Biomedical subjects
Publications and source records attributed to N Kraus.
Auditory middle latency responses (MLRs) have been recorded in 217 patients ranging in age from 6 days to 20 years. The probability of obtaining MLR components Na and Pa was higher with a high-pass filter setting of 15 Hz, 12 dB/octave as compared to 3 Hz, 6 dB/octave. This effect was found at all ages tested. Age-related latency effects were apparent with 3 Hz but not 15 Hz filtering.
The auditory brainstem response (ABR) was used to study the development of 8th nerve and auditory brainstem function in 71 unanesthetized gerbils. Initial replicable responses were observed on day 14. Six vertex-positive waves and a slow negative response (SNR) were obtained in response to a 100 dB HL (re adult threshold) click stimulus on day 20. A general pattern of development characterized by decreasing threshold and wave latencies and increasing amplitudes was found. Latency changes occurred in two stages; rapid decreases in the third postnatal week, followed by a period of gradual decline toward adult latencies during the fourth and fifth weeks. Greater changes in absolute latency were observed for later waves. Development of adult-like thresholds and resistance of response detectability (presence or absence) to increasing stimulus rates occurred prior to or simultaneous with maturation of wave latencies. Increases in amplitude with age continued to adulthood for waves IV and SNR, while other waves declined in amplitude after day 20. The maturation of the ABR overlapped with the emergence and development of the auditory middle latency response (MLR). Waves B (adult latency 16 ms) and C (adult latency 25 ms) were discernable at approximately the same age that a replicable ABR was first obtained, and wave A (adult latency 14 ms) shortly thereafter. The general pattern of decreasing ABR wave thresholds and latencies with age seen in the gerbil is similar to that found in other mammals, including humans. However, the development of mature response characteristics appeared to proceed at a somewhat independent rate among the different ABR and MLR waves. The emergence of the MLR before several ABR waves suggests that development of auditory function in the gerbil may not follow a strictly sequential pattern.
Although the clinical use of the middle latency response (MLR) in adults is fairly straightforward, its use is complicated by maturational changes that continue throughout the first decade of life. In order to telescope the time period of this long developmental course, we have approached the study of MLR maturation using the gerbil as an animal model. The course of MLR obtained over the temporal lobe development was characterized in the Mongolian gerbil ranging in age from 10 days to 3 months of life. The adult gerbil MLR consists of two positive peaks (A and C) at 11 and 25 ms, respectively, and a negative component (B) at 16 ms. These components emerge in a systematic fashion as a function of age. The present work supports a strong age effect of increased MLR detectability in the gerbil, similar to findings reported for humans. Wave A was infrequently detected in young animals, but when present, it occurred at adult latencies. The latency of waves B and C decreased systematically with age. The amplitude of all components increased with age, similar to findings in humans. The fact that adult-like thresholds were obtained shortly after birth indicates that when present, MLRs may be a good index of hearing threshold. Effects of stimulating across a wide range of intensities were described. The gerbil model appears appropriate for the study of development of the central auditory system function.
Auditory middle-latency responses (MLRs) were obtained from 71 unanesthetized gerbils ranging in age from 10 to greater than 90 days. Effects of age, stimulation rate, high- and lowpass filter settings and filter slope were examined. MLR amplitude decreased significantly with increased stimulation rate at all ages, at rates up to 40/s. The detection of MLR waves (presence or absence) varied inversely with the rate of stimulation only in immature subjects. The amplitude of waves B (15 ms) and C (25 ms) was significantly larger with a highpass filter setting of 3 Hz as compared to 10 and 30 Hz. This effect was significantly more pronounced in developing animals as compared to adults. MLR amplitude was greater with a filter slope of 6 dB/octave as compared to 48 dB/octave, (10-2,000 Hz) and this effect was also significantly greater in developing animals than in adults. There was no interaction between lowpass filter setting and age (100 vs. 2,000 Hz). A prominent positive wave occurring at approximately 50 ms was present in the 48 dB/octave condition although it was not observed with 6 dB/octave filtering. The clinical use of the MLR requires a better understanding of the effects of stimulus and recording procedures on the response, and how they vary as a function of subject age.
Binaural interaction in the guinea pig middle latency response (MLR) was studied using two stimulus paradigms: binaural click stimuli and monaural click stimuli with contralateral white noise. During monaural click stimulation, the MLR is largest in amplitude over the contralateral temporal lobe. Binaural click stimulation reduces the amplitude of this response. Monaurally evoked click responses are also altered by the presentation of continuous white noise in the contralateral ear. The addition of white noise results in an increase in amplitude particularly of components A (12 msec) and B (17 msec). These alterations in response amplitude are specific to the MLR with no change occurring in the auditory brain-stem response (ABR). These findings appear to reflect interaction between the generators of middle latency response.
Auditory middle latency responses (MLRs) were mapped on the cortical surface of the unanesthetized guinea pig. The MLR consists of two positive peaks, designated A and C, with latencies of approximately 11 and 29 msec respectively, and a negative trough B, at 18 msec. Results suggest that each MLR component appears to have different generator sites and specific stimulus-response characteristics. The present work suggests that positive MLR components A and C have different generator sources because each component was maximally recorded from a different location over the contralateral temporal lobe. Little MLR activity was evident outside an area roughly 4 mm X 4 mm for each component.
The nature of auditory middle latency responses (MLRs) in children has been the subject of considerable debate. In order to study MLRs as a function of age, MLRs were obtained in 217 subjects ranging in age from 6 days to 20 years, all with normal auditory brain-stem responses (ABRs). Subjects were classified into several diagnostic categories: normal; communicative disorders (language delay, learning disability); mentally retarded, multiply handicapped; and post-meningitic. Age effects, the effects of diagnostic category, and possible differences in MLRs of males vs. females and right vs. left ears were examined. The detectability of both Na and Pa was found to increase significantly as a function of age. Detection of these MLR components became similar to adult values (approaching 100% detectability) at approximately 10 years of age. No significant differences were found among diagnostic categories. There were also no significant differences in the detectability of MLRs in males as compared to females, and there were no right vs. left ear differences. The strong age effect which appears to exist in the MLR influences their clinical use. When responses are present, they may be useful indicators of hearing sensitivity, but the absence of MLRs in children cannot be taken as an indication of hearing loss. Similarly, absent or abnormal MLRs cannot be interpreted as a manifestation of auditory pathway dysfunction, since there appears to be little difference in MLRs in normal subjects and MLRs in patients with a wide range of neurologic, cognitive, and speech and language disorders.
Auditory brainstem (ABR) and middle latency responses (MLR) were obtained from each ear in 8 crab-eating macaques, 4 white-handed gibbons, 4 siamangs and 2 orangutans. Macaques ranged in age from 5 days to 15 years with the 6 older animals in age-matched, male-female pairs. From each animal, latency-intensity functions were obtained and multiple MLR recordings were measured at 60 and 70 dB. Latency-intensity functions, interwave intervals, thresholds and percent detectability were calculated for ABR waveforms. Waves II and IV were largest in amplitude and were most consistently detected at low stimulus intensities in all species tested. Waves I and II had adult latencies in the youngest animal tested (5-day-old macaque), while waves III and IV were prolonged in comparison to the 15-month-old macaque, in whom latencies had reached adult values. There were no apparent sex differences in evoked potentials in the age-matched, male-female pairs. A broad, negative MLR at 7-13 ms was observed in all animals. Longer latency MLRs varied among animals of the same species, but were replicable in some individuals, including the youngest macaque (5 days) and orangutan (7 months). These data were compared to responses obtained in humans, other primates and other vertebrates.
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.
Interpretation of auditory brain stem response (ABR) findings can be problematic in cases where waves III and V are absent. Such findings can be attributed to profound hearing loss, brain stem neuropathology, or both. Over a 3-year period, 48 patients with no known brain stem damage and on whom audiologic data were available were found to have no response by ABR or absent waves III and V. Severe to profound hearing loss was documented in 38 cases, audiometric data were equivocal in 3 cases, and 7 patients showed pure tone sensitivity ranging from normal hearing to moderate impairment. Thus 15% had better hearing sensitivity than might have been expected from their ABR findings. Each of these patients also exhibited abnormal acoustic reflex findings. We report the electrophysiological (ABR, MLR, acoustic reflex), medical (history, neurological, EEG, CT scan) and behavioral (audiometric, speech and language, learning disabilities, psychological) data which characterize this group of patients.
Auditory brainstem response (ABR) was used to assess possible brainstem damage in 60 patients recovering from bacterial meningitis. Clear evidence of brainstem abnormalities was evident in 10% of the patients tested. Another 15% had ABRs classified as borderline normal. We evaluated various clinical and demographic factors to determine their predictive value with regard to neurologic abnormalities. Brainstem involvement was most likely when meningitis was complicated by seizures, hydrocephalus, nerve palsies (not including the eighth nerve), and a hemoglobin level of less than 11 g/dL, and when pretreatment symptoms persisted for longer than three days. Instances of partial and complete reversibility of brainstem damage were documented, indicating that reorganization of brainstem structures persisted after patients were discharged from the hospital.
Auditory brainstem response (ABR) was used to assess possible hearing loss in 60 patients recovering from bacterial meningitis. The ABR results were consistent with either unilateral or bilateral hearing loss in 35% of the cases tested. Of these, 15% were conductive-type hearing loss. Twelve percent had sensorineural hearing losses and normal brainstem function. The remaining 8% had elevated ABR thresholds coincident with findings suggestive of neuropathology of the auditory brainstem pathways. A case of reversible sensorineural hearing loss was documented. Various clinical and demographic factors were examined to determine their predictive value with regard to hearing loss. As expected, otitis media occurred significantly with conductive hearing loss. Type of pathogen (Streptococcus pneumoniae) and hospitalization greater than two weeks were significantly correlated with sensorineural hearing loss. As meningitis typically affects young children who are difficult to test with conventional audiometry, ABR provides an effective means of testing hearing in this population.
Auditory brainstem response screening at 40 and 60 dB was conducted in 100 infants in the neonatal intensive care unit to determine initial failure rate and prevalence of abnormality on follow-up. Of our NICU population, 20% failed one or both of the screening levels: 9% failed at 60 dB in both ears, and 11% failed at 40 dB in one or both ears. On follow-up, half of the 60 dB failure group were found to have sensorineural or conductive impairment and represent the 2% to 4% prevalence of serious otologic-audiologic problems generally found in an NICU population. Subsequent improvement (reversal) of the retest ABR records of the remaining infants in the 60 dB failure group was thought to be related to neural changes in the brainstem associated with recovery from hypoxic episodes. A transient or reversible conductive deficit appeared to account for the majority of failures at 40 dB. We recommend the screening protocol be expanded to include threshold and latency measures in infants who fail the initial screening. The transient nature of many ABR abnormalities makes postdischarge ABR, otologic, audiologic, and neurologic examinations mandatory before any inferences are made about hearing loss or neurodevelopmental disorders.
Middle-latency responses (MLR) in humans were studied using an unconventional recording technique with wide bandpass filters. Such filtering permitted simultaneous recording of the auditory brain stem response (ABR) thus facilitating comparisons between the two responses. Effects of sedation (chloral hydrate and diazepam), stimulus-related properties and the coronal distribution of MLRs were examined. Mild sedatives did not appear to affect either MLRs or ABRs. MLRs differed from ABRs in their stimulus-related properties, implying that the neuronal mechanisms underlying their generation are not the same. The amplitude of the MLR component, Pa, was largest at the vertex and symmetrically distributed over the temporal lobes. MLR components Na and Pa and ABR wave V were reliably obtained in all subjects at moderate and high stimulus intensities. At low stimulus levels, however, the detectability of wave V was more robust than the middle-latency components. Thus ABR appears to be the test of choice when hearing sensitivity is in question. MLRs are likely to be most clinically useful in patients with neurological or central auditory processing disorders.
Single unit activity was monitored in rabbit auditory association cortex (AC) throughout the acquisition of classically conditioned, nictitating-membrane response. The CS was a tone burst at the characteristic frequency of each neuron. Rabbits which were pseudoconditioned or received conditioning trials but did not learn the response served as control groups. Significant alterations in CS-evoked firing rate were termed 'response plasticity'. Neurons in conditioned animals were more than twice as likely to show response plasticity during the 250 ms CS-US interval than neurons in control animals. Such differences were evident both in the early (0-60 ms) and late (60-250 ms) portions of the CS-US interval. Most early changes appeared at 21-40 ms after CS onset. Response plasticity was most commonly manifested as an increase or decrease in CS-evoked firing rate with little change in the response pattern (PST histogram shape). In some neurons, subcomponents of response patterns (early or late portions of the CS-US interval) were observed to change independently of each other. Spontaneous rate and UCS-evoked activity were not modified with learning. Early in training (transition trials), neural activity evoked by the tone CS in conditioned animals was not different from that in controls. Response plasticity was most pronounced after the CR was first learned (trained trials) and stabilized once the Cr was well established (overtrained trials). Recording sites of neurons showing conditioning-related response plasticity were co-extensive with those of cells that did not.
Auditory brain stem (ABR) and middle latency responses (MLR) were recorded in a patient with bilateral temporal lobe lesions. Audiological and higher cortical functions were assessed using conventional behavioral methods. Roentgenological findings were presented for localizing the lesions. Initially the patient showed no behavioral response to sound. Subsequently the patient reported inconsistent awareness of environmental sounds and pure tone sensitivity was impaired to a severe degree. Higher cortical function was essentially intact and the patient was not aphasic. ABR and acoustic reflex findings were consistent with normal functioning of the auditory periphery and brain stem pathways. MLR component Pa was absent bilaterally. These findings suggest that MLR component is bilaterally generated in the temporal lobes. Auditory cortex appears to play a role in auditory sensitivity in humans.
Auditory middle latency response (MLRs) and auditory brain stem responses (ABRs) were simultaneously recorded in 24 patients with cortical lesions primarily affecting the temporal lobes. Site of lesion was documented by computerized tomography (CT) scan and behavioral profiles assessing language and other higher cortical functions were obtained. In patients with normal ABRs and either left or right hemisphere lesions, MLR components Na and Pa obtained at the vertex were of normal shape and latency. Exceptions to this occurred in 2 patients: one with bilateral temporal lobe lesions, the second with an infraventricular left temporal lobe lesion extending into the thalamic radiations. Although Na and Pa shape and latency were for the most part unaltered, Pa amplitude tended to cluster at the low end and below normal values. MLR recorded in the coronal plate showed Pa amplitude to be attenuated or absent over the damaged temporal lobe relative to the vertex or the intact hemisphere. This finding contrasts with data from normal subjects where Pa amplitude is largest at the vertex and essentially symmetrical about the temporal lobes. Patients showing an atypical amplitude distribution tended to have lesions involving auditory cortex and adjacent white matter projections. No obvious correlations between MLR abnormalities and behavioral findings regarding receptive and expressive language processes were found. Pa appears to be affected by temporal lobe lesions involving auditory cortex and thalamic projections. Our findings support the hypothesis that Pa is bilaterally generated by two symmetrical, vertically oriented dipole sources located about the temporal lobes.
The following data were obtained from microelectrode exploration of rabbit auditory cortex (AC). (1) Location of AC--Major portions of the rabbit's right hemisphere were stereotaxically mapped for auditory responsive and non-responsive regions. Auditory responsive regions were found to lie behind the rhinal sulcus, extending from its midpoint to its inferior border. (2) Frequency selectivity--Characteristic frequencies (CFs) ranged from 0.4 to 33 kHz. Sharp, multipeaked and broad tuning curves were described. (3) Response patterns--A variety of post-stimulus-time (PST) histogram shapes were obtained in response to tonal stimuli. The response of a given neuron often varied with changes in stimulus frequency or intensity. (4) Latency--Neural response latencies ranged from 10 to 100 msec following stimulus onset. (5) Spontaneous rate--In the absence of acoustic stimulation, spike discharges ranged from less than 1 spike/sec to 48 spikes/sec. Spontaneous rates of less than 5 spikes/sec were measured in 42% of the neurons. Rates in excess of 15 spikes/sec occurred in fewer than 18% of the cells examined. (6) Response variability--Stimulus-evoked activity was seen to vary over time. Changes consisted of an overall increase or attenuation of discharge rate, as well as modifications of selected portions of the response pattern (PST histogram shape). The characteristics of single unit activity in rabbit auditory cortex are consistent with findings reported in other species.