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 electr...

How stimulation frequency and intensity impact on the long-lasting effects of coordinated reset stimulation

“…We here demonstrated that over a wide range of stimulation parameters favorable acute effects do not automatically lead to favorable long-lasting, sustained after-effects. This is in agreement with a computational study in the same model, but performed in only a restricted parameter range [78], as well as with an EEG experiment performed in tinnitus patients [114]. To characterize stimulation induced effects, we here used the average synaptic weight [Eq (10)] and the average amount of neuronal synchrony [Eq (11)].…”

“…On the one hand this finding might inspire future computational and pre-clinical studies aiming at specifically designing stimulation protocols for long-lasting (as opposed to acute) desynchronization. On the other hand, this finding is significant for the development of clinical calibration procedures for CR stimulation, see [114].…”

The state of the art of sound therapy for subjective tinnitus in adults

“…Epidural recordings from the secondary auditory cortex in tinnitus patients showed that abnormal θ-band activity was highly correlated with tinnitus loudness. 97 Adamchic proposed that the temporal pattern of neurons plays a key role in shaping synaptic connections, 98 and this suggests that MEG might objectively reflect tinnitus by recording abnormal cortex activities.…”

“…Patients using CR showed a stable effect in on- and off-stimulation, while patients receiving noisy CR-like stimulation (the noisy CR-like stimulation shares the basic rhythmic CR pattern with CR, but the stimulation tones are randomly selected from a larger frequency range that are not related to the tinnitus pitch) only showed efficacy in on-stimulation. 26 , 68 Tass argued that ideally, the CR stimulation should be limited to the area of enhanced synchronized activity. The distance of the stimulation sites (frequencies) needs to be controlled, and the distance should be sufficient to achieve optimal desynchronizing CR effects.…”

Global resting‐state functional connectivity of neural oscillations in tinnitus with and without hearing loss

“…As such, much work has been dedicated to identifying neural correlates of conscious tinnitus perception through comparison of spontaneous resting‐state oscillations in brain activity in individuals with and without tinnitus using silently acquired recording modalities that are noninvasive such as magnetoencephalography (MEG) or electroencephalography. In response to theories of aberrant oscillatory behavior in tinnitus and their supporting evidence, many proposed treatments are aimed at directly or indirectly altering oscillatory activity in the hopes of delivering symptom relief (Adamchic et al, 2017; Adamchic, Hauptmann, & Tass, 2012; De Ridder, Joos, & Vanneste, 2016; De Ridder, Song, & Vanneste, 2013; De Ridder & Vanneste, 2012; Hartmann, Lorenz, Müller, Langguth, & Weisz, 2014; Larson & Cheung, 2012, 2013; Silchenko, Adamchic, Hauptmann, & Tass, 2013; Weisz, Lüchinger, Thut, & Müller, 2014). Previous MEG studies investigating the functional pathology of tinnitus have resulted in mixed findings, with some studies suggesting functional abnormalities in and around auditory cortex (Hartmann et al, 2014) or in connectivity between auditory cortex and other brain regions (Zobay, Palmer, Hall, Sereda, & Adjamian, 2015).…”