Normal variations in the morphology of auditory brainstem response (ABR) waveforms: a study in wistar rats

Abstract

Auditory brainstem evoked responses (ABR) have been used for decades to assess auditory function. Surprisingly, despite the fact that rats are one of the most widely used experimental models in hearing, there have been no studies that have characterized in detail the normal morphological variations that occur in ABR waves. Therefore, the goal of this study was to characterize the patterns of ABR waves in rats to establish baseline criteria that could be used to identify abnormalities. Rats were stimulated with pure tone sounds at different frequencies and ABR waves were classified based on morphology. The most definitive finding was that, unlike what is observed in human ABRs, wave II of the rat ABR was the most prominent. Additionally, wave III was the smallest and, in many cases, was not apparent at low frequencies. Wave III was frequently involved in the formation of complexes, often appearing as a small wave or adjoining primarily wave IV. Complexes were common at low and medium frequencies and rare at high frequencies. These results indicate that knowledge of the different wave patterns in normal rats is fundamental to understanding how the wave morphology changes in pathological conditions that could lead to hearing impairment.

Introduction

The auditory brainstem response (ABR) is an evoked potential recording technique commonly used to study auditory function in either normal or pathological conditions. This technique is easy to use and is non-invasive, making it ideal for use in both clinical and experimental studies. ABRs are recorded far-field from the scalp and are typically comprised of five to seven vertex positive waves that appear within the first 10 ms after an auditory stimulus (Chiappa et al., 1979, Chen and Chen, 1991, Reichmuth et al., 2007, Parkkonen et al., 2009). The localization of the sources or generator of each wave is still unclear (Simpson et al., 1985, Kuwada et al., 1986, Chen and Chen, 1991, Newton et al., 1992, Church et al., 2004, Church et al., 2007, Church et al., 2010, Church et al., 2012, Reichmuth et al., 2007, Parkkonen et al., 2009); however, for most mammalian species, it is generally accepted that the responses of the neuronal activity in the auditory nerve, cochlear nucleus (CN), superior olivary complex (SOC), lateral lemniscus (LL) and inferior colliculus (IC) correspond to waves I, II, III, IV and V, respectively (Simpson et al., 1985, Chen and Chen, 1991, Reichmuth et al., 2007). Nevertheless, several studies have reported noticeable differences between rodent ABRs and the ABRs of other mammals. In the mouse, it has been suggested that wave II is generated by the posterior ventral CN, wave III by the anterior ventral CN and the trapezoid body, wave IV by the SOC and wave V by the LL and the IC (Parham et al., 2001). It has been proposed that in rats, wave IV is generated by the LL and IC and wave V by the medial geniculate body and/or thalamo-cortical radiations (Henry, 1979). Another study in rats using radiofrequency lesions in auditory brainstem nuclei has shown that lesions in the LL are associated with changes in waves IV and V, while lesions in the IC did not significantly affect any ABR waves (Chen and Chen, 1991).

Thus, it is possible that differences in the sources of the ABR waves in different species could lead to functional modifications in the pattern and morphology of the waves. For instance, in humans, waves I, III, and V are the most common and are frequently used to measure ABR parameters, such as inter-peak latencies (see Chiappa, 2007, Burkard and Don, 2007 for review). Waves III and V are also the largest, and therefore, they are often used to determine hearing thresholds and to identify the remaining waves (see Chiappa, 2007, Burkard and Don, 2007 for review). Conversely, wave II is the largest in rats, and wave III is the smallest; wave V is not commonly used for the evaluation of ABR parameters (Overbeck and Church, 1992, Church et al., 2010, Church et al., 2012). Due to these obvious differences, caution should be taken in using ABR measures that are standardized in humans for the evaluation of rat ABRs.

In human ABRs, waves IV and V forming up to six different patterns that include five different complexes, which were observed in 86% of the 52 patients included in an study by Chiappa et al. (1979). According to Chiappa et al. (1979), knowing the normal variations of the waves is a fundamental factor in the interpretation of ABRs. Surprisingly, even though there is a wealth of studies that have evaluated rat ABR parameters, such as threshold, latency and amplitude (Borg, 1982, Chen and Chen, 1991, Newton et al., 1992, Overbeck and Church, 1992, Pukkila et al., 1997, Fujioka et al., 2006, Kujawa and Liberman, 2006, Church et al., 2007, Church et al., 2010, Church et al., 2012, Hougaard et al., 2007, Bielefeld et al., 2008, Hu and Cai, 2010), to date, a detailed characterization of the normal variations found in the morphology and patterns of the ABR waves has not yet been performed. The goal of the current study was to determine and evaluate the patterns of normal ABR waves in Wistar rats, which are one of the most widely used animal models for the study of the auditory function and thus, to establish criteria for the adequate evaluation and diagnosis of the normal ABR and to detect possible abnormalities that may occur after experimental or pathological conditions that induce hearing impairment.