Short latency somatosensory and spinal evoked potentials: power spectra and comparison between high pass analog and digital filter

Medium nerve somatosensory evoked potentials (SSEPs) and intraoperative spinal evoked potentials were analyzed using different analog and zero phase shift digital high pass filter and by power spectrum. Additionally, high pass analog and digital filtering was performed on various sine, triangular and rectangular waves manufactured by a wave form generator. Recordings were also transformed to the 1st and 2nd time derivatives. The great abundance of spectral energy for scalp recorded median nerve SSEPs was below 125 c/sec but lower energy fast frequency components consistently extended to 500 c/sec. Power spectrum of the Erb's point compound nerve action potential revealed a wide band of spectral energy commencing at about 50-100 c/sec, peaking at about 250-270 c/sec and extending to nearly 1000 c/sec. This suggests that synchronous axonal activity generates predominantly faster frequencies above 100 c/sec. High pass analog filter confers phase non-linearity which results in various distortions including latency shift and a morphological change which may be visually similar to the 1st or 2nd time derivatives. High pass zero phase shift digital filter removes selected low frequencies without accompanying phase distortion. This accentuates fast peaks seen at open bandpass as well as transition points between baseline and component ascent or descent. Zero phase shift digital filter may also generate peaks that are not visualized at open pass but which reflect the sum of frequencies which were not removed by filtering. These peaks do not necessarily correspond to discrete singular neuroanatomical structures. Although peaks observed in high pass analog and digital filter appear similar and comparable, their underlying activity may be of different origin. This is because high pass analog filter projects a considerable amount of overlap from earlier onto later waves. For clinical correlation it is important that restricted bandpass analog or digitally filtered recordings be compared with open pass data. Only those peaks visualized in both open and restricted bandpass can be considered authentic. Examples of spinal and scalp SSEPs indicate that selective filtering may, under certain circumstances, distinguish axonal or lemniscal from synaptic generators.     

Effects of analog and digital filtering on brain stem auditory evoked potentials

Most investigators of the brains stem auditory evoked potentials utilize analog filters to reduce the noise content of the averaged signals, but different investigators use different filter bandwidths. Data presented in this note compare the effects of different upper and lower cutoff frequencies for both analog and zero-phase shift digital filters. Effects on response wave form and on measured values of amplitude and latency of wave V are considered. It is concluded that, for given cutoff frequencies, analog filtering causes more distortion of the response than digital filtering, due primarily to phase distortion introduced by the analog filter. It is likely that differences in filter cutoff frequencies, especially lower cutoff frequencies, are a significant source of variability in results reported by different investigators.     

The effect of different high-pass filter settings on peak latencies in the event-related potentials of schizophrenics, patients with Parkinson's disease and controls.

Eighteen schizophrenic patients, 16 patients with idiopathic Parkinson's disease, and the same numbers of age, sex and education matched controls were examined with oddball experiments for the generation of P3. Individual averages were high-pass filtered at different cut-off frequencies with single-pole digital filters with equivalent analogue Butterworth filter profiles. The purpose of this procedure was to simulate analogue high-pass filters used in clinical studies from different centres and to examine their potential effect on group differences. Increasing high-pass filters resulted in a phase lead for all peaks examined (N1, P2, N2, P3). The only group differences were found for P3, which showed a greater phase lead in controls than in the patient groups, usually resulting in a more pronounced group difference. Similar wave forms and filter properties could be modelled by synthetic wave forms consisting of sine waves of different frequencies.     

An analysis of the human brain stem auditory evoked response yielding new criteria for defining its abnormality

The human brain stem auditory evoked response (BAER) is analysed into 3 main constituent components: a slow background wave, a repetitive wave, and a 3rd (delayed) component which is of relatively short duration, and which does not begin until about 5 ms after the click stimulus. In a group of responses from healthy subjects, the amplitude and latency variabilities of the delayed component are found to be small. In the BAER, as usually recorded from vertex-ipsilateral earlobe electrodes, the peaks I, II, III, IV and VI are identified with the crests of the repetitive wave. Based on this correlation, it is suggested that these peaks may be generated from a common source. Existing criteria for defining abnormality of the BAER are interpreted in terms of the constituent components found from the analysis. New criteria are proposed which involve the amplitudes and latencies of these components.     

EMG artifact minimization during clinical EEG recordings by special analog filtering

A multichannel analog filter for minimizing EMG artifact in routine EEG recordings is described. A 20-channel readily portable version has been implemented which can be easily interfaced with standard electroencephalographs at the auxiliary input/output connectors, in such a way that the filter can be inserted or removed for all channels simultaneously, or, selected channels can be filtered individually. That such an on-line filter be explored was suggested by the remarkable results for minimizing EMG artifact from EEG recordings at seizure onset by off-line computer-based digital filtering recently reported by Gotman, Ives and Gloor. A 4-pole Butterworth filter, i.e., having a maximally flat amplitude response in the passband and having a cut-off frequency, i.e., 30% attenuation point, of 12.5 Hz was selected, the same cut-off frequency as that of the digital filter used by Gotman et al. With this cut-off frequency, which represents a compromise, residual EMG artifact is relatively small. With higher cut-off frequencies, EMG artifact can appear as pseudo-beta activity. Minimization of pseudo-beta activity is obtained, however, at the expense of the elimination of true beta activity. On the other hand, activity of alpha frequencies or lower can be readily identified in the filter output, even with severe EMG artifact in the unfiltered EEG. Other problems in EMG filtering are discussed. Since the analog filter has a non-linear phase characteristic, in contrast to the linear phase characteristic of the finite-impulse-response digital filter used by Gotman et al., the possibility existed that distortion of the wave form of EEG spikes could result, as well as attenuation of their amplitudes. However, the wave forms of filtered spikes in the write-out of the analog filter were found to be essentially identical with those from a one-channel on-line finite-impulse-response computer-based filter having a linear phase characteristic. This finding indicates that phase shift in the analog filter is not a problem, at least for clinical EEG.     

Brain-stem auditory evoked responses as indicators of early brain insult

The relationship between cranial ultrasonograms (SONOs) and brain-stem auditory evoked responses (BAERs) was evaluated in 2 independent samples of newborn infants at risk for brain injury (n = 113 and 203). Features of the BAER wave forms subjected to stepwise linear discriminant analysis formed the basis of an algorithm used to detect and follow early brain injury. Using this algorithm, information derived from BAERs reliably predicted SONO abnormalities at least 82.3% of the time in the initial study which was replicated with the second sample (77.3%). The wave I component latency (CL) and the wave III-V inter-peak latency interval (IPL) were independent of each other, and both contributed to a prediction of SONO abnormality. Possible mechanisms for these BAER results include compromise to the cochlear membrane or to the auditory nerve itself as well as prolongation of transmission in the brain-stem due to brain-stem hemorrhage, edema, or compression. Normative BAER values and non-linear regression functions for the wave I, III and V CLs, and the I-III, III-V, and I-V IPLs were calculated across age using data from 109 infants who demonstrated normal BAER patterns and had no history of SONO abnormalities. Our analyses indicate BAER techniques, where a single higher intensity is used to produce the BAER wave form, are both valid and efficient for use in the evaluation of early brain injury.     

Effects of hypothermia on the cat brain-stem auditory evoked response

Effects of systematic hypothermia on the brain-stem auditory evoked resposes (BAERs) in 4 pentobarbital anesthetized adult cats placed on total cardiopulmonary bypass were investigated. Hypothermia was achieved by slowly cooling the bypass blood through a heat exchanger. Serial BAERs were recorded at 2 min intervals as brain temperature was lowered from 37 to 22°C and then rewarmed over a 1–2 h period. Temperatures were recorded from the brain, esophagus and rectum. Three effects were produced by controlled systemic hypothermia. First, latencies of each component wave (I–V) of the BAER increased exponentially as brain temperature was lowered to 19°C. Latencies of earlier waves (I–III) increased less than those of the later waves (IV–V). Arrhenius plots of inverse latency (rate) versus reciprocal of the absolute temperature generated a family of straight lines of similar slope for each of the 5 component waves of the BAER. The activation energy for each of the 5 BAER waves was derived from the slope of the Arrhenius plot. The mean and standard deviation of the activation energy of all 5 waves was 9.7 ± 0.5 kcal/mole°C. The fact that the activation energy was similar for each BAER component wave (I–V) indicated that the increase in latencies for all 5 waves was governed by the same rate-limiting, temperature-dependent process(es). Second, the rise time and duration of each of the component waves of the BAER increased with decreasing temperature, Third, wave amplitudes increased from 37 to 32°C in a quasiparabolic relation and then, decreased at approximately a linear rate. The BAER wave form completely disappeared below 20.3°C. Slow rewarming of the brain to its initial temperature restored the BAER component waves to their original latencies and amplitudes.     

Comparison of filtering methods for extracellular gastric slow wave recordings

Background  Extracellular recordings are used to define gastric slow wave propagation. Signal filtering is a key step in the analysis and interpretation of extracellular slow wave data; however, there is controversy and uncertainty regarding the appropriate filtering settings. This study investigated the effect of various standard filters on the morphology and measurement of extracellular gastric slow waves. Methods  Experimental extracellular gastric slow waves were recorded from the serosal surface of the stomach from pigs and humans. Four digital filters: finite impulse response filter (0.05–1 Hz); Savitzky‐Golay filter (0–1.98 Hz); Bessel filter (2–100 Hz); and Butterworth filter (5–100 Hz); were applied on extracellular gastric slow wave signals to compare the changes temporally (morphology of the signal) and spectrally (signals in the frequency domain). Key Results  The extracellular slow wave activity is represented in the frequency domain by a dominant frequency and its associated harmonics in diminishing power. Optimal filters apply cutoff frequencies consistent with the dominant slow wave frequency (3–5 cpm) and main harmonics (up to ～2 Hz). Applying filters with cutoff frequencies above or below the dominant and harmonic frequencies was found to distort or eliminate slow wave signal content. Conclusions & Inferences  Investigators must be cognizant of these optimal filtering practices when detecting, analyzing, and interpreting extracellular slow wave recordings. The use of frequency domain analysis is important for identifying the dominant and harmonics of the signal of interest. Capturing the dominant frequency and major harmonics of slow wave is crucial for accurate representation of slow wave activity in the time domain. Standardized filter settings should be determined.     

Temporal artery pulse amplitude wave shapes in migraineurs: A methodological investigation

This paper describes three atypical wave forms observed in temporal artery pulse amplitude recordings. Analysis of concurrent EMG records showed that two of these wave forms, spikes and spasms, were associated with muscle changes and may be regarded as artefacts. The third wave form, double peak, was not associated with EMG changes and may represent a local vascular dysfunction. Double peaks were observed to occur more frequently in migraineurs and specifically at the site of pain onset. Explanations for double peaks are discussed. It is concluded that they indicate a dysfunction in the regulation of vascular tonicity. This dysfunction is described as variable tonicity.     

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

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

Failure of 5-hydroxytryptophan to modulate brain stem auditory evoked responses in myelin deficient mutant qk mice

The effect of 5-hydroxytryptophan (5-HTP) on brain stem auditory evoked response (BAER) amplitude in Quaking (qk) and normal littermate mice was examined. Administration of 5-hydroxytryptophan (5-HTP) (75 mg/kg, i.p.) to normal mice increased the amplitude of BAER peaks I, II, and III but had no effect on peak IV. In qk mice, however, 5-HTP did not affect the amplitude of any BAER peaks. Our data indicate that although 5-HTP increased BAER amplitude in normal mice, it failed to modulate BAER in qk mice. These findings are consistent with the possibility that 5-HTP receptor sites associated with myelin basic protein may be reduced in the myelin-deficient mutant qk mice.     

A study of the transition from spindles to spike and wave discharge in feline generalized penicillin epilepsy: EEG features

Earlier work suggested that the epileptic bursts occurring in the form of spike and wave discharges in feline generalized penicillin epilepsy were closely related to spindles. The present study showed that after i.m. penicillin, spindles elicited by single-shock midline thalamic stimulation gradually change into spike and waves. Hybrid forms are often seen during the transition phase. The transformation of spindles into spike and waves initially involves an increase in amplitude and the development of positive phases of spindle waves. Furthermore, every second (or in cats with lesions of the midbrain reticular formation, every second and third) spindle wave is gradually eliminated and replaced by a slow wave. The remaining enhanced spindle wave becomes the spike of the spike and wave complex. In conformity with this development, spectral analysis shows that no gradual frequency shift occurs during this transformation, but that the intraburst frequency decreases by a half or a third in one step from that characteristic of spindles to that typical for spike and waves. Spindle and spike and wave frequencies vary from cat to cat, but the above ratios are constant across animals. The spike and waves of cats with lesions of the midbrain reticular formation resemble those of human generalized epilepsy more closely than those induced in intact animals. A continuous transition from spindles to spikes and wave is thus demonstrable suggesting that spike and wave bursts are elicited by the same thalamocortical volleys which normally induce spindles.     

Effects of high-pass filter frequency and slope on BAEP amplitude, latency and wave form

The effects of increases in analogue high-pass filter frequency and slope on the BAEP were investigated in a group of 20 subjects. Frequency effects were additionally compared to the wide-band recorded signal and slope effects to a zero-phase shift filter, all filters being digitally simulated. Absolute amplitude, latency and interpeak latency were significantly reduced by both progressive filter frequency and steepness. Additionally, different effects on the ascending and descending limbs of waves I, III and V were observed which explain wave form distortions. The results suggest that filtering should be limited to, at most, 6 dB/oct and 100 Hz frequency.     

Cortical responses to speech sounds and their formants in normal infants: maturational sequence and spatiotemporal analysis

Cortical auditory evoked potentials (AEPs) to the synthesized syllables [da[ and [ta[ and to the isolated 3 formants of [da[ were obtained from 32 normal infants studied at monthly intervals from birth through 3 months and at 6 months of age. A bilateral array of 16 electrodes referenced to the mid-occiput permitted a topographic analysis of the cortical AEPs at selected latencies. A differential maturational sequence was seen: a predominantly negative cortical AEP wave form became positive, first over the frontocentral region (around term), and then over the temporal region (at 1-2 months). The timing of these electrophysiological changes coincides with a differential anatomical maturational sequence in the auditory cortex, as myelination and synaptogenesis are more advanced in primary than secondary auditory areas at term. All infants in this study followed this developmental sequence. However, there was no systematic effect of the center frequency of the formant stimuli on the maturational level of their respective cortical AEPs, suggesting a relative maturational equivalence in those regions of auditory cortex responding to stimuli across the frequency range present in human speech. In term infants, an initial midline positivity and bitemporal negativities were asynchronous in their peak and offset latencies. suggesting independent generators for each of these components. In infants from 3 to 6 months of age, cortical AEP wave forms consisted of 2 initial positive peaks followed by a negative peak. While the wave forms were similar over midline and lateral scalp, spatiotemporal analysis revealed differences in the latency of onset, duration and in the spatial extent of these components, again suggesting that 2 bilateral, temporally overlapping generators contribute to the cortical AEP. No systematic topographic difference was observed in the cortical AEPs elicited by each of the 3 formants, which differed in center frequencies.     

No close correlation between brainstem auditory function and peripheral auditory threshold in preterm infants at term age.

OBJECTIVE: To determine whether central auditory function in preterm infants correlates with peripheral auditory threshold and whether threshold elevation affects central auditory function. METHODS: Brainstem auditory evoked response (BAER) was recorded at term age using maximum length sequence (MLS) with 91-910/s clicks in 133 preterm infants (gestation 28-36 weeks). The relationship between MLS BAER variables and BAER threshold was analyzed. RESULTS: The latencies and amplitudes of all MLS BAER waves correlated significantly with BAER threshold. However, no correlation was found between MLS BAER interpeak intervals and BAER threshold at any rates. In preterm infants with a threshold >20dB nHL (n=30), MLS BAER wave latencies were all significantly longer than in those with a threshold < or = 20dB nHL (n=103) (P<0.01-0.001). MLS BAER wave amplitudes were significantly smaller than in those 20dB nHL (P<0.05-0.001). However, no interpeak intervals differed significantly between the two groups of infants. V/I amplitude ratio was similar in the two groups. These findings were true of all click rates. Click rate-dependent changes in MLS BAER of the preterm infants with an elevated BAER threshold are generally similar to those with a normal threshold. CONCLUSIONS: Brainstem auditory function does not closely correlate with peripheral auditory threshold at term in preterm infants. Elevation in peripheral threshold due to middle ear disorders does not significantly affect functional status of the auditory brainstem. SIGNIFICANCE: Short term peripheral conductive auditory abnormality does not significantly affect the immature central auditory function.     

Bessel filtering of brain stem auditory evoked potentials

It has been shown previously that conventional high-pass filtering of the brain stem auditory evoked potential (BAEP) results in significant wave form distortion. This distortion can be drastically reduced by using digital filters with zero-phase properties, but this approach requires the use of a digital computer. The Bessel filter is an approximation to a linear phase characteristic, and has the advantage that it may be implemented using analog circuitry. We have considered its use as an alternative-to-digital zero-phase filtering. For the low-pass case, the Bessel phase characteristic is approximately linear throughout the pass band. However, for the high-pass case there is significant phase non-linearity extending well into the pass band. Typical Bessel high-pass filters seriously distort the BAEP wave form; thus, these filters are not an acceptable alternative to the zero-phase digital approach.     

Analysis of frequency components in time series data

We describe a method for assessing the periodic elements of variations in a time series and illustrate it with examples drawn from infant cardiac beat-to-beat intervals. Compared with averaging techniques, the procedure has the advantage of providing quantification of periodical elements in a non-stationary time series. Moreover, the procedure is robust to artifacts such as those which frequently contaminate beat-to-beat interval data. The method examines successive increments of the time-series plot, and when they become negative or positive, peaks and troughs are noted in the curve. Two successive troughs confine a wave which may be described by its amplitude and period. The set of all waves, terminated by the sequence of troughs, is defined as the "high-frequency component" of the series. Waves of the next low-frequency component are delineated when only the high-frequency peaks (or troughs) are considered. Thus, low-frequency peaks are defined as peaks of the curve formed by the high-frequency peaks, and lower-frequency troughs are the troughs of the curve formed by the high-frequency troughs. The process iterates to assess variations at lower and lower frequencies and any specific frequency component is being characterized by the median and interquartile range of its wave amplitudes and wave periods.     

Auditory brainstem of the ferret: maturation of the brainstem auditory evoked response

A longitudinal study of developmental changes in the brainstem auditory evoked response (BAER) was made on 19 ferrets between postnatal days 25 (P25) and 50. Responses to free-field click stimuli were recorded from anaesthetized animals, and compared with data obtained from 8 adult ferrets. A reproducible BAER was first recordable on P27, although the response onset was generally later in smaller animals. BAER onset preceded eye opening, which started on P32. Adult-like thresholds were observed in all animals by P40, but the age at which they were attained was also dependent on size. The BAER in the adult ferret consists of 4 main vertex-positive peaks occurring in the first 5 ms following transient acoustic stimulation. In the youngest animals the presence of an additional peak (between II and III) and the slurring of peaks III and IV were consistent features. The individual peaks undergo an asymmetrical pattern of development, with mean peak I latency attaining an adult value at P40, while mean peak IV latency is still 115% of the mean adult value at that age. BAERs could routinely be recorded using high stimulus presentation rates (greater than 40/s), though an increase in absolute and interpeak latencies occurred, the extent of which decreased with age. The pattern of BAER development in the ferret is compared with that in other species, and the concept of the 'silent period' (period between conception and onset of hearing) as a standard unit of auditory development is introduced.     

Frequency domain EEG source localization of ictal epileptiform activity in patients with partial complex epilepsy of temporal lobe origin.

The aim of this study was to investigate whether EEG source localization in the frequency domain, using the FFT dipole approximation (Lehmann, D. and Michel, C.M. Electroenceph. clin. Neurophysiol., 1990, 76: 271-276), would be useful for quantifying the frequency content of epileptic seizure activity. Between one and 7 extracranially recorded seizures were analyzed in each of 7 patients with mesolimbic epilepsy, who were seizure-free after temporal lobe resection. The full scalp frequency spectrum for the first 4 s after seizure onset, as well as for subsequent periods, was determined. Power peaks in the spectra were identified, and an instant dipole fit was performed for the frequencies corresponding to these peaks. Ictal frequencies, ranging between 3.5 and 8.5 Hz, showed a variable degree of stability over time in the different patients. For a particular frequency, dipole results were similar during the different phases of seizure development. In patients with more than one prominent frequency, dipole results for the different frequencies were similar. Dipole results were also similar between patients. We conclude that dipole localization of dominant frequencies, as obtained from full scalp FFT analysis, gives quite reproducible results for seizures originating in the mesial temporal area. The method may become a useful tool for the pre-surgical identification of patients with mesolimbic epilepsy.     

Brain-stem auditory evoked potentials in the alligator. Effects of temperature and hypoxia

Brain-stem auditory evoked potentials (BAEPs) were recorded from young alligators (Alligator mississippiensis), and the effects of hypothermia, hyperthermia and hypoxia on the wave forms were determined. The wave form shape was similar to the human BAEP, although extra waves were routinely seen. The responses were highly repeatable and varied in a predictable manner as a function of stimulus frequency, polarity, intensity, and body temperature. Rarefaction clicks produced longer wave form latencies than condensation clicks. BAEPs were present over the entire temperature range studied (0-36 degrees C). In contrast, mammalian BAEPs disappear over the temperature range of 20-27 degrees C, and seizures occur at 20-21 degrees C. At temperatures below 20 degrees C, the alligator BAEP peak amplitudes decreased with decreased temperature, but latencies only decreased slightly. At temperatures above 20 degrees C the peak amplitudes increased, and the latencies decreased with temperature. Peak I was largely unaffected by temperature change, while peaks IIIa and V increased 0.015 and 0.018 msec/degree C, respectively, at temperatures above 24 degrees C. Transient brain hypoxia, achieved by inverting the alligator, produced a progressive decrease in BAEP waves to an isoelectric amplitude without greatly altered latencies. The reverse sequence of changes was seen during recovery. Postural effects on blood flow were documented in two alligators with implanted flow probes. Carotid artery blood flow decreased 43% with body inversion, in both anesthetized and unanesthetized alligators, but no sequelae from the hypoxia could be detected. Metabolic differences between mammals and the alligator may account for the alligator's resistance to hypothermia, hyperthermia and hypoxia.