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Acoustic Coordinated Reset Neuromodulation: A Systematic Review of a Novel Therapy for Tinnitus.

ABSTRACT: BACKGROUND:There are growing technological advances in the development of sound-based methods for the treatment of tinnitus. Most of these methods intend to affect the speculated underlying neurological causes of tinnitus. Acoustic coordinated reset (CR) neuromodulation is one of them. A novel method that as of yet seems inadequately reviewed. PURPOSE:To evaluate the current evidence on acoustic CR neuromodulation as a method for the treatment of tinnitus and to assess whether the method can be implemented in daily clinical practice. METHODS:A systematic literature search was performed in 13 databases in the period from February 1, 2015 to May 1, 2016. Studies regarding acoustic CR neuromodulation as a treatment method for tinnitus were included in the present review. RESULTS:A total of 8 studies were eligible for being reviewed comprising a total of 329 patients. Overall, the evidence level of the published literature was low. The main findings in the included studies were that acoustic CR neuromodulation was safe and well tolerated and most patients reported reduction of tinnitus symptoms. The neurophysiological basis of the method was claimed to be desynchronization, anti-kindling, and change of abnormal frequency couplings in a widespread tinnitus network comprising both auditory and non/auditory brain areas based on EEG analyses. CONCLUSION:The available evidence is insufficient for clinical implementation of acoustic CR neuromodulation. The limited level of evidence suggests that acoustic CR neuromodulation may have positive effects on tinnitus symptoms. Preliminary electroencephalographic data are compatible with the claim that tinnitus reduction after CR treatment is mediated by a desynchronizing effect. However, a proof for this claim is still lacking.

SUBMITTER: Wegger M

PROVIDER: S-EPMC5304262 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Acoustic Coordinated Reset Neuromodulation: A Systematic Review of a Novel Therapy for Tinnitus.

Wegger Marie M Ovesen Therese T Larsen Dalia Gustaityte DG

Frontiers in neurology 20170213

<h4>Background</h4>There are growing technological advances in the development of sound-based methods for the treatment of tinnitus. Most of these methods intend to affect the speculated underlying neurological causes of tinnitus. Acoustic coordinated reset (CR) neuromodulation is one of them. A novel method that as of yet seems inadequately reviewed.<h4>Purpose</h4>To evaluate the current evidence on acoustic CR neuromodulation as a method for the treatment of tinnitus and to assess whether the ...[more]

PMID: 28243221

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Project description:Chronic subjective tinnitus is an auditory phantom phenomenon characterized by abnormal neuronal synchrony in the central auditory system. As shown computationally, acoustic coordinated reset (CR) neuromodulation causes a long-lasting desynchronization of pathological synchrony by downregulating abnormal synaptic connectivity. In a previous proof of concept study acoustic CR neuromodulation, employing stimulation tone patterns tailored to the dominant tinnitus frequency, was compared to noisy CR-like stimulation, a CR version significantly detuned by sparing the tinnitus-related pitch range and including substantial random variability of the tone spacing on the frequency axis. Both stimulation protocols caused an acute relief as measured with visual analogue scale scores for tinnitus loudness (VAS-L) and annoyance (VAS-A) in the stimulation-ON condition (i.e. 15 min after stimulation onset), but only acoustic CR neuromodulation had sustained long-lasting therapeutic effects after 12 weeks of treatment as assessed with VAS-L, VAS-A scores and a tinnitus questionnaire (TQ) in the stimulation-OFF condition (i.e. with patients being off stimulation for at least 2.5 h). To understand the source of the long-lasting therapeutic effects, we here study whether acoustic CR neuromodulation has different electrophysiological effects on oscillatory brain activity as compared to noisy CR-like stimulation under stimulation-ON conditions and immediately after cessation of stimulation. To this end, we used a single-blind, single application, cross over design in 18 patients with chronic tonal subjective tinnitus and administered three different 16-minute stimulation protocols: acoustic CR neuromodulation, noisy CR-like stimulation and low frequency range (LFR) stimulation, a CR type stimulation with deliberately detuned pitch and repetition rate of stimulation tones, as control stimulation. We measured VAS-L and VAS-A scores together with spontaneous EEG activity pre-, during- and post-stimulation. Under stimulation-ON conditions acoustic CR neuromodulation and noisy CR-like stimulation had similar effects: a reduction of VAS-L and VAS-A scores together with a decrease of auditory delta power and an increase of auditory alpha and gamma power, without significant differences. In contrast, LFR stimulation had significantly weaker EEG effects and no significant clinical effects under stimulation-ON conditions. The distinguishing feature between acoustic CR neuromodulation and noisy CR-like stimulation were the electrophysiological after-effects. Acoustic CR neuromodulation caused the longest significant reduction of delta and gamma and increase of alpha power in the auditory cortex region. Noisy CR-like stimulation had weaker and LFR stimulation hardly any electrophysiological after-effects. This qualitative difference further supports the assertion that long-term effects of acoustic CR neuromodulation on tinnitus are mediated by a specific disruption of synchronous neural activity. Furthermore, our results indicate that acute electrophysiological after-effects might serve as a marker to further improve desynchronizing sound stimulation.

Project description:Current theories of tinnitus assume that the phantom sound is generated either through increased spontaneous activity of neurons in the auditory brain, or through pathological temporal firing patterns of the spontaneous neuronal discharge, or a combination of both factors. With this in mind, Tass and colleagues recently tested a number of temporally patterned acoustic stimulation strategies in a proof of concept study. Potential therapeutic sound regimes were derived according to a paradigm assumed to disrupt hypersynchronous neuronal activity, and promote plasticity mechanisms that stabilize a state of asynchronous spontaneous activity. This would correspond to a permanent reduction of tinnitus. The proof of concept study, conducted in Germany, confirmed the safety of the acoustic stimuli for use in tinnitus, and exploratory results indicated modulation of tinnitus-related pathological synchronous activity with potential therapeutic benefit. The most effective stimulation paradigm is now in clinical use as a sound therapy device, the acoustic coordinated reset (CR®) neuromodulation (Adaptive Neuromodulation GmbH (ANM), Köln, Germany).To measure the efficacy of CR® neuromodulation, we devised a powered, two-center, randomized controlled trial (RCT) compliant with the reporting standards defined in the Consolidated Standards of Reporting Trials (CONSORT) Statement. The RCT design also addresses the recent call for international standards within the tinnitus community for high-quality clinical trials. The design uses a between-subjects comparison with minimized allocation of participants to treatment and placebo groups. A minimization approach was selected to ensure that the two groups are balanced with respect to age, gender, hearing, and baseline tinnitus severity. The protocol ensures double blinding, with crossover of the placebo group to receive the proprietary intervention after 12 weeks. The primary endpoints are the pre- and post-treatment measures that provide the primary measures of efficacy, namely a validated and sensitive questionnaire measure of the functional impact of tinnitus. The trial is also designed to capture secondary changes in tinnitus handicap, quality (pitch, loudness, bandwidth), and changes in tinnitus-related pathological synchronous brain activity using electroencephalography (EEG).This RCT was designed to provide a confident high-level estimate of the efficacy of sound therapy using CR® neuromodulation compared to a well-matched placebo intervention, and uniquely in terms of sound therapy, examine the physiological effects of the intervention against its putative mechanism of action.ClinicalTrials.gov, NCT01541969.

Project description:Chronic subjective tinnitus is characterized by abnormal neuronal synchronization in the central auditory system. As shown in a controlled clinical trial, acoustic coordinated reset (CR) neuromodulation causes a significant relief of tinnitus symptoms along with a significant decrease of pathological oscillatory activity in a network comprising auditory and non-auditory brain areas, which is often accompanied with a significant tinnitus pitch change. Here we studied if the tinnitus pitch change correlates with a reduction of tinnitus loudness and/or annoyance as assessed by visual analog scale (VAS) scores. Furthermore, we studied if the changes of the pattern of brain synchrony in tinnitus patients induced by 12 weeks of CR therapy depend on whether or not the patients undergo a pronounced tinnitus pitch change. Therefore, we applied standardized low-resolution brain electromagnetic tomography (sLORETA) to EEG recordings from two groups of patients with a sustained CR-induced relief of tinnitus symptoms with and without tinnitus pitch change. We found that absolute changes of VAS loudness and VAS annoyance scores significantly correlate with the modulus, i.e., the absolute value, of the tinnitus pitch change. Moreover, as opposed to patients with small or no pitch change we found a significantly stronger decrease in gamma power in patients with pronounced tinnitus pitch change in right parietal cortex (Brodmann area, BA 40), right frontal cortex (BA 9, 46), left temporal cortex (BA 22, 42), and left frontal cortex (BA 4, 6), combined with a significantly stronger increase of alpha (10-12 Hz) activity in the right and left anterior cingulate cortex (ACC; BA 32, 24). In addition, we revealed a significantly lower functional connectivity in the gamma band between the right dorsolateral prefrontal cortex (BA 46) and the right ACC (BA 32) after 12 weeks of CR therapy in patients with pronounced pitch change. Our results indicate a substantial, CR-induced reduction of tinnitus-related auditory binding in a pitch processing network.

Project description:BackgroundAbnormal synchronization of neuronal activity in dopaminergic circuits is related to motor impairment in Parkinson's disease (PD). Vibrotactile coordinated reset (vCR) fingertip stimulation aims to counteract excessive synchronization and induce sustained unlearning of pathologic synaptic connectivity and neuronal synchrony. Here, we report two clinical feasibility studies that examine the effect of regular and noisy vCR stimulation on PD motor symptoms. Additionally, in one clinical study (study 1), we examine cortical beta band power changes in the sensorimotor cortex. Lastly, we compare these clinical results in relation to our computational findings.MethodsStudy 1 examines six PD patients receiving noisy vCR stimulation and their cortical beta power changes after 3 months of daily therapy. Motor evaluations and at-rest electroencephalographic (EEG) recordings were assessed off medication pre- and post-noisy vCR. Study 2 follows three patients for 6+ months, two of whom received daily regular vCR and one patient from study 1 who received daily noisy vCR. Motor evaluations were taken at baseline, and follow-up visits were done approximately every 3 months. Computationally, in a network of leaky integrate-and-fire (LIF) neurons with spike timing-dependent plasticity, we study the differences between regular and noisy vCR by using a stimulus model that reproduces experimentally observed central neuronal phase locking.ResultsClinically, in both studies, we observed significantly improved motor ability. EEG recordings observed from study 1 indicated a significant decrease in off-medication cortical sensorimotor high beta power (21-30 Hz) at rest after 3 months of daily noisy vCR therapy. Computationally, vCR and noisy vCR cause comparable parameter-robust long-lasting synaptic decoupling and neuronal desynchronization.ConclusionIn these feasibility studies of eight PD patients, regular vCR and noisy vCR were well tolerated, produced no side effects, and delivered sustained cumulative improvement of motor performance, which is congruent with our computational findings. In study 1, reduction of high beta band power over the sensorimotor cortex may suggest noisy vCR is effectively modulating the beta band at the cortical level, which may play a role in improved motor ability. These encouraging therapeutic results enable us to properly plan a proof-of-concept study.

Project description:Objectives: To systematically review studies on the effect of treatment of subjective tinnitus in children. Data Sources: We searched for studies in MEDLINE and EMBASE databases, after which additional studies were hand searched using Scopus databases. The methods are described in the study protocol, which has been registered in the PROSPERO register. PRISMA guidelines were followed in the reporting of this study. Eligibility Criteria: We considered for inclusion randomized controlled trials (RCTs), observational studies, case reports, and case series, with tinnitus as primary outcome in children (0-18 years old) with acute or chronic subjective tinnitus. We excluded studies in which both children and adults participated but outcomes were not specifically reported for children, as well as animal studies, studies with a non-original study design and studies about children with pulsatile or objective tinnitus. Data Selection: Two reviewers independently assessed studies for eligibility and quality, collected and extracted data. Statistical analyses were performed in case of homogeneous outcomes. Results: The search yielded a total of 4,447 studies. Of these, 147 eligible studies were selected. One case report and five observational studies met the eligibility criteria. Three studies applied counseling and (simplified-)TRT and reported improvement in tinnitus outcome in 68 out of 82 children after 3-6 months of treatment. Two studies used pharmacological treatments and reported improvement in 74 out of 86 patients after 10 days to 3 months of treatment. One study reported the outcome of biofeedback therapy, describing an improvement in tinnitus loudness and annoyance after 2 months of treatment. Conclusion: Due to the high risk of bias of the included studies, we cannot determine the effectiveness of the treatment of subjective tinnitus in children. Also, owing to brief follow-up periods, it is not possible to draw conclusions regarding long-term effects. Randomized controlled trials with longer follow-up periods are necessary to provide substantial evidence of the effects of therapies for children affected by tinnitus. https://www.crd.york.ac.uk/prospero/ Systematic Review Registration:https://www.crd.york.ac.uk/prospero/, identifier [CRD42020178134].

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Acoustic Coordinated Reset Neuromodulation: A Systematic Review of a Novel Therapy for Tinnitus.

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Acoustic Coordinated Reset Neuromodulation: A Systematic Review of a Novel Therapy for Tinnitus.

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