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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-fre-quency 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 respon-sive 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 synchroni-zation in the 13 and c 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 activ-ity. Furthermore, results suggest desynchronization of thalamocortical 13 and c oscillations as a mechanism of tinnitus suppres-sion by MGB DBS.

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 suggest that deep brain stimulation (DBS) is as a promising treatment to suppress 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. This study will evaluate the safety and therapeutic effects of DBS in the MGB in severe tinnitus sufferers.Methods: Bilateral DBS of the MGB will be applied in six patients with severe and refractory tinnitus. A double-blinded, randomized 2x2 crossover design (stimulation ON and OFF) will be applied, followed by a period of six months 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: Whilst carefully balancing risks and benefits and taking ethical considerations into account, this study explores the safety and feasibility of DBS in severe refractory tinnitus, by extensive assessment of clinical and neurophysiological outcome measures. Additionally, important insights in the underlying mechanism of tinnitus and hearing function might be revealed. Trial registration: ClinicalTrials.gov NCT03976908 (June 6, 2019)

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.

Tinnitus is one of the major health care problems of the current era. So far, therapies have aimed at symptomatic relief, but fail to eliminate the actual phantom sound. The studies in this thesis investigate the effects of deep brain stimulation (DBS) in central auditory structures on tinnitus suppression in a preclinical setting. The novel results indicate that DBS of multiple targets (dorsal cochlear nucleus, medial geniculate body) in the auditory circuit alleviates tinnitus-like behaviour in rats. Follow-up experiments explored neural mechanisms that might underlie tinnitus pathophysiology and DBS. This research classified four different functional classes of neurons in the medial geniculate body and postulated on their distinctive roles in tinnitus pathophysiology. Furthermore, it was measured that DBS causes thalamocortical desynchronization. Finally, a protocol is presented for a first-in-human application of DBS in patients with serious and therapy resistant tinnitus. This study is currently executed at the Maastricht University Medical Centre.

BackgroundThe medial geniculate body (MGB) of the thalamus plays a central role in tinnitus pathophysiology. Breakdown of sensory gating in this part of the auditory thalamus is a potential mechanism underlying tinnitus. The alleviation of tinnitus-like behavior by high-frequency stimulation (HFS) of the MGB might mitigate dysfunctional sensory gating.ObjectiveThe study aims at exploring the role of the MGB in sensory gating as a mandatory relay area in auditory processing in noise-exposed and control subjects, and to assess the effect of MGB HFS on this function.MethodsNoise-exposed rats and controls were tested. Continuous auditory sequences were presented to allow assessment of sensory gating effects associated with pitch, binary grouping, and temporal regularity. Evoked potentials (EP) were recorded from the MGB and acquired before and after HFS (100 Hz).ResultsNoise-exposed rats showed differential modulation of MGB EP amplitudes, confirmed by significant main effects of stimulus type, pair position and temporal regularity. Noise-exposure selectively abolished the effect of temporal regularity on EP amplitudes. A significant three-way interaction between HFS phase, temporal regularity and rat condition (noise-exposed, control) revealed that only noise-exposed rats showed significantly reduced EP amplitudes following MGB HFS.ConclusionThis is the first report that shows thalamic filtering of incoming auditory signals based on different sound features. Noise-exposed rats further showed higher EP amplitudes in most conditions and did not differentiate the temporal regularity. Critically, MGB HFS was effective in reducing amplitudes of the EP responses in noise-exposed animals.HighlightsEP findings indicate sensory gating in the MGB in rats.Noise exposure alters EP amplitudes in the MGB.HFS selectively suppresses EP responses in noise-exposed animals.

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.

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.

Summary 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.

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 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 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.