Middle Latency Response Amplitude Research Articles

Hearing protection and damage mitigation in Chinchillas exposed to repeated low-intensity blasts

Repeated exposures to blast overpressure (BOP) introduce hearing complaints in military service members even with the use of hearing protection devices (HPDs). Although epidemiology and animal studies have been performed to investigate the damage formation mechanism of blast-induced hearing damage, there is still a lack of understanding and therapeutic solutions, especially for HPD-protected ears. Recent studies revealed the potential therapeutic function of liraglutide, a glucagon-like peptide-1 receptor agonist, to facilitate post-blast hearing restoration in chinchillas. This study is a continuation and summary of the previous studies performed by Jiang et al. (2021, 2022) to investigate the damage mitigation function of liraglutide treatment in chinchillas with open and protected ears after repeated low-intensity blast exposures within 28 days of observation.Chinchillas were divided into six experimental groups: pre-blast treatment, post-blast treatment, and blast control with ears open or protected by earplug (EP). All animals were exposed to six consecutive blasts at the level of 3–5 psi (21–35 kPa) on Day 1. Hearing function tests including auditory brainstem response (ABR), distortion product otoacoustic emission (DPOAE), and middle latency response (MLR) were performed on Day 1 (pre- and post-blast) and Days 4, 7, 14, and 28 after blast exposure.Results indicated that the damage mitigation function of the liraglutide treatment in the open-ear chinchillas was reflected by the significantly lower ABR threshold shifts in the drug treatment groups than in the blast controls. In EP groups, the higher ABR wave I/V ratio and lower MLR amplitude observed in the drug-treated chinchillas suggested that the post-blast hyperactivities in the auditory system might be potentially ameliorated by the liraglutide treatment. The 28-day-long experiment showed the effect of liraglutide treatment increased with time in both open and EP groups.This study demonstrated that the use of HPDs prevented the blast-induced complications in the middle ear and reduced the damage caused in the central auditory system. The liraglutide treatment showed an effect increasing with time and different outcomes in open and EP chinchillas. This innovation in the animal model of chinchilla provides insights to investigate subtle changes in the higher-level structures of the auditory system.

Auditory Brainstem and Middle Latency Responses Measured Pre- and Posttreatment for Hyperacusic Hearing-Impaired Persons Successfully Treated to Improve Sound Tolerance and to Expand the Dynamic Range for Loudness: Case Evidence.

In this report of three cases, we consider electrophysiologic measures from three hyperacusic hearing-impaired individuals who, prior to treatment to expand their dynamic ranges for loudness, were problematic hearing aid candidates because of their diminished sound tolerance and reduced dynamic ranges. Two of these individuals were treated with structured counseling combined with low-level broadband sound therapy from bilateral sound generators and the third case received structured counseling in combination with a short-acting placebo sound therapy. Each individual was highly responsive to his or her assigned treatment as revealed by expansion of the dynamic range by at least 20 dB at one or more frequencies posttreatment. Of specific interest in this report are their latency and amplitude measures taken from tone burst-evoked auditory brainstem response (ABR) and cortically derived middle latency response (MLR) recordings, measured as a function of increasing loudness at 500 and 2,000 Hz pre- and posttreatment. The resulting ABR and MLR latency and amplitude measures for each case are considered here in terms of pre- and posttreatment predictions. The respective pre- and posttreatment predictions anticipated larger pretreatment response amplitudes and shorter pretreatment response latencies relative to typical normal control values and smaller normative-like posttreatment response amplitudes and longer posttreatment response latencies relative to the corresponding pretreatment values for each individual. From these results and predictions, we conjecture about the neural origins of the hyperacusis conditions (i.e., brainstem versus cortical) and the neuronal sites responsive to treatment. The only consistent finding in support of the pre- and posttreatment predictions and, thus, the strongest index of hyperacusis and positive treatment-related effects was measured for MLR latency responses for wave Pa at 2,000 Hz. Other response indices, including ABR wave V latency and wave V-V' amplitude and MLR wave Na-Pa amplitude for 500 and 2,000 Hz, appear either ambiguous across and/or within these individuals. Notwithstanding significant challenges for interpreting these findings, including associated confounding effects of their sensorineural hearing losses and differences in the presentation levels of the toneburst stimuli used to collect these measures for each individual, our limited analyses of three cases suggest measures of MLR wave Pa latency at 2,000 Hz (reflecting cortical contributions) may be a promising objective indicator of hyperacusis and dynamic range expansion treatment effects.

迷走神経刺激がラット聴皮質における順応反応に及ぼす影響

Vagus nerve stimulation (VNS) causes neuromodulatory effects in the cerebral cortex, which are useful not only for therapy on intractable epilepsy but also for enhancement of higher brain functions such as cognition and memory. Recently, it has been reported that VNS may also affect auditory-evoked neural activities. However, it remains to be elucidated how and where VNS modulates neural activities in the auditory cortex. Here we examined effects of VNS on adaptation of neural activities in response to repeated stimuli in the rat auditory cortex. Both a surface and depth microelectrode array recorded auditory evoked potentials in response to click trains and oddball stimuli. We quantified a repetition rate transfer function (RRTF) and common stimulus-specific adaptation (SSA) index (CSI) from the amplitude of middle-latency response (P1). Consequently, VNS affected temporal response property and increased SSA in the layer 1 and 5/6 of auditory cortex. This result suggests that VNS strengthens adaptation in the auditory cortex in a layer-specific manner.

The Influence of Aging on Interaural Asymmetries in Middle Latency Response Amplitude

Auditory-evoked potentials (EPs) provide a more objective assessment of central auditory nervous system (CANS) dysfunction when compared to behavioral measures because they do not require a behavioral response (Anderson and Kraus, 2010). In this regard, the middle latency response (MLR) has been considered an important component of CANS assessment (Jerger et al, 1988); however, its large within-group variability limits its usefulness (Musiek et al, 1999). It has been argued that performing intratest calculations on the MLR (e.g., difference in EP amplitude when stimulating the left ear versus the right ear) can reduce the within-group variability of the MLR and enhance its clinical usefulness (Musiek et al, 1999; Weihing et al, 2012). To date, it has not been investigated how well these MLR intratest measures reduce within-group variability in adults of various ages, nor has it been shown that these intratest measures are sensitive to aging-related changes in the CANS. The two primary goals of the present study were (1) to determine if calculating an intratest MLR measure, the difference in MLR Na-Pa peak-to-peak amplitude on left versus right ear stimulation (i.e., "ear effects"), will reduce within-group variability in adults of various ages; and (2) to determine if ear effect magnitude will change as a function of aging. Ear effects were measured in both quiet and in noise to determine if the addition of noise enhanced any age-related-effects. A cross-sectional study was conducted. The researchers studied 30 adults ranging in age from 20-80 yr with hearing sensitivity of 25 dB HL or better at the octave frequencies from 500-2000 Hz, and no history of neurologic issues. Adults were assigned to one of three age groups based on their chronological age, which were young adults, middle-aged adults, and older adults. MLRs were acquired using a Nicolet Spirit 2000 during a single laboratory visit. To determine if within-group variability decreased significantly with ear effects, variability for absolute amplitude measures was compared to ear effect variability using the Pitman t-test. To examine potential effects of background noise and aging, data were analyzed using a mixed-factorial analysis of variance with the within-subjects factor "background noise" and the between-subjects factor "age group." Within-group variability was significantly reduced by calculating ear effects for the youngest group only. Additionally, the oldest adults in the present sample showed significantly larger ear effects than younger and middle-aged adults. This effect did not appear to be a result of differences in peripheral hearing sensitivity. Finally, introducing noise into the paradigm did not influence the observed effects. Ear effects become larger in older adults possibly as a result of age-related changes in the subcortical and/or cortical generators of the MLR. Failure of the ear effect calculation to reduce within-group variability in the middle-aged and older adults suggests that interaural asymmetries in MLR amplitude become more variable across participants who are older than 50 yr. Information obtained from this measure may benefit the development of treatment plans for older adults with hearing difficulties.

Ear and electrode effects reduce within-group variability in middle latency response amplitude measures

Objectives: To establish normative amplitude values for relative difference measurements of the middle latency response (MLR) in normal-hearing pediatrics and to determine if these measurements provided a significant reduction of within-group variability when compared to raw, absolute amplitude measures. A relative amplitude difference is defined in the present paper as the difference in Na-Pa amplitude between two electrodes (e.g. |Na-Pa at C3 minus Na-Pa at C4|, or electrode effects) or between two ears (e.g. |Na-Pa on left ear stimulation minus Na-Pa on right ear stimulation|, or ear effects). In contrast, an absolute amplitude is defined as a single Na-Pa measurement made at one electrode for stimulation of one ear (e.g. Na-Pa measured at C3 on left ear stimulation). Design: Cross-sectional study. Study sample: 155 pediatrics with normal peripheral and central hearing, and no history of psychological, neurological, or learning disability issues. Results: Within-group variability was significantly smaller for relative differences when compared to absolute amplitude measures. Electrode effects showed significantly less variability than ear effects. Normative values for ear and electrode effects were reported. Conclusions: Relative differences may provide better utility in the clinical diagnosis of central auditory pathology in pediatrics when compared to absolute amplitude measures because these difference measures show significantly lower variability when examined across subjects.

Behavioral and Electrophysiologic Binaural Processing in Persons with Symmetric Hearing Loss

Binaural hearing improves our ability to understand speech and to localize sounds. Hearing loss can interfere with binaural cues, and despite the success of amplification, ∼25% of people with bilateral hearing loss fit with two hearing aids choose to wear only one (e.g., Brooks and Bulmer, 1981). One explanation is reduced binaural processing, which occurs when the signal presented to one ear interferes with the perception of the signal presented to the other ear (e.g., Jerger et al, 1993). Typical clinical measures, however, are insensitive to binaural processing deficits. The purpose of this study was to determine the extent to which behavioral measures of binaural performance were related to electrophysiological measures of binaural processing in subjects with symmetrical pure-tone sensitivity. The relationship between middle latency responses (MLRs) and behavioral performance on binaural listening tasks was assessed by Spearman's rho correlation analyses. Separate repeated measures analyses of variance (RMANOVAs) were performed for MLR latency and MLR amplitude. Nineteen subjects were recruited for the present study based on a clinical presentation of symmetrical pure-tone sensitivity with asymmetrical performance on a word-recognition in noise test. This subpopulation of patients included both subjects with and subjects without hearing loss. Monaural and binaural auditory processing was measured behaviorally and electrophysiologically in right-handed subjects. The behavioral tests included the Words-in-Noise test (WIN), the dichotic digits test (DDT), and the 500 Hz masking level difference (MLD). Electrophysiologic responses were measured by the binaural interaction component (BIC) of the MLR. The electrophysiological responses were analyzed to examine the effects of peak (Na, Pa, and Nb) and condition (monaural left, monaural right, binaural, and BIC) on MLR amplitude and latency. Significant correlations were found among electrophysiological measures of binaural hearing and behavioral tests of binaural hearing. A strong correlation between the MLD and the binaural Na-Pa amplitude was found (r = .816). The behavioral and electrophysiological measures used in the present study clearly showed evidence of reduced binaural processing in ∼10 of the subjects in the present study who had symmetrical pure-tone sensitivity. These results underscore the importance of understanding binaural auditory processing and how these measures may or may not identify functional auditory problems.

Effect of auditory training on the middle latency response in children with (central) auditory processing disorder

The purpose of this study was to determine the middle latency response (MLR) characteristics (latency and amplitude) in children with (central) auditory processing disorder [(C)APD], categorized as such by their performance on the central auditory test battery, and the effects of these characteristics after auditory training. Thirty children with (C)APD, 8 to 14 years of age, were tested using the MLR-evoked potential. This group was then enrolled in an 8-week auditory training program and then retested at the completion of the program. A control group of 22 children without (C)APD, composed of relatives and acquaintances of those involved in the research, underwent the same testing at equal time intervals, but were not enrolled in the auditory training program. Before auditory training, MLR results for the (C)APD group exhibited lower C3-A1 and C3-A2 wave amplitudes in comparison to the control group [C3-A1, 0.84 microV (mean), 0.39 (SD--standard deviation) for the (C)APD group and 1.18 microV (mean), 0.65 (SD) for the control group; C3-A2, 0.69 microV (mean), 0.31 (SD) for the (C)APD group and 1.00 microV (mean), 0.46 (SD) for the control group]. After training, the MLR C3-A1 [1.59 microV (mean), 0.82 (SD)] and C3-A2 [1.24 microV (mean), 0.73 (SD)] wave amplitudes of the (C)APD group significantly increased, so that there was no longer a significant difference in MLR amplitude between (C)APD and control groups. These findings suggest progress in the use of electrophysiological measurements for the diagnosis and treatment of (C)APD.

Auditory evoked potentials for monitoring during anaesthesia: A study of data quality

The auditory evoked potential termed the middle latency response (MLR) has been suggested as an indicator of adequacy of anaesthesia during surgery. However, the response is small and must be extracted from high levels of background noise. A key consideration in using the MLR for clinical monitoring is whether data quality is sufficient to detect small changes. The aim of this study was to investigate the quality of the MLR recorded during anaesthesia, as a rigorous analysis of data quality is lacking in many studies. MLR recordings from patients sedated in intensive care after cardiac surgery were compared to recordings from a reference group of young volunteers with normal hearing. Data quality was measured with the F sp parameter. A bootstrap analysis was used to measure statistical response presence and to detect within-subject changes during clinical anaesthesia. Noise levels were high in the normative group probably due to myogenic and EEG activity. With 5 Hz click stimulation, MLR presence in the normative group was below 30%. Response presence improved using stimulation paradigms with chirps or maximum length sequences and reached 100% with a combination of maximum length sequences and chirps. F sp values generally improved during anaesthesia as noise levels reduced and MLR presence was 100% for MLS click stimulation. Changes in the MLR amplitude with propofol infusion rate were small. Some within-subject changes in MLR amplitude were detected using the bootstrap analysis, but 100% detection was not possible. Conclusion: Obtaining good quality MLR data in awake subjects is challenging. Data quality improves during clinical anaesthesia and with advanced stimulation methods, but reliable detection of changes in the MLR for clinical monitoring remains a challenge.

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.

The Auditory Middle Latency Response, Evoked Using Maximum Length Sequences and Chirps, as an Indicator of Adequacy of Anesthesia

The auditory evoked potential known as the middle latency response (MLR), evoked with regular click stimulation at around 5 Hz, has been suggested as an indicator of adequacy of anesthesia. The MLR is a very small signal embedded in high levels of background noise, so it can take a long time to acquire. However, using a stimulus paradigm of chirps presented in a maximum length sequence, the acquisition of the MLR can be improved compared to using conventional click stimulation. In this pilot study, we investigated this new technique in a clinical environment. Significant changes in MLR amplitude, but not latency, were measured for six of seven subjects in association with changes in responsiveness to command using the isolated forearm technique. The absence of any latency shift differs from other studies of the MLR during anesthesia and highlights the limited understanding of the relationship between anesthesia and the MLR.

Sensitivity of the auditory middle latency response of the guinea pig to interaural level and time differences

This study examines the extent to which the auditory middle latency response (MLR) of the guinea pig is sensitive to sound localization cues such as interaural level and time differences (ILD and ITD, respectively). The MLR was recorded with an epidural electrode placed over the auditory cortex of an anesthetized guinea pig. Click stimuli were presented monaurally or binaurally with various ILDs and ITDs. The MLR was much larger for contralateral stimulation than for ipsilateral stimulation, and its amplitude was intermediate for diotic stimulation. The MLR amplitude was sensitive to both ILD and ITD: it decreased as the ipsilateral stimulus increased in level or advanced in time relative to the contralateral stimulus. The steep slope of the amplitude-versus-ITD function fell within an ITD range of ±330 μs, namely the guinea pig’s physiological ITD range. The response reduction that resulted from increasing the relative level of the ipsilateral level could be cancelled out by advancing the contralateral onset time relative to the ipsilateral onset time. This parallels the “time-intensity trading” in sound lateralization exhibited in human psychophysics. The results imply that the binaural interaction in the guinea pig MLR reflects aspects of neural processes that are involved in sound localization.

Effect of noise exposure on gap detection in rats

The effects of intense (110–120 dB) noise exposure (broadband noise for one hour) on temporal resolution was estimated in rats by measuring the behavioural gap detection threshold (GDT). Changes in GDT after 120 dB noise exposure were compared with changes in the threshold and amplitude of middle latency responses (MLR) recorded in response to tone stimuli. GDT values increased from 1.6 to 4.3 or 7.8 ms after exposure to 110 or 115 dB SPL, respectively; GDT recovered to pre-exposure values in 3–7 days. Three main types of noise-induced changes were observed after 120 dB SPL exposure: (I) GDT changes similar to those following noise exposure to 115 dB SPL and maximal hearing threshold shifts (TSs) at high frequencies of about 45 dB; (II) more pronounced changes in GDT (up to 60 ms) with maximal hearing threshold shifts of about 65 dB and (III) a lack of reliable responses to gap during the first weeks post-exposure with maximal hearing threshold shifts of about 80 dB. An increased GDT was present two months after noise exposure in animals with types II and III post-exposure changes; enhanced MLR amplitudes were also found in most of these in the first post-exposure week. The pronounced deficit in gap detection in some rats after 120 dB SPL noise exposure may signal the presence of a noise-induced tinnitus.

Dynamics of the contralateral white noise-induced enhancement in the guinea pig's middle latency response

The peak-to-peak amplitude of temporal middle latency response (MLR) of the guinea pig, evoked by a click in the contralateral ear, according to the recording side, is increased with the presence of continuous white noise (CWN) in the ipsilateral ear and this specialty is defined as the white noise enhancement (WNE). This phenomenon is evaluated as an interesting electrophysiological finding from the viewpoint of binaural interaction and in this study, its dynamic specifications were investigated. After the beginning of ipsilateral CWN, significant WNE was observed at 275th ms and it reached to a maximum, with an increase more than 40%, at 350th ms. After a habituation occurred, WNE reached to 20% on the 4th second by gradually decreasing and came to a steady state. In the time window between 2 and 5 ms after CWN started, a surprising amplitude decrease is observed. Therefore, CWN causes an effect, like a click, in the short-term and this on-response type effect originates from low level binaural centers, which decreases the MLR amplitude. However, the same CWN increases the MLR amplitude (WNE) by the effects over the high level binaural centers in the succeeding period, by its continuous characteristic.

Effects of isoflurane on auditory middle latency (MLRs) and steady-state (SSRs) responses recorded from the temporal cortex of the rat

Auditory steady-state responses (SSRs) are believed to result from superimposition of middle latency responses (MLRs) evoked by individual stimuli during repetitive stimulation. Our previous studies showed that besides linear addition of MLRs, other phenomena, mainly related to the adaptive properties of neural sources, interact in a complex way to generate the SSRs recorded from the temporal cortex of awake rats. The aim of this study was to evaluate the effects of the inhalational general anesthetic, isoflurane, on MLRs and SSRs at several repetition rates (30–60 Hz) recorded from the temporal cortex of rats. Auditory evoked potentials were obtained by means of epidural electrodes in the awake condition and during anesthesia at three isoflurane concentrations (0.38, 0.76 and 1.13 vol.% in oxygen). MLR latency significantly increased during anesthesia in a concentration-dependent manner, while MLR amplitude, even when significantly attenuated with respect to the mean awake baseline value, failed to correlate with isoflurane concentration. SSRs decreased in amplitude and increased in phase during anesthesia in a concentration-dependent manner and the anesthetic-induced decrease of SSR amplitude appeared to be higher than the corresponding MLR attenuation. SSR prediction curves synthesized by linear addition of MLRs failed to predict SSRs in both amplitude and phase. Moreover, phase discrepancies proved to be higher during anesthesia. Our results suggest that MLRs and SSRs recorded from the temporal cortex of the rat exhibit differential sensitivity to isoflurane and that isoflurane could enhance the role of rate-dependent effects in SSR generation.

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.

Susceptibility to noise exposure during postnatal development in rats

Susceptibility to noise-induced hearing loss was studied during maturation in 20 female pigmented rats (strain Long–Evans). Young rats, 3, 4, 5 and 6–7 weeks old, were exposed for 1 h to a broad-band noise with an intensity of 120 dB SPL. The thresholds and amplitudes of middle latency responses (MLR) recorded from electrodes implanted on the surface of the auditory cortex were analyzed before and after noise exposure. The results were compared with data from our previous study, in which the effects of broad-band noise exposure on MLR were investigated in adult rats [Syka, J. and Rybalko, N. (2000) Hear. Res. 139, 59–68]. The hearing thresholds of 3–7 week old rats before noise exposure were within the normal adult range. Noise exposure in young rats produced an adult-like pattern with an elevation of hearing thresholds. One–two weeks post-exposure a recovery of MLR thresholds was observed, though full recovery only occurred in the low frequency range. Recovery of hearing thresholds in the high frequency range depended on the age of the animal at the time of exposure. In all animals aged less that 6–7 weeks, exposure resulted in a permanent threshold shift in the range of 4–32 kHz. The mean values of permanent threshold shifts at 16 kHz (the frequency of maximal hearing loss) were 53.0±4.5, 47.6±9.6, 37.5±7.5 and 27±10 dB for rats exposed at 3, 4, 5 and 6–7 weeks of age, respectively. Similar to adult rats, young rats exposed to noise exhibited an enhancement of MLR amplitudes. This amplitude enhancement was more pronounced in the high frequency range. In several rats exposed at 3–5 weeks of age, the recovery period to normal amplitudes was substantially prolonged and lasted 4–8 weeks in comparison with 1–2 weeks in adult rats. These results demonstrate a greater susceptibility to noise exposure in rats during the first 5 postnatal weeks.

Threshold shifts and enhancement of cortical evoked responses after noise exposure in rats

The effect of exposure to various types of noise (broadband, high-frequency or low-frequency) was studied in adult pigmented rats. Thresholds and amplitudes of middle latency responses (MLR) recorded from electrodes implanted on the surface of the auditory cortex were analyzed before and after noise exposure. Exposure to noise with intensities ranging from 105 to 120 dB for 1 h produced only temporary threshold shifts (TTS). Exposure to broadband noise produced TTS throughout the whole frequency range of the rat’s hearing, mostly expressed at frequencies of maximal hearing sensitivity (16–32 kHz). Hearing loss produced by high- or low-frequency noise exposure was related to the spectral characteristics of the noise. The exposure to high-intensity noise may also result in amplitude enhancement of the MLR. This phenomenon was seen mainly after broadband noise exposure and occurred in response to both low-frequency and high-frequency test stimuli. High-frequency and low-frequency noise produced amplitude enhancement mainly at frequencies which corresponded to the maximum exposure energy. In contrast to the relatively similar values of TTS obtained in different rats under the same conditions of noise exposure, great inter-individual variability was found in the MLR amplitude enhancement. In all rats the dynamics of recovery functions for amplitude enhancement were different from those for MLR thresholds. The data indicate that whereas post-exposure TTS are related to peripheral changes, the post-exposure MLR amplitude enhancement is most probably connected with a change in the processing of auditory information in the central nervous system.

Possible modulation of auditory middle latency responses by nitric oxide in the inferior colliculus of anaesthetized rats

Nitric oxide (NO) is a short-lived radical species endowed with intercellular signalling functions in the mammalian brain. In the present study we have investigated the effects of focal injection into one inferior colliculus of N ω-nitro- L-arginine methyl ester ( L-NAME), a nitric oxide synthase inhibitor, on the acoustic middle latency responses (MLRs) evoked by click stimuli and recorded from the auditory cortex in anaesthetized rats. Microinfusion of L-NAME (1.0 mM) did not alter the latency of MLRs nor did it affect the evoked brain stem responses (ABRs). By contrast, L-NAME reduced P 1a—N 1 amplitude of MLRs by 51.7 ± 6.6% (mean ± SEM; n = 5) and almost complete recovery to background amplitude was obtained 15–25 min after treatment. The less active isomer, D-NAME (1.0 mM; n = 5), failed to produce consistent effects on the evoked MLRs. A higher concentration of L-NAME (5.0 mM; n = 5) yielded a 69.0 ± 13.3% inhibition whereas maximum inhibition produced by 0.5 mM ( n = 3) L-NAME was ≌10% of control value. The inhibitory effect typically evoked by 1.0 mM L-NAME was prevented by treating rats with L-arginine (5.0 mM; n = 5), the endogenous precursor of NO synthesis. Reduction of MLR amplitude was also obtained in rats receiving intracollicular injection of dizocilpine (MK801; 1.0 μM) and LY274614 (1.0 mM), two selective [ N-methyl- D-aspartate (NMDA) receptor antagonists. In conclusion, the present data support a role for intracollicular NO in the processing and transmission of the acoustic input to the auditory cortex in the rat.

Auditory Evoked Responses in Children During Hypothermic Cardiopulmonary Bypass

Variations in core temperature and cerebral blood flow during open heart surgery may affect auditory brainstem responses (ABRs) and middle latency responses (MLRs) in both adults and children. We documented the changes in ABRs of two infants (ages 3 and 11 weeks, respectively) with variations in core temperature during hypothermic cardiopulmonary bypass and total circulatory arrest and compared them with those of a 19-year-old adult. Changes in MLRs that occurred in association with reductions in cerebral blood flow as monitored by transcranial Doppler are also reported in a 6-year-old child. With the reductions in temperature in both infants and the young adult, ABR latencies increased and amplitudes decreased. Effects of hypothermia on ABR latencies were completely reversed by rewarming. MLR amplitudes were transiently reduced during periods of normothermic hypoperfusion. Hypothermia partially prevented these changes, and normoperfusion after rewarming recovered MLRs. Monitoring ABRs and MLRs may be a useful technique for assessment of brain function during hypothermic cardiopulmonary bypass in children and infants.

Primary auditory pathway and reticular activating system dysfunction in Alzheimer's disease.

Patients with Alzheimer's disease (AD) have pathologic involvement of several important components of the primary auditory pathway, including the inferior colliculus, medial geniculate body, primary auditory cortex, and secondary auditory cortex. The main components of the brainstem auditory evoked response (BAER) and middle latency response (MLR) reflect the function of portions of the primary auditory pathway, including those affected pathologically in AD. The amplitude of the P1 component of the MLR reflects the degree of neuronal activity of midbrain portions of the ascending reticular activating system (ARAS) with cortical cholinergic projections. To determine whether there is dysfunction of the primary auditory pathway and ARAS in AD, we compared simultaneous BAER and MLR component latency and amplitude measurements in patients with mild-moderate AD (n = 35) and age-matched healthy elderly controls (n = 34). There were significant latency delays in brainstem transmission time (BAER I-V interpeak latency; p < 0.05) and in primary auditory cortex evoked potential generation (MLR Pa latency; p < 0.05) in the AD group compared with controls. In addition, there was a significant reduction in the P1 component amplitude of the MLR in the AD group (p < 0.01). These results indicate dysfunction of the primary auditory pathway and ARAS in patients with mild-moderate AD and support the hypothesis that impairment of auditory function and of arousal are intrinsic features of AD.