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.

Fitting prelingually deafened adult cochlear implant users based on electrode discrimination performance.

OBJECTIVE: This study investigated the hypotheses that (1) prelingually deafened CI users do not have perfect electrode discrimination ability and (2) the deactivation of non-discriminable electrodes can improve auditory performance. DESIGN: Electrode discrimination difference limens were determined for all electrodes of the array. The subjects' basic map was subsequently compared to an experimental map, which contained only discriminable electrodes, with respect to speech understanding in quiet and in noise, listening effort, spectral ripple discrimination and subjective appreciation. STUDY SAMPLE: Subjects were six prelingually deafened, late implanted adults using the Nucleus cochlear implant. RESULTS: Electrode discrimination difference limens across all subjects and electrodes ranged from 0.5 to 7.125, with significantly larger limens for basal electrodes. No significant differences were found between the basic map and the experimental map on auditory tests. Subjective appreciation was found to be significantly poorer for the experimental map. CONCLUSIONS: Prelingually deafened CI users were unable to discriminate between all adjacent electrodes. There was no difference in auditory performance between the basic and experimental map. Potential factors contributing to the absence of improvement with the experimental map include the reduced number of maxima, incomplete adaptation to the new frequency allocation, and the mainly basal location of deactivated electrodes.

Bimodal Hearing Aid Retention after Unilateral Cochlear Implantation.

The goal of this study was to investigate contralateral hearing aid (HA) use after unilateral cochlear implantation and to identify factors of influence on the occurrence of a unilateral cochlear implant (CI) recipient becoming a bimodal user. A retrospective cross-sectional chart review was carried out among 77 adult unilateral CI recipients 1 year after implantation. A bimodal HA retention rate of 64% was observed. Associations with demographics, hearing history, residual hearing and speech recognition ability were investigated. Better pure-tone thresholds and unaided speech scores in the non-implanted ear, as well as a smaller difference in speech recognition scores between both ears, were significantly associated with HA retention. A combined model of HA retention was proposed, and cut-off points were determined to identify those CI recipients who were most likely to become bimodal users. These results can provide input to clinical guidelines concerning bimodal CI candidacy.

The cross-sectional area of the vagus nerve is not reduced in Parkinson's disease patients.

Background: Recent studies have revealed the importance of the gut brain axis in the development of Parkinson's disease (PD). It has also been suggested that the cross-sectional area (CSA) of the vagus nerve can be used in the diagnosis of PD. Here, we hypothesize that the CSA of the vagus nerve is decreased in PD patients compared to control participants. Methods: In this study we measured the CSA of the vagus nerve on both sides in 31 patients with PD and 51 healthy controls at the level of the common carotid artery using high-resolution ultrasound. Results: The mean CSA of the left vagus nerve in the PD and the control group was respectively 2.10 and 1.90 and of the right respectively 2.54 and 2.24 mm2. There is no difference in CSA of the vagus nerve in PD patients compared to controls (p = .079). The mean CSA of the right vagus nerve was significantly larger than the left (p < .001). Age, sex and autonomic symptoms were no significant predictors of the CSA of the vagus nerve. Conclusion: These findings show that the CSA of the vagus nerve using ultrasonography is not a reliable diagnostic tool in the diagnosis of PD.

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).

Self-assessment of unilateral and bimodal cochlear implant experiences in daily life.

OBJECTIVE: The subjective experiences were assessed of cochlear implant (CI) users either wearing or not wearing a hearing aid (HA) at the contralateral ear. DESIGN: Unilateral CI-recipients were asked to fill out a set of daily-life questionnaires on bimodal HA use, hearing disability, hearing handicap and general quality of life. STUDY SAMPLE: Twenty-six CI-recipients who regularly use a contralateral HA (bimodal group) and twenty-two CI-recipients who do not use a HA in the contralateral ear (unilateral group). RESULTS: Comparisons between both groups (bimodal versus unilateral) showed no difference in self-rated disability, hearing handicap or general quality of life. However within the group of bimodal listeners, participants did report a benefit of bimodal hearing ability in various daily life listening situations. CONCLUSIONS: Bimodal benefit in daily life can consistently be experienced and reported within the group of bimodal users.

A Mid-scala Cochlear Implant Electrode Design Achieves a Stable Post-surgical Position in the Cochlea of Patients Over Time-A Prospective Observational Study.

INTRODUCTION: Cochlear implant (CI) electrode design impacts the clinical performance of patients. Stability and the occurrence of electrode array migration, which is the postoperative movement of the electrode array, were investigated using a mid-scalar electrode array and postoperative image analysis. METHODS: A prospective observational study was conducted. A mid-scalar electrode was surgically placed using a mastoidectomy, followed by a posterior tympanotomy and an extended round-window or cochleostomy insertion. A few days after surgery and 3 months later Cone Beam Computed Tomography (CBCT) was performed. The two different CBCT's were fused, and the differences between the electrode positions in three dimensions were calculated (the migration). A migration greater than 0.5 mm was deemed clinically relevant. RESULTS: Fourteen subjects participated. The mid-scalar electrode migrated in one patient (7%). This did not lead to the extrusion of an electrode contact. The mean migration of every individual electrode contact in all patients was 0.36 mm (95% confidence interval 0.22-0.50 mm), which approximates to the estimated measurement error of the CBCT technique. CONCLUSION: A mid-scalar electrode array achieves a stable position in the cochlea in a small but representative group of patients. The methods applied in this work can be used for providing postoperative feedback for surgeons and for benchmarking electrode designs.

The Benefits of Bimodal Aiding on Extended Dimensions of Speech Perception: Intelligibility, Listening Effort, and Sound Quality.

The benefits of combining a cochlear implant (CI) and a hearing aid (HA) in opposite ears on speech perception were examined in 15 adult unilateral CI recipients who regularly use a contralateral HA. A within-subjects design was carried out to assess speech intelligibility testing, listening effort ratings, and a sound quality questionnaire for the conditions CI alone, CIHA together, and HA alone when applicable. The primary outcome of bimodal benefit, defined as the difference between CIHA and CI, was statistically significant for speech intelligibility in quiet as well as for intelligibility in noise across tested spatial conditions. A reduction in effort on top of intelligibility at the highest tested signal-to-noise ratio was found. Moreover, the bimodal listening situation was rated to sound more voluminous, less tinny, and less unpleasant than CI alone. Listening effort and sound quality emerged as feasible and relevant measures to demonstrate bimodal benefit across a clinically representative range of bimodal users. These extended dimensions of speech perception can shed more light on the array of benefits provided by complementing a CI with a contralateral HA.

Monaural Beamforming in Bimodal Cochlear Implant Users: Effect of (A)symmetric Directivity and Noise Type.

OBJECTIVE: To evaluate monaural beamforming in bimodally aided cochlear implant (CI) users. DESIGN: The study enrolled twelve adult bimodal listeners with at least six months of CI-experience and using a contralateral hearing aid (HA) most of the daytime. Participants were uniformly fitted with the same CI speech processor and HA, giving access to an identical monaural beamformer in both ears. A within-subject repeated measures design evaluated three directional configurations [omnidirectional, asymmetric directivity (in CI alone) and symmetric directivity (in both CI and HA)] in two noise types [stationary and fluctuating]. Bimodal speech reception thresholds (SRT) as well as listening effort ratings were assessed in a diffuse noise field. RESULTS: Symmetric monaural beamforming provided a significant SRT improvement of 2.6 dB SNR, compared to 1.6 dB SNR for asymmetric monaural beamforming. Directional benefits were similarly observed in stationary and fluctuating noise. Directivity did not contribute to less listening effort in addition to improvement in speech intelligibility. Bimodal performance was about 7 dB SNR worse in fluctuating than in stationary noise. CONCLUSIONS: Monaural beamforming provided substantial benefit for speech intelligibility in noise for bimodal listeners. The greatest benefit occurred when monaural beamforming was activated symmetrically in both CI and HA. Monaural beamforming does not bridge the gap between bimodal and normal hearing performance, especially in fluctuating noise. Results advocate further bimodal co-operation. TRIAL REGISTRATION: This trial was registered in www.trialregister.nl under number NTR4901.

Prognostic significance of metallothionein in human gastrointestinal cancer.

PURPOSE: Metallothionein (MT) is a small protein with a high affinity for divalent heavy metal ions. This metalloproteinis involved in many (patho)physiological processes, like metal homeostasis and detoxification, cell proliferation, apoptosis, therapy resistance, and protection against oxidative damage. Alterations in the immunohistochemical expression of MT have been reported for various human tumors, and a high expression has been found to be associated with a poor clinical outcome. We showed previously that gastrointestinal cancer is accompanied by a decrease in MT expression, but the most malignant phenotypes had the highest MT levels. The purpose of the present study was to assess the clinical relevance of MT in gastrointestinal cancer. EXPERIMENTAL DESIGN: In this study, we determined the MT levels, by radioimmunoassay, in intestinal tissue of 251 patients with colorectal cancer and 81 patients with gastric cancer and assessed the relation with the overall survival of these patients. RESULTS: More than 74% of the carcinomas were found to have a lower MT level than their corresponding normal mucosa. In colorectal cancer patients, but not in gastric cancer patients, a high MT level in both the carcinomas and normal mucosa was, however, significantly associated with a poor overall survival, independently from clinicopathological features. CONCLUSIONS: Overexpression of MT in intestinal tissue of colorectal cancer patients is a prognostic marker for a poor overall survival. In gastric cancer, however, MT expression in the gastric mucosa is not of prognostic significance. This observation emphasizes the clinical relevance of this multifunctional metalloprotein in colorectal carcinogenesis and therapy.