Biomedical subjects

R E Lasky

Publications and source records attributed to R E Lasky.

At least 19 recordsLinked to original sources

PubMed2001

The effects of elevated blood lead levels and succimer chelation therapy on physical growth in developing rhesus monkeys.

Seventy-two female rhesus monkeys were randomly assigned to three lead exposure conditions (none, birth to 1 year, birth to 2 years). In a completely crossed design, the lead-exposed and control monkeys were randomized to placebo or chelation therapy which began at 1 year of age. Dosing was conducted daily beginning on day 8 postpartum. The lead dose levels were adjusted biweekly to gradually elevate the blood lead level of each monkey to a target of 1.69-1.93 micromol/L (35-40 microg/dL). Succimer (or placebo) was administered orally (30 mg/kg/day for 5 days and 20 mg/kg/day for 14 additional days) for a total 19-day treatment regimen. There were two separate chelation regimes at 53 and 65 weeks of age. Succimer therapy in combination with lead abatement reduced blood lead levels significantly faster than lead abatement alone; however, that advantage disappeared once succimer therapy was discontinued. Weight, crown-rump length, and head circumference were measured regularly. Growth in weight, length, and head circumference did not vary significantly as a function of blood lead levels. Succimer chelation therapy did not significantly affect weight, length, or head circumference through 2 years of age.

Administration, Oral↗

PubMed1999

Otoacoustic emission, evoked potential, and behavioral auditory thresholds in the rhesus monkey (Macaca mulatta).

Distortion product otoacoustic emission (DPOAE), auditory brainstem evoked response (ABR), and behavioral thresholds were recorded in a group of 15 adult rhesus monkeys with normal auditory function. DPOAE thresholds were recorded with stimulus parameters selected to maximize signal-to-noise ratio. Additional averaging at the lowest frequencies ensured comparable noise levels across frequencies. DPOAE thresholds decreased with increasing frequency (f(2)=0.5-16 kHz) and at 16 kHz were close to 0 dB SPL. ABR thresholds were best from 1 through 16 kHz (32-38 dB peSPL); higher at 0.5 (45 dB peSPL), 24 (39 dB peSPL), and 30 kHz (49 dB peSPL). At all levels including threshold, the early ABR waves (II and I) were more prominent at the high frequencies while the later waves (IV and V) were more prominent at the low frequencies. The behavioral thresholds recorded were similar to those reported by other researchers although elevated by about 10 dB presumably because of the complexity of the threshold task. DPOAE and ABR thresholds can be reliably and efficiently recorded in the rhesus monkey and provide information concerning site of processing in the auditory pathway not directly available from behavioral data.

Acoustic Stimulation↗

PubMed1999

Neural networks applied to retrocochlear diagnosis.

Methodologies have been developed, based on insights from signal detection theory, to evaluate quantitatively the diagnostic performance of tests. Several studies have demonstrated that, in fact, performance of a test battery can be inferior to the best of the tests it includes. These studies have been quite persuasive in damping enthusiasm for the test battery approach. Because the results of all tests in a battery were weighted equally in these studies, it is not surprising that an individual test with good sensitivity and specificity is more effective diagnostically than a combination of tests with poorer sensitivity and specificity. The authors of many of these studies were well aware of the limitations of this approach. In the present study, neural networks were applied to evaluate audiological tests used to predict retrocochlear pathology by differentially weighting the results of the tests in the battery. This technique avoids some of the limitations of previous approaches. Of the audiological tests evaluated in the present analysis, the superiority of the auditory brainstem evoked response (ABR) in predicting retrocochlear disease was again demonstrated. However, the results also demonstrated that identification accuracy could be improved by combining the ABR with other tests (in this case contralateral acoustic reflex at 2000 Hz, ipsilateral acoustic reflex at 2000 Hz, tone decay, and word recognition score). Further, it was demonstrated that performance could be improved over that obtained using dichotomous test measures (i.e., positive or negative presence of pathology) by using raw test measures in conjunction with ABR.

Adult↗

PubMed1999

The development of auditory event related potentials in the rhesus monkey (Macaca mulatta).

Auditory event related potentials were recorded from neonatal, 3-month, and 3-year old rhesus monkeys. Auditory brainstem evoked responses (ABRs) were reliably recorded at all ages. ABR latencies decreased with age. Age effects were greater the more centrally generated the wave. Wave I amplitude decreased with age, Wave II increased, and Wave IV remained about the same. Stimulus rate effects were greater in neonates than older monkeys. Stimulus frequency also affected the ABR, but not differentially as a function of age. Recording montage had a significant effect on the recorded waveform. Wave I tended to be larger in amplitude in horizontal recordings and front-back recordings, while the later waves were relatively more prominent in more vertical montages. Middle latency evoked responses and late potentials were less reliably recorded than the ABR. Their reproducibility improved with age. Auditory event related potentials are promising measures of auditory function for research requiring nonhuman primate models of the developing human.

Adaptation, Physiological↗

PubMed1998

Nonlinear functional modeling of scalp recorded auditory evoked responses to maximum length sequences.

The purpose of this study was to model the adult human's scalp recorded evoked response to auditory pulses separated by varying inter pulse intervals (IPIs). The responses modeled probably reflect auditory nerve and brainstem generators. The subjects were 10 young adult humans with normal hearing. They were presented pseudo random sequences of pulses (maximum length sequences, MLSs) in order to characterize their system response. For the stimuli and the responses modeled accounting for temporal nonlinearities (interactions among the pulses) improved model performance only marginally. Nonlinear contributions to the models decreased with increasing interval between the input pulses. Increasing the memory of the model beyond 20 ms did not increase modeled performance dramatically. Model performance varied as a function of minimum IPI (MIPI) of the MLSs. At the shortest MIPI overall model performance deteriorated (due, in part, to a decrease in SNR), but nonlinear effects became relatively more important. At the longest MIPI performance also deteriorated, possibly due to the increasing influence of longer latency, more variable evoked potential components. Modeled performance generalized to responses recorded in the same recording session to the same and different MLSs. This study confirms the similarity between MLS linear kernels and conventionally averaged evoked responses--both are adapted responses reflecting the IPIs of the evoking stimuli.

Acoustic Stimulation↗

PubMed1998

Distortion product otoacoustic emissions in human newborns and adults. I. Frequency effects.

This study varied stimulus frequency and recorded distortion product otoacoustic emissions (DPOAEs) in human newborns and adults. Because of outer and middle ear acoustics, the same auditory input resulted in higher newborn stimulus sound pressure levels across a broad frequency range in the occluded outer ear canal. Noise levels in the canal were 5-15 dB lower for adults at frequencies less than about 3 kHz. The 2 f1-f2 DPOAE was the most reliably recorded DPOAE except at the lowest frequencies assessed. At the lowest frequencies the 2 f2-f1 DPOAE was more frequently recorded than any other DPOAE. There were no striking developmental differences in the kinds of DPOAEs that were recorded. The amplitudes of consecutively recorded 2 f1-f2 DPOAEs were generally within 1.5 dB of each other for all age groups (slightly better reproducibility for adults than newborns). The phases of consecutively recorded 2 f1-f2 DPOAEs were generally within 15 degrees of each other (often less than 10 and 5 degrees for newborns and adults respectively). At the highest frequencies assessed (f2 = 4.2-9.9 kHz) all subjects had similar amplitude 2 f1-f2 DPOAEs. At lower frequencies adult 2 f1-f2 amplitudes were significantly less than those of newborns. At the lowest frequencies reliably assessed (f2 = 1.5-2.1 kHz) term newborns had significantly larger 2 f1-f2 DPOAEs than preterm newborns. Newborn and adult 2 f1-f2 DPOAE amplitude X f2/f1, functions were quite similar although there were reliable differences. Age related differences in the outer and middle ears may explain some of the differences in DPOAEs that were observed.

Acoustic Stimulation↗

PubMed1998

Distortion product otoacoustic emissions in human newborns and adults. II. Level effects.

This study varied the levels of the primaries and recorded distortion product otoacoustic emissions (DPOAEs) from human newborns and adults. Preterm as well as term newborns were tested. The 2 f1-f2 DPOAE was the most reliably recorded DPOAE, especially at low levels of the primaries. Amplitude and phase reproducibility deteriorated with decreasing level of the primaries. Newborn DPOAEs were slightly less reproducible than adult DPOAEs. The underlying DPOAE I/O functions were nonmonotonic for both newborns and adults. Unity gain characterized the initial increasing portion of those functions in most subjects. Although newborn and adult I/O functions were similar, they did differ. In particular, adult functions tended to be more linear with saturation at higher primary levels. Some of the newborn functions saturated at very low stimulus levels. Although differences in cochlear mechanics may explain developmental difference in DPOAE I/O functions, developmental differences in the resonance characteristics of the outer and middle ears may also be involved.

Acoustic Stimulation↗

PubMed1998

Hearing loss in survivors of neonatal extracorporeal membrane oxygenation (ECMO) therapy and high-frequency oscillatory (HFO) therapy.

Survivors of extracorporeal membrane oxygenation (ECMO) therapy and high-frequency oscillatory (HFO) therapy during the newborn period were followed to evaluate their hearing. Eleven of the 66 ECMO survivors (16.7%) were diagnosed with significant hearing loss after being discharged from the neonatal intensive care unit (NICU). This rate of hearing loss is consistent with other reports of hearing loss in ECMO survivors. The majority of ECMO survivors with hearing loss developed a bilateral sloping hearing loss; the high frequencies were more impaired than the low frequencies. The hearing of nine ECMO survivors with hearing loss was assessed with auditory brainstem evoked responses (ABRs) in the newborn period prior to discharge from the NICU. Seven of nine ECMO survivors with hearing loss passed their newborn ABR screen. This result is consistent with the results of other researchers. Eight newborns receiving ECMO therapy had congenital diaphragmatic hernias (CDH). Three of these newborns (37.5%) were subsequently diagnosed as having a hearing loss. The combination of CDH and ECMO therapy may be a strong predictor of hearing loss. Six HFO survivors with hearing losses were also followed. Their losses were similar to the ECMO survivors with hearing loss, including the progressive nature of the loss (all five of these newborns with neonatal ABR screens passed them only to later be diagnosed with a hearing loss). A growing body of research indicates that newborns experiencing severe oxygen deprivation are at risk for progressive hearing loss.

Acoustic Impedance Tests↗

PubMed1997

Rate and adaptation effects on the auditory evoked brainstem response in human newborns and adults.

Auditory evoked brainstem response (ABR) latencies increased and amplitudes decreased with increasing stimulus repetition rate for human newborns and adults. The wave V latency increases were larger for newborns than adults. The wave V amplitude decreases were smaller for newborns than adults. These differences could not be explained by developmental differences in frequency responsivity. The transition from the unadapted to the fully adapted response was less rapid in newborns than adults at short (= 10 ms) inter stimulus intervals (ISIs). At longer ISIs (= 20 ms) there were no developmental differences in the transition to the fully adapted response. The newborn transition occurred in a two stage process. The rapid initial stage observed in adults and newborns was complete by about 40 ms. A second slower stage was observed only in newborns although it has been observed in adults in other studies (Weatherby and Hecox, 1982; Lightfoot, 1991; Lasky et al., 1996). These effects were replicated at different stimulus intensities. After the termination of stimulation the return to the wave V unadapted response took nearly 500 ms in newborns. Neither the newborn nor the adult data can be explained by forward masking of one click on the next click. These results indicate human developmental differences in adaptation to repetitive auditory stimulation at the level of the brainstem.

Acoustic Stimulation↗

PubMed1996

Auditory evoked brain stem responses to trains of stimuli in human adults.

OBJECTIVE: This study describes the effect of train length, interstimulus interval, intertrain interval (ITI), and stimulus duration on the transition from the unadapted to the adapted wave V auditory evoked brain stem response (ABR). DESIGN: ABRs were recorded to stimuli presented at two different rates: a slow rate characterizing the unadapted response and a fast rate characterizing the adapted response. Trains of stimuli (a sequence of stimuli separated by intervals of silence) also were presented. Different stimulus parameters defining the trains were varied. RESULTS: Given a sufficiently long ITI, the latency prolongation to the first three or four stimuli in a train was rapid. It was similar for trains differing in number of stimuli. After the first three or four stimuli, there was a more gradual latency prolongation as a function of stimulus number. Shorter ITIs had the effect of prolonging the latencies to all the stimuli in the trains, reducing the rate of latency prolongation over the first few stimuli, and causing responses to trains of different length to differ (e.g., two click train responses were shorter latency than four click train responses). An unexpected result was the latency prolongation of wave Vs after the presentation of the stimulus trains. CONCLUSIONS: In response to a train of clicks, there seems to be a rapid increase in wave V latency to the first few clicks in the train followed by a more gradual latency prolongation to subsequent clicks in the train.

Adult↗

PubMed1995

Distortion product otoacoustic emissions in Macaca mulatta and humans.

Distortion product otoacoustic emissions (DPOAEs) were compared in eight rhesus monkeys (Macaca mulatta) and eight normal hearing humans. DPOAEs were recorded in three conditions. In the first condition, DPOAEgrams were generated for monkeys and humans from approximately f2 = 0.5-20 kHz. Monkeys had larger amplitude DPOAEs at all frequencies except around f2 = 1 kHz. In the second condition, DPOAE amplitudes increased and then decreased as the separation between the primaries increased. These functions were similar in the two species except at the lowest frequencies assessed. In the third condition, the levels of the primaries were varied independently. Monkeys had steeper input/output (I/O) functions than humans. The slopes of DPOAE I/O functions increased with frequency in both species. When the levels of both primaries were increased simultaneously, DPOAE I/O functions were well described by power functions throughout the intensity range assessed (from threshold to 65 dB SPL). Monkey I/O functions tended to be expansive power functions at all but the lowest frequencies, while human I/O functions tended to be compressive power functions except at the highest frequencies assessed. Other differences in I/O functions f2 = 8 kHz may indicate species specific differences at high (for human) frequencies.

Acoustic Stimulation↗

PubMed1995

Auditory evoked brainstem and middle latency responses in Macaca mulatta and humans.

Early (ABRs) and middle (MLRs) surface-recorded auditory evoked potentials were compared in eight adult monkeys (Macaca mulatta) and eight adult humans. Responses whose probable generators were the cochlear nucleus and lateral lemniscus were of shorter latency and larger amplitude in monkeys. Relative to humans, ABR response latencies in monkeys were less affected by stimulus intensity, stimulus rate, and masker level. In contrast, monkey amplitudes were relatively more affected by those same stimulus parameters. The most prominent MLR wave was longer in latency and greater in amplitude in humans than the homologous wave in monkeys. The reduction in amplitude of that wave with increasing rate was greater for humans than monkeys. Temporal interactions (the effect of prior stimuli on the response to current stimulation) were investigated from a non-linear systems identification framework using maximum length sequences (MLSs). Both monkey and human auditory systems were second and probably third-order systems at the levels assessed. As the separations between the stimulus pulses decreased, evidence for temporal interactions became more prominent, reached a maximum, and then decreased with further decreases in stimulus pulse separation. At the highest stimulus rates presented, variations in temporal spacing among stimuli had less of an effect on monkey than human evoked responses.

Acoustic Stimulation↗

PubMed1995

A comparison of binaural interactions using traditional and maximum length sequence evoked response paradigms.

OBJECTIVE: Two paradigms, the traditional binaural interaction (BI) paradigm and a maximum length sequence (MLS) BI paradigm were evaluated to investigate BI effects. DESIGN: Evoked response BI effects were assessed at different levels of the auditory pathway in two experiments. Each experiment consisted of three conditions: a traditional BI paradigm using conventional stimuli, a traditional BI paradigm using MLS stimuli, and a MLS BI paradigm using MLS techniques to recover kernels reflecting BIs. Eleven normal-hearing young adults served as subjects. RESULTS: There was evidence for BI effects on the auditory evoked brain stem response (ABR) and the middle latency response (MLR) using the traditional BI paradigm and conventional stimuli. With the same paradigm and MLS stimuli there was evidence for BI effects on the MLR but not the ABR. The more robust conventional effects may be explained by the larger amplitude evoked responses recorded conventionally due to the slower stimulation rates and more efficient signal to noise enhancement. BI effects were observed for both the ABR and MLR by recording BI kernels in the MLS BI paradigm. CONCLUSIONS: MLS BI kernels can be recorded in normal hearing adults. The MLS BI paradigm offers three potential advantages in recording binaural effects; avoidance of some of the methodological problems associated with traditional BI paradigms, faster stimulus rates permitting a more complete characterization of binaural rate effects, and more rapid data collection.

Acoustic Stimulation↗

PubMed1994

A framework for assessing the relative efficiency of stimulus sequences in evoked response measurements.

A general matrix-based framework for characterizing the performance of cross-correlation techniques for recovering the response to an arbitrary stimulus sequence is presented. In general an infinite number of recovery sequences can be identified for any given stimulus sequence. The recovery sequence that minimizes the noise in the recovered response is derived and the effect of the recovery operation on the noise is analyzed. This general framework is employed to develop analytic expressions for the relative efficiencies of conventional signal averaging and binary MLS based methods for the most commonly used recovery operation and the one that optimizes SNR assuming the background noise is uncorrelated. The results depend on the ratio of response length to MLS minimum pulse interval and the amplitude loss as a function of stimulus rate. Examples based on measured amplitude loss functions for ABR recordings are employed to evaluate the relative efficiencies of MLS techniques. When the noise is uncorrelated conventional signal averaging is from two to five times as efficient as MLS techniques. The relative advantage of averaging is shown to decrease when the noise is dominated by low-frequency components.

Evoked Potentials, Auditory, Brain Stem↗

PubMed1994

Distortion-product otoacoustic emission input/output functions as a function of frequency in human adults.

Two issues concerning distortion-product otoacoustic emission (DPE) input/output functions were addressed in the present study. The first was to characterize those functions from threshold to 65 dB SPL. The second concerned the extent to which DPE input/output functions vary as a function of frequency. DPE input/output functions were generated at 20 frequencies from 537 to 10,009 Hz from eight normal-hearing subjects. Replicate functions were generated within an experimental session and with more than 4 months separating sessions. Given the impressive reproducibility of the DPE measurements, the input/output functions recorded can be interpreted as the consequences of stable physiologic processes and not unimportant variability (measurement noise). These input in dB/output in dB functions were generally linear functions with slopes less than unity indicating compression of the DPE output as a function intensity of the input. The slopes of the DPE input/output functions increased as a function of frequency to approaching one at the highest frequencies tested. DPE magnitudes tended to be more similar across frequencies at high intensities. At the lower intensities, DPE magnitudes varied as a function of input frequency, explaining the difference in slope of the input/output functions. There were a small number of markedly nonmonotonic, nonlinear functions. The functions presented included a greater number of intensities and frequencies and were less susceptible to explanations implicating the variability of the measurements than previous studies. The results, however, were quite consistent with those studies.

Acoustic Stimulation↗

PubMed1993

The effect of forward masker duration, rise/fall time, and integrated pressure on auditory brain stem evoked responses in human newborns and adults.

The effects of duration, rise/fall time, integrated pressure, and intensity of a forward masker on the auditory brain stem evoked response (ABR) were examined in three studies. Keeping peak masker intensity constant, integrated masker pressure was a better predictor of ABR latency prolongation than masker duration or rise/fall time in human newborns. Masker effects varied as a function of masker intensity. Greater ABR latency prolongation was observed for more intense maskers. Furthermore, latency prolongation was observed with increasing masker duration for high-intensity, but not low-intensity maskers. Forward masking had a greater effect on newborn wave V latencies than adult wave V latencies; however, increasing masker duration had similar effects on newborn and adult wave V latencies.

Acoustic Stimulation↗

PubMed1993

Temporal masking of human auditory evoked brain stem responses using two simultaneously presented maximum length sequences.

Two simultaneously presented maximum length sequences (MLSs) were used to investigate temporal nonlinearities. Not only did the recorded auditory evoked brain stem responses to these stimuli predictably increase in latency and decrease in amplitude as a function of the temporal interactions between MLSs, but thresholds were elevated by more than 20 dB. Simultaneous MLS paradigms make it possible to investigate a number of nonlinearities in the auditory system efficiently. This study also demonstrated that binaural MLS techniques can be used to assess auditory function even in individuals with asymmetric hearing losses without fear of crossover effects.

Acoustic Stimulation↗

PubMed1993

Binaural maximum length sequence auditory-evoked brain-stem responses in human adults.

This study compared monaural and binaural maximum length sequence auditory-evoked brain-stem responses (MLS ABRs) in normal hearing adults. The first experiment demonstrated that reliable binaural MLS ABRs could be recorded which were essentially the same as those recorded monaurally. The second experiment generalized this finding by assessing a range of intensities including threshold stimuli. ABR thresholds, wave V latency x intensity and amplitude x intensity functions, wave V latency and amplitude reproducibility, and waveform reproducibility were comparable for the monaural and binaural MLS ABRs with some minor qualifications. In the third experiment, comparability of monaural and binaural MLS ABRs was generalized to a range of rates from those used conventionally to rates far faster than possible with signal averaging. Again, there was little difference between the binaural and monaural MLS ABRs over the range of rates assessed.

Acoustic Stimulation↗