Estimation of in vivo human brain-to-skull conductivity ratio from simultaneous extra- and intra-cranial electrical potential recordings.

OBJECTIVE: The present study aims to accurately estimate the in vivo brain-to-skull conductivity ratio by means of cortical imaging technique. Simultaneous extra- and intra-cranial potential recordings induced by subdural current stimulation were analyzed to get the estimation. METHODS: The effective brain-to-skull conductivity ratio was estimated in vivo for 5 epilepsy patients. The estimation was performed using multi-channel simultaneously recorded scalp and cortical electrical potentials during subdural electrical stimulation. The cortical imaging technique was used to compute the inverse cortical potential distribution from the scalp recorded potentials using a 3-shell head volume conductor model. The brain-to-skull conductivity ratio, which leads to the most consistent cortical potential estimates with respect to the direct intra-cranial measurements, is considered to be the effective brain-to-skull conductivity ratio. RESULTS: The present estimation provided consistent results in 5 human subjects studied. The in vivo effective brain-to-skull conductivity ratio ranged from 18 to 34 in the 5 epilepsy patients. CONCLUSIONS: The effective brain-to-skull conductivity ratio can be estimated from simultaneous intra- and extra-cranial potential recordings and the averaged value/standard deviation is 25+/-7. SIGNIFICANCE: The present results provide important experimental data on the brain-to-skull conductivity ratio, which is of significance for accurate brain source localization using piece-wise homogeneous head models.

High-resolution EEG: cortical potential imaging of interictal spikes.

BACKGROUND: It is of clinical importance to localize pathologic brain tissue in epilepsy. Noninvasive localization of cortical areas associated with interictal epileptiform spikes may provide important information to facilitate presurgical planning for intractable epilepsy patients. METHODS: A cortical potential imaging (CPI) technique was used to deconvolve the smeared scalp potentials into the cortical potentials. A 3-spheres inhomogeneous head model was used to approximately represent the head volume conductor. Five pediatric epilepsy patients were studied. The estimated cortical potential distributions of interictal spikes were compared with the subsequent surgical resections of these same patients. RESULTS: The areas of negativity in the reconstructed cortical potentials of interictal spikes in 5 patients were consistent with the areas of surgical resections for these patients. CONCLUSIONS: The CPI technique may become a useful alternative for noninvasive mapping of cortical regions displaying epileptiform activity from scalp electroencephalogram recordings.

Electrical status epilepticus in slow wave sleep: prospective case study of a cortical hearing impairment.

The development of a central hearing impairment is described in a young girl with risk factors for hearing impairment that included mosaic Down syndrome, leukemia, and chemotherapy. This case is unusual in the prospective regularity with which hearing was assessed from birth. The diagnosis is electrical status epilepticus in slow wave sleep, a rare childhood disorder, which was associated with lack of responsiveness to auditory signals, regression of emerging speech and language and other cognitive skills, and abnormal electroencephalographic (EEG) activity in both hemispheres. Treatment of the disorder with anticonvulsant medications and steroids has ameliorated the condition by suppressing the abnormal EEG activity and allowing substantial improvements in cognitive and social skills, although communication skills are improving more slowly.

Infantile botulism: pitfalls in electrodiagnosis.

Botulism in infants, unless recognized early, is associated with high mortality and morbidity. The diagnosis is suspected when infants present with sudden onset of weakness, respiratory failure, and constipation and is confirmed by demonstration of botulinum toxin in stool several weeks later. Electrodiagnosis allows quick and reliable confirmation of botulism. Low-amplitude compound muscle action potentials, tetanic or post-tetanic facilitation, and the absence of post-tetanic exhaustion support the diagnosis. Two infants with confirmed botulism did not exhibit the characteristic electrodiagnostic features, demonstrating the pitfalls in electrodiagnosis of infantile botulism.

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.

Temporal distortion products (kernel slices) evoked by maximum-length-sequences in auditory neuropathy: evidence for a cochlear pre-synaptic origin.

When special pseudo-random stimuli sequences (maximum length sequences: MLS) are combined with a deconvolution analysis technique, it is possible to derive new evoked potential components that are called kernels. The kernels give a measure of the temporal interactions that take place between the responses to successive stimuli. This may provide an objective neurophysiological test for the exploration of a dimension of hearing which has hitherto been limited to psychophysical methods. Until now, auditory short-latency kernels obtained by the MLS method have been related to the late portion of the brainstem auditory evoked potential (BAEP), suggesting that temporal interactions occur rather late in the auditory pathways. We report 4 children without any BAEP neural components, who all retained isolated cochlear microphonic potentials. Three of them produced click-evoked otoacoustic emissions and two of them demonstrated only moderately impaired audiometric thresholds. This combination of absent BAEP neural components with preserved otoacoustic emissions and cochlear microphonic potential corresponds to a peculiar pattern of auditory dysfunction recently coined "auditory neuropathy'. All 4 children exhibited well-defined kernels at latencies consistent with the microphonic potential. These data indicate that the cochlea itself can generate kernels at a presynaptic level. They open up the question of the identification of the physiological site(s) responsible for the generation of MLS-evoked kernels.

Auditory neuropathy: a report on three cases with early onsets and major neonatal illnesses.

We report 3 children without any brainstem auditory evoked potential (BAEP) neural component who all retained isolated cochlear microphonic potentials as well as click-evoked otoacoustic emissions. Two of them demonstrated only moderately impaired audiometric thresholds. These features correspond to a peculiar pattern of auditory dysfunction recently coined "auditory neuropathy'. In contrast with the published previous cases of auditory neuropathy presenting with an acquired hearing deficit as children or young adults, all 3 children had a history of major neonatal illness and the auditory neuropathy was already demonstrated in the first months of their lives.

The effects of lead on otoacoustic emissions and auditory evoked potentials in monkeys.

Auditory functioning was assessed in two groups of adult rhesus monkeys (11 years of age). One (n = 11) received modest exposure to lead early in life and the other (n = 8) served as controls and did not receive any lead supplementation. Two lead-exposed monkeys had abnormal distortion product otoacoustic emissions (DPEs) and smaller amplitude or absent evoked potentials. These monkeys had abnormal distortion product otoacoustic emission (DPEs) and smaller amplitude or absent evoked potentials. These monkeys had the highest blood levels recorded in their respective groups. For the remaining lead-exposed monkeys there was little difference between their DPEs and the DPEs of the control monkeys with one exception. DPE amplitudes of the control monkeys increased more rapidly as a function of stimulus level than those of the lead-exposed monkeys at most frequencies. There was also a significant but modest effect of lead exposure on the auditory brain stem evoked responses (ABRs) of these lead-exposed monkeys. There was no apparent effect on the middle latency evoked responses (MLRs), although that result could be due to the relatively greater variability of the MLR.

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.

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.

A spatial feature extraction and regularization model for the head-related transfer function.

A functional representation is proposed for complex valued (amplitude and phase) head-related transfer functions (HRTFs), including both frequency and spatial dependence. The frequency variation is spanned by a set of eigentransfer functions (EFs) that are generated using the Karhunen-Loève expansion. Any HRTF is represented as a weighted combination of the EFs where the weights are functions of the HRTFs spatial location and are termed spatial characteristic functions (SCFs). Samples of the SCFs are obtained by projecting the measured HRTFs onto the EFs. A regularization framework is employed to obtain a functional representation for the SCFs by fitting each set of SCF samples with a two-dimensional spline. Acoustic validation of the model's fidelity and predictive capability is provided using 2188 measured HRTFs from a KEMAR manikin and 1816 measured HRTFs from an anesthetized live cat. Errors between measured and modeled HRTFs are generally less than one percent. Larger errors occur in the contralateral regions for KEMAR and lower back regions for the cat as a consequence of the relatively small HRTF amplitudes resulting from head shadowing. Methods for reducing these errors are discussed.

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.

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.

External ear transfer function modeling: a beamforming approach.

In this article, a beamformer is proposed as a functional model for the spatial and temporal filtering characteristics of the external ear. The output of a beamformer is a weighted combination of the data received at an array of spatially distributed sensors. The beamformer weights and array geometry determine its spatial and temporal filtering characteristics. A procedure is described for choosing the weights to minimize the mean-squared error between the beamformer response and the measured response of the external ear. The effectiveness of the model is demonstrated by designing a beamformer of several hundred weights that duplicates and interpolates the measured external ear response of a cat over broad ranges of frequency and direction. A limited investigation of modeling performance as a function of array geometry is reported.

Auditory distortion products measured with averaged auditory evoked potentials.

The purpose of this investigation was to describe the properties of averaged auditory evoked potential distortion products (AEP-DPs) in guinea pigs. This study provided a step toward developing a clinical index of nonlinear processing of auditory signals and supplied a baseline for studies evaluating the effect of cochlear damage on AEP-DPs. The amplitude of the AEP-DPs was evaluated as a function of f2/f1 ratio (1.12-1.52) and primary frequency (500 Hz-2000 Hz). The amplitude of the AEP cubic difference tone (AEP-CDT) increased with increasing f2/f1 ratio for the 500-Hz f1 primary and remained constant for the 800-Hz and 1700-Hz f1 primaries. The AEP-CDT generated by the 1100-Hz and 1400-Hz f1 primaries was maximum for the middle f2/f1 ratios (1.22, 1.32, and 1.42). The AEP-CDT could not be distinguished from the noise floor for the 2000-Hz f1 primary. The AEP difference tone (AEP-DT) was larger and more frequently identified than the AEP-CDT. The amplitude of the AEP-DT decreased with an increase in f2/f1 ratio. The decrease was more pronounced for low-frequency f1 primaries than for high-frequency f1 primaries.

Effects of relative starting phase and frequency separation of two-tone stimuli on the brain-stem auditory-evoked response.

Brain-stem auditory-evoked responses (BAERs) were obtained in six normal-hearing adults using single-tone and two-tone stimuli arithmetically centered around 4000 Hz. Two-tone stimuli varied in frequency separation from 200 to 3200 Hz, and started in-phase (homophasic) or 180 deg out-of-phase (antiphasic) with each other. Responses to each of the single-tone components of the two-tone stimuli were elicited and then summed for comparison with responses to the two-tone stimuli. Results indicated no significant difference in wave V latency between homophasic or antiphasic two-tone conditions, and summed single-tone conditions. Under the homophasic condition, the mean latency for the widest frequency separation of the tones was significantly longer than those for narrower separations. A significant difference in wave V amplitude between two-tone phase conditions was found for frequency separations of 200, 400, and 3200 Hz only. Summed single-tone BAERs demonstrated a significantly larger wave V amplitude than responses from either two-tone phase condition at all frequency separations.

Nonlinear system identification by m-pulse sequences: application to brainstem auditory evoked responses.

The purpose of this paper is to introduce a method for characterizing the nonlinear behavior of the auditory system. The method uses an m-pulse sequence as the stimulus and employs a general nonlinear framework for the auditory system. Like Sutter's binary m-sequence approach, the m-pulse sequence approach is computationally efficient since calculation of the first-order input-output cross-correlation function is all that is necessary for obtaining the nonlinear characteristics of the system. The nonlinear system characteristics are reflected in pulse kernels in contrast to binary kernels associated with the binary m-sequence approach. By assuming the system under study is a third-order nonlinear system, binary and pulse kernels are shown to be related to Volterra kernels. The results suggest that the m-pulse sequence can be used to study the system nonlinear effects of varying the stimulus repetition rate more effectively than conventional methods. Preliminary physiological data obtained by applying m-pulse sequences to the brainstem auditory evoked response (BAER) clearly illustrates the feasibility of obtaining replicable evoked responses using this method.

Electrophysiological evidence of nonlinear distortion products to two-tone stimuli.

Spectral analysis of auditory-evoked potential recordings from ten normal-hearing subjects to two-tone signals revealed energy at difference tone (DT = f2-f1) and cubic difference (CDT = 2f1-f2) frequencies that was not present in the acoustic signal. Control experiments and calibrations provided substantial evidence supportive of the biological nature of these auditory nonlinearities, suggesting that they are not the result of electromagnetic, acoustic, or analytic artifact. Amplitudes of DT- and CDT-evoked responses were evaluated for rarefaction and condensation signals with f1 = 510 and 800 Hz across frequency ratios (f2/f1) of 1.16, 1.26, 1.36, and 1.46. Additionally, time-domain summation and subtraction of separately collected evoked responses to rarefaction and condensation signals were performed to demonstrate that these electrophysiological DT and CDT responses reflect their expected quadratic and cubic nature. Suggestions for development of clinical applications of assessing auditory nonlinearities using this methodology are provided.

The effect of probe tube reference placement on sound pressure level variability.

This study examined the effect of external microphone reference placement on peak sound pressure level (pSPL) and measurement variability. Nine normal subjects were seated in a double-walled sound suite, 1 m and 0 degrees azimuth from a wall-mounted speaker. Digitized Gaussian noise was presented at 80 dB pSPL with a 500 msec duration and was measured through a probe tube microphone assembly. Replicated measurements were made at five locations external to the pinna. They were: anterior-superior and posterior-superior positions simulating hearing aid microphone placement (locations 1 and 2) and 2, 4, and 6 cm lateral to the lateral edge of the pinna (locations 3, 4, and 5). Means, standard deviations, and ranges were compared, and statistical analyses were performed. The highest pSPL values were recorded lateral to the pinna, and the lowest values were obtained at the simulated hearing aid positions. ANOVAs indicated a main effect for pSPL, and post hoc testing demonstrated a significant difference between the posterior-superior and 2 cm lateral to the pinna positions. Variability was largest at the posterior-superior and 6 cm positions, and lowest 2 cm from the pinna. From this study, we concluded that pSPL and variability are both important criteria for selecting an optimal reference microphone site and both can affect the accuracy of ear canal measurements. A reference site 2 cm from the pinna eliminates attenuation of the signal and is the least variable site.

A comparison of maximum length and Legendre sequences for the derivation of brain-stem auditory-evoked responses at rapid rates of stimulation.

Experiments were performed in which brain-stem auditory-evoked responses (BAERs) were elicited by two types of pseudorandom pulse trains: maximum length sequences (MLS) and Legendre sequences (LGS). In experiment 1, each pulse sequence was presented at 50 dB nHL with minimum pulse intervals varying from 1 to 10 ms. Wave V latency increased and wave V amplitude decreased with decreasing minimum pulse intervals, with no significant effect of the type of sequence (MLS vs LGS), and no significant interaction between sequence and minimum pulse interval in terms of wave V amplitude or latency. In a second experiment, the minimum pulse interval was held constant at 4 ms, while MLS and LGS levels were varied from 20 to 60 dB nHL. With increasing click intensity, there is a decrease in wave V latency and an increase in wave V amplitude. There was no significant effect of type of sequence (LGS vs MLS) or interaction between type of sequence and stimulus intensity for wave V amplitude or latency. Despite the obvious violation of the assumptions (linearity and stationarity) underlying the application of maximum length sequence analysis and Legendre sequence analysis, both techniques produced reliable responses remarkably similar in morphology to evoked responses obtained by conventional averaging. The results of these experiments support the possibility that analysis methods based on pseudorandom pulse sequences may prove more efficient in data collection and provide a more thorough description of the electrophysiologic behavior of the auditory system compared to conventional averaging.