Brainstem evoked auditory potentials in tinnitus: A best-evidence synthesis and meta-analysis

Abstract

Introduction: Accumulating evidence suggests a role of the brainstem in tinnitus generation and modulation. Several studies in chronic tinnitus patients have reported latency and amplitude changes of the different peaks of the auditory brainstem response, possibly reflecting neural changes or altered activity. The aim of the systematic review was to assess if alterations within the brainstem of chronic tinnitus patients are reflected in short- and middle-latency auditory evoked potentials (AEPs).

Methods: A systematic review was performed and reported according to the PRISMA guidelines. Studies evaluating short- and middle-latency AEPs in tinnitus patients and controls were included. Two independent reviewers conducted the study selection, data extraction, and risk of bias assessment. Meta-analysis was performed using a multivariate meta-analytic model.

Results: Twenty-seven cross-sectional studies were included. Multivariate meta-analysis revealed that in tinnitus patients with normal hearing, significantly longer latencies of auditory brainstem response (ABR) waves I (SMD = 0.66 ms, p < 0.001), III (SMD = 0.43 ms, p < 0.001), and V (SMD = 0.47 ms, p < 0.01) are present. The results regarding possible changes in middle-latency responses (MLRs) and frequency-following responses (FFRs) were inconclusive.

Discussion: The discovered changes in short-latency AEPs reflect alterations at brainstem level in tinnitus patients. More specifically, the prolonged ABR latencies could possibly be explained by high frequency sensorineural hearing loss, or other modulating factors such as cochlear synaptopathy or somatosensory tinnitus generators. The question whether middle-latency AEP changes, representing subcortical level of the auditory pathway, are present in tinnitus still remains unanswered. Future studies should identify and correctly deal with confounding factors, such as age, gender and the presence of somatosensory tinnitus components.

Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021243687, PROSPERO [CRD42021243687].

Keywords: auditory brainstem responses (ABRs); auditory evoked potentials; brainstem; frequency-following responses (FFRs); middle-latency responses (MLRs); systematic review; tinnitus.

Figure 1

Schematic representation of the auditory pathway and corresponding AEP components through stimulation with a click. These components include the auditory short-latency responses or auditory brainstem responses (ABR) (waves I-VI) (blue), the auditory middle latency responses (N0-Pb) (red), and the auditory late-latency responses (N1-P3) (green). Localization of the neuronal generators of the ABR waves are also depicted. Created with BioRender.com, AEPs adapted from Burkard et al. (21), Lammers (29).

Figure 2

PRISMA flowchart of the study selection procedure. From: Page et al. (99).

Figure 3

Standardized mean differences for the different ABR components across studies comparing tinnitus patients with hearing loss to controls. The studies of Attias et al. (97) and Rosenhall et al. (98) could not be included in this analysis, since numerical results of different ABR components were not reported in these papers.

Figure 4

Forest plot of the primary multivariate analysis of ABR components in studies comparing tinnitus patients without hearing loss to controls. Results are grouped according to ABR component. Results from individual papers are presented as Standardized Mean Differences (SMD) ± 95% confidence intervals. Overall results from the primary meta-analytic model are given for each component. SMD with 95% confidence intervals are represented by diamonds, while error bars correspond to credibility/prediction intervals, defined as the intervals where ~95% of the true outcomes are expected to fall.