Chirp-evoked potentials in the awake and anesthetized rat. A procedure to assess changes in cortical oscillatory activity

Steady-state potentials are oscillatory responses generated by rhythmic stimulation of a sensory pathway. The frequency of the response, which follows the frequency of stimulation and potentially indicates the preferential working frequency of the auditory neural network, is maximal at a stimulus rate of 40 Hz for auditory stimuli in humans, but may be different in other species. Our aim was to explore the responses to different frequencies in the rat. The stimulus was a tone modulated in amplitude by a sinusoid with linearly-increasing frequency from 1 to 250 Hz ("chirp"). Time-frequency transforms were used for response analysis in 12 animals, awake and under ketamine/xylazine anesthesia. We studied whether the responses were due to increases in amplitude or to phase-locking phenomena, using single-sweep time-frequency transforms and inter-trial phase analysis. A progressive decrease in the amplitude of the response was observed from the maximal values (around 15 Hz) up to the limit of the test (250 Hz). The high-frequency component was mainly due to phase-locking phenomena with a smaller amplitude contribution. Under anesthesia, the amplitude and phase-locking of lower frequencies (under 100 Hz) decreased, while the phase-locking over 200 Hz increased. In conclusion, amplitude-modulation following responses differ between humans and rats in response range and frequency of maximal amplitude. Anesthesia with ketamine/xylazine modifies differentially the amplitude and the phase-locking of the responses. These findings should be taken into account when assessing the changes in cortical oscillatory activity related to different drugs, in healthy rodents and in animal models of neurodegenerative diseases.     

Brain-stem auditory evoked potentials in squirrel monkey (Saimiri sciureus)

To more fully characterize brain-stem auditory evoked potentials (BAEPs) in non-human primates, BAEPs were recorded from chronically implanted epidural electrodes in 10 squirrel monkeys (Saimiri sciureus). The effects of stimulus intensity, repetition rate, and anesthesia (ketamine 20 mg/kg i.m.) on peak latencies and inter-peak intervals were evaluated. Monkey wave forms consisted of approximately 7 peaks (I-VII), each exhibiting similar latencies across sessions, with later peaks exhibiting greater variability. In some subjects, additional peaks (IIa, IIIa) and slow potentials were recorded. The slow potentials provided a substratum for peaks IV through VII. As with human, monkey peaks exhibited systematic changes in latency with changes in stimulus intensity or repetition rate. These shifts included significant decreases in latency with increasing intensity for peaks I-IV and increases in latency with increases in repetition rate for peaks III, V, and VI. Inter-peak intervals were similar to those observed in human. Furthermore, ketamine anesthesia significantly delayed the latencies of most peaks (except I, V, and VII). Some differences between monkey and human BAEPs were evident in the relative amplitude of specific peaks. For example, peak V is typically most prominent in human, while this was true for peak III in monkey. The similarities between unanesthetized monkey and human inter-peak intervals suggest that the times required for impulses to reach particular brain-stem areas are conserved across primate species that vary in brain size. This supports the hypothesis that comparably numbered BAEP peaks in monkey and human index homologous processes. The data also suggest that the differences between animal and human BAEPs commonly reported may result from the use of anesthetics. In summary, unanesthetized monkey BAEPs resemble human BAEPs in morphology, number of peaks, polarity, latency variability, inter-peak intervals, slow potentials superimposed on the high-frequency peaks, and variations in morphology, amplitude, and resolution of peaks as a function of recording site. Thus, unanesthetized monkey BAEPs may be an excellent model for investigating the neural substrates of human BAEP or for determining species differences in acoustic processing among primates.     

Auditory brain-stem, middle- and long-latency evoked potentials in mild cognitive impairment.

OBJECTIVE: Mild cognitive impairment (MCI) is a selective episodic memory deficit in the elderly with a high risk of Alzheimer's disease. The amplitudes of a long-latency auditory evoked potential (P50) are larger in MCI compared to age-matched controls. We tested whether increased P50 amplitudes in MCI were accompanied by changes of middle-latency potentials occurring around 50 ms and/or auditory brain-stem potentials. METHODS: Auditory evoked potentials were recorded from age-matched controls (n = 16) and MCI (n = 17) in a passive listening paradigm at two stimulus presentation rates (2/s, 1/1.5 s). A subset of subjects also received stimuli at a rate of 1/3 s. RESULTS: Relative to controls, MCI subjects had larger long-latency P50 amplitudes at all stimulus rates. Significant group differences in N100 amplitude were dependent on stimulus rate. Amplitudes of the middle-latency components (Pa, Nb, P1 peaking at approximately 30, 40, and 50 ms, respectively) did not differ between groups, but a slow wave between 30 and 49 ms on which the middle-latency components arose was significantly increased in MCI. ABR Wave V latency and amplitude did not differ significantly between groups. CONCLUSIONS: The increase of long-latency P50 amplitudes in MCI reflects changes of a middle-latency slow wave, but not of transient middle-latency components. There was no evidence of group difference at the brain-stem level. SIGNIFICANCE: Increased slow wave occurring as early as 50 ms may reflect neurophysiological consequences of neuropathology in MCI.     

Effects of stimulus repetition rate on slow and fast components of auditory brain-stem responses

Effects of stimulus repetition rate on the slow and fast components of the auditory brain-stem response (ABR) were investigated in 10 adult subjects with normal hearing. The ABRs were recorded with click stimuli at repetition rates of 8, 13.3, 23.8, 40 and 90.9/sec and at an intensity level of 55 dB nHL. Power spectral analysis of the averaged responses was performed. Then the responses were divided into a slow component (0-400 Hz) and a fast component (400-1500 Hz) by using digital filtering technique. The magnitude of the slow component was little affected with increasing stimulus rate from 8/sec to 90.9/sec, while successive waves of the fast component, including wave V, decreased in amplitude as stimulus rate was increased. The latency of the slow component and each wave of the fast component was prolonged with increasing click rates. The shift of latency became longer in the later waves than in the earlier waves.     

Effects of simulated high altitude on event-related potential (P300) and auditory brain-stem responses.

OBJECTIVE: This study investigated the effect of hyobaric hypoxia on cognitive function. METHODS: We recorded the auditory brain-stem response (ABR) and auditory-evoked event-related potentials (ERP) in 7 male subjects during a rapid ascent to a simulated 4500 m altitude from their acclimatized altitude of 610 m. The amplitude and latency of each component of ABR and of ERP were assessed. RESULTS: Compared with the values at 610 m, at 4500 m the latencies of both waves I and V of ABR significantly increased, with no change in I-V interpeak latency; and the amplitude of wave I decreased, with no change in the amplitude of wave V. The increase in altitude affected neither the amplitude nor the latency of N100. The P300 latency was prolonged significantly after exposure to hypobaric-hypoxic conditions for 2h, with no significant change in amplitude. At 4500 m, the P300 latency returned to the baseline value after oxygen was inhaled. CONCLUSIONS: Our results suggest it is possible to boost cognitive processing by supplying oxygen even when auditory stimulus intensity decreases under hypobaric and hypoxic conditions, and that P300 latency is affected by hypoxic more than hypobaric conditions. SIGNIFICANCE: This study demonstrated that each component of ABR and the latency of both N100 and P300 are important to record when the effects of hypobaric hypoxia on cognitive function are investigated.     

Generation of the 40-Hz auditory steady-state response (ASSR) explained using convolution

OBJECTIVE: In this study, the superposition theory of the 40-Hz auditory steady-state response (ASSR) generation is investigated using auditory brainstem response (ABR) and middle latency responses (MLRs) obtained with 40 Hz jittered sequences with the continuous loop averaging deconvolution (CLAD) algorithm. METHODS: Click sequences at around 40 Hz with high (maximum length sequence), medium and low jitters were presented to normal hearing awake adult subjects monaurally. Overlapping MLR responses were deconvolved using the frequency domain CLAD method. In addition, conventional auditory MLRs at 4.88 Hz and ASSRs at 39.1 Hz were obtained in all subjects. Synthetic ASSRs were constructed using different rate and jitter MLRs as base recordings. Contributions of the primary components were investigated by wave elimination using phasors. RESULTS: Findings indicate that the generation of the 40-Hz ASSRs can be explained successfully by the superposition of the ABR and MLR waves generated at that stimulation rate. N(a)-P(a) and N(b)-P(b) components of the MLR contribute about equally (45% each), while the wave V of the ABR contributes a lesser amount (10%). CONCLUSIONS: Forty-Hertz ASSRs are composite responses generated by the superposition of the major waves of the ABR and the MLR. Dramatic amplitude increase of the ASSR at 40Hz is primarily due to the superposition of the resonating P(b) component to the P(a) wave. SIGNIFICANCE: Several unexplained properties of the 40-Hz ASSR can be explained by the stimulus and brain state dependent characteristics of the slow ABR, the P(a) and the P(b) components of the MLR.     

Midlatency auditory evoked responses: differential effects of sleep in the human

Middle latency responses (MLRs) in the 10-100 msec latency range, evoked by click stimuli, were studied in 14 adult volunteer subjects during sleep-wakefulness to determine whether such changes in state were reflected by any MLR component. Evoked potentials were collected in 500 trial averages during continuous presentation of 1/sec clicks during initial awake recordings and thereafter during a 2 h afternoon nap or all-night sleep session. Continuously recorded EEG, EOG and EMG were scored for wakefulness, stages 2-4 of slow wave sleep (SWS), and rapid eye movement (REM) sleep during each evoked potential epoch. The major components included in this study and their latency ranges, as determined by peak latency measurements from the awake records, were: ABR V, 5-8 msec, Pa, 30-40 msec, Nb, 45-55 msec, and P1, 55-80 msec. In agreement with previous reports, ABR V and Pa showed no amplitude changes from wakefulness to either SWS or REM. Not previously reported, however, was the dramatic decrease and disappearance of P1 during SWS and its reappearance during REM to an amplitude similar to that during wakefulness. This unique linkage between a particular evoked potential component and sleep-wakefulness indicates that its generator system must be functionally related to states of arousal. Relevant data from the cat model suggest that the generator substrate for P1 may be within the ascending reticular activating system.     

Reproducibility of auditory brain-stem evoked responses as a function of the stimulus, scorer and subject

The reproducibility of auditory brain-stem evoked response (ABR) measurements was determined in a series of studies. ABRs were recorded from pre-term (32 and 36 weeks) newborns, term newborns, and adults to 3 different stimuli. Records were scored blindly with no knowledge of the subject, stimulus eliciting the response, or other records by that subject. Two scorers (inter-scorer reliability) and a single scorer over time (intra-scorer reliability) could score records using explicit criteria with a high degree of agreement. In contrast variability between replicate records to the same stimulus from the same subject was considerable. Intra-subject variability was not strongly affected by the age of the subject but was a function of the eliciting stimulus (the low intensity and fast repetition rate stimuli elicited more variable responses than loud, slow stimuli) and the wave measured (wave I latency was significantly more variable than the other measurements). Healthy, term newborns were studied to investigate the reproducibility of ABRs in the first few days after birth. There was a rapid reduction in ABR latency in the first 6-12 h after birth and a more gradual reduction thereafter. The prolonged latencies observed immediately after birth were associated with an elevation in ABR threshold. The reduction in latency was observed in vaginal and cesarean deliveries. These same effects were observed for amplitude of the ABR, but the trends were generally not significant. Despite the large changes in ABR latency within the first few days after birth, ABR latencies in response to some stimuli were significantly correlated between sessions separated by all intervals tested, ranging from 2 h to 2 days.     

Postnatal development of auditory function in the chicken revealed by auditory brain-stem responses (ABRs)

Auditory evoked brain-stem responses (ABRs) were recorded from the surfaces of the brain of lightly anesthetized newborn (1-7 days old) and adult (7-9 weeks old) chickens as a measure of the development of auditory processing. One-day-old and older chickens showed a series of waves within 5 msec after the stimulus onset. This precocity of the ABR in chickens contrasts with the first appearance of the ABR in cats at 4 days of age. The ABR onset latency was shorter in adult chickens than in newborns. This indicates that developmental modifications of mechanical transmission in the external and middle ear or cytodifferentiation of the sensory hair cells of the basillar papilla and the neurons of the acoustic nerve continue postnatally. Within the complex wave form of the response, most of the inter-wave latencies decreased with maturation, indicating that development of the central auditory pathway also continues postnatally. One inter-wave latency (N1 to P3-4) was significantly shorter (P less than 0.05) in adults than in newborns for intense click stimuli, and even among newborns, this inter-wave latency was significantly shorter in 6- and 7-day-old specimens than in 1-3-day-old specimens. It seems likely that changes in the N1 to P3-4 inter-wave latency reflect changes in evoked activity of second order auditory neurons that are located in the nucleus angularis and nucleus magnocellularis, and that intensive developmental changes occur in these neurons during the first postnatal week. The ABR recorded in chickens is a reliable measure of functional activity in the auditory system which is reproducible between individuals and capable of demonstrating developmental changes in specific segments of the wave form.     

On the dual structure of the auditory brainstem response in dogs.

OBJECTIVE: To use the over-complete discrete wavelet transform (OCDWT) to further examine the dual structure of auditory brainstem response (ABR) in the dog. METHODS: ABR waveforms recorded from 20 adult dogs at supra-threshold (90 and 70dBnHL) and threshold (0-15dBSL) levels were decomposed using a six level OCDWT and reconstructed at individual scales (frequency ranges) A6 (0-391Hz), D6 (391-781Hz), and D5 (781-1563Hz). RESULTS: At supra-threshold stimulus levels, the A6 scale (0-391Hz) showed a large amplitude waveform with its prominent wave corresponding in latency with ABR waves II/III; the D6 scale (391-781Hz) showed a small amplitude waveform with its first four waves corresponding in latency to ABR waves I, II/III, V, and VI; and the D5 scale (781-1563Hz) showed a large amplitude, multiple peaked waveform with its first six waves corresponding in latency to ABR waves I, II, III, IV, V, and VI. At threshold stimulus levels (0-15dBSL), the A6 scale (0-391Hz) continued to show a relatively large amplitude waveform, but both the D6 and D5 scales (391-781 and 781-1563Hz, respectively) now showed relatively small amplitude waveforms. CONCLUSIONS: A dual structure exists within the ABR of the dog, but its relative structure changes with stimulus level. SIGNIFICANCE: The ABR in the dog differs from that in the human both in the relative contributions made by its different frequency components, and the way these components change with stimulus level.     

Response enhancement and reduction of the auditory brain-stem response in a forward-masking paradigm

Alterations in the probe evoked auditory brain-stem response (ABR) were evaluated in 15 normal-hearing subjects using several stimulus configurations in a tone-on-tone forward-masking paradigm. The stimulus parameters manipulated in the study included: masker frequency; relative intensity of the masker; overall intensity of the masker-probe pair; and masker rise-fall time. Latency increases for waves III and V and an amplitude reduction for wave III were observed under some stimulus conditions. These changes were interpreted in terms of partial forward-masking effects. The masking effects were shown: to be maximal for masker frequencies in close proximity to the probe; to increase with increasing level of masker; to be independent of the overall level of the masker-probe pair; and, to decrease with increasing rise-fall time of the masker. Collectively, the forward-masking effects were interpreted as peripheral in origin, although, an additional brain-stem locus was not ruled out. In contrast, the same stimuli which increased wave III and V latencies and reduced wave III amplitude produced a robust amplitude increment in wave V which was termed enhancement. Wave V enhancement was shown: to be maximal for masker frequencies in close proximity to the probe; to decrease with increasing masker level; and, to decrease with faster rise-fall times of the masker. The processes mediating wave V enhancement are not clear, however, it was concluded that wave V enhancement probably reflects the resultant of a complex central neuronal interaction, presumably in the vicinity of the wave V generator(s).     

Auditory brain-stem responses in hydrocephalic patients

Auditory brain-stem response (ABR) was measured in 40 patients (80 ears) with confirmed hydrocephalus. Eighty-eight percent of these patients showed some form of ABR abnormality. Responses indicative of brain-stem dysfunction consisted of prolonged I-V interwave latency (38%), reduced V/I amplitude ratio (33%), and abnormalities in wave-shape of components III (27%) and V (53%). In addition, 70% of the patients had elevated ABR thresholds; 45% had responses in excess of 20 dB HL and the remaining 25% had no ABR activity. The etiology of the hydrocephalus, head circumference and brain-stem symptoms were not associated with particular ABR abnormalities. Communicating hydrocephalus correlated significantly with both prolonged I-V conduction time and absence of ABR activity, compared with non-communicating hydrocephalus. Four of the 9 patients retested showed ABR improvement on follow-up; one patient showed deterioration. The results were compared to our prior studies of ABR in 60 post-meningitic patients and in 100 severely neurologically impaired institutionalized children in whom the incidence of intrinsic brainstem abnormalities was one-third and two-thirds that of the hydrocephalic group, respectively. The results of this study suggest that ABR can be used to document clinically unsuspected brain-stem pathology that may accompany hydrocephalus. Auditory brain-stem dysfunction is likely to complicate the assessment of hearing sensitivity in hydrocephalic patients.     

Quantitative analysis of reversible dysfunction of brain-stem midline structures caused by disturbance of basilar artery blood flow with the auditory brain-stem responses

To clarify the effects of disturbances in basilar artery blood flow, basilar artery angiospasm was induced in 2 cats and 4 guinea pigs and auditory brain-stem responses (ABRs) were continuously recorded preceding, during and following the angiospasm. The angiospasm caused specific ABR changes in that waves II (P2-N2) and III (P3-N3) were attenuated without any corresponding amplitude reduction of P4. Those changes were equivalent following stimulation of either ear. Moreover, the ABR changes gradually recovered within 5 h. On the basis of the animal experiments, 52 patients with subarachnoid hemorrhage, supratentorial tumor showing increased intracranial pressure or hydrocephalus were selected for repeated ABR examinations. ABR abnormalities similar to those observed in the animal experiment were obtained especially from the patients exhibiting grade 3 or 4 symptomatology with subarachnoid hemorrhage. In these cases, the wave III to wave IV-V amplitude ratio was significantly decreased. In some cases the ABR abnormalities and the wave III to wave IV-V amplitude ratio recovered as the clinical course improved. These results support the conclusion that specific ABR changes (wave III to wave IV-V amplitude ratio) reflect transient ischemic dysfunction of the midline portion of the brain-stem caused by disturbances of basilar artery blood flow.     

The effects of ketamine-xylazine anesthesia on cerebral blood flow and oxygenation observed using nuclear magnetic resonance perfusion imaging and electron paramagnetic resonance oximetry

Ketamine-xylazine is a commonly used anesthetic for laboratory rats. Previous results showed that rats anesthetized with ketamine-xylazine can have a much lower cerebral partial pressure of oxygen (P(t)O(2)), compared to unanesthetized and isoflurane anesthetized rats. The underlying mechanisms for the P(t)O(2) reduction need to be elucidated. In this study, we measured regional cerebral blood flow (CBF) using nuclear magnetic resonance (NMR) perfusion imaging and cortical P(t)O(2) using electron paramagnetic resonance (EPR) oximetry in the forebrain of rats under isoflurane, ketamine, ketamine-xylazine and isoflurane-xylazine anesthesia. The results show that in ventilated rats ketamine at a dose of 50 mg/kg does not induce significant changes in CBF, compared to isoflurane. Ketamine-xylazine in combination causes 25-65% reductions in forebrain CBF in a region-dependent manner. Adding xylazine to isoflurane anesthesia results in similar regional reductions in CBF. EPR oximetry measurements show ketamine increases cortical P(t)O(2) while xylazine decreases cortical P(t)O(2). The xylazine induced reduction in CBF could explain the reduced brain oxygenation observed in ketamine-xylazine anesthetized rats.     

Differential impact of hypothermia and pentobarbital on brain-stem auditory evoked responses.

Two experiments were conducted to determine the effects of hypothermia and pentobarbital anesthesia, alone and in combination, on the brain-stem auditory evoked responses (BAERs) of rats. In experiment I, unanesthetized rats were cooled to colonic temperatures 0.5 and 1.0 degrees C below normal. In experiment II, 2 groups of rats were cooled and tested at 37.5, 36.0, 34.5 and 31.5 degrees C. One group was anesthetized during testing and the other group was awake. The rat BAER was sensitive to cooling of 1 degree C or less. Peak latencies were prolonged and peak-to-peak amplitudes were increased by hypothermia alone. The effect on amplitude may be related to the time course of temperature change or to stimulus level. Pentobarbital significantly affected both latencies and amplitudes over and above the effects of cooling. The specific effects of pentobarbital differed by BAER peak and by temperature. The findings point up the importance of the potential confound of anesthetic drugs in most of the evoked potential literature on hypothermia and, for the first time, quantify the complex interactions between pentobarbital and temperature which affect the BAER wave form.     

Effects of stimulus intensity on posterior tibial nerve somatosensory evoked potentials.

Relationships between stimulus intensity and peak latencies and amplitudes in posterior tibial nerve somatosensory evoked potential patterns were evaluated in ten healthy subjects. Eight intermediate latency peaks between 30 and 125 milliseconds (ms) after stimulus onset and seven amplitudes were analyzed. In general, there was a decrease in latency with each increase in stimulus intensity over a five step intensity range between 5 and 19 milliamps (mA) for most peaks. Similarly, increases in amplitudes generally occurred with increases in stimulus intensity for most peaks. Later peaks N105 and P115 as well as amplitudes P90-N105 and N105-P115 were least sensitive to stimulus intensity changes. The greatest changes in peak latency and amplitude occurred as stimulus intensity was increased from 7 to 11 mA. Beyond 11 mA relatively little change was observed in either peak latencies or amplitudes. Under anesthesia, by contrast, there was no stimulus intensity-peak latency interaction and beyond 11 mA there were decreases in amplitudes. Possible reasons for these findings are discussed.     

The effects of hypothermia on the latencies of the auditory brain-stem response (ABR) in the rhesus monkey

The effect of hypothermia on the ABR latencies was evaluated in 14 rhesus monkeys. Data from 6 preliminary experiments showed that middle ear pressure decreased with decreasing body temperature and consequently, all experiments were conducted on animals with tympanostomy tubes inserted to maintain constant middle ear pressure. All animals were sedated with curare and anesthetized with ketamine. Hypothermia was induced by applying ice packs to the animal's body. Rectal temperatures and the ABR to click stimuli were recorded at 3-5 min intervals over a temperature range of from 38 degrees C to 20 degrees C. The pattern of latency change is characterized by increasing latency with decreasing temperature, a greater rate of change for temporally later waves and increasing rate of change for any one wave with decreasing temperature. An exponential function was applied to the data and explained at least 93% of the variances in latency. In general, a single exponential identical for all waves of an animal explained the latency change between 37 and 26 degrees C. Below 26 degrees C, a second and sometimes a third function was required. These findings are similar to those reported previously and to those describing the effect of maturation on the ABR.     

Effects of pentylenetetrazole and 4-aminopyridine on the auditory brainstem response (ABR) and on the hearing sensitivity in the guinea pig in vivo

For exploring a possible connection between the reduced hearing sensitivity and certain abnormalities in the auditory brainstem responses (ABRs) in generalized epilepsy, the effects of two convulsing agents, namely pentylenetetrazole (PTZ) and of 4-aminopyridine (4-AP), on: (1). the cortical activity (EEG), (2). the hearing threshold and (3). the amplitudes and latencies of the ABR waves evoked by a stimulus of high intensity (100 dB) were investigated in guinea pigs. All animals injected (i.p.) with 100mg/kg PTZ or with 2mg/kg 4-AP developed generalized seizures, followed by characteristic EEG patterns for the post-ictal period, that were accompanied by a marked reduction of the hearing sensitivity (as indicated by the elevated threshold of the ABR), as well as by retro-cochlear changes (as judged by the changes in the later ABR waves in response to 100 dB). For instance, both convulsing agents decreased the amplitude and increased the latency of P4, that is the wave component of the ABRs generated in the lateral superior olivary nucleus and while PTZ increased the latency of P3, the wave component of the ABRs generated in the medial superior olivary nucleus, 4-AP dramatically increased its amplitude. Comparison of recordings taken at specific times for the duration of the post-ictal period (i.e. within about 1h for PTZ and 2h for 4-AP) reveals that the extent of the changes on the EEG matches with the increase in the auditory threshold and with the extent of the changes on the later waves of the ABR elicited by 100 dB. These data indicate that changes in the activity of the lateral and the medial nuclei of the superior olivary complex (SOC) accompany the hearing loss and the post-ictal epileptic cortical activity.     

Effects of ketamine anesthesia on the rat brain-stem auditory evoked potential as a function of dose and stimulus intensity

Because ketamine is both an abused substance and a commonly used veterinary anesthetic, its effects on brain and sensory functions are of interest. The present study examined the dose-dependent effects of ketamine anesthesia in the rat, using the brain-stem auditory evoked potential (BAEP) as an objective, quantitative measure of this substance's acute effects on brain and sensory electrophysiology. The animal subjects were 11 young adult female Long-Evans rats. BAEPs were recorded from skull screw electrodes during a baseline period as well as after saline and ketamine treatments. Ketamine was administered (i.p.) in 2 serial doses. The first dose (100 mg/kg) was followed 30-40 min later by a second dose (also 100 mg/kg). Equal volumes of normal saline were also injected serially. An interval of 1-2 weeks occurred between the saline and ketamine treatments, with treatment order counterbalanced. Normothermia was maintained to control for possible temperature-related effects. Ketamine produced prolongations in the latencies of all BAEP components (P1 through P6) that were statistically significant relative to baseline values. These latency shifts were progressively greater for waves P1 through P4 (shifts in P5 and P6 approximated the P4 shift). The effect of the second ketamine injection was to nearly double the latency shifts. Ketamine also had significant and complex effects on BAEP amplitudes that were dependent on dose and stimulus intensity. The results of the present study challenge the belief that the BAEP is resistant to the effects of anesthetics and suggest that the BAEP is useful in characterizing the CNS and sensory effects of these pharmacological agents.     

Auditory brain-stem evoked potentials in cat after kainic acid induced neuronal loss. II. Cochlear nucleus.

Auditory brain-stem potentials (ABRs) were studied in cats for up to 6 weeks after kainic acid had been injected unilaterally into the cochlear nucleus (CN) producing extensive neuronal destruction. The ABR components were labeled by the polarity at the vertex (P, for positive) and their order of appearance (the arabic numerals 1, 2, etc.). Component P1 can be further subdivided into 2 subcomponents, P1a and P1b. The assumed correspondence between the ABR components in cat and man is indicated by providing human Roman numeral designations in parentheses following the feline notation, e.g., P2 (III). To stimulation of the ear ipsilateral to the injection, the ABR changes consisted of a loss of components P2 (III) and P3 (IV), and an attenuation and prolongation of latency of components P4 (V) and P5 (VI). The sustained potential shift from which the components arose was not affected. Wave P1a (I) was also slightly but significantly attenuated compatible with changes of excitability of nerve VIII in the cochlea secondary to cochlear nucleus destruction. Unexpectedly, to stimulation of the ear contralateral to the injection side, waves P2 (III), P3 (IV), and P4 (V) were also attenuated and delayed in latency but to a lesser degree than to stimulation of the ear ipsilateral to the injection. Changes in binaural interaction of the ABR following cochlear nucleus lesions were similar to those produced in normal animals by introducing a temporal delay of the input to one ear. The results of the present set of studies using kainic acid to induce neuronal loss in auditory pathway when combined with prior lesion and recording experiments suggest that each of the components of the ABR requires the integrity of an anatomically diffuse system comprising a set of neurons, their axons, and the neurons on which they terminate. Disruption of any portion of the system will alter the amplitude and/or the latency of that component.