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Acute effects and after-effects of acoustic coordinated reset neuromodulation in patients with chronic subjective tinnitus.

ABSTRACT: 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.

SUBMITTER: Adamchic I

PROVIDER: S-EPMC5476468 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Acute effects and after-effects of acoustic coordinated reset neuromodulation in patients with chronic subjective tinnitus.

Adamchic Ilya I Toth Timea T Hauptmann Christian C Walger Martin M Langguth Berthold B Klingmann Ingrid I Tass Peter Alexander PA

NeuroImage. Clinical 20170528

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 ...[more]

PMID: 28652968

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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.

Project description:ObjectiveThis study aimed to understand the demographics, clinical characteristics, and psychoacoustic status of subjective tinnitus patients to explore the factors associated with acute and chronic tinnitus in the general hospitals of Shanghai.MethodsA cross-sectional study was conducted to investigate the clinical characteristics and psychoacoustic status of subjective tinnitus patients with history greater than 1 month. Data were collected during January 2021 and January 2022 from eight general hospitals in five districts of Shanghai, China. All patients accepted questionnaires and acoustic examination, then SPSS 22.0 and GraphPad Prism 8.0.2 were applied for data analysis.ResultsAmong the 359 tinnitus patients, 126 cases were diagnosed with acute tinnitus, 58 cases were subacute tinnitus, and 175 cases were chronic tinnitus. Patients with acute and chronic tinnitus differed in terms of side of tinnitus, hearing loss, frequency of tinnitus, severity of tinnitus, anxiety, depression, and sleep status. Different characteristics were included in the multivariate ordinal logistic regression analysis. Persistent tinnitus (OR = 2.00, p = .008), high frequency hearing loss (OR = 4.77, p < .001), depression (OR = 1.23, p < .001) were found to be positively associated with the course of tinnitus. Unilateral tinnitus (OR = 0.48, p = .003), mild (OR = 0.29, p = .001) and moderate (OR = 0.46, p = .038) hearing loss, VAS scores (OR = 0.82, p = .032), anxiety (OR = 0.81, p < .001), THI scores (OR = 0.98, p = .002), and sleep disorders (OR = 0.94, p = .025) were found to be negatively associated with the course of tinnitus.ConclusionPatients with acute tinnitus were at greater risk for anxiety, sleep disturbances, and exacerbation of tinnitus perception, and those with chronic tinnitus were at greater risk for depression.Lay summaryOur study demonstrated that patients with acute tinnitus were at greater risk for anxiety, sleep disturbances, and exacerbation of tinnitus perception, and those with chronic tinnitus were at greater risk for depression.

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Acute effects and after-effects of acoustic coordinated reset neuromodulation in patients with chronic subjective tinnitus.

Publications

Acute effects and after-effects of acoustic coordinated reset neuromodulation in patients with chronic subjective tinnitus.

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