Abstract

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.

Highlights

  • Network dynamics—occurring at multiple levels and spatio-temporal scales—play a crucial role in several physiologic and pathophysiologic domains (Bashan et al, 2012; Ivanov et al, 2016)

  • The y-axis in each subfigure of Figure 4 represents the residual of visual analogue scale (VAS)-L during coordinated reset (CR), and the x-axis represents the residual of the gap index after removing the linear effects of the residual variance of 5-PTA

  • Several lines of evidence suggest that stimulus amplitudes and the intimately associated parameter of spatial stimulation profiles can have major impacts on the degree of desynchronization achievable

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Summary

Introduction

Network dynamics—occurring at multiple levels and spatio-temporal scales—play a crucial role in several physiologic and pathophysiologic domains (Bashan et al, 2012; Ivanov et al, 2016). Chronic tinnitus is such a network phenomenon, across both auditory and non-auditory brain areas (Schlee et al, 2008). An EEG study revealed that acoustic coordinated reset (aCR) induced spread of desynchronization of tinnitus-related abnormal neuronal synchrony from auditory to non-auditory brain areas (Silchenko et al, 2013; Adamchic et al, 2014b). We here study a first and fundamental step in manipulating the complex network of auditory and non-auditory brain areas by analyzing the impact of the spacing of aCR stimulation tones on acute therapeutic effects of aCR stimulation

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