Functional biomarkers that distinguish between tinnitus with and without hyperacusis

Abstract

To the Editor:We recently observed that tinnitus is associated with reduced auditory input that fails to increase neural gain due to diminished stimulus-evoked responses. [1][2][3] This was in contrast to views that suggested a homeostatic increase in neural gain to generate central hyper-excitability leading to tinnitus. 4 A curative therapy for tinnitus currently does not exist. Its progress is mostly impeded by the existing controversial views about the neural correlate of tinnitus that, depending on predictions, either would require the suppression or the enhancement of brain activity. We hypothesized that different neural correlates of tinnitus, whether with or without the co-occurrence of hyperacusis, contributed to this dilemma. To test this hypothesis, we recruited 43 controls and 50 audiologically examined tinnitus patients with and without a co-occurrence of hyperacusis (Tables S1 and S2) and performed brainstem audiometry (ABR) and functional imaging of brain activity (fMRI).Among the group of 50 tinnitus patients, 20 could be identified with the co-occurrence of hyperacusis (T+H group) from the HKI hyperacusis questionnaire (Figure 1A). 5 The overall score of the Goebel and Hiller Score (G-H-S) tinnitus questionnaire 6 was significantly higher for the T+H group than the tinnitus-only patients (T group) (Figure 1B, p < .001***) for nearly all subscores (Figure S1, p < .002***). In the T+H group (Figure 1D) but not the T group (Figure 1C), auditory perceptional difficulty became worse for patients with self-rated tinnitus loudness ≤15 dB HL (Figure 1E, Figure S2). The T and T+H group differences in annoyance and distress were not linked to differences in hearing sensitivity (Figure S3A-C, p > .5), since pure tone audiometry (PTA) thresholds (Supporting Material 1 ) were not different between groups. In contrast, supra-threshold ABR by brainstemevoked response audiometry (BERA) 1,2 revealed group differences: In T group, significantly reduced ABR wave V amplitude together with significantly prolonged interpeak latency (IPL) I-V (Figure 1F,H,J; Table S3) and reducedThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Too Blind to See the Elephant? Why Neuroscientists Ought to Be Interested in Tinnitus

“…Previous studies analyzing patients with tinnitus and hyperacusis (T+H group) and patients without hyperacusis (T-group) revealed evidence for the existence of tinnitus subcategories (Hofmeier et al 2018 , 2021 ). When tinnitus co-occurred with hyperacusis, stimuli-evoked increases in sound-evoked, supra-threshold ABR amplitudes and fMRI BOLD responses in the medial geniculate body (MGB) as well as in the auditory cortex were found (Hofmeier et al 2021 ; Koops and van Dijk 2021 ; Refat et al 2021 ).…”

“…Previous studies analyzing patients with tinnitus and hyperacusis (T+H group) and patients without hyperacusis (T-group) revealed evidence for the existence of tinnitus subcategories (Hofmeier et al 2018 , 2021 ). When tinnitus co-occurred with hyperacusis, stimuli-evoked increases in sound-evoked, supra-threshold ABR amplitudes and fMRI BOLD responses in the medial geniculate body (MGB) as well as in the auditory cortex were found (Hofmeier et al 2021 ; Koops and van Dijk 2021 ; Refat et al 2021 ). While a higher sound-evoked fMRI BOLD activity in cortical and subcortical auditory structures was observed in the tinnitus group with hyperacusis compared to the tinnitus group without hyperacusis, an enhanced response to sound was not found in the tinnitus frequency regions (Koops and van Dijk 2021 ).…”

“…This auditory fiber type has been suggested to drive shifts in inhibitory responses through enhanced central neural gain that are possibly involved in tinnitus (Schaette and McAlpine 2011 ; Shore et al 2016 ). Alternatively, a critical diminution of specifically fast (high-SR) auditory fiber processing has been suggested to be causally linked to tinnitus through shifts in tonic inhibitory responses that lead to a loss of central neural gain (Hofmeier et al 2018 , 2021 ; Knipper et al 2020 ; Möhrle et al 2019 ; Refat et al 2021 ; Rüttiger et al 2013 ; Singer et al 2013 ).…”

“…As such, the community might reconsider the lost function of high-SR, low threshold neurons in defined tinnitus frequency channels as a bottom-up mechanism and as a rationale to explain numerous observations: Reduced auditory brainstem and cortical responses in tinnitus (Bramhall et al 2019 ; Hofmeier et al 2018 ; Koops et al 2020 ), reduced functional connectivity in the auditory pathway (Boyen et al 2014 ; Lanting et al 2014 ), and increased latencies in tinnitus (Hofmeier et al 2018 , 2021 ; Majhi et al 2019 ; Milloy et al 2017 ; Möhrle et al 2019 ) in connection with decreased myelination of the auditory pathway in tinnitus patients (Koops et al 2021 ). The latter was observed by fixel 2 -based analysis in which a tinnitus-related atrophy of the left acoustic radiation near the medial geniculate body was the first evidence of a decrease in myelination of the auditory pathway (Koops et al 2021 ).…”

“…While a higher sound-evoked fMRI BOLD activity in cortical and subcortical auditory structures was observed in the tinnitus group with hyperacusis compared to the tinnitus group without hyperacusis, an enhanced response to sound was not found in the tinnitus frequency regions (Koops and van Dijk 2021 ). On the other hand, in tinnitus patients without hyperacusis the auditory responsiveness, including spontaneous and evoked fMRI BOLD responses was reduced (Hofmeier et al 2021 ; Refat et al 2021 ). Not only the annoyance, tinnitus loudness and bilateral tinnitus are higher in the T+H group (Hofmeier et al 2021 ; Ralli et al 2017 ; Refat et al 2021 ; Schecklmann et al 2014 ), but the co-occurrence of tinnitus with hyperacusis also leads to an increase of tinnitus duration over time (Refat et al 2021 ; Vielsmeier et al 2020 ).…”