Abstract
The exact neurophysiological basis of chronic tinnitus, which affects 10-15% of the population, remains unknown and is controversial at many levels. It is an open question whether phantom sound perception results from increased central neural gain or not, a crucial question for any future therapeutic intervention strategies for tinnitus.We performed a comprehensive study of mild hearing-impaired participants with and without tinnitus, excluding participants with co-occurrences of hyperacusis. A right-hemisphere correlation between tinnitus loudness and auditory perceptual difficulty was observed in the tinnitus group, independent of differences in hearing thresholds. This correlation was linked to reduced and delayed sound-induced suprathreshold auditory brain responses (ABR wave V) in the tinnitus group, suggesting subsided rather than exaggerated central neural responsiveness. When anatomically predefined auditory regions of interest were analysed for altered sound-evoked BOLD fMRI activity, it became evident that subcortical and cortical auditory regions and regions involved in sound detection (posterior insula, hippocampus), responded with reduced BOLD activity in the tinnitus group, emphasizing reduced, rather than increased, central neural gain. Regarding previous findings of evoked BOLD activity being linked to positive connectivities at rest, we additionally analysed r-fcMRI responses in anatomically predefined auditory regions and regions associated with sound detection. A profound reduction in positive interhemispheric connections of homologous auditory brain regions and a decline in the positive connectivities between lower auditory brainstem regions and regions involved in sound detection (hippocampus, posterior insula) were observed in the tinnitus group. The finding went hand-in-hand with the emotional (amygdala, anterior insula) and temporofrontal/stress-regulating regions (prefrontal cortex, inferior frontal gyrus) that were no longer positively connected with auditory cortex regions in the tinnitus group but were instead positively connected to lower-level auditory brainstem regions. Delayed sound processing, reduced sound-evoked BOLD fMRI activity and altered r-fcMRI in the auditory midbrain correlated in the tinnitus group and showed right hemisphere dominance as did tinnitus loudness and perceptual difficulty. The findings suggest that reduced central neural gain in the auditory stream may lead to phantom perception through a failure to energize attentional/stress-regulating networks for contextualization of auditory-specific information. Reduced auditory-specific information flow in tinnitus has until now escaped detection in humans, as low-level auditory brain regions were previously omitted from neuroimaging studies.Trial registration: German Clinical Trials Register DRKS0006332.
Highlights
IntroductionA phantom auditory sensation, affects approximately 1015 % of the general population.It is generally accepted that tinnitus is linked to increased spontaneous firing rates following deafferentation of auditory nerves (Brozoski et al, 2002; Chen and Jastreboff, 1995; Eggermont, 2012; Eggermont, 2015; Eggermont and Roberts, 2015; Kalappa et al, 2014; Kaltenbach et al, 2004; Kwon et al, 1999; Norena and Eggermont, 2003; Schaette and Kempter, 2012a; Shore et al, 2016; Weisz et al, 2005; Weisz et al, 2007; Yang and Bao, 2013)
A reduced and delayed sound-induced auditory brainstem response that co-occurred with both reduced sound-evoked subcortical and cortical BOLD Functional magnetic resonance imaging (fMRI) activity and with reduced interhemispheric resting-state functional connectivity MRI (r-fcMRI) connectivities in auditory-specific regions was shown in this study in the tinnitus group
The findings are discussed in the context of a failure to increase central neural gain in tinnitus and a loss of context-specific recruitment of attentional cues due to an HPA axis imbalance
Summary
A phantom auditory sensation, affects approximately 1015 % of the general population.It is generally accepted that tinnitus is linked to increased spontaneous firing rates following deafferentation of auditory nerves (Brozoski et al, 2002; Chen and Jastreboff, 1995; Eggermont, 2012; Eggermont, 2015; Eggermont and Roberts, 2015; Kalappa et al, 2014; Kaltenbach et al, 2004; Kwon et al, 1999; Norena and Eggermont, 2003; Schaette and Kempter, 2012a; Shore et al, 2016; Weisz et al, 2005; Weisz et al, 2007; Yang and Bao, 2013). Almost all of the literature currently assumes that the generation of the elevated spontaneous activity is correlated with the percept of tinnitus through increased central neural gain in lower or higher brain levels (Marks et al, 2018; Noreña, 2015; Schaette and Kempter, 2012a; Schaette and McAlpine, 2011a; Sedley et al, 2016; Yang and Bao, 2013; Yang et al, 2011) Within this view deafferented regions may generate increases in the discharge rate in the brainstem to compensate for deprived auditory input (Noreña, 2015; Schaette and Kempter, 2012a; Schaette and McAlpine, 2011a). This is suggested to lead to elevated cortical activity essential for perception of tinnitus following disinhibition along the auditory path and auditory cortex (Roberts et al, 2010) accompanied by increased correlations with the SFR (Eggermont and Roberts, 2012)
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