas and processed the spiral ganglion for TRPV1 expression at four posttrauma intervals (2 hours, 24 hours, 12 days, and 16.9 months). We measured TRPV1 immunodensity in the apical, middle, and basal turns of the cochlea. We found a significant interaction (p = .039) between posttrauma interval and regional cochlear receptor expression: For survival intervals between 24 hours and 2 weeks, TRPV1 density increased in all cochlear regions; at the longest survival interval (16.9 months), TRPV1 density was dramatically reduced in the basal region. We also psychophysically tested the long-survival subjects, which showed evidence of 20-kHz tonal tinnitus. These results suggest that TRPV1 may participate after cochlear injury in a signal cascade that is responsible for the neuroplastic events leading to tinnitus and hyperacusis.

Incapacitating hypersensitivity to one's own body sounds due to a dehiscence of bone overlying the superior semicircular canal. A case report.

We present a case study of a 49-year-old patient with an 8-year history of hypersensitivity to sound produced by intrinsic but not extrinsic sources. Findings that indicated an organic problem were: a supranormal bone conduction threshold of -25 to -15 dB HL from 0.25 to 1 kHz with an air-bone gap of 15 to 45 dB HL, a lower threshold and larger amplitude for vestibular-evoked myogenic potentials, eye movement reactions to sound and trunk pitch sway in response to sound. Results of immitance audiometry and otoacoustic emission testing were within normal limits and indicative of intact middle ear conductance. A high-resolution CT scan of the temporal bone demonstrated a dehiscence of bone overlying the superior semicircular canal. These findings support previous research indicating that auditory energy reaches the cochleo-vestibular receptor systems more easily via transmission through cerebrospinal fluid than through bone. Therefore, a dehiscence of the bone overlying the superior semicircular canal may lead to hypersensitivity to intrinsic sound. We recommend that similar findings in other patients be followed up with an evaluation of middle ear function and the temporal bone with high-resolution CT scan.

Drop attacks secondary to superior canal dehiscence syndrome.

Two patients with unprovoked drop attacks were found to have dehiscence of the superior semicircular canal on CT of the temporal bone. Both had conductive hearing loss, preservation of stapedius reflex, and abnormal vestibular evoked myogenic potentials. Neither had sound- or pressure-induced nystagmus. Repair of the dehiscence in one case stopped the drop attacks, supporting a causal relationship between the dehiscence and the drop attacks.

Central hyperacusis with phonophobia in multiple sclerosis.

Hearing disorders are a well-described symptom in patients with multiple sclerosis (MS). Unilateral or bilateral hyperacusis or deafness in patients with normal sound audiometry is often attributed to demyelinating lesions in the central auditory pathway. Less known in MS is a central phonophobia, whereby acoustic stimuli provoke unpleasant and painful paresthesia and lead to the corresponding avoidance behaviour. In our comparison collective, patient 1 described acute shooting pain attacks in his right cheek each time set off by the ringing of the telephone. Patient 2 complained of intensified, unbearable noise sensations when hearing nonlanguage acoustic stimuli. Patient 3 noticed hearing unpleasant echoes and disorders of the directional hearing. All patients had a clinical brainstem syndrome. ENT inspection, sound audiometry and stapedius reflex were normal. All three patients had pathologically changed auditory evoked potentials (AEPs) with indications of a brainstem lesion, and in magnetic resonance imaging (MRI) demyelinating lesions in the ipsilateral pons and in the central auditory pathway. The origin we presume in case 1 is an abnormal impulse conduction from the leminiscus lateralis to the central trigeminus pathway and, in the other cases, a disturbance in the central sensory modulation. All patients developed in the further course a clinically definite MS. Having excluded peripheral causes for a hyperacusis, such as, e.g., an idiopathic facial nerve palsy or myasthenia gravis, one should always consider the possibility of MS in a case of central phonophobia. Therapeutic possibilities include the giving of serotonin reuptake inhibitors or acoustic lenses for clearly definable disturbing frequencies.

Temporal bone pathology in a case of Cogan's syndrome.

Cogan's syndrome (CS) presents typical and atypical types. Typically, there are episodes of nonsyphilitic keratitis and audiovestibular dysfunction. Atypically, there are inflammatory changes in other eye structures and other organ systems, particularly the cardiovascular system. The temporal bone pathology in a case of CS shows changes that are similar to those observed in other autoimmune disorders associated with audiovestibular dysfunction. The following pathologic features characterize autoimmune inner ear disease: 1. acute labyrinthitis resulting in atrophy of inner ear tissues including the sense organs and their supporting structures; 2. endolymphatic hydrops; 3. focal and diffuse proliferation of fibrous tissue and bone; and 4. retrograde neuronal degeneration. These pathologic findings are consistent with an inflammatory (and possibly ischemic) attack on the membranous labyrinth.