Effect of age on ocular vestibular-evoked myogenic potentials using air-conducted sound

Diagnostic testing of the vestibular system is an essential component for the correct treatment and rehabilitation of patients with balance dysfunction. Stimulus-related electromyogenic changes can be recorded from the extraocular muscles and is termed ocular vestibular-evoked myogenic potential (oVEMP). These changes are a reflection of the otolith organ functionality. The purpose of this study was to investigate the effect of age on the amplitude, threshold, and latency of the oVEMP, to establish age-appropriate


Introduction
Diagnostic testing of the vestibular system is an essential component of treating patients with balance dysfunction. Until now, very recent testing methods primarily evaluated the integrity of the horizontal semicircular canal, which is only a portion of the vestibular system. Recent advances in technology have afforded clinicians the ability to assess otolith function through vestibular-evoked myogenic potential (VEMP). VEMP is a short latency muscle potential that is created when the vestibular system is presented with loud sound. This sonomotor response can be easily recorded from surface electrodes placed over sternocleidomastoid muscles (SCMs) [1], and it represents signal averaged attenuation of tonic electromyogenic (EMG) activity. A VEMP response recorded from SCM, also referred to as cervical vestibular-evoked myogenic potential or 'cVEMP' emanates from the saccule and has been a wellestablished clinical test of vestibular functions [2].
In addition to the SCM, stimulus-related EMG changes can be recorded from the extraocular muscles. Rosengren et al. [3] and Todd et al. [4] recorded short latency (10 ms) negative-going evoked myogenic potential from surface electrodes placed beneath the eye in response to acoustic stimulation. They termed these potentials as ocular vestibular-evoked myogenic Effect of age on ocular vestibular-evoked myogenic potentials using air-conducted sound

Results and conclusion
The main outcome measures are amplitude, latency, and threshold of the oVEMP. In this study, oVEMP was present contralaterally in 88% of healthy participants (44 of 50 ears), and the percentage of the presence of oVEMP decreased with age stratification to 60% in the oldest age group (>55 years). When we examined the younger groups in this study, we found 100% response rate for participants under the age of 45 years, whereas the response rate was only 80% in the fourth group (age range, 45-55 years) and 60% in the fifth group (age > 55 years). In the current study, an age effect on oVEMP N1-P1 amplitude and threshold was observed. Significantly reduced amplitude and a significantly increased threshold were observed in the two oldest age groups (>45 years) compared with other age groups. However, oVEMP N1 latency was stable for all age groups less than 55 years but significantly increased in the oldest age group above 55 years. The well-documented neuroanatomic age-related changes that occur in the peripheral vestibular system may explain the commonly reported decrease in the response rate and a decrease in the amplitude with age. However, oVEMP N1 latency represents the function of the time required for the afferent limb of reflex, central transmission and the efferent limb of reflex, and muscle activation. Therefore, the age-dependent increase in N1 latency may occur as a result of degradation of central vestibular system processing, rather than as a result of diminished peripheral vestibular system function.
on 50 ears (50 participants) divided into five groups according to age, and each group contained 10 participants: the first group from 10 to 25 years, the second group from 25 to 35 years, the third group from 35 to 45 years, the fourth group from 45 to 55 years, and the fifth group over 55 years old. Exclusion criteria for all participants included complaints of dizziness or imbalance, known otologic disease, neurologic disease, conductive hearing loss or known disease affecting the cervical vertebrae or spinal cord, and any significant findings on bedside tests examination (spontaneous and positional nystagmus, Romberg's test positive).

Ethical considerations
Ethical approvals from the Alexandria Petrol Hospital were granted to carry out this study. Patients were informed that they will be a part of a research study and were asked to sign written consent.

Preparation
Otoscopy was performed to confirm no occlusion in the external auditory canal. Hearing sensitivity and middle ear status were determined by conducting air-conduction and bone-conduction threshold audiometry, tympanometry, and acoustic reflex.

Recording of ocular vestibular-evoked myogenic potential
For oVEMP recording, participants were seated in a comfortable chair. An electrode montage and recording characteristics similar to those reported by Chihara et al. [9] were used to record oVEMP.
Disposable silver chloride electrodes were used. The active electrodes were placed infraorbitally beneath the eye (i.e. infraorbital 1 cm), and the reference electrodes were placed directly beneath the active electrode (i.e. infraorbital 3 cm). The ground electrode was placed at Fpz. Electrode impedances were maintained below 5 kΩ (Fig. 1). When recording oVEMP, the participants were seated and instructed to keep their head at midline and gaze at target positioned 30° upward at midline. This eye position was maintained for 30 s, which permitted the acquisition of 100-150 samples per run.
A Natus Bio-Logic Navigator Pro auditory-evoked potential unit (Natus Medical Incorporated, San Carlos, CA, USA) was used to obtain and average oVEMP activity. Stimuli for oVEMP recording were presented monaurally through Bio-Logic standard foam insert earphones. Stimuli consisted of 500 Hz Blackman-gated tone bursts with a 2 ms increase/decrease time, and no plateau presented at a rate of 5.1/s. All participants were presented with 95 dB nHL stimulus. If no oVEMP was potentials, or 'oVEMPs'. The oVEMP represents stimulus-evoked initiation of EMG activity [1].
Further research confirmed that this negative peak at 10 ms (N10) component response was vestibular in origin and most likely originating from the otolith-ocular pathway. Whether it is utricular in origin or saccular and utricular in origin is still a matter of debate in the most contemporary literature [3][4][5][6][7][8].
oVEMP are optimally recorded as a response from extraocular muscles slightly below the eye contralateral to stimulation, as it originates from the otolith organs [3]. This response is myogenic in nature rather than being a response to eye movement, and arises from the vestibuloocular reflex [3,4,9,10]. The oVEMP is recorded from the contralateral inferior oblique muscle when in a flexed state [3], although some hypothesize that the inferior rectus may also contribute to the response [10]. Previous cVEMP research [4,11] suggested that the oVEMP response at the level of the extraocular muscles is excitatory because of its initial negative peak response.
The inferior extraocular muscles are best activated when the eyes are in superomedial gaze [3,5,6,8,10]. Rosengren et al. [12] described the neuronal pathway for oVEMP by the vestibulo-ocular reflex; activation of the vestibular nerve and vestibular nuclear complex traveling up the medial longitudinal fasciculus decussate at some point, ending at the oculomotor nuclei, ocular nerves, and the extraocular muscles.
The oVEMP response could be elicited by variable stimuli such as air conduction, bone conduction, forehead tap, and galvanic stimulation, although airconducted and bone-conducted stimulation are the most studied. A 500-Hz tone burst when using an air-conducted stimulus is more effective in producing optimal results than when using a click stimulus [9].
There has not yet been a large-scale study examining the effect of age on the amplitude, latency, and threshold of an air-conduction oVEMP.
The oVEMP, if found to be generated from the utricle, may provide diagnostic information that is complementary to the cVEMP. Accordingly, the purpose of this study was to investigate the effect of age on the amplitude, latency, and threshold of the oVEMP.

Participants and methods
The study was carried out on healthy participants with normal hearing, who were neurologically free. Tests were carried out in the Audiology Unit of Alexandria Petrol Hospital (Egypt). The study was carried out In 88% of the healthy participants (44 of 50 ears), negative/positive biphasic responses with short latency in response to air-conducted 500 Hz tone bursts were obtained from electrodes placed beneath the eye contralateral to the stimulation. When we examined the younger groups in this study, we found 100% response rate for participants under the age of 45 years, whereas the response rate was only 80% in the fourth group (age range, 45-55 years) and 60% in the fifth group (age>55 years). The percentage of absence of oVEMP increases with age reaching up to 40% in the last age group (>55 years) ( Table 2).
We carried out analysis of variance analysis to investigate the effect of age on characteristic parameters of oVEMP. No significant differences were found among the first four age groups for N1 latency, but there was a significant increase in N1 latency in the oldest age group (>55 years) compared with the young age groups (Fig. 2). The effect of age was significant for N1-P1 amplitude and threshold. N1-P1 amplitude decreased and threshold increased in the oldest age groups (>45 years) when compared with the first three age groups (<45 years) (Figs. 3 and 4).
Correlation study was performed between age and different oVEMP parameters (Table 3), which showed no correlation between age and N1 latency. However, there was significant negative correlation for N1-P1 amplitude and positive correlation for oVEMP threshold.

Discussion
The purpose of this study was to further describe the normal characteristics of oVEMP with respect to recorded at this level, the recording session was terminated, and the participant was entered into database as having absent response. In all others, oVEMP thresholds were obtained in descending 5 dB steps. One channel recording was conducted for contralateral oVEMP waveforms. One hundred sweeps of EMG activity were recorded on the side contralateral to acoustic stimulation. The activity was collected with a −10.5 ms pre/poststimulus time, was amplified ×100 000, and was filtered (1-1000 Hz). An artifact-rejection system was used. All tracings were replicated a minimum of one time so that repeatability of the data could be assessed.

Results
The study was carried out on 50 healthy participants (50 ears). The ages ranged from 15 to 73 years (Table 1).  P value for F test (analysis of variance) for comparing between the different studied group; a Significant with group I; b Significant with group II; c Significant with group III; d Significant with group IV; *Statistically significant at P ≤ 0.05; MC, Monte Carlo test of significance. Ocular vestibular-evoked myogenic potential waveform in response to 500-Hz air-conducted tone burst.

Figure 1
age-stratified normal participants. In this study, oVEMP was present contralaterally in 88% of the healthy participants (44 of 50 ears), and the percentage of the presence of oVEMP decreased with age to 60% in the oldest age group (>55 years). Chihara et al. [9] also reported 90% oVEMP response rate with a sample of only 10 participants, all under the age of 60 years.
Others have reported 100% response rate, although each of these studies were limited to a small number of participants, all below 35 years of age [4,13,14].
In the current study, an age effect on oVEMP N1-P1 amplitude and threshold was observed. A significantly reduced amplitude and a significantly increased threshold were observed in the oldest age groups (>45 years) compared with others. However, oVEMP N1 latency was stable for all age groups less than 55 years but significantly increased in the oldest age group above 55 years. Similar age effect was observed for cVEMP recording [10,15]. Several recent studies have also examined the effect of age on the oVEMP response [7,16,17]. Both Iwasaki et al. [7] and Tseng et al. [17] recorded oVEMP in response to boneconducted vibration stimuli, and Nguyen et al. [16] recorded oVEMP in response to air-conducted click, air-conducted 500 Hz tone burst, and vibratory stimuli for participants ranging from young to elderly adults. Similar to this study, the previous studies [7,16,17] reported significant decrease in amplitude with increasing age. Our current study and that by Nguyen et al. [16] reported that age did not affect N1 latency in individuals with age less than 55 years, but in this study N1 latency was significantly increased in the oldest age group above 55 years, which was similar to Iwasaki et al. [7] and Tseng et al. [17] who reported significant increase in N1 latency with increasing age.
The well-documented neuroanatomic age-related changes that occur in the peripheral vestibular system [18] may explain the commonly reported decrease in the response rate and a decrease in the amplitude with age. However, oVEMP N1 latency occurs as a function of the time required for the afferent limb of reflex, central transmission and the efferent limb of reflex, and muscle activation. Therefore, the age-dependent increase in N1 latency may occur as oVEMP, ocular vestibular-evoked myogenic potential; r, Pearson's coefficient; *Statistically significant at P ≤ 0.05.

Figure 4
a result of degradation of central vestibular system processing, rather than as a result of diminished peripheral vestibular system function.