Auditory brain-stem evoked potentials in cat after kainic acid induced neuronal loss. I. Superior olivary complex

Auditory brain-stem potentials (ABRs) were studied in cats for up to 45 days after kainic acid had been injected unilaterally or bilaterally into the superior olivary complex (SOC) to produce neuronal destruction while sparing fibers of passage and the terminals of axons of extrinsic origin connecting to SOC neurons. The components of the ABR in cat were labeled by their 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 labeled P1a and P1b. The correspondences we have assumed between the ABR components in cat and man are indicated by providing a Roman numeral designation for the human component in parentheses following the feline notation, e.g., P4 (V). With bilateral SOC destruction, there was a significant and marked attenuation of waves P2 (III), P3 (IV), P4 (V), P5 (VI), and the sustained potential shift (SPS) amounting to as much as 80% of preoperative values. Following unilateral SOC destruction the attenuation of many of these same ABR components, in response to stimulation of either ear, was up to 50%. No component of the ABR was totally abolished even when the SOC was lesioned 100% bilaterally. In unilaterally lesioned cats with extensive neuronal loss (> 75%) the latencies of the components beginnign at P3 (IV) were delayed to stimulation of the ear ipsilateral to the injection site but not to stimulation of the ear contralateral to the injection. Binaural interaction components of the ABR were affected in proportion to the attenuation of the ABR. These results are compatible with multiple brain regions contributing to the generation of the components of the ABR beginning with P2 (III) and that components P3 (IV), P4 (V), and P5 (VI) and the sustained potential shift depend particularly on the integrity of the neurons of the SOC bilaterally. The neurons of the lateral subdivision (LSO) and the medial nucleus of the trapezoid body (MNTB) of the SOC have a major role in generating waves P3 (IV) and P4 (V).     

Auditory brain-stem responses evoked by electrical stimulation of the cochlear nucleus in human subjects

When auditory nerve function is lost due to surgical removal of bilateral acoustic tumors, a sense of hearing may be restored by means of an auditory brain-stem implant (ABI), which electrically stimulates the auditory pathway at the level of the cochlear nucleus. Placement of the stimulating electrodes during surgical implantation may be aided by electrically evoked auditory brain-stem responses (EABRs) recorded intra-operatively. To establish preliminary standards for human EABRs evoked by electrical stimulation of the cochlear nucleus, short-latency evoked potentials were recorded from 6 ABI patients who were either already implanted or undergoing implantation surgery. Neural responses were distinguished from stimulus artifact and equipment artifact by their properties during stimulus polarity reversal and amplitude variation. Other properties contributed to further identification of the evoked potentials as auditory responses (EABRs). The response waveforms generally had 2 or 3 waves. The peak latencies of these waves (approximately 0.3, 1.3, and 2.2 msec) and the brain-stem localization of the region from which they could be elicited are consistent with auditory brain-stem origin.     

Auditory evoked potentials in the Japanese monkey.

Auditory sensitivity based on auditory brain stem response (ABR), whole nerve action potential (AP), and cochlear microphonics (CM) to tone bursts of 0.5-8 kHz were compared with behavioral audiometry in the Japanese monkeys. Although sensitivity loss at 4-6 kHz was observed in these potentials, an increase in sensitivity at 8 kHz was obtained only in the ABR. Thus the sensitivity loss at 4-6 kHz originates at the peripheral system and the increased sensitivity at 8 kHz originates at the central.     

Auditory evoked potentials in Down's syndrome

Short-, middle- and long-latency auditory evoked potentials (SAEPs, MAEPs and LAEPs) were examined in 12 subjects with Down's syndrome and in 12 age-matched normal subjects. In comparison with the normal subjects, Down subjects showed shorter latencies for SAEP peaks II, III, IV and V (and correspondingly shorter interpeak intervals I–II and I–III) so long as stimulus intensity was at least 45 dB SL. The MAEP peak Na had a longer latency in Down subjects than in normal subjects, but not the Pa latency. In passive oddball experiments for LAEPs, the latencies of all components from N1 to P3 were progressively longer in Down subjects, and the N2-P3 amplitude increased slightly between the first and fourth blocks of stimuli (whereas in the normal subjects it decreased). These alterations in auditory evoked potentials, which may correlate with cerebral alterations in organization and responsiveness responsible for deficient information processing, may constitute an electrophysiological pattern that is characteristic of Down's syndrome.     

Diagnostic role of brain-stem auditory evoked potentials in neurobrucellosis

Evoked potential audiometry and brain-stem auditory evoked potentials were evaluated in 15 patients with systemic brucellosis in whom brucella meningitis was suspected clinically. In 8 patients cerebrospinal fluid (CSF) was abnormal with high brucella titre, and evoked potentials were abnormal in all of them. In 7 patients the CSF was normal and evoked potentials were also normal. Brain-stem auditory evoked potential abnormalities were categorised into 4 types: (1) abnormal wave I, (2) abnormal wave V, both irreversible, (3) prolonged I–III interpeak latencies, and (4) prolonged I–V interpeak latencies, both reversible. These findings are of important diagnostic value and correlate well with the clinical features, aetiopathogenesis and final outcome.     

Origin and distribution of brain-stem somatosensory evoked potentials in humans

The distribution of somatosensory evoked potentials (SEPs) recorded from the brain-stem surface was studied to investigate their generator sources in 14 patients during surgical exploration of the posterior fossa. Two distinct SEPs of different morphologies and electrical orientation were obtained by median nerve stimulation. A small positive-large negative-late prolonged positive wave was recorded from the cuneate nucleus and its vicinity. There was a phase-reversal between the cuneate nucleus and the ventral surface of the medulla, depicting a dipole for dorso-ventral organization. From the pons and midbrain, triphasic waves with predominant negativity were obtained. This type of SEP had identical wave forms between dorsal, lateral and ventral surface of the pons and midbrain. It showed an increase in negative peak latency as the recording sites moved rostrally, suggesting an ascending axial orientation. In a patient with pontine hemorrhage, the killed end potential, a large monophasic positive potential was obtained from the lesion. This potential occurs when an impulse approaches but never passes beyond the recording electrode. Therefore, the triphasic SEP from the pons and midbrain reflects an axonal potential generated in the medial lemniscal pathway.     

The interstitial nucleus of Cajal of the cat. II. Effects of kainic acid lesion on vertical optokinetic nystagmus and after-nystagmus

The effects of bilateral lesions of the interstitial nucleus of Cajal (INC) by ka?nic acid on vertical optokinetic nystagmus (OKN) and after-nystagmus (OKAN) were studied in four cats: in three cats, in the acute stage from 1 to 60 days after the lesions; in the fourth cat, they were studied 3 years after the lesions were made. Histological control of lesions showed that the whole INC was bilaterally destroyed in two cats of the acute group and only the upper part of INC in the third cat. In the chronic cat, the density of cell bodies in both INC was lower than normal. In the acute group, the cats exhibited a spontaneous downward eye drift in light and in darkness. During an upward optokinetic stimulation, the effect of INC lesions was dramatic: upward slow phases and downward quick phases of OKN were abolished. Sixty days post lesions, small upward slow eye movements were again observed. During a downward optokinetic stimulation, the defect was much less; in particular, after a slight impairment of downward slow phases, during the first days post lesions, they recovered quickly. The secondary optokinetic after nystagmus (OKAN II) ensuing a downward OKN was cancelled and did not reappear 60 days post lesions. In the chronic stage, three years after the lesions, during an upward optokinetic stimulation, the cat showed upward slow phases with velocities close to normal. However, upward slow phases were curved: the velocity at the end of the slow phases was lower than at the beginning. After an upward OKN (the direction of slow phases gives the direction of the OKN and OKAN), the ensuing OKAN was present but abnormal.     

Auditory brain-stem evoked potentials to clicks at different presentation rates: estimating maturation of pre-term and full-term neonates

Auditory brain-stem evoked potentials ABEPs were recorded from 57 neonates ranging in gestational age between 27 and 43 weeks. Averages and standard deviations of I, III and V peak latencies, I–V, I–III and III–V inter-peak latency differences (IPLDs), for 10/sec and 55/sec clicks were calculated for each age group. An additional measure, the net effect of increasing stimulus rate (ISR), was calculated by subtracting 10/sec measures from their 55/sec counterparts. Correlations between ABEP measures and subject age were determined.The results of this study demonstrate a significant correlation between gestational age and electrophysiological measures of peripheral, as well as central, conduction: an inverse correlation between age and peak latencies as well as IPLDs. The slope of this correlation was steeper for the higher stimulus rate. The slope of 55/sec measures vs. age was the sum of the respective slopes of 10/sec measures and of ISR.The maturation of 10/sec measures may reflect white matter development, while ISR changes with gestational age represent maturation of synaptic efficacy. Thus, the maturation of 55/sec measures reflects the combined maturation of nerve conduction velocity and synaptic efficacy along the neonatal auditory nerve and brain-stem. This differential evaluation may enable more accurate determination of developmental age of neonates, with respect to total maturation as well as its constituents.     

Monitoring of brain-stem trigeminal evoked potentials. Clinical applications in posterior fossa surgery

Brain-stem trigeminal evoked potentials (BTEPs) were monitored intraoperatively in 17 patients during posterior fossa surgery. Satisfactory BTEP recording was performed in all patients without technical problems or interfering with the activity of the operating team. The BTEP was not altered by anesthetic agents or muscle relaxants. Intraoperative monitoring of the BTEP showed wave form alterations or increasing peak latencies in 10 patients. Among these patients, the BTEP demonstrated a dynamic correlation with the surgical process in 8 instances. Two major causative surgical manipulations were identified: cerebellar retraction in 4 cases and tumor dissection from the brain-stem in 6 cases. Withholding the dissection of the tumor, readjusting a cerebellar retractor or further modifying the surgical attitude resulted in partial or complete return of the wave form in 7 patients. The BTEP at the end of surgery proved to correlate with the immediate surgical outcome in most instances. We concluded that the intraoperative monitoring of the BTEP was feasible and suggested, despite the small number of patients, a potential value in the survey of brain-stem functions during posterior fossa surgery.     

Spatiotemporal characteristics of evoked potentials in the posterior ventrolateral nucleus of the cat thalamus

Evoked potentials (EPs) in the posterior ventrolateral nucleus (VPL) of the thalamus in response to electrical stimulation of the skin of the contralateral forelimb were studied. It was shown that they are formed by superposition of several electrical dipoles, one of which lies with two poles in VPL while the rest have one pole in VPL and the other in more caudal zones of the somatosensory system. The first phase of the EP in VPL consists of two components with different amplitude—frequency characteristics. The lability of the second component is low and it disappears if the frequency of stimulation rises above 20 Hz. The focus of maximal activity during contralateral stimulation of the skin of the forelimb occupies the same topographical position in VPL during development of the positive and negative phases of the EP. The steepness of rise of the ascending phase and the amplitude of the positive phase of the EP are greatest at the focus of maximal activity; in other regions the lines of equal steepness need not necessarily coincide with the equipotential lines; differences are especially noticeable in the sagittal plane.Institute of the Brain, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 4, No. 4, pp. 439–446, July–August, 1972.     

Chronic effects of phenytoin on brain-stem auditory evoked potentials in man

The effects of phenytoin (PHT) on brain-stem auditory evoked potentials (BAEPs) were studied in 65 epileptic patients who received long-term PHT monotherapy at therapeutic and supra-therapeutic levels with no clinical evidence of brain-stem toxicity. Abnormal BAEPs were found in 7.5% and 33.3% of patients with therapeutic and supra-therapeutic PHT levels respectively. Serum PHT levels had a trend towards a positive relationship with the I–V interpeak latency (IPL), and a significant negative relationship with the amplitudes of waves I and V. at supra-therapeutic levels, both I–V and I–III IPLs were significantly prolonged while at therapeutic evels onl I–III IPLs were prolonged. The absolute latency of wave I was prolonged in both the therapeutic and the supra-therapeutic groups. These results suggest that PHT acts both peripherally on either the auditory nerve or the cochlea, and centrally on brain-stem conduction.     

Postsynaptic potentials of motoneurons evoked by rubrofugal impulsation in the hypoglossal nucleus of the cat

The effect of stimulation of the ipsilateral and contralateral red nuclei on motoneurons of the hypoglossal nucleus was studied in cats anesthetized with chloralose and pentobarbital. In 35 (69%) of the 51 motoneurons tested, PSPs were generated in response to stimulation of the red nuclei by series of 3 to 5 stimuli of threshold strength and with a frequency of 500–600/sec. Of this number, 33 motoneurons responded to stimulation by EPSPs, whose latent periods varied from 3.5 to 14.0 msec (mean value for the ipsilateral red nucleus 5.7±0.75, for the contralateral nucleus 6.8±0.8 msec), whereas two motoneurons responded (after 6.2 msec) by IPSPs. Of the 35 motoneurons responding to stimulation of the red nuclei, stimulation of the lingual nerve evoked EPSPs in 31 and IPSPs in 4 (two of them were inhibited by rubrofugal impulses). IPSPs were generated as a result of stimulation of the lingual nerve in 16 motoneurons which did not respond to rubrofugal impulses.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 10, No. 1, pp. 62–66, January–February, 1978.     

Phenolic antioxidants attenuate hippocampal neuronal cell damage against kainic acid induced excitotoxicity

Increasing evidence supports the role of excitotoxicity in neuronal cell injury. Thus, it is extremely important to explore methods to retard or reverse excitotoxic neuronal injury. In this regard, certain dietary compounds are beginning to receive increased attention, in particular those involving phytochemicals found in medicinal plants in alleviating neuronal injury. In the present study, we examined whether medicinal plant extracts protect neurons against excitotoxic lesions induced by kainic acid (KA) in female Swiss albino mice. Mice were anesthetized with ketamine and xylazine (200 mg and 2 mg/kg body wt. respectively) and KA (0.25 microg in a volume of 0.5 microl) was administered to mice by intra hippocampal injections. The results showed an impairment of the hippocampus region of brain after KA injection. The lipid peroxidation and protein carbonyl content were significantly (P < 0.05) increased in comparison to controls. Glutathione peroxidase (GPx) activity (EC 1.11.1.9) and reduced glutathione (GSH) content declined after appearance of excitotoxic lesions. As GPx and GSH represent a major pathway in the cell for metabolizing hydrogen peroxide (H2O2), their depletion would be expected to allow H2O2 to accumulate to toxic levels. Dried ethanolic plant extracts of Withania somnifera (WS), Convolvulus pleuricauas (CP) and Aloe vera (AV) dissolved in distilled water were tested for their total antioxidant activity. The diet was prepared in terms of total antioxidant activity of plant extracts. The iron (Fe3+) reducing activity of plant extracts was also tested and it was found that WS and AV were potent reductants of Fe3+ at pH 5 5. CP had lower Fe3+ reducing activity in comparison to WS and AV. Plant extracts given singly and in combination 3 weeks prior to KA injections resulted in a decrease in neurotoxicity. Measures of lipid peroxidation and protein carbonyl declined. GPx activity and GSH content were elevated in hippocampus supplemented with WS and combination of WS + CP + AV. However, when CP and AV were given alone, the changes in the GPx activity and GSH content were not significant. Although the major factors involved in these properties of phytochemicals remain to be specified, the finding of this study has suggested that phytochemicals present in plant extracts mitigate the effects of excitotoxicity and oxidative damage in hippocampus and this might be accomplished by their antioxidative properties.     

Auditory evoked potentials from the primary auditory cortex of the cat: topographic and pharmacological studies

Wave VI (8.4 msec) of the brain-stem auditory evoked potential (BAEP) was maximal in a discrete region of primary auditory cortex (AI) of the anesthetized cat. Wave VI underwent rapid amplitude decreas over millimeter distances in the AI region and followed high stimulation rates. Wave VI did not show intracortical polarity inversion nor was it abolished by epicortical or intracortical GABA administration. The data are compatible with a wave VI source in the terminal axons of the thalamo-cortical radiations.Middle latency auditory responses (MAEPs) generated 10–40 msec after auditory stimulation were also recorded in a circumscribed area of AI. In contrast to wave VI, these primary auditory cortex potentials (Pa 18.3 msec; Nb 31.9 msec) underwent transcortical polarity inversion, correlated with intracortical multi-unit activity in the AI region and were reversibly altered or abolished by epicortical or intracortical GABA adminstration to the AI region. The data suggest that the Pa and Nb components of the cat MAEP are intracortically generated by neuronal elements in the AI region.     

Reappearance of brain-stem auditory evoked potentials after surgical treatment of a brain-stem hemorrhage: contributions to the question of wave generation

We report on a patient suffering a spontaneous hemorrhage primarily located in the right brain-stem; surgical correction of this led to a substantial improvement in clinical deficits. Brain-stem auditory evoked potentials (BAEPs) were recorded on postoperative days 18, 30, 55 and 205. Waves II through V were initially undetectable on stimulation of the damaged side, whereas the absence of peak V was the only abnormality seen on left-side stimulation. With the regression of the right lower mid-pontine deficits, the right waves gradually reappeared and normalized progressively. On the last recording, only a left wave V abnormality persisted. At that time, the patient had a moderate left hemisyndrome due to a circumscribed right upper pontine-midbrain lesion. Therefore, it can be suggested that the first 4 waves of BAEPs mainly originate in the ipsilateral pons, and the Vth in the contralateral higher regions.     

Auditory evoked potentials in distinguishing between peripheral and central tinnitus

Brainstem evoked response audiometry has been performed in 164 patients complaining of tinnitus, unilateral or bilateral. The latency of every wave and the latency between the peak of every wave have been compared with those obtained in a normal population (n = 57). The latency of the first wave is increased significantly at the same side of the tinnitus. But I-V latency is shorter at the side of the tinnitus. When this increase is absent, the I-V latency is prolonged the side of the tinnitus. It is possible to differentiate between tinnitus of peripheral origin and that of central origin, although the existence of unilateral deafness is constant. The same results have been obtained in the deaf patients with bilateral symmetric deafness, in accordance with Maurizi et al., 1985.     

Auditory brain-stem responses in the fragile X syndrome.

Auditory brain-stem responses (ABRs) were recorded from a group of 12 mentally retarded males with the fragile X (fra[X]). The responses were analyzed in terms of ABR thresholds, absolute latencies, and interpeak latencies. One patient had increased ABR thresholds, indicating hearing impairment. Five fra(X) subjects had prolonged I-V interpeak latencies. Comparisons between the fra(X) group (excluding one possible hard-of-hearing subject) and a control group of age-matched males with normal intelligence showed that the fra(X) group's interpeak latencies were significantly prolonged for the III-V and I-V but not for the I-III. This pattern of prolongation of interpeak latencies suggests that central, as opposed to peripheral, nervous-system dysfunction predominates in many patients having this syndrome. In addition, frequently observed prolongation of the transmission time may indicate that brain-stem white-matter functioning is also apt to be involved in this syndrome.     

Auditory evoked potentials to indifferent and meaningful stimuli in young children

Auditory evoked potentials (AEP) of the frontal, central and parietal cortical areas of the left hemisphere in response to an indifferent sound stimulus and to a stimulus with same physical characteristics, but with acquired informational significance, were studied in healthy children of the 3-d year of life. In the last case the amplitude of the AEPs in all recorded areas rose and the latencies of late components in the parietal area became longer. Moreover, the components of AEP got more complex owing to a greater manifestation of the late positive component P3 in all recorded areas and particularly in the parietal one.