Acoustic Coordinated Reset Neuromodulation in a Real Life Patient Population with Chronic Tonal Tinnitus.
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ABSTRACT:
SUBMITTER: Hauptmann C
PROVIDER: S-EPMC4629059 | biostudies-literature | 2015
REPOSITORIES: biostudies-literature
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Acoustic Coordinated Reset Neuromodulation in a Real Life Patient Population with Chronic Tonal Tinnitus.
Hauptmann Christian C Ströbel Armin A Williams Mark M Patel Nitesh N Wurzer Hannes H von Stackelberg Tatjana T Brinkmann Uwe U Langguth Berthold B Tass Peter A PA
BioMed research international 20151019
<h4>Purpose</h4>Primary tinnitus has a severe negative influence on the quality of life of a significant portion of the general population. Acoustic coordinated reset neuromodulation is designed to induce a long-lasting reduction of tinnitus symptoms. To test acoustic coordinated reset neuromodulation as a treatment for chronic, tonal tinnitus under real life conditions, an outpatient study "RESET Real Life" was commissioned by ANM GmbH. Herein we present the results of this study.<h4>Methods</h ...[more]
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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.
| S-EPMC5476468 | biostudies-literature
Project description: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.
| S-EPMC5304262 | biostudies-literature
Project description:Acoustic Coordinated Reset (CR) neuromodulation is a patterned stimulation with tones adjusted to the patient's dominant tinnitus frequency, which aims at desynchronizing pathological neuronal synchronization. In a recent proof-of-concept study, CR therapy, delivered 4-6 h/day more than 12 weeks, induced a significant clinical improvement along with a significant long-lasting decrease of pathological oscillatory power in the low frequency as well as ? band and an increase of the ? power in a network of tinnitus-related brain areas. As yet, it remains unclear whether CR shifts the brain activity toward physiological levels or whether it induces clinically beneficial, but nonetheless abnormal electroencephalographic (EEG) patterns, for example excessively decreased ? and/or ?. Here, we compared the patients' spontaneous EEG data at baseline as well as after 12 weeks of CR therapy with the spontaneous EEG of healthy controls by means of Brain Electrical Source Analysis source montage and standardized low-resolution brain electromagnetic tomography techniques. The relationship between changes in EEG power and clinical scores was investigated using a partial least squares approach. In this way, we show that acoustic CR neuromodulation leads to a normalization of the oscillatory power in the tinnitus-related network of brain areas, most prominently in temporal regions. A positive association was found between the changes in tinnitus severity and the normalization of ? and ? power in the temporal, parietal, and cingulate cortical regions. Our findings demonstrate a widespread CR-induced normalization of EEG power, significantly associated with a reduction of tinnitus severity.
| S-EPMC4216412 | biostudies-literature
Project description:BackgroundCurrent 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).Methods/designTo 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).DiscussionThis 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.Trial registrationClinicalTrials.gov, NCT01541969.
| S-EPMC3710266 | biostudies-literature
Project description:Acoustic coordinated reset (aCR) therapy for tinnitus aims to desynchronize neuronal populations in the auditory cortex that exhibit pathologically increased coincident firing. The original therapeutic paradigm involves fixed spacing of four low-intensity tones centered around the frequency of a tone matching the tinnitus pitch, f T , but it is unknown whether these tones are optimally spaced for induction of desynchronization. Computational and animal studies suggest that stimulus amplitude, and relatedly, spatial stimulation profiles, of coordinated reset pulses can have a major impact on the degree of desynchronization achievable. In this study, we transform the tone spacing of aCR into a scale that takes into account the frequency selectivity of the auditory system at each therapeutic tone's center frequency via a measure called the gap index. Higher gap indices are indicative of more loosely spaced aCR tones. The gap index was found to be a significant predictor of symptomatic improvement, with larger gap indices, i.e., more loosely spaced aCR tones, resulting in reduction of tinnitus loudness and annoyance scores in the acute stimulation setting. A notable limitation of this study is the intimate relationship of hearing impairment with the gap index. Particularly, the shape of the audiogram in the vicinity of the tinnitus frequency can have a major impact on tone spacing. However, based on our findings we suggest hypotheses-based experimental protocols that may help to disentangle the impact of hearing loss and tone spacing on clinical outcome, to assess the electrophysiologic correlates of clinical improvement, and to elucidate the effects following chronic rather than acute stimulation.
| S-EPMC10012992 | biostudies-literature
Project description:BackgroundThe discovery of abnormal synchronization of neuronal activity in the basal ganglia in Parkinson's disease (PD) has prompted the development of novel neuromodulation paradigms. Coordinated reset neuromodulation intends to specifically counteract excessive synchronization and to induce cumulative unlearning of pathological synaptic connectivity and neuronal synchrony.MethodsIn this prospective case series, six PD patients were evaluated before and after coordinated reset neuromodulation according to a standardized protocol that included both electrophysiological recordings and clinical assessments.ResultsCoordinated reset neuromodulation of the subthalamic nucleus (STN) applied to six PD patients in an externalized setting during three stimulation days induced a significant and cumulative reduction of beta band activity that correlated with a significant improvement of motor function.ConclusionsThese results highlight the potential effects of coordinated reset neuromodulation of the STN in PD patients and encourage further development of this approach as an alternative to conventional high-frequency deep brain stimulation in PD.
| S-EPMC4282372 | biostudies-literature
Project description:BACKGROUND:The phenomenon of short-term tinnitus suppression by different forms of acoustic stimulation is referred to as residual inhibition (RI). RI can be triggered in the majority of tinnitus cases and was found to be depending on the used intensity, length or types of sounds. Past research already stressed the impact of noise stimulation as well as the superiority of amplitude modulated (AM) pure tones at the individual tinnitus frequency for RI in tonal tinnitus. Recently a novel approach for the determination of noise-like tinnitus characteristics was proposed. OBJECTIVES:The aim of the present study was to investigate whether in participants with noise-like tinnitus RI can be increased by AM noise stimuli according to the individual tinnitus frequency range. METHODS:For this purpose the individual tinnitus characteristics (noise-like and tonal tinnitus) of 29 people affected by tinnitus (mean age = 55.59, 7 females, mean tinnitus duration = 159.97 months) were assessed via customizable noise-band matching. The objective was to generate bandpass filtered stimuli according to the individual tinnitus sound (individualized bandpass filtered [IBP] sounds). Subsequently, various stimuli differing in bandpass filtering and AM were tested with respect to their potential to induce RI. Participants were acoustically stimulated with 7 different types of stimuli for 3 min each and had to rate the loudness of their tinnitus after each stimuli. RESULTS:Results indicate a general efficacy of noise stimuli for the temporary suppression of tinnitus, but no significant differences between AM and unmodulated IBP. Significantly better effects were observed for the subgroup with noise-like tinnitus (n = 14), especially directly after stimulation offset. CONCLUSIONS:The study at hand provides further insights in potential mechanisms behind RI for different types of tinnitus. Beyond that, derived principles may qualify for new or extend current tinnitus sound therapies.
| S-EPMC6959056 | biostudies-literature
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.
| S-EPMC3319974 | biostudies-literature
Project description:Subjective tinnitus is a symptom characterized by the perception of sound with no external acoustic source, most often accompanied by co-morbidities. To date, the specific role of white matter abnormalities related to tinnitus reaches no consensus in the literature. The goal of this study was to explore the structural connectivity related to tinnitus percept per se, thus focusing on a specific population presenting chronic non-bothersome tinnitus of similar etiology (noise induced) without co-morbidities. We acquired diffusion-weighted images with high angular resolution in a homogeneous group of mildly impacted tinnitus participants (n = 19) and their matched controls (n = 19). We focused the study on two subsets of fiber bundles of interest: on one hand, we extracted the acoustic radiation and further included any intersecting fiber bundles; on the other hand, we explored the tracts related to the limbic system. We modeled the diffusion signal using constrained spherical deconvolution. We conducted a deep-learning based tractography segmentation and mapped Apparent Fiber Density (AFD) on the bundles of interest. C, as well as Fractional Anisotropy (FA) and FOD peak amplitude for comparison. Between group statistical comparison was performed along the 27 tracts of interest controlling for confounding hearing loss, tinnitus severity, and duration since onset. We tested a potential correlation with hearing loss, tinnitus duration and tinnitus handicap score along these tracts. In the tinnitus group, we observed increased AFD related to chronic tinnitus percept after acoustic trauma in two main white matter regions. First, in the right hemisphere, in the isthmus between inferior temporal and inferior frontal cortices, in the uncinate fasciculus (UF), and in the inferior fronto-occipital bundle (IFO). Second, in the left hemisphere, underneath the superior parietal region in the thalamo parietal tract and parieto-occipital pontine tract. Between-group differences in the acoustic radiations were not significant with AFD but were with FA. Furthermore, significant correlations with hearing loss were found in the left hemisphere in the inferior longitudinal fasciculus and in the fronto-pontine tract. No additional correlation was found with tinnitus duration nor with tinnitus handicap, as reflected by THI scores. The regions that displayed tinnitus related increased AFD also displayed increased FA. The isthmus of the UF and IFO in the right hemisphere appear to be involved with a number of neuropsychiatric and traumatic disorders confirming the involvement of the limbic system even in chronic non-bothersome tinnitus subjects, potentially suggesting a common pathway between these pathologies. White matter changes underneath the superior parietal cortex found here in tinnitus participants supports the implication of an auditory-somatosensory pathway in tinnitus perception.
| S-EPMC8163994 | biostudies-literature
Project description:Discrete phonological phenomena form our conscious experience of language: continuous changes in pitch appear as distinct tones to the speakers of tone languages, whereas the speakers of quantity languages experience duration categorically. The categorical nature of our linguistic experience is directly reflected in the traditionally clear-cut linguistic classification of languages into tonal or non-tonal. However, some evidence suggests that duration and pitch are fundamentally interconnected and co-vary in signaling word meaning in non-tonal languages as well. We show that pitch information affects real-time language processing in a (non-tonal) quantity language. The results suggest that there is no unidirectional causal link from a genetically-based perceptual sensitivity towards pitch information to the appearance of a tone language. They further suggest that the contrastive categories tone and quantity may be based on simultaneously co-varying properties of the speech signal and the processing system, even though the conscious experience of the speakers may highlight only one discrete variable at a time.
| S-EPMC2935883 | biostudies-literature