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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.

SUBMITTER: Cardon E

PROVIDER: S-EPMC7746183 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Cardon Emilie E Joossen Iris I Vermeersch Hanne H Jacquemin Laure L Mertens Griet G Vanderveken Olivier M OM Topsakal Vedat V Van de Heyning Paul P Van Rompaey Vincent V Gilles Annick A

PloS one 20201217 12

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 systematic ...[more]

PMID: 33332414

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Project description: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].

Project description:Transcranial magnetic stimulation (TMS)-evoked potentials (TEPs), recorded using electroencephalography (EEG), reflect a combination of TMS-induced cortical activity and multi-sensory responses to TMS. The auditory evoked potential (AEP) is a high-amplitude sensory potential-evoked by the "click" sound produced by every TMS pulse-that can dominate the TEP and obscure observation of other neural components. The AEP is peripherally evoked and therefore should not be stimulation site specific. We address the problem of disentangling the peripherally evoked AEP of the TEP from components evoked by cortical stimulation and ask whether removal of AEP enables more accurate isolation of TEP. We hypothesized that isolation of the AEP using Independent Components Analysis (ICA) would reveal features that are stimulation site specific and unique individual features. In order to improve the effectiveness of ICA for removal of AEP from the TEP, and thus more clearly separate the transcranial-evoked and non-specific TMS-modulated potentials, we merged sham and active TMS datasets representing multiple stimulation conditions, removed the resulting AEP component, and evaluated performance across different sham protocols and clinical populations using reduction in Global and Local Mean Field Power (GMFP/LMFP) and cosine similarity analysis. We show that removing AEPs significantly reduced GMFP and LMFP in the post-stimulation TEP (14 to 400 ms), driven by time windows consistent with the N100 and P200 temporal characteristics of AEPs. Cosine similarity analysis supports that removing AEPs reduces TEP similarity between subjects and reduces TEP similarity between stimulation conditions. Similarity is reduced most in a mid-latency window consistent with the N100 time-course, but nevertheless remains high in this time window. Residual TEP in this window has a time-course and topography unique from AEPs, which follow-up exploratory analyses suggest could be a modulation in the alpha band that is not stimulation site specific but is unique to individual subject. We show, using two datasets and two implementations of sham, evidence in cortical topography, TEP time-course, GMFP/LMFP and cosine similarity analyses that this procedure is effective and conservative in removing the AEP from TEP, and may thus better isolate TMS-evoked activity. We show TEP remaining in early, mid and late latencies. The early response is site and subject specific. Later response may be consistent with TMS-modulated alpha activity that is not site specific but is unique to the individual. TEP remaining after removal of AEP is unique and can provide insight into TMS-evoked potentials and other modulated oscillatory dynamics.

Project description:Purpose Complaints of auditory perceptual deficits, such as tinnitus and difficulty understanding speech in background noise, among individuals with clinically normal audiograms present a perplexing problem for audiologists. One potential explanation for these "hidden" auditory deficits is loss of the synaptic connections between the inner hair cells and their afferent auditory nerve fiber targets, a condition that has been termed cochlear synaptopathy. In animal models, cochlear synaptopathy can occur due to aging or exposure to noise or ototoxic drugs and is associated with reduced auditory brainstem response (ABR) wave I amplitudes. Decreased ABR wave I amplitudes have been demonstrated among young military Veterans and non-Veterans with a history of firearm use, suggesting that humans may also experience noise-induced synaptopathy. However, the downstream consequences of synaptopathy are unclear. Method To investigate how noise-induced reductions in wave I amplitude impact the central auditory system, the ABR, the middle latency response (MLR), and the late latency response (LLR) were measured in 65 young Veterans and non-Veterans with normal audiograms. Results In response to a click stimulus, the MLR was weaker for Veterans compared to non-Veterans, but the LLR was not reduced. In addition, low ABR wave I amplitudes were associated with a reduced MLR, but with an increased LLR. Notably, Veterans reporting tinnitus showed the largest mean LLRs. Conclusions These findings indicate that decreased peripheral auditory input leads to compensatory gain in the central auditory system, even among individuals with normal audiograms, and may impact auditory perception. This pattern of reduced MLR, but not LLR, was observed among Veterans even after statistical adjustment for sex and distortion product otoacoustic emission differences, suggesting that synaptic loss plays a role in the observed central gain. Supplemental Material https://doi.org/10.23641/asha.11977854.

Project description:(1) To characterize the influence of type 2 diabetes mellitus (DM) on cortical auditory-evoked potentials (CAEPs) separate from the effects of normal aging, and (2) to determine whether the disease-related effects are modified by insulin dependence.A cross-sectional study was conducted in a large cohort of Veterans to investigate the relationships among type 2 DM, age, and CAEPs in randomly selected participants with (N = 108) and without (N = 114) the disease and who had no more than a moderate hearing loss. Participants with DM were classified as insulin-dependent (IDDM, N = 47) or noninsulin-dependent (NIDDM, N = 61). Other DM measures included concurrent serum glucose, HbA1c, and duration of disease. CAEPs were evoked using a passive homogeneous paradigm (single repeating stimulus) by suprathreshold tones presented to the right ear, left ear, or both ears. Outcome measures were adjusted for the pure-tone threshold average for frequencies of 0.5, 1, and 2 kHz and analyzed for differences in age effects between participant groups using multiple regression.There is little variation across test ear conditions (left, right, binaural) on any CAEP peak in any of the groups. Among no-DM controls, P2 latency increases about 9 msec per decade of life. DM is associated with an additional delay in the P2 latency of 7 and 9 msec for the IDDM and NIDDM groups, respectively. Moreover, the slope of the function relating P2 latency with age is similar across participant groups and thus the DM effect appears constant across age. Effects on N1 latency are considerably weaker, with age effects of less than 4 msec per decade across all groups, and DM effects of only 2 (IDDM) or 3 msec (NIDDM). In the NIDDM group, the slope relating N1 latency to age is steeper relative to that observed for the no-DM group, providing some evidence of accelerated "aging" for this CAEP peak. DM does not substantially reduce N1-P2 amplitude and age relationships with N1-P2 amplitude are effectively absent. There is no association between pure-tone average at 0.5, 1, and 2 kHz and any aspect of CAEPs in this cohort.In a large cohort of Veterans, we found that type 2 DM is associated with prolonged N1 and P2 latencies regardless of whether insulin is required to manage the disease and independent of peripheral hearing thresholds. The DM-related effects on CAEP latencies are threefold greater for P2 compared with N1, and there is little support that at the cortical level, IDDM participants had poorer responses compared with NIDDM participants, although their responses were more variable. Overall, these results indicate that DM is associated with slowed preattentive neural conduction. Moreover, the observed 7 to 9 msec P2 latency delay due to DM is substantial compared with normal age changes in P2, which are 9 msec per decade of life in this cohort. Results also suggest that whereas N1 latency changes with age are more pronounced among individuals with DM versus without DM, there was no evidence for more rapid aging of P2 among patients with DM. Thus, the damage responsible for the major DM-related differences may occur early in the DM disease process. These cross-sectional results should be verified using a longitudinal study design.

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

Publications

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

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