Auditory-evoked Responses Research Articles

Complex segregation analysis of deafness in Dalmatians.

To use pedigree analysis to evaluate the feasibility of a major locus model for deafness in Dalmatians. 605 purebred Dalmatians from 42 families. Hearing loss was evaluated through the brainstem auditory-evoked response. Dogs were classified into mutually exclusive categories: normal hearing, unilaterally deaf, or bilaterally deaf. Information was collected on sex, coat color, presence or absence of a color patch at birth, and eye color. Statistical analyses were performed by use of regressive logistic models designed for complex segregation analysis. Genetic correlations among eye color, deafness, and color patch were estimated. Prevalence of hearing loss was 11% for dogs classified as unilaterally deaf and 5% for dogs that were bilaterally deaf. Complex segregation analysis detected statistical evidence of a single allele with an expected frequency of 0.21 that had an effect on the prevalence of deafness. Results of analyses suggested that this locus cannot completely explain the inheritance and incidence of deafness in Dalmatians. Genetic correlation estimates among deafness, eye color, and color patch revealed strong interrelationships among these characteristics. To reduce the incidence of hearing loss in Dalmatians, unilaterally deaf, blue-eyed dogs should not be considered as potential parents.

Auditory evoked responses and learning and awareness during general anesthesia.

There is a major distinction between conscious and unconscious learning. Monitoring the mid-latency auditory evoked responses (AER) has been proposed as a measure to ascertain the adequacy of the hypnotic state during surgery. In the present study, we investigated the presence of explicit and implicit memories after anesthesia and examined the relationships of such memories to the AER. We studied 180 patients scheduled for elective surgical procedures. After a thiopental induction, one of four anesthetics were studied: Opioid bolus: 7.5 microg x kg(-1) fentanyl, 70% N2O, with 2.5 microg x kg(-1) supplements as needed (n=100); Opioid infusion: Alfentanil 50 microg x kg(-1) bolus, 1-1.5 microg x kg(-1) x min(-1) infusion, 70% N2O (n=40); Isoflurane 0.3%: Fentanyl 1 microg x kg(-1), 70% N2O, isoflurane 0.3% expired (n=16); Isoflurane 0.7%: Fentanyl 1 microg x kg(-1), 70% N2O, isoflurane 0.7% expired (n=23). AER were recorded before anesthesia, 5 min after surgical incision and then every 30 min until the end of surgery. A tape of either the story of the "Three Little Pigs" or the "Wizard of Oz" was played continuously between the recordings. Explicit memory was assessed postoperatively by tests of recall and recognition, and implicit memory was assessed by the frequency of story-related free associations to target words from the stories, which were solicited twice during a structured interview. Six patients showed explicit recall of intraoperative events: All received the opioid bolus regimen. About 7% of patients reported dreaming during anesthesia. The incidence of picking the correct story that had been presented during anesthesia averaged 49%, i.e., very close to chance level. Overall, priming occurred only at the second association tests for the opioid bolus regimen, for which the frequency of an association to the presented story among those not giving an association to the control story was 26%, which was double the frequency (13%) of an association to the control story among those not giving an association to the presented story. This was significant by McNemar's test, P=0.02. There were significant associations between awareness, priming and AER, e.g., recall was associated with higher Nb amplitudes during anesthesia and priming was associated with shorter wave latencies. The incidence of awareness in patients anesthetized with nitrous oxide and bolus supplementation was 6%. Thus, this anesthetic technique did not reduce the risk of awareness compared with the use of nitrous oxide alone. Implicit memory occurred during nitrous oxide and bolus supplementation. Recording AER during anesthesia may help to predict awareness and implicit memory, particularly the former. The short contents of most of the dreams which were recalled could hamper future studies in this area.

Challenges of recording human fetal auditory-evoked response using magnetoencephalography.

Our goals were to successfully perform fetal auditory-evoked responses using the magnetoencephalography technique, understand its problems and limitations, and propose instrument design modifications to improve the signal quality and success rate. Fetal auditory-evoked responses were recorded from four fetuses with gestational ages ranging from 33-40+ weeks. The signals were recorded using a gantry-based superconducting quantum interference device. Auditory stimulus was 1 kHz tone burst. The evoked signals were digitized and averaged over an 800 ms window. After several trials of positioning and repositioning the subjects, we were able to record auditory-evoked responses in three out of the four fetuses. Since the superconducting quantum interference device array design was not shaped to fit over the mother's abdomen, we experienced difficulty in positioning the sensors over the fetal head. Based on this pilot study, we propose instrument design that may improve signal quality and success rate of the fetal magnetic auditory-evoked response.

Vestibular Function in Auditory Neuropathy

Auditory neuropathy is characterized by mild-to-moderate pure-tone hearing loss, poor speech discrimination out of proportion with this loss, absent or abnormal auditory brainstem responses and normal outer hair cell function as measured by otoacoustic emissions and cochlear microphonics. We followed three patients in our clinic whom we classified as auditory neuropathy patients. These patients also complained of balance disorders and we report our auditory and vestibular system analyses of these patients. The data presented herein include results of audiometric tests (serial pure-tone audiometry and speech discrimination tests), otoacoustic emissions, auditory-evoked brainstem responses and vestibular function tests (clinical tests of balance, electronystagmography, damped rotation tests and vestibular-evoked myogenic potentials). In all patients, pure-tone audiometry revealed mild-to-moderate sensorineural hearing loss, markedly poor speech discrimination scores and absent auditory-evoked brainstem responses, all in the presence of normal otoacoustic emissions. Balance tests (caloric tests and damped rotation test) were abnormal. Saccades, smooth pursuit eye movements and optokinetic nystagmus were normal in all patients. Neurological and motor system evaluations were normal in all patients. These three auditory neuropathy patients manifest a disorder of cochlear nerve function in the presence of normal outer hair cell activity. They additionally manifest a disorder of the vestibular nerve and its end organs. We conclude that, in patients with isolated auditory neuropathy, the vestibular branch of the VIIIth cranial nerve and its innervated structures may also be affected. We suggest the use of the term "cochlear neuropathy" to characterize those patients with involvement of only the auditory branch of the VIIIth cranial nerve and its innervation.

Blood-Perilymph Barrier and Ototoxicity: An In Vivo Study in the Rat

Cisplatin and gentamicin are two ototoxicants that are supposed to be transported by the paracellar route, i.e. via cellular junctions, to the perilymphatic compartment. This study was initiated to test the hypothesis that susceptive variation of individuals to ototoxic drugs may be explained by variability in transport properties. The transport of radioactive mannitol through the blood-perilymph barrier was correlated in vivo with the acute effect of cisplatin and gentamicin on auditory function. Transport of radioactive mannitol across the blood-perilymph barrier was monitored by sampling of scala vestibuli perilymph at 60 and 120 min after an intravenous infusion of the tracer to nephrectomized Long Evans rats. Counting of hair cell loss was performed in the animals receiving 16 mg/kg body weight cisplatin. The transport of radioactive mannitol across the blood-perilymph barrier did not correlate with the ototoxic effect of cisplatin, evaluated as changes in the auditory-evoked brainstem response thresholds or loss of outer hair cells. The results provide evidence that the barrier function is not involved in the interindividual variability of the ototoxic effect of cisplatin. Furthermore, it can be postulated that neither cisplatin nor gentamicin induce a disruption of endothelial cell junction stability in the inner ear.

Intrauterine growth retardation and brainstem auditory‐evoked response in preterm infants

Intrauterine growth retardation is frequently associated with intrauterine undernutrition, and can deleteriously affect brain function. Twenty‐eight premature small for gestational age infants were compared with 28 premature appropriate for gestational age infants to determine whether intrauterine growth retardation was associated with abnormalities in the auditory pathway in the early neonatal period. The auditory pathway was studied between 4‐18 wk of life by analysis of brainstem auditory‐evoked potentials elicited by a 10/s 75 decibel above normal adult hearing level (dB nHL) click stimulus presented at the infants'ears. Peak latencies of components I, III and V, and interpeak latencies I‐III, III‐V and I‐V, yielded no statistically significant differences between groups. The present study indicates that intrauterine growth‐retarded premature infants may not have abnormalities of brainstem auditory‐evoked response in the early neonatal period.

Electrophysiological and Behavioral Methods in Early Detection of Hearing Impairment

Background Recent advances in neonatal life-support systems have contributed to the survival of high-risk newborns. However, protection of the auditory system and the prevention of sequelae is still paramount in neonatal neurology. The aim of this study was to compare auditory-evoked responses with a toy test and acoustic reflex in the early detection of hearing loss in infants. Methods Three groups were studied. The first was composed of infants showing less than a 30 dB biaural threshold in the neurophysiological test. The second group was made up of infants showing peripheral alterations on one side or both ears. The third group was comprised of infants who showed no responses at 95 dB HL in both ears after neurophysiological testing. The neurophysiological test, toy test, and acoustic reflex were performed on the same day, with masked results given to each investigator. Sensitivity and specificity for each toy test and acoustic reflex were calculated afterward. Results Forty-five controls, 44 peripheral alterations, and 8 non-response infants were studied. Most patients studied were born prior to the 37 th week of gestation with a birthweight of less than 2,250 g, received required administration of potential ototoxic drugs and mechanical ventilation, and showed hyperbilirubinemia and hypoxia. Sensitivity for each toy was as follows: drum 0.54; wooden rattle 1.0, and metallic ratle 0.88. Specificity was 0.95, 1.0, and 1.0, respectively. Acoustic reflex sensitivity was 0.38 and specificity was 0.97. Conclusions Results suggest that the wooden and the metallic rattles of the toy test can be useful tools in the study of hearing in the high-risk infant and deserve more attention in future studies.

Trial-to-Trial Variability and State-Dependent Modulation of Auditory-Evoked Responses in Cortex

Recent experimental work has provided evidence that trial-to-trial variability of sensory-evoked responses in cortex can be explained as a linear superposition of random ongoing background activity and a stationary response. While studying single trial variability and state-dependent modulation of evoked responses in auditory cortex of ketamine/xylazine-anesthetized rats, we have observed an apparent violation of this model. Local field potential and unit spike trains were recorded and analyzed during different anesthesia depths-deep, medium, and light-which were defined by the pattern of ongoing cortical activity. Estimation of single trial evoked response was achieved by considering whole waveforms, rather than just one or two peak values from each wave. Principal components analysis was used to quantitatively classify waveforms on the basis of their time courses (i.e., shapes). We found that not only average response but also response variability is modulated by depth of anesthesia. Trial-to-trial variability is highest under medium levels of anesthesia, during which ongoing cortical activity exhibits rhythmic population bursting activity. By triggering the occurrence of stimuli from the spontaneously occurring burst events, we show that the observed variability can be accounted for by the background activity. In particular, the ongoing activity was found to modulate both amplitude and shape (including latency) of evoked local field potentials and evoked unit activity in a manner not predicted by linear superposition of background activity and a stereotyped evoked response. This breakdown of the linear model is likely attributable to rapid transitions between different levels of thalamocortical excitability (e.g., spike-wave discharges), although brain "state" is relatively fixed.

Hemispheric differences on auditory evoked response suppression in schizophrenia.

Using binaural stimuli, schizophrenia subjects have worse auditory evoked response (AER) suppression than normals in a paired-click paradigm. In this study we investigated hemispheric differences in AER suppression between groups using monaural and binaural stimulus presentation. Auditory evoked responses from 12 schizophrenia and 12 normal subjects were recorded with a 148-channel whole-head biomagnetometer. One hundred and twenty pairs of clicks were presented in three counterbalanced blocks (left, right, binaural). With monaural stimuli, patients had worse M100 suppression than normals in ipsilateral (effect size -2.13) but not in contralateral hemisphere (effect size -0.43). The groups did not differ on gamma band response suppression. Overall, the best group separations were obtained with binaural stimulus presentation on M100 suppression (effect size -4.14).

Auditory evoked responses to single tones and closely spaced tone pairs in children grouped by reading or matrices abilities.

Long latency auditory evoked responses (AER) were formed to single tones and rapid tone pairs. Using the t-statistic SPM technique, children with poorer WIAT reading scores demonstrated group difference overlying the left parietal and frontal language regions but just for AER to tone pair stimuli. Variables derived from these regions were not significantly different when the same subjects were grouped by K-BIT Matrices scores. When the same children were regrouped by Matrices scores and compared using the SPM technique, differences were now seen over the right hemisphere, especially in the parietal and frontotemporal regions, for both single and two-tone derived AERs. Variables derived from these regions were not significantly different for children when grouped by reading score. AER data support a specific deficit in two-tone stimulation for poorer reading children over the left hemisphere and also a deficit to both single and two-tone stimulation over the right hemisphere for children with poorer Matrices scores.

Effect of bolus doses of alfentanil on the arousal response to intubation, as assessed by the auditory evoked response

We have studied the effect of bolus doses of alfentanil on the arousal response to intubation, using the auditory evoked response (AER) of the electroencephalogram (EEG) in 45 anaesthetized patients. After induction of anaesthesia with propofol and 20 min of positive pressure ventilation via a laryngeal mask airway with 0.6 MAC of isoflurane and 50% nitrous-oxide in oxygen, patients received saline (control), or alfentanil 15 or 50 micrograms kg-1 before intubation. The early cortical AER before and after intubation in each group was measured and compared. After intubation, Pa amplitude increased in the saline group by 60% (95% CI +10 to +130), decreased in the low-dose alfentanil group by 11% (-38 to +29) and decreased further in the high-dose alfentanil group by 26% (-49 to +7). There were significant (P < 0.005) linear trends in the three group means for Pa amplitude. Similarly, Nb latency increased in the saline group by 30% (-2 to +73), decreased in the low-dose alfentanil group by 10% (-32 to +19) and decreased further in the high-dose alfentanil group by 19% (-39 to +7). There were significant (P = 0.02) linear trends in the three group means for Nb amplitude. Systolic and diastolic arterial pressures increased after intubation in the control group, and to a lesser extent in the low-dose alfentanil group, but decreased after high-dose alfentanil. Heart rate increased after intubation in the control group but decreased in both alfentanil groups, decreasing to a greater degree in the high-dose group. There were significant (P < 0.001) linear trends for all three haemodynamic variables in the three groups. We conclude that the increase in Pa amplitude after intubation was blocked by bolus administration of alfentanil and that this effect was dose dependent.

Effect of a bolus dose of midazolam on the auditory evoked response in humans

We have studied the effect of a bolus dose of midazolam on the auditory evoked response (AER) of the electroencephalogram (EEG) in nine patients. We measured the AER in the awake patient, at the point of loss of the eyelash reflex and when airway support was required. The eyelash reflex was lost at mean 1.78 (SD 0.5) min after administration of the midazolam bolus dose. Time to airway support in the seven patients who required it was 2.74 (1.26) min. Mean Nb latency in awake patients was 44.3 ms (95% CI 41.9-46.9) which was significantly shorter than Nb latency at the clinical end-points (P < 0.001). When the eyelash reflex was lost, Nb latency was 55.7 ms (95% CI 51.4-60.3) and when airway support was needed, it was 50.9 ms (95% CI 48.6-53.2). We conclude that loss of consciousness after midazolam was associated with an increase in mean Nb latency.

Multiple single units and population responses during inhibitory gating of hippocampal auditory response in freely-moving rats

Paired clicks were presented to awake, freely-moving rats to examine neuronal activity associated with inhibitory gating of responses to repeated auditory stimuli. The rats had bundles of eight microwires implanted into each of four different brain areas: CA3 region of the hippocampus, medial septal nucleus, brainstem reticular nucleus, and the auditory cortex. Single-unit recordings from each wire were made while the local auditory-evoked potential was also recorded. The response to a conditioning stimulus was compared to the response to a test stimulus delivered 500 ms later: the ratio of the test response to the conditioning response provided a measure of inhibitory gating. Auditory-evoked potentials were recorded at all sites. Overall, brainstem reticular nucleus neurons showed the greatest gating of local auditory-evoked potentials, while the auditory cortex showed the least. However, except for the auditory cortex, both gating and non-gating of the evoked response were recorded at various times in all brain regions. Gating of the hippocampal response was significantly correlated with gating in the medial septal nucleus and brainstem reticular nucleus, but not the auditory cortex. Single-unit neuron firing in response to the clicks was most pronounced in the brainstem reticular nucleus and the medial septal nucleus, while relatively few neurons responded in the CA3 region of the hippocampus and the auditory cortex. Taken together, these data support the hypothesis that inhibitory gating of the auditory-evoked response originates in the non-lemniscal pathway and not in cortical areas of the rat brain.

Effect of remifentanil on the auditory evoked response and haemodynamic changes after intubation and surgical incision

We have observed the effect of intubation and incision, as measured by the auditory evoked response (AER) and haemodynamic variables, in 12 patients undergoing hernia repair or varicose vein surgery who received remifentanil as part of either an inhaled anaesthetic technique using isoflurane or as part of a total i.v. technique using propofol. Anaesthesia was induced with remifentanil 1 microgram kg-1 and propofol, neuromuscular block was achieved with atracurium 0.6 mg kg-1 before intubation, and anaesthesia was maintained with a continuous infusion of remifentanil in combination with either a continuous infusion of propofol or inhaled isoflurane. The AER and haemodynamic variables were measured before and after intubation and incision. The effects of intubation and incision on the AER and haemodynamic variables were not significantly different between the remifentanil-propofol and remifentanil-isoflurane groups. However, the study had a low power for this comparison. When the data for the two anaesthetic combinations were pooled, the only significant effects were increases in diastolic arterial pressure and heart rate immediately after intubation; these were not seen 5 min after intubation. There were no cardiovascular responses to incision. There were no significant changes in the AER after intubation or incision.

Psychophysiological measures of (dis)inhibition as liability indicators for schizophrenia

Two psychophysiological measures, poor suppression of midlatency auditory-evoked responses in a paired stimulus paradigm and ocular motor abnormalities, may index genetic liability for schizophrenia. An important feature of these measures is that both patients and their nonpsychotic relatives exhibit basically the same performance. These measures may be successful endophenotypes for schizophrenia because they assess poor response inhibition associated with dysfunction of dorsolateral prefrontal cortex circuitry. Data bearing on this hypothesis are reviewed, and it is posited that assessment of the auditory-evoked gamma band response and saccade measures of inhibitory abilities are the most valid behavioral measures of schizophrenia's neuropathological correlates. The extant data suggest that psychophysiological studies of schizophrenia can provide consistent and theoretically meaningful information for localizing neuropathology and for assessing the genetics of this complex disorder.

Relationship between the Brainstem Auditory Evoked Response and Extraversion, Impulsivity, and Sociability

It has been suggested that the trait of extraversion is associated with physiological arousal (Eysenck, 1967). Both psychophysiological and behavioral studies have generally supported this statement (Eysenck & Eysenck, 1985). However, recent research has suggested that the trait of impulsivity is the trait most closely linked to the physiological arousal mechanisms believed to underlie extraversion (Revelle, Humphreys, Simon, & Gilliland, 1980). This study utilized brainstem auditory evoked responses (ABRs) to investigate which trait (extraversion, impulsivity, sociability) is most closely related to hypothesized ascending reticular activating system-regulated arousal processes. The results indicated that the full scale of extraversion was related to ABR wave V activity,r= .27,p< .025, with extraverts exhibiting slower ABR latencies compared to introverts. Analyses of the subscales indicated that sociability (r= .27,p< .025), rather than impulsivity (r= .05,p< .70), contributed more to this effect.

Modification of auditory pathway functions in patients with hearing improvement after middle ear surgery

We recorded auditory-evoked magnetic responses with a whole-scalp 122-channel neuromagnetometer from seven adult patients with unilateral conductive hearing loss before and after middle ear surgery. The stimuli were 50-msec 1-kHz tone bursts, delivered to the healthy, nonoperated ear at interstimulus intervals of 1, 2, and 4 seconds. The mean preoperative pure-tone average in the affected ear was 57 dB hearing level; the mean postoperative pure-tone average was 17 dB. The 100-msec auditory-evoked response originating in the auditory cortex peaked, on average, 7 msecs earlier after than before surgery over the hemisphere contralateral to the stimulated ear and 2 msecs earlier over the ipsilateral hemisphere. The contralateral response strengths increased by 5% after surgery; ipsilateral strengths increased by 11%. The variation of the response latency and amplitude in the patients who underwent surgery was similar to that of seven control subjects. The postoperative source locations did not differ noticeably from preoperative ones. These findings suggest that temporary unilateral conductive hearing loss in adult patients modifies the function of the auditory neural pathway. (Otolaryngol Head Neck Surg 1998;119:125-30.)

Influence of Sex in Neurotransmissor Evaluation by Brainstem Auditory Evoked Responses (BERA) in Healthy Term Infants with Hyperbilirubinemia 1010

To evaluate how the sex and bilitubin levels could induce abnormalities in latency wave I and V we studied the brainstem auditory evoked reponses in neonates with hyperbilirubinemia. We analysed 29 female neonates with total bilirubin levels of 17,88±4,29 mg/dl and 51 male neonates with total bilirubin levels of 18,87±4,62 mg/dl until 48 hours of life. Latence I-V were measured by BERA using monoaural 120 dB click stimuli in Amplied MK 15. Abnormal BERA was defined as latencies I-V > 5.5 ms. Statistical analysis was performed by Mann-Withney test:

Schizophrenia, sensory gating, and nicotinic receptors.

A series of human and animal investigations has suggested that altered expression and function of the alpha7-nicotinic cholinergic receptor may be responsible for the auditory sensory gating deficit characterized in schizophrenia patients and their relatives as diminished suppression of an auditory-evoked response (P50) to repeated stimuli. This finding, in conjunction with evidence for familial transmission of this sensory gating deficit, suggests a pathogenic role of the gene for the alpha7-nicotinic receptor in schizophrenia. This article considers the possible effects of this dysfunction in a broader context. Not only is this dysfunction consistent with difficulties in sensory gating, but it might also predispose patients to problems with learning efficiency and accuracy. Such learning problems could underlie schizophrenia patients' delusional thinking, hallucinations, and social dysfunction. In addition, heavy smoking in many schizophrenia patients is consistent with the high concentration of nicotine necessary to activate the receptor and with the receptor's extremely rapid desensitization. Finally, the receptor's possible role in cell growth and differentiation should be considered in connection with developmental deficits and other cellular abnormalities in schizophrenia.

The gamma band response may account for poor P50 suppression in schizophrenia.

The relationship between gamma band response (GBR) and P50 suppression was investigated among 10 DSM-IV schizophrenia patients and 10 normal comparison subjects using neuromagnetic and electrical recordings. In a paired-click paradigm, the neuromagnetic GBR and M100 suppression data improved schizophrenia-normal group separations over the typical electrical, vertex-recorded P50 suppression measure. The neuromagnetic GBR was also superior to the magnetic equivalent of P50 (M50) for discriminating schizophrenia and normal subjects. Our data are consistent with the hypothesis that P50 may be a subcomponent of the GBR, and that P50 suppression may be a proxy for GBR suppression. Measurement of the GBR should be given consideration as another, and perhaps better, means for evaluating auditory-evoked response abnormalities among schizophrenia patients.