Effects of isoflurane on the auditory brainstem responses and middle latency responses of rats

OBJECTIVE: To evaluate the effects of a volatile anesthetic, isoflurane, on auditory brainstem responses (ABRs) and middle latency responses (MLRs) recorded in rats. MATERIAL AND METHODS: ABRs and MLRs evoked by click stimuli were simultaneously recorded in eight rats in the awake condition and during anesthesia with isoflurane at clinically relevant concentrations. RESULTS: Vertex-recorded ABRs showed a significant increase in the latency of waves I-IV during anesthesia and the latency changes appeared to be significantly related to the isoflurane concentration. The I-IV interval also appeared to be significantly increased in comparison to the awake condition, while minor changes in ABR amplitudes were induced by isoflurane. MLRs, which were recorded by means of epidural electrodes implanted over the auditory cortex, appeared to be attenuated in amplitude and increased in latency during anesthesia. Only latency changes appeared to be significantly related to the isoflurane concentration. Moreover, "bursts" of high amplitude MLRs were observed during anesthesia at each concentration. CONCLUSION: The present findings indicate that both ABR and MLR latencies are increased by isoflurane in a concentration-dependent manner, whilst the anesthetic-induced attenuation in amplitude does not appear to be related to the isoflurane concentration.     

Human auditory middle latency responses: influence of stimulus type and intensity

Human auditory middle latency responses (MLR) to click and tone pip stimuli of different intensities were recorded by means of magnetoencephalography (MEG) and electroencephalography (EEG). Clicks elicited larger responses with significantly shorter latencies than the tone pips at the same intensity in dB sensation level (SL). Most MLR amplitudes increased and their latencies decreased with increasing stimulus intensity for both types of stimulation. Pa and Nb amplitudes saturated at intensities of 60 dB SL in the case of click stimulation. The shorter latencies of MLR evoked by the click were explained by its short rise time and the high frequency content of its spectrum. MEG source analysis yielded MLR sources which were clearly different from those of the slow cortical wave N1. They seem to be located in primary auditory areas along Heschl's gyrus.     

Auditory brainstem and middle latency responses in non-human primates

Auditory brainstem (ABR) and middle latency responses (MLR) were obtained from each ear in 8 crab-eating macaques, 4 white-handed gibbons, 4 siamangs and 2 orangutans. Macaques ranged in age from 5 days to 15 years with the 6 older animals in age-matched, male-female pairs. From each animal, latency-intensity functions were obtained and multiple MLR recordings were measured at 60 and 70 dB. Latency-intensity functions, interwave intervals, thresholds and percent detectability were calculated for ABR waveforms. Waves II and IV were largest in amplitude and were most consistently detected at low stimulus intensities in all species tested. Waves I and II had adult latencies in the youngest animal tested (5-day-old macaque), while waves III and IV were prolonged in comparison to the 15-month-old macaque, in whom latencies had reached adult values. There were no apparent sex differences in evoked potentials in the age-matched, male-female pairs. A broad, negative MLR at 7-13 ms was observed in all animals. Longer latency MLRs varied among animals of the same species, but were replicable in some individuals, including the youngest macaque (5 days) and orangutan (7 months). These data were compared to responses obtained in humans, other primates and other vertebrates.     

The latency of auditory nerve brainstem evoked responses to air- and bone-conducted stimuli

The auditory nerve brainstem evoked responses (ABRs) to bone conduction (BC) stimuli are longer in latency than those to air conduction (AC). In order to study the mechanism of this difference, ABR wave I was recorded in experimental animals in response to low intensity (0–20 dB above their threshold) logon stimuli delivered by BC and by using the same bone vibrator to generate the air-conducted stimulus. The BC stimuli were delivered to skull bone, and directly to the contents of the cranial cavity (brain and cerebrospinal fluid) through a craniotomy. ABR wave I in response to BC stimuli delivered to skull bone was significantly longer in latency than that to BC delivered on the brain, while there was no latency difference between AC stimuli and BC to the brain. Furthermore, the vibration (measured with an accelerometer) recorded on the brain during BC stimulation of skull bone was always delayed compared to that measured on the skull. Thus there is a delay in the transfer of vibratory energy from the skull bone to the underlying contents of the cranial cavity. From there, the delayed vibrations of the contents of the cranial cavity are transmitted to the inner ear. This is probably the mechanism of the longer latency BC response compared to the AC response.     

The influence of raised body temperature on auditory evoked brainstem responses

The influence of raised body temperature on the auditory evoked brainstem responses (BSER) has been investigated in 9 healthy volunteers. Ipsi- and contralateral BSER recordings were obtained before and after raising body temperature by at least 1 degree C by means of a specially constructed heat cradle. In two of the subjects further BSER recordings were obtained after their body temperature had been allowed to fall again to its preheated level. The results for wave V have been analysed in detail: the latency in the 5 men shortened from a mean of 5.84 ms (s.d. 0.193) to a mean of 5.62 ms (s.d. 0.185). For the 4 women the figures were 5.87 ms (s.d. 0.105) and 5.68 ms (s.d. 0.105). Using paired t-tests this change is highly significant (P less than 0.001). Similar changes were observed in the other waves although they were less consistent. In the 2 subjects who were allowed to cool again after heating, the BSER wave latencies returned to their preheated values. It is concluded that nerve conduction rates in the auditory pathway are influenced by body temperature and that this may have to be taken into account when interpreting BSER recordings.     

Effect of sleep on binaural interaction in auditory brainstem response and middle latency response.

Binaural interaction (BI) in auditory brainstem response (ABR) and middle latency response (MLR) was measured in 14 adults with normal hearing in the awake and asleep states. The ABR and MLR were recorded with click stimuli given monaurally and binaurally. Four peak-to-peak amplitudes of the response waveforms were measured, and the BI was determined from the amplitude difference between the summed monaural and binaural responses expressed in percent of the summed monaural responses. The magnitude of BI was smallest in ABR (waves I'-V) and largest in the later component of MLR (Pa-Nb) in both the waking and sleeping states. BI values for the peak-to-peak amplitudes in the ABR and MLR were significantly lower (p less than 0.025) in the sleeping state than in the waking state.     

Changes in the auditory middle latency responses during all-night sleep recording

The middle latency response (MLR) using wide band-pass filters shows marked changes in amplitude, latency and configuration in sleep. The components with latencies greater than 20 ms show the greatest variability. There is a significant increase in Pa latency in stages 2 and stages 3/4, and in some cases a disappearance of the Nb component with the development of a broad positivity of latency intermediate to Pa and Pb which dominates the response. The responses in REM are of similar latency and configuration as in wakefulness but of reduced amplitude. The 40 Hz response is markedly reduced in amplitude in all sleep stages reflecting a decrease in the contribution of the middle latency components to this composite response. This appears to arise through a loss of 40 Hz periodicity in slow wave sleep and an increase in the slow 10 Hz component. In REM sleep, there is an overall reduction in amplitude. Much of the reported variability of the MLR in the literature arises from the widely differing band-pass filters used and the inadequate control for level of arousal. Both these factors have been shown to produce significant changes in the response.     

Comparison of noise-induced changes of auditory brainstem and middle latency response amplitudes in rats

Auditory brainstem responses (ABRs) and middle latency responses (MLRs) were compared after noise exposure to elucidate the specific effects of a loud sound on the central auditory system in rats. Rats were exposed twice for 1 h to broad-band noise (BBN) of 118 dB SPL (first exposure) and 122 dB SPL (second exposure) with an interval between the exposures of three weeks. The first noise exposure produced threshold shifts (TSs) amounting to 5-45 dB, and the second exposure resulted in 40-70 dB TSs. The slope of MLR amplitude-intensity functions (AIFs) increased significantly in correlation with the TS, resembling loudness recruitment. However, maximal MLR amplitudes measured at 8 kHz increased after the first and second noise exposures to almost equal values in individual animals regardless of the TS. In addition, maximum MLR amplitude enhancement was dependent on pre-exposure MLR voltage, probably reflecting the level of metabolic activity or neurotransmitter processes in individual animals. In contrast to MLR amplitudes, ABR amplitudes were suppressed after noise exposure without changing the slope of ABR AIFs. The MLR changes reflect the specific effects of noise exposure on the central auditory system.     

Amplitude--intensity functions for auditory middle latency responses in hearing-impaired subjects

Results from animal studies show that hearing loss can result in increased neural responsiveness within the central auditory system. This study employed auditory middle latency evoked responses to compare central auditory responsiveness in human males with and without hearing loss. Measurements of auditory middle latency responses (MLRs) recorded from 14 normal hearing males were compared with MLR measures from 14 males with high-frequency, sensorineural hearing loss. Sixteen toneburst stimuli (four frequencies x four intensities) were used. Slopes of the amplitude-intensity functions for the several components of the MLR were obtained for each subject at frequencies below, near, and above the audiometric edge. Analysis of variance (ANOVA) revealed a significant group effect for MLR component Pa-Na, with less steep slopes at all frequencies for the hearing-impaired group. The ANOVA also showed a trend towards a significant group effect for Pb-Nb. Two-sample t-tests performed for Pb-Nb for each of the four tonebursts showed a frequency-specific effect. For Pb-Nb there was a statistically greater mean slope for the hearing-impaired group at the toneburst frequency associated with the audiometric edge.     

The effect of sleep on the auditory brainstem response (ABR) and the middle latency response (MLR)

The ABR and the MLR were measured without interruption in 4 subjects during a whole night of natural sleep and compared with the awake responses. The conventional EEG activity was monitored during the whole procedure, which permitted a precise rating of the sleep stage during each recording period. Only minor changes were found in the latencies for the ABR during sleep. The MLR responses showed quite dramatic changes in morphology and latencies. Our results appear to indicate that the 40/sec stimulus presentation mode of the MLR will not be very effective during sleep due to the pronounced latency shifts of the different peaks in the MLR. The 40/sec response is based on an inter-peak latency of 25 msec. If this presumption is not fulfilled the different waves in the 40/sec response will not be superimposed and consequently enhanced in the averaging procedure.     

Brainstem and middle latency auditory evoked responses in rabbits with halothane anaesthesia

The effects of different concentrations of halothane (0.5, 1 and 1.5%) in brainstem and middle latency auditory evoked responses were studied in 14 adult rabbits. The animals were firstly curarized, tracheostomized and ventilated mechanically. Various recording were made under these conditions for control purposes. During the experiment, arterial pressure, temperature, arterial concentrations of O2, CO2 and pH were monitored. Halothane produce an increase in latency a decrease in amplitude and at higher concentrations even abolished the later waves of middle latency auditory evoked responses. Brainstem potentials are stable, but slight changes in latency were observed at high concentrations (1.5%). Modifications of these potentials as a result of the different concentrations of this anaesthetic in relation with the recordings obtained in the animals curarized without anaesthesia are discussed and the results compared with previous reports in humans.     

Sound-evoked myogenic potentials and responses with 3-ms latency in auditory brainstem response.

OBJECTIVES: The vestibular-evoked myogenic potential (VEMP) has shed new light on vestibular testing. A large negative deflection with a 3-ms latency within the auditory brainstem response (ABR) has been reported in some patients with deafness. This negative deflection has been termed the N3 potential and it is assumed to be a vestibular-evoked potential. This study investigated the relationship between the VEMP and the N3 potential. STUDY DESIGN: Prospective evaluation of the VEMP and the N3 potential in 21 patients. METHODS: The oto-neurological tests, including caloric test, hearing sensitivity test, VEMP, and ABR, were performed and data were analyzed. RESULTS: The average hearing threshold ranged from 65 to above 110 dB, which includes 9 (37.5%) totally deaf ears. The N3 potentials were recorded in 10 (41.7%) ears. A normal VEMP was detected in 16 (66.7%) ears. Canal paresis was observed in 11 (45.8%) ears. CONCLUSIONS: Both the VEMP and the N3 potential appear to originate from the sacculus, but because the characteristics of these two responses are not identical, additional factors might be involved in the generation of the N3 potential.     

Relationship between head size and latency of the auditory brainstem response

This investigation examines the relationship between the head size of 22 normally hearing individuals and the latency of their respective auditory brainstem responses (ABR). The absolute latency of wave V and the I-V interpeak interval were examined in 12 female and 10 male subjects with varying head sizes. Strong positive correlations were obtained between head size and the latency of both wave V and the I-V interpeak interval. The evidence suggests that this relationship is based upon subject differences in brain size which is reflected in head size. Head size appears to be an important source of intersubject variability which should be considered in order to increase the clinical usefulness of the ABR.     

Effects of age on the adult auditory middle latency response

The middle latency components of the auditory evoked response were obtained from a group of normal-hearing, healthy female subjects from 22 to 68 years of age. Recordings were made at several intensity levels to assess the level-dependence of any age-related effects. Cross-sectional analyses revealed that the amplitude of component Pa grows linearly with age, becoming significantly larger in older (50-68 years of age) compared to younger (22-37 years) subjects. The amplitude-intensity function is steeper in the older subjects by a factor of two. Correlational analyses suggested that at higher intensity levels age accounts for about 20% of the variance in the amplitude of Pa. A positive shift in response baseline was observed in the older subjects, and could contribute to the age-related increase in the absolute amplitude of Pa. However, a similar increase in the peak-to-peak and area measures of Pa suggests that some of the increase in the magnitude of Pa is independent of baseline shift. A confounding of age and hearing sensitivity in this study makes it difficult to interpret the age-related effects as strictly central in nature.     

Electrophysiological correlates of azimuth and elevation cues for sound localization in human middle latency auditory evoked potentials

OBJECTIVE: To study, in humans, the effects of sound source azimuth and elevation on primary auditory cortex binaural activity associated with sound localization. DESIGN: Middle Latency Auditory Evoked Potentials (MLAEPs) were recorded from three channels, in response to alternating polarity clicks, presented at a rate of 5/sec, at nine virtual spatial locations with different azimuths and elevations. Equivalent dipoles of Binaural Interaction Components (BICs) of MLAEPs were derived from 15 normally and symmetrically hearing adults by subtracting the response to binaural clicks at each spatial location from the algebraic sum of responses to stimulation of each ear alone. The amplified potentials were averaged over 4000 repetitions using a dwell time of 78 micro sec/address/channel. Variations in magnitudes, latencies and orientations of the dipole equivalents of cortical activity were noted in response to the nine spatial locations. RESULTS: Middle-latency BICs included six major components corresponding in latency to the vertex-neck recorded components of MLAEP. A significant decrease of equivalent dipole magnitude was observed for two of the components: Pa2 in response to clicks in the backward positions (medium and no elevation); and Nb in response to clicks in the back and front positions (medium and no elevation) in the midsagittal plane. In the coronal plane, Pa2 equivalent dipole magnitude significantly decreased in response to right-horizontal (no elevation) clicks. Significant effects on equivalent dipole latencies of Pa2 were found for backward positions (no elevation) in the midsagittal plane. No significant effects on Pa2 and Nb equivalent dipole orientations were found across stimulus conditions. CONCLUSIONS: The changes in equivalent dipole magnitudes and latencies of MLAEP BICs across stimulus conditions may reflect spectral tuning in binaural primary auditory cortex neurons processing the frequency cues for sound localization.     

Accuracy of averaged auditory brainstem response amplitude and latency estimates

Objective: The aims were to 1) establish which of the four algorithms for estimating residual noise level and signal-to-noise ratio (SNR) in auditory brainstem responses (ABRs) perform better in terms of post-average wave-V peak latency and amplitude errors and 2) determine whether SNR or noise floor is a better stop criterion where the outcome measure is peak latency or amplitude. Design: The performance of the algorithms was evaluated by numerical simulations using an ABR template combined with electroencephalographic (EEG) recordings obtained without sound stimulus. The suitability of a fixed SNR versus a fixed noise floor stop criterion was assessed when variations in the wave-V waveform shape reflecting inter-subject variation was introduced. Study sample: Over 100?hours of raw EEG noise was recorded from 17 adult subjects, under different conditions (e.g. sleep or movement). Results: ABR feature accuracy was similar for the four algorithms. However, it was shown that a fixed noise floor leads to higher ABR wave-V amplitude accuracy; conversely, a fixed SNR yields higher wave-V latency accuracy. Conclusion: Similar performance suggests the use of the less computationally complex algorithms. Different stop criteria are recommended if the ABR peak latency or the amplitude is the outcome measure of interest.     

A study of auditory middle latency responses in relation to electrode combinations and stimulus conditions

Auditory middle latency responses were recorded from healthy right-handed subjects. Acoustic clicks at a rate of 10/s were presented to the subjects via headphones. Using the electrode combination unilateral mastoid-nose tip, responses characterized by two early negative waves (about 11.5 and 18 ms peak latencies), followed by a late positive one (about 30 ms peak latency), were elicited by binaural stimulation (50-dB SL clicks). The waveform of responses from the unilateral mastoid-nose tip combination was similar to that recorded from a combination of the same side mastoid and a balanced noncephalic reference electrode, although the phase was opposite to that recorded from the Cz-unilateral mastoid combination. Auditory middle latency responses were recorded simultaneously from right mastoid and left mastoid and referenced to the nose tip; interaural differences in amplitude were found in most subjects. The amplitudes of the early components for binaural stimulation were larger than those for monaural stimulation.     

Effects of stimulus rate and gender on the auditory middle latency response

The effects of stimulus rate and gender on the auditory middle latency response (AMLR) waveforms were examined in 20 young adult male and female subjects. Four different repetition rates were presented to subjects (1.1/sec, 4.1/sec, 7.7/ sec, and 11.3/sec). Stimulus repetition rate had a significant effect on Pa latency, Pa amplitude, and Pb amplitude. Pa and Pb amplitudes decreased with increasing the stimulus rate, and Pa latency significantly increased with increasing the stimulus rate. No significant differences were seen on Pb latency or site of recording. Gender had a significant effect on Pa latency and Pa amplitude. Pa latencies were longer in male subjects, and Pa amplitudes were larger in female subjects. Gender did not have a significant effect on the Pb waveform.