Systematic review and meta-analysis of late auditory evoked potentials as a candidate biomarker in the assessment of tinnitus

Abstract

Subjective tinnitus, the perception of sound in the absence of any sound source, is routinely assessed using questionnaires. The subjective nature of these tools hampers objective evaluation of tinnitus presence, severity and treatment effects. Late auditory evoked potentials (LAEPs) might be considered as a potential biomarker for assessing tinnitus complaints. Using a multivariate meta-analytic model including data from twenty-one studies, we determined the LAEP components differing systematically between tinnitus patients and controls. Results from this model indicate that amplitude of the P300 component is lower in tinnitus patients (standardized mean difference (SMD) = -0.83, p < 0.01), while latency of this component is abnormally prolonged in this population (SMD = 0.97, p < 0.01). No other investigated LAEP components were found to differ between tinnitus and non-tinnitus subjects. Additional sensitivity analyses regarding differences in experimental conditions confirmed the robustness of these results. Differences in age and hearing levels between the two experimental groups might have a considerable impact on LAEP outcomes and should be carefully considered in future studies. Although we established consistent differences in the P300 component between tinnitus patients and controls, we could not identify any evidence that this component might covary with tinnitus severity. We conclude that out of several commonly assessed LAEP components, only the P300 can be considered as a potential biomarker for subjective tinnitus, although more research is needed to determine its relationship with subjective tinnitus measures. Future trials investigating experimental tinnitus therapies should consider including P300 measurements in the evaluation of treatment effect.

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

“…Furthermore, AEP components needed to be reported in a minimum of three papers to be included in the meta-analysis. This is in analogy to Cardon et al (33). In a multivariate meta-analysis, covariances between the sampling errors of various outcome measures are a necessary addition to the model.…”

“…In the review by Cardon et al (33), the parietocentral (34) P300 is put forward as a potential biomarker for tinnitus at cortical level. The current review proves that by acquiring ABR waves I, III, and V, changes earlier on in the auditory pathway, more specifically at brainstem level, can be revealed in some tinnitus patients.…”

“…We were not able to draw any conclusions on possible differences in MLR and FFR potentials, mainly because insufficient studies investigating these components could be included in our systematic review. Since our review was able to highlight AEP changes at brainstem level and the review by Cardon et al (33) did so for the cortical level, there still remains a knowledge gap about whether changes occur at subcortical level. Since MLRs are considered to represent subcortical activation (22) and FFRs arise from multiple cortical and subcortical sources (25,86), these potentials might help to fill in this knowledge gap.…”

“…However, the correlations between several outcome measures within one paper, which is required information to compute these covariances, are often not reported. To account for this lack of information, a variance-covariance matrix was constructed based on correlations between different AEP components in a dataset used in our previously published study in which ABRs in young adults with and without tinnitus were acquired (33,43). In order to assess statistical heterogeneity in this multivariate model, forest plots were inspected and I 2 was computed according to the approach described by Jackson et al (44).…”

“…FFR recordings are increasingly considered a valuable tool to index the current functional state of the auditory system (32). The recently published systematic review and meta-analysis by Cardon et al (33) provides an overview of the literature regarding long-latency AEPs in subjective tinnitus patients. A decreased amplitude and prolonged latency of P300 was observed, resulting in the consideration of this potential as a prospective biomarker for subjective tinnitus.…”