Latency Characteristics of Auditory Brainstem Responses to Click and LS CE-Chirp Stimuli Under Monaural and Binaural Conditions

Abstract

Background and Objectives

The auditory brainstem response (ABR) represents a critical tool for evaluating auditory pathways. Although absolute and inter-peak latencies (IPLs) are commonly analyzed, the differences between different stimulus types and presentation modes, particularly during binaural processing, remain underexplored. This study compared the absolute latencies, IPLs, and binaural interaction component (BIC) latencies of ABRs elicited by click and LS CE-chirp stimuli under both monaural and binaural conditions. The present study analyzed the clinical features of cochlear function in Ramsay-Hunt syndrome.

Subjects and Methods

Twenty-one adults with normal hearing aged 22-25 years underwent ABR testing using click and LS CE-chirp stimuli under binaural, right ear, and left ear conditions. Their absolute latencies, IPLs, and BIC latencies for waves I, III, and V were recorded. BIC latencies were calculated by subtracting each subject’s binaural wave latency from their mean monaural latency.

Results

The subjects’ LS CE-chirp stimuli elicited significantly longer wave V latencies under binaural vs monaural conditions, although their click-evoked ABRs did not show significant differences across the different presentation modes evaluated. The wave III latencies were significantly longer for the LS CE-chirp stimuli under the binaural and right-ear conditions. The IPLs showed stimulus- and ear-dependent differences, with LS CE-chirps evoking shorter IPLs vs. regular clicks under some conditions. The BIC latencies for waves III and V were significantly longer for the LS CE-chirp stimuli, whereas those for wave I showed no significant differences.

Conclusions

LS CE-chirp stimuli enhanced ABR detectability and revealed longer binaural processing times, particularly at higher auditory brainstem levels. These findings support the utility of LS CE-chirp in terms of assessing binaural integration and central auditory processing.

Introduction

Auditory brainstem responses (ABRs) are widely used in clinical settings to assess hearing sensitivity. One of the key parameters analyzed in ABR measurements is the absolute latency of waveforms, which reflects the time required for neural responses to propagate through different levels of the auditory brainstem. Additionally, inter-peak latencies (IPLs) provide insights into neural conduction time between specific auditory brainstem nuclei, allowing for a deeper understanding of both normal auditory processing and potential pathophysiological conditions [1,2]. In cases where both conductive and retrocochlear disorders coexist, minor latency prolongations due to retrocochlear pathology can be masked by the conductive delay, making differential diagnosis challenging [3]. Clinically, the ability to record wave I is crucial for determining the IPL I–V, which serves as a key marker for retrocochlear pathology. However, in conductive hearing loss cases, wave I is often absent, limiting the clinicians to use IPL I–V as a diagnostic tool. When wave I is present, the IPL I–V remains normal in both conductive and cochlear hearing loss, whereas a prolonged IPL I–V is indicative of retrocochlear pathology, such as vestibular schwannoma [4]. Thus, IPL V analysis is clinically valuable in neurodiagnostic ABR, as it helps distinguish retrocochlear lesions (prolonged IPL I–V) from conductive and cochlear pathologies (normal IPL I–V).

Comparing these parameters under monaural and binaural stimulation conditions can enhance our understanding of auditory processing mechanisms, particularly in terms of binaural integration and lateralization [5]. Binaural stimulation studies have revealed distinct latency patterns compared to monaural stimulation, with prolonged latencies observed in binaural conditions due to the additional neural processing demands at the superior olivary complex [1]. This is particularly evident in wave V, which represents the core of binaural auditory processing in the brainstem. Understanding these latency differences in monaural and binaural ABRs has significant implications for diagnosing central auditory processing disorders, evaluating binaural hearing benefits in hearing aid and cochlear implant users, and refining ABR protocols for more precise auditory assessments [6].

An additional aspect of auditory processing that can be assessed using ABRs is binaural interaction, which reflects neural mechanisms involved in sound localization and binaural integration at the brainstem level. The binaural interaction component (BIC) of the ABR is derived by subtracting the amplitude or frequency of binaurally evoked ABR from the sum of monaural ABRs from both ears. There is growing evidence that the BIC component observed in binaural auditory evoked potentials originates at the level of the lateral superior olive (LSO) in the brainstem, a key structure involved in the processing of both interaural level differences and interaural time differences [7]. The latency of the BIC systematically increases as interaural level differences and interaural time differences become larger [8]. The LSO, which also contributes to the generation of early ABR components, particularly wave III in binaural conditions, plays a central role in encoding binaural spatial cues [9]. This convergence of evidence highlights the LSO’s critical involvement in both electrophysiological and neuroanatomical correlates of binaural processing. Research has demonstrated that the BIC can be elicited using various stimuli, such as clicks and LS CE-chirps, and that its amplitude varies depending on the stimulus type [10-12]. However, the investigation of BIC latency has been relatively limited compared to BIC amplitude. Variations in BIC latencies across different stimulus types may provide valuable insights into how the auditory system integrates binaural cues.

Recent research trends have focused on the use of different stimulus types, such as clicks and LS CE-chirps, to optimize ABR measurements. Click stimuli have been the gold standard for decades due to their broad frequency spectrum and well-established normative data [13]. However, LS CE-chirp stimuli have gained attention for their ability to compensate for cochlear travel-time delays, leading to more synchronized neural responses and improved wave detectability [13,14]. A study has shown that LS CE-chirp-ABRs often result in longer absolute latencies and IPLs compared to click-ABRs [15]. This difference is attributed to the spectral and temporal characteristics of LS CE-chirp stimuli, which enhance phase-locking and neural synchrony across auditory brainstem structures [16]. While direct comparisons between binaural and monaural latencies using LS CE-chirp stimuli are scarce, it is plausible to infer that the enhanced synchronization and amplitude observed with monaural LS CE-chirp stimuli could influence binaural processing.

Given the growing clinical and research interest in binaural processing, the present study aims to investigate absolute latencies, IPLs, and BIC latencies elicited by click and LS CE-chirp stimuli under different lateral presentation conditions (binaural, right ear, and left ear). By analyzing these parameters, we seek to enhance our understanding of stimulus-dependent differences in ABR responses and their implications for auditory diagnostics and neurophysiological assessments.

Subjects and Methods

Participants

A total of 21 adults (7 males and 14 females) with normal hearing, aged 22 to 25 years (mean: 23.19, standard deviation: 0.93), participated in this study. Before the experiment, all participants completed demographic questionnaires confirming the absence of any history of hearing impairments. Hearing sensitivity was verified through pure-tone audiometry and tympanometry, with all participants exhibiting normal hearing thresholds (<15 dB HL) across 250–8,000 Hz and presenting type A tympanograms. The study protocol was approved by the Institutional Review Board of Tongmyong University (TUIRB-2022-003). Informed consent was obtained from all participants before the study began.

ABR recording and data management procedure

ABRs were recorded in a soundproof booth using the Eclipse system (Interacoustics Ltd.) with Etymotic Research ER-2 insert earphones as the stimulus transducer. Ambu Neuroline 720 surface electrodes (Ambu Inc.) were positioned in a two-channel vertical montage, with the non-inverting electrode at Fz, inverting electrodes on the bilateral mastoids, and the ground electrode at Fpz. Electrode impedances were maintained below 3 kΩ. Click and LS CE-chirp stimuli were presented in rarefaction polarity at 65 dB nHL with a stimulus rate of 32.1 Hz, and 3,000 sweeps were collected per condition. Bayesian weighting was applied to enhance signal stability by mitigating noise and artifacts. Filtering parameters were set to 100–3,000 Hz, and an artifact rejection threshold of ±40 μV was used. ABRs were recorded under binaural, right ear, and left ear conditions. The order of recording conditions was randomized. Participants were instructed to relax, keep their eyes closed, and sleep if possible. Waves I, III, and V were identified by three independent audiologists with at least 3 years of clinical experience in ABR analysis.

Typically, BICs are obtained by subtracting the binaural ABR waveform from the sum of the monaural ABRs recorded from the right and left ears [10,11]. The latency of the BIC is most commonly measured at waves III and V, as these waves are associated with binaural processing in the superior olivary complex and inferior colliculus. In this study, we extended our analysis to include BICs for wave I to assess whether BICs are specifically identifiable at waves III and V, rather than at earlier auditory processing stages. Instead of generating BIC waveforms using specialized research software, we extracted latency values for each ABR peak and calculated the BIC latency offline using Microsoft Excel 365. The BIC latency was determined by subtracting the binaural latency from the average of monaural latencies at each ABR peak.

Statistical analysis

Statistical analyses were conducted using SPSS version 27.0 (IBM Corp.). Given the small sample size and the non-normal distribution of the data, nonparametric tests were employed. A significance level of p<0.05 was set for all statistical comparisons. The Friedman test was utilized to assess differences in absolute latencies and IPLs across different presentation conditions (binaural, right ear, and left ear). Post-hoc comparisons, when significant differences were found, were performed using the Wilcoxon signed-rank test. Additionally, comparisons of absolute latencies, IPLs, and BICs between click and LS CE-chirp stimuli were conducted using the Wilcoxon signed-rank test.

Results

Absolute latencies

Table 1 presents not only the mean absolute latencies and IPLs but also the detection rates of waves I, III, and V under each condition. Among the 21 participants, the detection rate of wave I was notably lower compared to waves III and V, particularly for click stimuli. This can be attributed to the lower amplitude and higher susceptibility to noise for wave I, making it less detectable in some recordings. In contrast, LS CE-chirp stimuli demonstrated consistently higher wave detection rates across all waves, reflecting their improved synchrony and neural recruitment. Fig. 1 illustrates the example of click- and LS CE-chirp-ABR waveforms derived from one participant (subject 3).

Table 1.

Absolute latencies, IPLs, and detection rates of ABR waves (I, III, and V) for click and LS CE-chirp stimuli across lateral presentation conditions

Latency analysis	Click			LS CE-chirp
	Binaural	Right	Left	Binaural	Right	Left
Absolute latency
Wave I
Latency (ms)	1.785±0.286	1.781±0.275	1.776±0.283	1.97±0.226	1.945±0.219	1.967±0.206
Detection rate (%)	80.95 (17/21)	80.95 (17/21)	80.95 (17/21)	95.23 (20/21)	90.47 (19/21)	95.23 (20/21)
Wave III
Latency (ms)	3.807±0.209	3.795±0.305	3.912±0.240	4.01±0.278	3.961±0.306	3.986±0.365
Detection rate (%)	95.23 (20/21)	95.23 (20/21)	80.95 (17/21)	100 (21/21)	100 (21/21)	100 (21/21)
Wave V
Latency (ms)	5.694±0.247	5.737±0.251	5.743±0.244	5.812±0.348	5.719±0.395	5.683±0.398
Detection rate (%)	95.23 (20/21)	95.23 (20/21)	95.23 (20/21)	100 (21/21)	100 (21/21)	100 (21/21)
IPL
Wave I-III
IPL (ms)	2.29±0.756	2.281±0.681	1.816±0.864	2.134±0.345	2.201±0.544	2.113±0.417
Detection rate (%)	80.95 (17/21)	80.95 (17/21)	80.95 (17/21)	95.23 (20/21)	90.47 (19/21)	95.23 (20/21)
Wave III-V
IPL (ms)	1.887±0.191	1.942±0.227	2.417±1.475	1.802±0.145	1.757±0.138	1.697±0.183
Detection rate (%)	95.23 (20/21)	95.23 (20/21)	80.95 (17/21)	100 (21/21)	100 (21/21)	100 (21/21)
Wave I-V
IPL (ms)	4.177±0.721	4.223±0.716	4.233±0.761	3.936±0.355	3.959±0.509	3.81±0.419
Detection rate (%)	80.95 (17/21)	80.95 (17/21)	80.95 (17/21)	95.23 (20/21)	90.47 (19/21)	95.23 (20/21)

Values are presented as mean±standard deviation or percentage. Detection rate=number of participants with identifiable waveforms/total number of participants (n=21). ABR, auditory brainstem responses; IPL, inter-peak latencies.

Fig. 1.

Representative click- and LS CE-chirp-evoked auditory brainstem response waveforms from a single participant (subject 3). Waveforms displaying peaks I, III, and V are shown from top to bottom, organized by stimulus condition: red (right ear), blue (left ear), and black (binaural).

The number of waves detected in each condition is presented in Table 1. ABR waves evoked by LS CE-chirp stimuli were obtained more frequently than those evoked by click stimuli. The group mean absolute latencies and IPLs of ABR waves for both binaural and monaural conditions are also shown in Table 1. As expected, the absolute latency increased progressively from wave I to wave V, consistent with neural transmission along the auditory pathway.

A Friedman test was conducted to examine the effects of presentation ear on latency differences for click and LS CE-chirp stimuli. A significant difference in wave V latency was observed across binaural, right-ear, and left-ear presentations for LS CE-chirp-ABRs (χ²(2)=12.025, p<0.01). However, no significant differences in latency were found for click-ABRs across the three presentation conditions. Post-hoc Wilcoxon signed-rank tests revealed that the wave V latency of LS CE-chirp-ABRs elicited by binaural stimulation was significantly longer than that elicited by either right-ear (Z=-2.719, p<0.05) or left-ear stimulation (Z=-3.326, p<0.001). No significant differences in wave V latency were found between right-ear and left-ear presentations for LS CE-chirp-ABRs (Z=0.665, p=0.506).

To examine latency differences between click and LS CE-chirp stimuli, a series of Wilcoxon signed-rank tests were conducted for each wave (Table 2). The results showed that wave III latency was significantly longer for LS CE-chirp stimuli than for click stimuli in the binaural (Z=-3.623, p<0.001) and right-ear conditions (Z=-2.843, p<0.01). No significant latency differences were found between click and LS CE-chirp stimuli for wave I or wave V across any presentation condition.

Table 2.

Result of Wilcoxon signed-rank test comparing absolute latency of click and LS CE-chirp

	Binaural			Right			Left
	Wave I	Wave III	Wave V	Wave I	Wave III	Wave V	Wave I	Wave III	Wave V
p	0.098	＜0.001***	0.058	-1.422	0.004**	0.906	0.055	0.244	0.600
Z	-1.656	-3.623	-1.898	0.155	-2.843	0.118	-1.915	-1.164	0.524

^**p＜0.01;

^***p＜0.001.

Inter-peak latencies

A series of Friedman tests were conducted to examine IPL differences across presentation ears. No significant differences in IPLs were observed for click stimuli across binaural, right ear, and left ear conditions. However, significant differences were found for LS CE-chirp stimuli in IPL III–V (χ²(2)=6.222, p<0.05) and IPL I–V (χ²(2)=6.694, p<0.05). Post-hoc Wilcoxon signed-rank tests indicated that IPL III–V (Z=-2.391, p<0.05) and IPL I–V (Z=-2.698, p<0.01) were significantly longer for binaural presentation compared to left ear presentation.

The IPL I–III, III–V, and I–V intervals were generally consistent across stimulus types and ears, although LS CE-chirp stimuli tended to produce slightly shorter IPLs in monaural conditions compared to click stimuli. To statistically assess the effect of stimulus type on IPLs, Wilcoxon signed-rank tests were conducted (Table 3). The results showed that IPL III–V for right ear presentation (Z=2.759, p<0.01) and IPL I–V for left ear presentation (Z=2.377, p<0.05) were significantly longer for click stimuli compared to LS CE-chirp stimuli. No other IPL comparisons reached statistical significance.

Table 3.

Result of Wilcoxon signed-rank test comparing IPL of click and LS CE-chirp

	Binaural			Right			Left
	IPL I-III	IPL III-V	IPL I-V	IPL I-III	IPL III-V	IPL I-V	IPL I-III	IPL III-V	IPL I-V
p	0.856	0.054	0.411	0.695	0.006**	0.147	0.433	0.070	0.017*
Z	0.181	1.924	0.822	0.392	2.759	1.449	-0.784	1.812	2.377

^*p＜0.05;

^**p＜0.01.

IPL, inter-peak latency.

Binaural interaction components

The group mean BIC latencies for waves I, III, and V under click and LS CE-chirp stimulus conditions are presented in Table 4. The degree of mean BIC values theoretically reflect the monaural and binaural difference, where more negative values suggest prolonged neural processing times under binaural stimulation relative to monaural conditions. A Friedman test revealed a significant difference in BIC latency for LS CE-chirp stimuli (χ²(2)=7.547, p<0.05), whereas no significant differences were found for click stimuli (χ²(2)=1.284, p=0.526). Post-hoc Wilcoxon signed-rank tests showed that BIC latency for wave V was significantly longer than for wave I (Z=-2.091, p<0.05) and wave III (Z=2.625, p<0.01) for LS CE-chirp stimuli. However, no significant difference was found between wave I and wave III latencies.

Table 4.

Group mean BIC latencies of wave I, III, and V for click and LS CE-chirp stimuli

	Click			LS CE-chirp
	Wave I	Wave III	Wave V	Wave I	Wave III	Wave V
Mean	-0.006	0.074	0.046	-0.012	-0.036	-0.112
SD	0.110	0.100	0.108	0.211	0.109	0.084

SD, standard deviation; BIC, binaural interaction component.

Further comparison of BIC latencies between click and LS CE-chirp stimuli revealed that wave III (Z=2.652, p<0.01) and wave V latency (Z=3.604, p<0.001) were significantly longer for LS CE-chirp stimuli than for click stimuli. However, the latency of wave I did not show a statistically significant difference between the two stimuli (Z=-0.881, p=0.378).

Discussion

This study investigated the absolute latencies, IPLs, and BICs of ABRs elicited by click and LS CE-chirp stimuli across different lateral presentation conditions. Our findings reveal significant differences in some characteristics of latencies depending on stimulus type and presentation condition, contributing to a better understanding of ABR characteristics in both clinical and research contexts.

As widely recognized, the absolute latencies of ABR waves systematically increase with wave number, regardless of stimulus type or presentation ear. A previous study has reported that binaural stimulation can result in slightly longer ABR latencies compared to monaural stimulation, likely due to the additional neural processing required to integrate inputs from both ears [17]. However, some studies have found no significant latency differences between binaural and monaural stimulation [18,19]. When we compared the absolute latency of click-ABR, binaural and monaural stimulation difference in latency was not found at all waves. However, LS CE-chirp-ABR showed that binaural presentation tends to have longer latency than monaural presentation for wave V. This eventually resulted in longer IPL III-V and IPL I-V evoked by binaural presentations than those evoked by monaural presentations, especially left ear for LS CE-chirp-ABR. Wave III is generated in part by the cochlear nucleus and superior olivary complex in the brainstem [4]. The superior olivary complex is the first major site where binaural interactions occur. Wave V is primarily generated by the inferior colliculus, a major midbrain structure involved in processing binaural cues. The longer wave V latency for LS CE-chirp stimuli under binaural conditions may reflect additional processing demands at the level of the inferior colliculus. The temporally extended energy distribution of LS CE-chirp may require more extensive neural integration, particularly when bilateral signals are processed simultaneously.

Overall, the absolute latencies of ABR waves, particularly I and V, were similar between click and LS CE-chirp stimuli. This suggests that the ABR system compensates for onset and offset timing in LS CE-chirp, aligning neural activation with click stimuli by adjusting the temporal sequence during stimulus construction. However, absolute latency differences between click- and LS CE-chirp-evoked ABRs were observed exclusively for wave III, with LS CE-chirp stimuli eliciting longer latencies than click stimuli in the binaural and right-ear conditions. The absence of a significant latency difference in the left-ear condition remains unclear. This finding is partially consistent with Dzulkarnain, et al. [15], who reported significantly prolonged wave I and III absolute latencies for LS CE-chirp-ABRs compared to click-ABRs when using rarefaction polarity. They attributed the increase in latency to a slight delay in activating the lower brainstem auditory neurons, particularly the neural generators of waves I and III, when stimulated with LS CE-chirps. This delayed activation consequently results in a prolonged ABR waveform latency compared to click stimuli.

The IPLs, particularly the I–V interval, are generally shorter with LS CE-chirp stimuli, suggesting more synchronized neural firing due to the design of LS CE-chirp stimuli [20,21]. Our results align with findings showing that IPL III–V in the right ear and IPL I–V in the left ear are shorter for LS CE-chirp stimuli compared to click stimuli. This trend, though not statistically significant for wave III, appears to result from a delayed absolute latency of wave I and III, combined with a shorter absolute latency of wave V. The delayed latency of waves I and III is likely attributed to the longer duration of the LS CE-chirp stimulus compared to the click stimulus [20].

The BIC reflects neural processing of interaural differences in time and intensity, primarily occurring within the superior olivary complex and subsequent auditory brainstem pathways. Typically, BIC amplitude and latency are analyzed by deriving the BIC waveform through the subtraction of the binaural ABR response from the sum of monaural responses, a process commonly implemented using computational programs [22,23]. However, in this study, BIC latency was obtained using a different approach. Rather than extracting BIC curves, we calculated BIC latency by subtracting the binaural ABR peak latency from the averaged monaural latencies of the right and left ears. The resulting negative values theoretically represent the BIC, with larger negative values indicating longer binaural processing times compared to monaural conditions. As expected, the mean BIC values for wave I were the smallest, regardless of stimulus type. This finding supports the notion that BIC latency is primarily observed at waves III and V, which correspond to neural processing at higher levels of the auditory brainstem [24,25]. In line with this, our result showed that the BIC latencies for waves III and V were significantly longer for LS CE-chirp stimuli compared to click stimuli, whereas wave I did not exhibit a significant difference. This result is in agreement with previous research indicating that later ABR waves, particularly wave V, are more influenced by binaural interaction effects and stimulus timing modifications introduced by LS CE-chirp stimuli [6]. The significantly longer BIC wave V latency compared to wave I and wave III for LS CE-chirp stimuli suggests that LS CE-chirp stimuli may enhance binaural processing mechanisms, likely due to their extended temporal energy distribution.

The majority of our findings for absolute frequency, IPL, and BIC showed significant differences when using LS CE-chirp stimuli compared to click stimuli. The enhanced prominence of ABR responses with LS CE-chirp stimuli underscores their potential for more effectively assessing binaural auditory function. The prolonged BIC latencies and altered IPL patterns observed with LS CE-chirp stimuli may serve as sensitive electrophysiological markers of delayed or inefficient binaural processing at the brainstem level. In clinical settings, such measures could aid in identifying functional deficits that are not readily apparent through behavioral testing alone. For example, in patients with central auditory processing disorder or mild traumatic brain injury, where binaural temporal integration is often disrupted, latency-based BIC indices may enhance diagnostic sensitivity.

Differences in waveform detectability between stimuli may affect the interpretation of latency and IPL findings. LS CE-chirp stimuli, by enhancing neural synchrony, yielded higher detection rates and more stable latency measures, particularly for wave I. In contrast, lower detectability with click stimuli may have introduced variability by excluding weak responses. Therefore, some latency differences may reflect detectability disparities rather than true physiological differences, warranting cautious interpretation of stimulus-based comparisons.

While our study provides valuable insights into ABR waveform characteristics under different stimulus and presentation conditions, some limitations should be considered. First, the sample size was relatively small, which may limit the generalizability of the findings. Second, individual variations in neural conduction time and background noise levels may have affected wave detectability, particularly for wave I. In addition, the non-traditional approach to BIC calculation adopted in this study may limit the direct comparability of our findings with previous research. While the conventional method derives BIC waveforms through point-by-point subtraction of binaural and summed monaural responses, we employed a latency-based estimation due to practical constraints. Although this approach does not yield amplitude-based BIC metrics, it offers a pragmatic and interpretable measure of binaural processing latency, providing valuable insight despite its methodological divergence from standard practices. The use of a single stimulus intensity (65 dB nHL) may restrict the generalizability of our findings. ABR latency characteristics and BIC responses are known to vary with intensity, and future studies should examine responses across a broader intensity range. Future studies should consider larger sample sizes and examine the impact of stimulus intensity and frequency specificity on ABR waveforms to further elucidate LS CE-chirp-evoked responses across diverse clinical populations.