Sensory gating functions of the auditory thalamus: Adaptation and modulations through noise-exposure and high-frequency stimulation in rats.

The medial geniculate body (MGB) of the thalamus is an obligatory relay for auditory processing. A breakdown of adaptive filtering and sensory gating at this level may lead to multiple auditory dysfunctions, while high-frequency stimulation (HFS) of the MGB might mitigate aberrant sensory gating. To further investigate the sensory gating functions of the MGB, this study (i) recorded electrophysiological evoked potentials in response to continuous auditory stimulation, and (ii) assessed the effect of MGB HFS on these responses in noise-exposed and control animals. Pure-tone sequences were presented to assess differential sensory gating functions associated with stimulus pitch, grouping (pairing), and temporal regularity. Evoked potentials were recorded from the MGB and acquired before and after HFS (100 Hz). All animals (unexposed and noise-exposed, pre- and post-HFS) showed gating for pitch and grouping. Unexposed animals also showed gating for temporal regularity not found in noise-exposed animals. Moreover, only noise-exposed animals showed restoration comparable to the typical EP amplitude suppression following MGB HFS. The current findings confirm adaptive thalamic sensory gating based on different sound characteristics and provide evidence that temporal regularity affects MGB auditory signaling.

The Effect of Noise Trauma and Deep Brain Stimulation of the Medial Geniculate Body on Tissue Activity in the Auditory Pathway.

Tinnitus is defined as the phantom perception of sound. To date, there is no curative treatment, and contemporary treatments have failed to show beneficial outcomes. Deep brain stimulation has been suggested as a potential therapy for refractory tinnitus. However, the optimal target and stimulation regimens remain to be defined. Herein, we investigated metabolic and neuronal activity changes using cytochrome C oxidase histochemistry and c-Fos immunohistochemistry in a noise trauma-induced rat model of tinnitus. We also assessed changes in neuronal activity following medial geniculate body (MGB) high-frequency stimulation (HFS). Metabolic activity was reduced in the primary auditory cortex, MGB and CA1 region of the hippocampus in noise-exposed rats. Additionally, c-Fos expression was increased in the primary auditory cortex of those animals. Furthermore, MGB-HFS enhanced c-Fos expression in the thalamic reticular nucleus. We concluded that noise trauma alters tissue activity in multiple brain areas including the auditory and limbic regions. MGB-HFS resulted in higher neuronal activity in the thalamic reticular nucleus. Given the prominent role of the auditory thalamus in tinnitus, these data provide more rationales towards targeting the MGB with HFS as a symptom management tool in tinnitus.

A Protocol to Investigate Deep Brain Stimulation for Refractory Tinnitus: From Rat Model to the Set-Up of a Human Pilot Study.

BACKGROUND: Chronic tinnitus can have an immense impact on quality of life. Despite recent treatment advances, many tinnitus patients remain refractory to them. Preclinical and clinical evidence suggests that deep brain stimulation (DBS) is a promising treatment to suppress tinnitus. In rats, it has been shown in multiple regions of the auditory pathway that DBS can have an alleviating effect on tinnitus. The thalamic medial geniculate body (MGB) takes a key position in the tinnitus network, shows pathophysiological hallmarks of tinnitus, and is readily accessible using stereotaxy. Here, a protocol is described to evaluate the safety and test the therapeutic effects of DBS in the MGB in severe tinnitus sufferers. METHODS: Bilateral DBS of the MGB will be applied in a future study in six patients with severe and refractory tinnitus. A double-blinded, randomized 2 × 2 crossover design (stimulation ON and OFF) will be applied, followed by a period of six months of open-label follow-up. The primary focus is to assess safety and feasibility (acceptability). Secondary outcomes assess a potential treatment effect and include tinnitus severity measured by the Tinnitus Functional Index (TFI), tinnitus loudness and distress, hearing, cognitive and psychological functions, quality of life, and neurophysiological characteristics. DISCUSSION: This protocol carefully balances risks and benefits and takes ethical considerations into account. This study will explore the safety and feasibility of DBS in severe refractory tinnitus, through extensive assessment of clinical and neurophysiological outcome measures. Additionally, important insights into the underlying mechanism of tinnitus and hearing function might be revealed. TRIAL REGISTRATION: ClinicalTrials.gov NCT03976908 (6 June 2019).

Noise-induced neurophysiological alterations in the rat medial geniculate body and thalamocortical desynchronization by deep brain stimulation.

The thalamic medial geniculate body (MGB) is uniquely positioned within the neural tinnitus networks. Deep brain stimulation (DBS) of the MGB has been proposed as a possible novel treatment for tinnitus, yet mechanisms remain elusive. The aim of this study was to characterize neurophysiologic hallmarks in the MGB after noise exposure and to assess the neurophysiological effects of electrical stimulation of the MGB. Fourteen male Sprague-Dawley rats were included. Nine subjects were unilaterally exposed to a 16-kHz octave-band noise at 115 dB for 90 min, five received sham exposure. Single units were recorded from the contralateral MGB where spontaneous firing, coefficient of variation, response type, rate-level functions, and thresholds were determined. Local field potentials and electroencephalographical (EEG) recordings were performed before and after high-frequency DBS of the MGB. Thalamocortical synchronization and power were analyzed. In total, 214 single units were identified (n = 145 in noise-exposed group, n = 69 in control group). After noise exposure, fast-responding neurons become less responsive or nonresponsive without change to their spontaneous rate, whereas sustained- and suppressed-type neurons exhibit enhanced spontaneous activity without change to their stimulus-driven activity. MGB DBS suppressed thalamocortical synchronization in the ß and γ bands, supporting suppression of thalamocortical synchronization as an underlying mechanism of tinnitus suppression by high frequency DBS. These findings contribute to our understanding of the neurophysiologic consequences of noise exposure and the mechanism of potential DBS therapy for tinnitus.NEW & NOTEWORTHY Separate functional classes of MGB neurons might have distinct roles in tinnitus pathophysiology. After noise exposure, fast-responding neurons become less responsive or nonresponsive without change to their spontaneous firing, whereas sustained and suppressed neurons exhibit enhanced spontaneous activity without change to their stimulus-driven activity. Furthermore, results suggest desynchronization of thalamocortical ß and γ oscillations as a mechanism of tinnitus suppression by MGB DBS.

Voice and Vocal Fold Condition Following Short-Term General Anesthesia: A Prospective Study.

BACKGROUND: Dysphonia, with or without laryngeal changes, has been reported as a complication following prolonged intubation. In contrast, it is unknown if laryngeal changes also occur following short-term airway instrumentation. The objectives of this study were to determine the prevalence of laryngeal changes in patients undergoing short-term routine general anesthesia using an endotracheal tube (ETT) or supraglottic airway (SGA), and to identify predictors to these changes. METHODS: Standardized voice assessments were performed preoperatively, postoperatively, and at follow-up on adults undergoing general anesthesia for an elective procedure of less than three hours requiring an ETT or a SGA. The standardized voice assessment protocol comprised a rigid videolaryngostroboscopy, the Voice Handicap Index (VHI), and acoustic voice analysis. The effects of demographic and anesthetic characteristics and type of airway instrumentation on the videolaryngostroboscopic variables were studied using multilevel logistic regression. Multilevel linear regression was used to reveal preoperative versus postoperative changes in VHI and acoustic voice scores. RESULTS: Overall, the prevalence of postoperative laryngeal changes was low. Significant postoperative laryngeal changes were found for the variables right-sided vocal fold redness in the ETT group (P = 0.048) and right-sided vocal fold blood vessels in both groups (ETT versus SGA). However, after adjustment for all demographic and anesthetic characteristics in the regression model, the effect of the type of airway instrumentation (ETT versus SGA) on the variable right-sided vocal fold redness was no longer significant. CONCLUSIONS: ETT and SGA short-term airway instrumentation are vocal fold function sparing techniques with negligible laryngeal changes.

Alleviation of Tinnitus With High-Frequency Stimulation of the Dorsal Cochlear Nucleus: A Rodent Study.

Deep brain stimulation of the central auditory pathway is emerging as a promising treatment modality for tinnitus. Within this pathway, the dorsal cochlear nucleus (DCN) plays a key role in the pathophysiology of tinnitus and is believed to be a tinnitus generator. We hypothesized that high-frequency stimulation (HFS) of the DCN would influence tinnitus-related abnormal neuronal activity within the auditory pathway and hereby suppress tinnitus. To this end, we assessed the effect of HFS of the DCN in a noise-induced rat model of tinnitus. The presence of tinnitus was verified using the gap prepulse inhibition of the acoustic startle response paradigm. Hearing thresholds were determined before and after noise trauma by measuring the auditory brainstem responses. In addition, changes in neuronal activity induced by noise trauma and HFS were assessed using c-Fos immunohistochemistry in related structures. Results showed tinnitus development after noise trauma and hearing loss ipsilateral to the side exposed to noise trauma. During HFS of the DCN, tinnitus was suppressed. There was no change in c-Fos expression within the central auditory pathway after HFS. These findings suggest that DCN-HFS changes patterns of activity and results in information lesioning within the network and hereby blocking the relay of abnormal tinnitus-related neuronal activity.

Inhibition of Experimental Tinnitus With High Frequency Stimulation of the Rat Medial Geniculate Body.

BACKGROUND: Neuromodulation is a promising treatment modality for tinnitus, especially in chronic and severe cases. The auditory thalamus plays a key role in the pathophysiology of tinnitus, as it integrates and processes auditory and limbic information. OBJECTIVE: The effect of high frequency stimulation and low frequency stimulation of the medial geniculate bodies on tinnitus in a noise-induced tinnitus rat model is assessed. MATERIALS AND METHODS: Presence of tinnitus was verified using the gap-induced prepulse inhibition of the acoustic startle response paradigm. Hearing thresholds were determined before and after noise trauma with auditory brainstem responses. Anxiety-related side-effects were evaluated in the elevated zero maze and open field. RESULTS: Results show tinnitus development after noise exposure and preserved hearing thresholds of the ear that was protected from noise trauma. We found that high frequency stimulation of the medial geniculate bodies suppressed tinnitus. This effect maintained directly after stimulation when the stimulator was turned off. Low frequency stimulation did not have any effects on the gap:no-gap ratio of the acoustic startle response. CONCLUSION: High frequency stimulation of the MGB has a direct and residual suppressing effect on tinnitus in this animal model. Low frequency stimulation of the MGB did not inhibit tinnitus.

Computerized Dynamic Posturography does not detect measured CVEMP and OVEMP abnormalities.

BACKGROUND: Computerized Dynamic Posturography (CDP)was developed by the American space program to assess imbalance in astronauts, and eventually evolved into a clinical diagnostic tool. However it is not a specific measure of vestibular function. Vestibular Evoked Myogenic Potential testing (VEMPs) is a new clinical tool which is sensitive and specific for measuring otolithic pathology, especially in the atypical vestibular patient. RESEARCH QUESTION: As posturography measures ability to maintain balance, and VEMP testing measures the structures responsible for this, we wondered if CDP results would correlate with VEMP abnormalities in the clinical setting. METHODS: We analysed 180 patients sequentially referred to our unit for vestibular complaints. All patients had a full battery of vestibular assessments. We correlated VEMP results with CDP results to look for abnormality patterns and correlations. An occasional patient's only abnormality was on CDP RESULTS: There was a high rate of VEMP abnormalities seen, which correlates with the fact that our referral base consists of patients with chronic vestibular complaints. The rate of VEMP abnormalities was the same in patients with normal CDP and those with abnormal CDP. SIGNIFICANCE: Our results do not suggest that CDP is unnecessary, but we feel that they emphasize the idea that these tests are measuring two different aspects of balance control. In some patients, all assessments are abnormal, but in some patients only one assessment is abnormal, suggesting that these modalities measure different things and are all important in the diagnostic armamentarium. Hopefully in the near future, the use of virtual reality will reduce the cost of CDP to the point where it can be made widely accessible to patients and clinicians.

Deep brain stimulation of the inferior colliculus in the rodent suppresses tinnitus.

In animal models of tinnitus pathological neuronal activity has been demonstrated. Deep brain stimulation disrupts pathological neuronal activity and might therefore be a potential treatment for patients who suffer severely from tinnitus. In this study, the effect of DBS in the inferior colliculi is investigated in an animal model of tinnitus. The external cortex of the inferior colliculus was targeted because of the key position of the inferior colliculus within the auditory network and the relation of the external cortex with the limbic system. In this study we show the effect of DBS in the inferior colliculus on tinnitus using a within-subject experimental design. After noise trauma, rats showed a significant increase in gap:no gap ratio of the gap-induced prepulse inhibition at 16 and 20kHz (p<0.05), indicating the presence of tinnitus in these frequency bands. During DBS the gap:no gap ratio returned back to baseline (p<0.05). Hearing thresholds before and during DBS did not differ, indicating that hearing function is probably not impaired by electrical stimulation. In summary, this study shows that DBS of the inferior colliculi is effective in reducing behavioral signs of tinnitus in an animal model. Impaired hearing function could not be objectified as a side effect of stimulation.

The inflatable thymus herniation of the normal mediastinal thymus: A case report and review of the literature.

Anterior neck masses in young children can be a diagnostic challenge for otolaryngologists and radiologists. We present a rare case of herniation of normal mediastinal thymus in a four-year-old girl. Additional medical features as an inguinal hernia and trochlear nerve paresis raised the question whether there is a causal relationship or an association. A connective tissue disorder could not be diagnosed as possible causal factor to the abnormal movement of the mediastinal thymus. Awareness and recognition of this benign phenomenon is important in order to avoid unnecessary biopsy or surgery. Diagnosis can be confirmed by ultrasonography. Magnetic Resonance Imaging might be valuable in order to obtain more information about the extension of the mass.

Tinnitus: Is there a place for brain stimulation?

Tinnitus is the perception of a "phantom sound" and has a high prevalence. Although many therapies have been investigated within the last decades, there is still no effective standard therapy. Animal studies and human functional imaging studies revealed that tinnitus perception is associated with many complex changes in multiple brain structures. There is growing evidence that brain stimulation might be able to interrupt the local altered neuronal activity and hereby inhibit tinnitus perception. In this editorial review, an update is given on the most promising targets for brain stimulation. Promising structures for stimulation are the dorsal cochlear nucleus, the inferior colliculus and the medial geniculate body of the thalamus. For cortical stimulation, the auditory cortex is considered as a target. Nevertheless, the field is waiting for evidence from well-designed clinical trials, based on supporting evidence from experimental/mechanistic research, to support or discourage the application of brain stimulation in tinnitus.

[A man with a swelling in the palm of his hand]. / Een man met een zwelling in zijn handpalm.

A 41-year-old man had a palpable mass on the volar side of his hand. X-ray, ultrasound and MRI showed an inhomogeneous tumour with calcification. Histologic examination ruled out the suspicion of a liposarcoma. The surgeon successfully excised the ossifying lipoma, which is a rare variant of a common lipoma and can clinically and radiologically mimic malignant neoplasms.