Reduced sound-evoked and resting-state BOLD fMRI connectivity in tinnitus

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.

Top-down and Bottom-up Regulated Auditory Phantom Perception

“…As previously mentioned, the global TQ score can be computed to measure the general level of psychological and psychosomatic distress. In several studies, this measure has been shown to be a reliable and valid instrument in different countries (Hiller and Goebel, 1992;McCombe et al, 2001). A three-point scale is given for all items, ranging from "true" (2 points) to "partly true" (1 point) and "not true" (0 points).…”

“…": 0 ϭ no tinnitus and 10 ϭ as loud as imaginable) was assessed to measure the subjective loudness. Also the Tinnitus Questionnaire (TQ) was assessed (Hiller and Goebel, 1992;Hiller et al, 1994). This scale is comprised of 52 items and is a well established measure for the assessment of a broad spectrum of tinnitus-related psychological complaints.…”

“…A three-point scale is given for all items, ranging from "true" (2 points) to "partly true" (1 point) and "not true" (0 points). The total score (from 0 to 84) was computed according to standard criteria published in previous work (Hiller and Goebel, 1992;Hiller et al, 1994). See Table 1 for an overview of the tinnitus characteristics.…”

Exposing Pathological Sensory Predictions in Tinnitus Using Auditory Intensity Deviant Evoked Responses

“…The search for effective treatments is greatly hampered by limited understanding of its mechanisms. Its major risk factor is hearing loss, which leads to increased central gain (i.e., increased firing rate and/or synchrony in for a given input) (Gold and Bajo, 2014), although a review of current evidence suggests that these changes may be contributory to tinnitus, but not sufficient to cause it (Sedley, 2019), while other evidence suggests that gain increases may be irrelevant, or even protective, with respect to tinnitus (Rüttiger et al, 2013;Singer et al, 2013;Hofmeier et al, 2018), and the presence or absence of hyperacusis can confound results (Gu et al, 2010;Möhrle et al, 2019). We have recently proposed a theory of tinnitus causation, which shares some features with an earlier theory (De Ridder et al, 2014a), in which a crucial process is the learning of a default "tinnitus prediction" by higher perceptual centers (Sedley et al, 2016).…”

Neuroanatomical Alterations in Patients With Tinnitus Before and After Sound Therapy: A Combined VBM and SCN Study

“…According to our previous research, tinnitus has been proven to be a symptom characterized by abnormal resting-state functional magnetic resonance imaging (rs-fMRI) (11)(12)(13)(14). The brain regions involved include sound detection regions, such as the insula and hippocampus (15,16), and auditory and nonauditory brain regions (17), such as the parahippocampal gyrus (18), posterior cingulate cortex (19), and anterior cingulate cortex (20). In recent years, the study of brain microstructure has also received increasing attention.…”