Stress and Tinnitus; Transcutaneous Auricular Vagal Nerve Stimulation Attenuates Tinnitus-Triggered Stress Reaction

Introduction Tinnitus can become a strong stressor for some individuals, leading to imbalance of the autonomous nervous system with reduction of parasympathetic activity. It can manifest itself as sleep disturbances, anxiety and even depression. This condition can be reversed by bioelectrical vagal nerve stimulation (VNS). Conventional invasive VNS is an approved treatment for epilepsy and depression. Transcutaneous VNS (taVNS) stimulating the auricular branch of the vagus nerve has been shown to activate the vagal pathways similarly as an implanted VNS. Therefore, taVNS might also be a therapeutic alternative in health conditions such as tinnitus-related mental stress (TRMS). This retrospective study in 171 TRMS patients reports the clinical features, psychophysiological characteristics, and results of the heart rate variability (HRV) tests before and after test-taVNS. This study also reports the therapy outcomes of 113 TRMS patients treated with taVNS, in combination with standard tinnitus therapy. Methods Diagnostic tinnitus and hearing profiles were defined. To detect possible cardiac adverse effects, test-taVNS with heart rate monitoring as well as pre- and post-stimulation HRV tests were performed. Daily taVNS home therapy was prescribed thereafter. To assess therapeutic usefulness of taVNS, 1-year follow-up outcome was studied. Results of HRV tests were retrospectively analyzed and correlated to diagnostic data. Results The large majority of patients with TRMS suffer from associated symptoms such as sleep disturbances and anxiety. Baseline HRV data showed that more than three quarters of the 171 patients had increased sympathetic activity before test-taVNS. Test-taVNS shifted mean values of different HRV parameters toward increased parasympathetic activity in about 80% of patients. Test-taVNS did not cause any cardiac or other side effects. No significant adverse effects were reported in follow-up questionnaires. Conclusion TRMS is an example of a stress condition in which patients may benefit from taVNS. As revealed by HRV, test-taVNS improved parasympathetic function, most efficiently in patients with a low starting HRV level. Our tinnitus treatment program, including taVNS, effectively alleviated tinnitus stress and handicap. For wider clinical use, there is a great need for more knowledge about the optimal methodology and parameters of taVNS.Peer reviewe

Migraine and motion sickness: what is the link?

The brainstem is a structurally complex region, containing numerous ascending and descending fibres that converge on centres that regulate bodily functions essential to life. Afferent input from the cranial tissues and the special senses is processed, in part, in brainstem nuclei. In addition, brainstem centres modulate the flow of pain messages and other forms of sensory information to higher regions of the brain, and influence the general excitability of these cortical regions. Thus, disruptions in brainstem processing might evoke a complex range of unpleasant symptoms, vegetative changes and neurovascular disturbances and that, together, form attacks of migraine. Migraine is linked with various co-morbid conditions, the most prominent being motion sickness. Symptoms such as nausea, dizziness and headache are common to motion sickness and migraine; moreover, migraine sufferers have a heightened vulnerability to motion sickness. As both maladies involve reflexes that relay in the brainstem, symptoms may share the same neural circuitry. In consequence, subclinical interictal persistence of disturbances in these brainstem pathways could not only increase vulnerability to recurrent attacks of migraine but also increase susceptibility to motion sickness. Mechanisms that mediate symptoms of motion sickness and migraine are explored in this paper. The physiology of motion sickness and migraine is discussed, and neurotransmitters that may be involved in the manifestation of symptoms are reviewed. Recent findings have shed light on the relationship between migraine and motion sickness, and provide insights into the generation of migraine attacks

Comparison of efficacy and safety of intranasal Midazolam with syrup Chloral hydrate for procedural sedation of children undergoing Auditory Brainstem evoked Response audiometry: A Randomized, Double-blinded, Placebo controlled trial

OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of intranasal Midazolam compared to syrup Chloral hydrate for procedural sedation in children undergoing Auditory Brainstem evoked Response audiometry (ABR). METHODS: A prospective, randomized, double-blinded placebo controlled trial was carried out in the audiology lab of a tertiary care hospital over a period of 18 months. 82 children between the age group of 1 to 6 years (mean 2 years) irrespective of their developmental maturity, belonging to ASA class I and II who were referred for ABR testing were recruited. Children were randomized to receive either midazolam spray with oral placebo or syrup chloral hydrate with nasal placebo spray. The nasal spray was dosed at 0.5 mg/kg delivered as 100mcg per spray and oral syrup at a dose of 50 mg/kg. Those children who did not show onset of sedation at 30 minutes were administered the second dose at half the initial dose. Randomization was computer generated and allocation concealment was achieved by opaque sequentially numbered sealed envelopes that were employed serially to the participating children. The primary outcome measured were safety which was measured in terms of heart rate, respiratory rate, oxygen saturation and efficacy was measured in terms of level of consciousness (uninterrupted sleep without movement) and successful completion of the procedure. The various secondary outcomes were time to onset of sedation, time to parental separation, nature of parental separation, duration of procedure, parental satisfaction, audiologist’s satisfaction, time to recovery and number of attempts. RESULTS: The trial was completed over a period of 18 months when 41 children were studied in each arm. Both the drugs were found to be safe with no major adverse events. One child who had received Midazolam developed transient hypoxia. It was corrected with appropriate head positioning. Minor side effects noted were sneezing, hiccups and crying. Children on Chloral hydrate had an earlier onset of sedation (66% of children) at or less than 30 minutes as compared to only 33% from the Midazolam group. Developmentally delayed children had an earlier onset of sedation compared to developmentally normal group irrespective of the drug they received. Parental separation was earlier for chloral hydrate group at 20 minutes than for midazolam at 30 minutes. There was no statistically significant difference in the duration of procedure. There was a significant difference noted in the time to recovery (Chloral hydrate children (78 minutes) as compared to Midazolam children (105 minutes). Parental and audiologists satisfaction were higher for Chloral hydrate (95% and 75% respectively) than for Midazolam (49% and 29%). A larger number of patients (80%) slept with the first dose of Chloral hydrate as against Midazolam children who required a second dose. Overall, sedation was successful among 95% of children who received chloral hydrate compared to 51% of children who received Midazolam. Once sedation was achieved, both the drugs were efficacious in maintaining sedation with no intra-procedural interruption in sedation. CONCLUSION: Intranasal Midazolam and oral Chloral hydrate are both safe and efficacious for pediatric procedural sedation in ABR. However, Chloral hydrate had a superior efficacy to intranasal Midazolam with an earlier time to onset of sedation, a faster recovery, better parental and audiologist’s satisfaction and successful sedation even with the first attempt. There was no difference in the duration of the procedure. Developmentally delayed children showed an earlier onset of sedation and faster recovery compared to their normal counterparts irrespective of the drug regimen they received

Transcranial Direct Current Stimulation Combined With Listening to Preferred Music Alters Cortical Speech Processing in Older Adults

Emerging evidence suggests transcranial direct current stimulation (tDCS) can improve cognitive performance in older adults. Similarly, music listening may improve arousal and stimulate subsequent performance on memory-related tasks. We examined the synergistic effects of tDCS paired with music listening on auditory neurobehavioral measures to investigate causal evidence of short-term plasticity in speech processing among older adults. In a randomized sham-controlled crossover study, we measured how combined anodal tDCS over dorsolateral prefrontal cortex (DLPFC) paired with listening to autobiographically salient music alters neural speech processing in older adults compared to either music listening (sham stimulation) or tDCS alone. EEG assays included both frequency-following responses (FFRs) and auditory event-related potentials (ERPs) to trace neuromodulation-related changes at brainstem and cortical levels. Relative to music without tDCS (sham), we found tDCS alone (without music) modulates the early cortical neural encoding of speech in the time frame of ∼100–150 ms. Whereas tDCS by itself appeared to largely produce suppressive effects (i.e., reducing ERP amplitude), concurrent music with tDCS restored responses to those of the music+sham levels. However, the interpretation of this effect is somewhat ambiguous as this neural modulation could be attributable to a true effect of tDCS or presence/absence music. Still, the combined benefit of tDCS+music (above tDCS alone) was correlated with listeners’ education level suggesting the benefit of neurostimulation paired with music might depend on listener demographics. tDCS changes in speech-FFRs were not observed with DLPFC stimulation. Improvements in working memory pre to post session were also associated with better speech-in-noise listening skills. Our findings provide new causal evidence that combined tDCS+music relative to tDCS-alone (i) modulates the early (100–150 ms) cortical encoding of speech and (ii) improves working memory, a cognitive skill which may indirectly bolster noise-degraded speech perception in older listeners

Effect of unilateral hearing loss on the speech-evoked auditory brainstem response in the presence of noise

Speech-evoked auditory brainstem responses (ABRs) were acquired in quiet and in the presence of noise at two study sessions to investigate 1) test-retest variability and 2) subcortical representation of speech stimuli. Participants were adults with normal hearing in both ears who listened monaurally and adults with unilateral deafness. Results indicate consistency in responses across sessions and several differences between hearing groups for magnitudes of discrete components

The hunt for hidden hearing loss in humans: From preclinical studies to effective interventions

Many individuals experience hearing problems that are hidden under a normal audiogram. This not only impacts on individual sufferers, but also on clinicians who can offer little in the way of support. Animal studies using invasive methodologies have developed solid evidence for a range of pathologies underlying this hidden hearing loss (HHL), including cochlear synaptopathy, auditory nerve demyelination, elevated central gain, and neural mal-adaptation. Despite progress in pre-clinical models, evidence supporting the existence of HHL in humans remains inconclusive, and clinicians lack any non-invasive biomarkers sensitive to HHL, as well as a standardized protocol to manage hearing problems in the absence of elevated hearing thresholds. Here, we review animal models of HHL as well as the ongoing research for tools with which to diagnose and manage hearing difficulties associated with HHL. We also discuss new research opportunities facilitated by recent methodological tools that may overcome a series of barriers that have hampered meaningful progress in diagnosing and treating of HHL.Australian GovernmentDepartment of Health & AgeingMinistry of Science and Innovation, Spain (MICINN) Spanish GovernmentAndalucia European Regional Development Fund PID2020-119073GB-I00 B-TIC-382-UGR2

Stimulus frequency modulates brainstem response to respiratory-gated transcutaneous auricular vagus nerve stimulation

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Speech-evoked auditory brainstem response in children with unilateral hearing loss

Speech-evoked auditory brainstem responses (ABRs) and speech recognition measures were evaluated in children with unilateral hearing loss (UHL) and normal hearing (NH). There were significant differences between the two hearing groups for several components of the response in quiet and in noise. Children with UHL performed worse than children with NH on all speech recognition measures in quiet and in noise

Nimodipine in otolaryngology: from past evidence to clinical perspectives

As L-type voltage-gated calcium channels (VGCCs) control Ca(2+) influx and depolarisation of cardiac and vascular smooth muscle, they represent a specific therapeutic target for calcium channel blockers (CCBs), which are approved and widely used to treat hypertension, myocardial ischaemia and arrhythmias. L-type currents also play a role in calcium entry in the sensory cells of the inner ear. In hair cells of both cochlea and labyrinth, calcium cytoplasmic influx is the first physiological process that activates complex intracellular enzymatic reactions resulting in neurotransmitter release. Excessive calcium ion entry into sensory cells, as a consequence of L-VGCCs malfunction is responsible for over-activation of phospholipase A2 and C, protein kinase II and C, nitric oxide synthase and both endonucleases and depolymerases, which can cause membrane damage and cellular death if the cytoplasmic buffering capacity is overcome. Nimodipine, a highly lipophilic 1-4 dihydropyridine that easily crosses the brain-blood barrier, is generally used to reduce the severity of neurological deficits resulting from vasospasm in patients with subarachnoid haemorrhage. Moreover, due to its selective blocking activity on L-channel calcium currents, nimodipine is also suggested to be an effective countermeasure for cochlear and vestibular dysfunctions known as channelopathies. Indeed, experimental data in amphibians and mammalians indicate that nimodipine has a stronger efficacy than other CCBs (aminopyridine, nifedipine) on voltage-dependent whole-cell currents within hair cells at rest and it is the only agent that is also effective during their mechanically induced depolarisation. In humans, the efficacy of nimodipine is documented in the medical management of peripheral vestibular vertigo, sensorineural hearing loss and tinnitus, even in a pathology as complex as Ménière's disease. Nimodipine is also considered useful in the prophylaxis of damage to the facial and cochlear nerves caused by ablative surgery of cerebellopontine tumours; it has been recently hypothesised to accelerate functional recovery of recurrent nerve lesions during thyroid cancer surgery. Further trials with adequate study design are needed to test the efficacy of nimodipine in the treatment of vertigo due to cerebrovascular disease and vestibular migraine.As L-type voltage-gated calcium channels (VGCCs) control Ca(2+) influx and depolarisation of cardiac and vascular smooth muscle, they represent a specific therapeutic target for calcium channel blockers (CCBs), which are approved and widely used to treat hypertension, myocardial ischaemia and arrhythmias. L-type currents also play a role in calcium entry in the sensory cells of the inner ear. In hair cells of both cochlea and labyrinth, calcium cytoplasmic influx is the first physiological process that activates complex intracellular enzymatic reactions resulting in neurotransmitter release. Excessive calcium ion entry into sensory cells, as a consequence of L-VGCCs malfunction is responsible for over-activation of phospholipase A2 and C, protein kinase II and C, nitric oxide synthase and both endonucleases and depolymerases, which can cause membrane damage and cellular death if the cytoplasmic buffering capacity is overcome. Nimodipine, a highly lipophilic 1-4 dihydropyridine that easily crosses the brain-blood barrier, is generally used to reduce the severity of neurological deficits resulting from vasospasm in patients with subarachnoid haemorrhage. Moreover, due to its selective blocking activity on L-channel calcium currents, nimodipine is also suggested to be an effective countermeasure for cochlear and vestibular dysfunctions known as channelopathies. Indeed, experimental data in amphibians and mammalians indicate that nimodipine has a stronger efficacy than other CCBs (aminopyridine, nifedipine) on voltage-dependent wholecell currents within hair cells at rest and it is the only agent that is also effective during their mechanically induced depolarisation. In humans, the efficacy of nimodipine is documented in the medical management of peripheral vestibular vertigo, sensorineural hearing loss and tinnitus, even in a pathology as complex as Ménière's disease. Nimodipine is also considered useful in the prophylaxis of damage to the facial and cochlear nerves caused by ablative surgery of cerebellopontine tumours; it has been recently hypothesised to accelerate functional recovery of recurrent nerve lesions during thyroid cancer surgery. Further trials with adequate study design are needed to test the efficacy of nimodipine in the treatment of vertigo due to cerebrovascular disease and vestibular migraine