利用参数模型提取诱发脑电（EP）及其在40Hz EEG和EP间关联研究中的应用

提出一种基于参数模型的信号处理方法,用于诱发脑电（ＥＰ）的提取,这种方法可以得到单次ＥＰ波形的无偏、最小方差估计。用刺激强度实验验证了该方法在实际情况下的有效,进一步将其应用于刺激前ＥＥＧ与ＥＰ的关联研究,得到了刺激前４０Ｈｚ的ＥＥＧ成分与晚潜伏期听觉诱发脑电幅度有极显著负相关的结果,表明刺激前及状态确定对ＥＰ有影响。     

利用参数模型提取诱发脑电（EP）及其在40Hz EEG和EP间关联研究中的应用

提出一种基于参数模型的信息处理方法,用于诱发脑电的提取,这种方法可以得到单次ＥＰ波形的无偏,最小方差估计,用刺激强度实验验证了该方法在实际情况下的有效,进一步将其应用于刺激前ＥＥＧ与ＥＰ的关联研究,得到了刺激前４０Ｈｚ的ＥＥＧ成分与晚潜伏期听觉诱发脑电幅度有极显著负相关的结果,表明刺激前及状态确定对ＥＰ有影响。     

Method for recording short latency evoked potentials using an EKG artifact elimination procedure

This paper describes the application of an EKG elimination procedure¹, previously reported by the authors, to evoked potentials (EPs) recording using a non-cephalic reference. The method consists of three separate steps: data acquisition, EKG artifact elimination, and EP averaging. EKG artifacts are eliminated from the raw EEG by applying a four step procedure to the simultaneously recorded EEG, EKG and stimulus pulse. The steps are: synchronized partition of the raw EEG, EKG averaging, synchronized repetition, and synchronized subtraction of the EKG estimate from the raw EEG. Average EP values are then obtained by averaging the processed EEG using the stimulus pulse as a trigger. Somatosensory evoked potentials to a hand reference, averaged using the proposed method, were compared with those obtained by two conventional averaging methods, and were shown to be more clearly defined. The advantage of the proposed method for recording short latency EP values with a non-cephalic reference is that it requires fewer sweeps and thus takes less time than other methods. The proposed method may also be applicable to the recording of other EP values.     

Steady-state analysis of somatosensory evoked potentials

We report the development of a new method for frequency domain analysis of steady-state somatosensory evoked potentials (SEPs) to amplitude-modulated electrical stimulation, which can be recorded in significantly less time than traditional SEPs. Resampling techniques were used to compare the steady-state SEP to traditional SEP recordings, which are based on signal averaging in the time domain of cortical responses to repetitive transient stimulation and take 1–2 min or more to obtain a satisfactory signal/noise ratio. Median nerves of 3 subjects were stimulated continuously with electrical alternating current at several modulation frequencies from 7 to 41 Hz. Amplitude modulation was used to concentrate the power in higher frequencies, away from the modulation frequency, to reduce the amount of stimulus artifact recorded. Data were tested for signal detectability in the frequency domain using the T_circ² statistic. A reliable steady-state response can be recorded from scalp electrodes overlying somatosensory cortex in only a few seconds. In contrast, no signal was statistically discriminable from noise in the transient SEP from as much as 20 s of data. This dramatic time savings accompanying steady-state somatosensory stimulation may prove useful for monitoring in the operating room or intensive care unit.     

Evoked cortical potentials to simple and complex visual signals in children

The analysis of steadily recorded components of evoked potentials (EP) in different areas of cerebral cortex during tachistoscopic presentation of a homogeneous square, checker-board pattern and schematic drawings of human faces (face-pattern) of 6 degrees size was performed in children aged from 6,5 to 7 years. During contour detection, characterized by significant EP differences between responses to a checker-board pattern and a homogeneous square, the most pronounced changes were observed in the visual projection area of the cortex. Reaction to a complex visual stimulus, characterized by differences of EP to fase and checker-board patterns, had maximal manifestation in the temporo-parieto-occipital area. The changes observed during both operations were noted for EP components appearing up to 250 msec following stimulation. It is suggested that they are connected with the activity of cortical receptive fields. The data obtained are discussed on the basis of hypothesis of a difference between cortical mechanisms of single operations involved in visual perception.     

Fundamental stimulus for erythropoietin production in the neonatal rat

A mild degree of hemolytic anemia was induced in neonatal rats by a single subcutaneous injection with phenylhydrazine (PHZ). The ability to respond to this challenge was determined by monitoring serum erythropoietin (EP) levels at 6 and 12 hr. At 6 hr after PHZ, EP reached a level of 4.25 ± 1.03 U/ml, and at the 12-hr interval it had increased to 6.12 ± 1.49 U/ml. Based on these data, it is our suggestion that PHZ-induced hemolysis affords an effective stimulus for EP production in the neonatal rodent.     

Effects of changing illuminance on somatosensory function

Artificial sources of illumination can be easily used, regardless of the time and place, to improve visibility at night and in dark places. Illuminance and color temperature are particularly important factors since they are known to elicit physiological effects. However, the relationship between changes in illuminance and somatosensory function has not been sufficiently clarified. Thus, the purpose of this study was to construct a laboratorial model to examine the effects of lowering or raising illuminance on somatosensory function. Three illuminance levels (200 lx, 50 lx, and 0 lx), which were changed using all combinations, and an artificial sensory stimulus maintained at a constant intensity were presented to the subjects of this study. Objective sensory function in response to the sensory stimulus was investigated by somatosensory evoked potential (SEP), and subjective sensory evaluation in response to the stimulus was investigated using a visual analogue scale (VAS) and by interview. In many cases, the SEP amplitude and VAS value tended to decrease when illuminance was lowered and tended to increase when illuminance was raised. However, in a few cases, SEP amplitude and VAS value tended to increase in spite of the low illuminance. The occurrence of attention responses and unpleasant emotional responses caused by lowering the illuminance seems to be related to this study finding.     

Female-female mounting among goats stimulates sexual performance in males

The hypothesis that female-female mounting is proceptivity in goats, in that male goats are aroused by the visual cues of this mounting behavior, was tested. Once a week, male goats were randomly selected and placed in a test pen in which they were allowed to observe one of six selected social or sexual stimulus conditions. The stimulus conditions were one familiar male with two estrous females (MEE); three estrous females that displayed female-female mounting (E(m)); three estrous females that did not mount (E(nm)); three non-estrous females (N(E)); three familiar males (M); and no animals in the pen (Empty). After 10 min, the stimulus animals were removed, and an estrous female was placed in the test pen with the male for a 20-min sexual performance test. During sexual performance tests, the frequencies and latencies of all sexual behaviors were recorded. This procedure was repeated so all males (n = 6) were tested once each test day, and all the stimulus conditions were presented each test day. This was repeated weekly until all males had been exposed to each stimulus condition. Viewing mounting behavior, whether male-female or female-female, increased the total number of sexual behaviors displayed, increased ejaculation frequency, and decreased latency to first mount and ejaculation, post-ejaculatory interval, and the interval between ejaculations. We conclude that male goats are aroused by the visual cues of mounting behavior, and that female-female mounting is proceptivity in goats.     

Detection of neurological injury using time-frequency analysis of the somatosensory evoked potential

Somatosensory evoked potentials (SEPs) can be monitored during critical surgery to help detect or possibly prevent post-operative injury to the brain. This paper presents the application of time-frequency analysis to detect both temporal and spectral changes in the SEP waveform that may occur due to injury. Time-frequency distributions, which provide a measure of signal energy at both a specific time and frequency, were computed for averaged SEPs acquired from anesthetized cats during various stages of hypoxic injury and then recovery. Wigner distributions of SEP waveforms were found to contain a peak of signal energy at a specific time and frequency, a peak that is altered during injury. Four characteristics of the distribution peak that demonstrate changes due to injury were computed: peak time, peak frequency, peak power, and peak sharpness. Peak time was found to increase while peak frequency, peak power, and peak sharpness were found to decrease during injury. Furthermore, the total signal power in a time-frequency space around the normal peak location was monitored by developing a time-frequency window filter (TFWF) method. For all cases, onset of hypoxia was detected an average of 2.75 min earlier by the TFWF method than by the conventional amplitude measurement method. Time-frequency analysis of EP signals may therefore be useful as a monitoring tool for early detection of brain injury.     

Distribution of lumbar spinal evoked potentials and their correlation with stimulation-induced paresthesiae

In 7 awake patients with neuropathic lower extremity pain, spinal somatosensory evoked potentials (SEP) were elicited from the non-painful leg by electrical stimulation of the peroneal nerve and mechanical stimulation of the hallux ball. Recording was made epidurally in the thoraco-lumbar region by means of an electrode temporarily inserted for trial of pain-suppressing stimulation.In response to peroneal nerve stimulation, two major SEP complexes were found. The first complex consisted, as has been described earlier, of an initial positivity (P12), a spike-like negativity (N14), a slow negativity (N16) and a slow positivity (P23). The second complex consisted of a slow biphasic wave, conceivably mediated by a supraspinal loop. Both complexes had a similar longitudinal distribution with amplitude maxima at the T12 vertebral body.The SEP evoked by mechanical hallux ball stimulation had a relatively small amplitude, and there was no significant second complex. The relationship between stimulus intensity and SEP amplitude was negatively accelerating.The longitudinal distribution of spinal SEP was compated with the somatotopic distribution of paresthesiae induced by stimulation through the epidural electrode. It was found that stimulation applied at the level of maximal SEP generally induced paresthesiae in the corresponding peripheral region. Therefore, spinal SEP may be used as a guide for optimal positioning of a spinal electrode for therapeutic stimulation when implanted under general anesthesia.An attempt was made to record the antidromic potential in the peroneal nerve elicited from the dorsal columns by epidural stimulation. The antidromic response was, however, very sensitive to minimal changes of stimulus strength and body position of the patient, and was also contaminated by simultaneously evoked muscular reflex potentials.Thus, peripheral responses evoked by epidural stimulation appeared too unreliable to be useful for the permanent implantation of a spinal electrode for therapeutic stimulation.     

Evoked potentials of the cerebral cortex during the comparison of visual stimuli

Visual evoked potentials (EP) were recorded when the test subjects accomplished the tasks of a comparison of a current stimulus with the previous one, the stimuli being presented in a continuous sequence. In the first task, rare repetition of two stimuli (Russian letters) in the continuously changing flow of stimuli was relevant, and the test subject had to press the button when it happened; in the second task, the relevant stimulus was a rare change in the flow of stimuli. The influence of the stimulus repetition/change factor on EP was analyzed. The processes related to the comparison of the current and previous stimuli were most manifest in four time intervals: 120–140, 180–210, 260–280, and 350–370 ms. The occipito-temporal component of EP revealed in the interval of 180–210 ms, which we denoted as the negative component of visual mismatch (NCVM), proved a special component, differing in its functional and temporal characteristics from theN _2b component. WhereasN _2b is modulated by the factor of stimulus probability, the NCVM by that of stimulus repetition/change.     

A comparison of forepaw and vibrissae somatosensory cortical evoked potentials in the rat

Somatosensory evoked potentials were elicited in anesthetized rats by electrical stimulation of the forepaw (F-SEP) or the vibrissae (V-SEP) and were compared in order to study which of these is more valid animal model for studying the physiology and pathophysiology of somatosensory evoked potentials (SEPs) that are often recorded in man in a clinical setting. Intensity and rate functions were measured for the two potentials. The V-SEPs had larger amplitudes than the F-SEPs at high stimulus intensity and low stimulus rate. Furthermore, the ratios of the maximal amplitude of the F-SEP to that of the V-SEP (0.66) and of the areas under the curves of the two responses (0.75) reflected the smaller representation of the forepaw in the primary somatosensory cortex of the rat, compared to the vibrissae (ratio of cortical areas about 0.79). The differences should be taken into account when using median nerve SEP in the rat as a model of the human SEP. Study of V-SEPs in rat may provide insight into trigeminal nerve SEPs in man, which are also occasionally used for neurological evaluation.     

Auditory brain-stem (ABP) and somatosensory evoked potentials (SEP) in an animal model of a synaptic lesion: elevated plasma barbiturate levels

Experiments were conducted to determine whether a consistent pattern of auditory nerve brain-stem evoked potential (ABP) abnormalities could be demonstrated in the presence of a synaptic lesion model in cats (elevated levels of the barbiturate thiopental). The ABP in response to low (10/sec) and high (80/sec) stimulus rates was recorded. In order to differentiate between the effects of the elevated drug levels on axonal propagation and on synaptic transmission, the early components of the somatosensory evoked potential (SEP) were also recorded, with particular attention to the first SEP wave, which is solely an axonal event without any intervening synapse. Calculations showed that the effect on synapses was 3.0–9.5 times greater than the effect of the drug on axonal propagation. As the level of barbiturates increased (representing a more severe synaptic lesion), the interpeak latencies of the ABP and the SEP became progressively prolonged, more so than the dependence of the first waves of both the ABP and the SEP on drug level. In general, amplitudes were not affected. At progressively elevated drug levels, higher stimulus repetition rates did not have an increasingly greater effect than lower rates on evoked response latencies and amplitudes so that this study also shows that the use of elevated stimulus rates does not hold much promise in the diagnosis of synaptic lesions.     

Measures of neuronal response based on nonparametric tests

Two response indices characterizing the stimulus effect on spontaneously active neurons are developed. They are based on a non-parametric comparison of interspike interval distributions under the spontaneous and the stimulus condition. The response indices obtained with repeated stimuli can be combined into a single multiple-trial index. The method is tested both with different types of simulated spike activity and with actual single unit activity recorded from an auditory centre of a songbird.Supported by Deutsche Forschungsgemeinschaft within Sonderforschungsbereich 114 (Bionach)     

Single evoked potential reconstruction by means of wavelet transform

We would like to propose a method of single evoked potential (EP) extraction free from assumptions and based on a novel approach — the wavelet representation of the signal. Wavelets were introduced by Grossman and Morlet in 1984. The method is based on the multiresolution signal decomposition. Wavelets are already used for speech recognition, geophysics investigations and fractal analysis. This method seems to be a useful improvement upon Fourier Transform analysis, since it provides simultaneous information on frequency and time localization of the signal. We would like to introduce wavelet formalism for the first time to brain signal analysis. One of the most important problems in this field is the analysis of evoked potentials. This signal has an amplitude several times smaller than EEG, therefore stimulus-synchronized averaging is commonly used. This method is based on several assumptions. Namely it is postulated that: 1) EP are characterized by a deterministic repeatable pattern, 2) EEG has purely stochastic character, 3) EEG and EP are independent. These assumptions have been challenged e.g. the variability of the EP pattern was demonstrated by John (1973) by means of factor analysis. In view of the works of Sayers et al. (1974) and Baar (1988) EP reflects the reorganization of the spontaneous activity under the influence of a stimulus and it is connected with the redistribution of EEG phases. Several attempts to overcome the limitation of the averaging method have been made. Heintze and Künkel (1984) used an autoregressive moving average (ARMA) model to extract evoked potentials from 2 segments. This was possible under two condiitons: high signal to noise ratio and clear separation of the EEG and EP spectra. These assumptions are not easy to fulfill, though. Cerutti et al. (1987) modeled background EEG activity by means of an AR process and event related brain activity by ARMA. In this way they were able to find a filter extracting single EP. Nevertheless, their method was not quite free of assumptions, since they since they used averaged EP to define their ARMA filter. In the following we shall briefly describe the method of the multiresolution decomposition and we will apply it to the analysis and reconstruction of single evoked potentials.     

Facilitation of electroporative drug uptake and cell killing by electrosensitization

Cell permeabilization by electric pulses (EP), or electroporation, is widely used for intracellular delivery of drugs and plasmids, as well as for tumour and tissue ablation. We found that cells pre‐treated with 100‐μs EP develop delayed hypersensitivity to subsequent EP applications. Sensitizing B16 and CHO cells by splitting a single train of eight 100‐μs EP into two trains of four EP each (with 5‐min. interval) decreased the LD₅₀ 1.5–2 times. Sensitization profoundly enhanced the electroporation‐assisted uptake of bleomycin, a cell‐impermeable cytotoxic agent accepted for killing tumours by electrochemotherapy. EP exposures that were not lethal per se caused cell death in the presence of bleomycin and proportionally to its concentration. Sensitizing cells by a split‐dose EP exposure increased bleomycin‐mediated lethality to the same extent as a 10‐fold increase in bleomycin concentration when using a single EP dose. Likewise, sensitization by a split‐dose EP exposure (without changing the overall dose, pulse number, or amplitude) enhanced the electroporative uptake of propidium up to fivefold. Enhancement of the electroporative uptake appears a key mechanism of electrosensitization and may benefit electrochemotherapy and numerous applications that employ EP for cell permeabilization.     

Evaluation of reference sites for scalp potentials evoked by painful and non-painful sural nerve stimulation

The objective of this study was to evaluate reference sites for recording the middle- and long-latency scalp potentials elicited by painful and non-painful sural nerve stimulation. Somatosensory evoked potentials (SEPs) were recorded from the scalp, the mastoid, the earlobe, the neck, and the wrist. Each site was referenced to the sterno-vertebral (SV) electrode, which is a balanced non-cephalic reference with essentially no ECG contamination.There was little or no activity recorded between the wrist and SV, and the SV was located within a region extending from the rostral neck to the wrist where the potentials were stable over space. Hence, the SV reference is indifferent for the middle- and long-latency potentials evoked by painful and non-painful sural nerve stimulation. There was, however, significant activity recorded from the earlobe and mastoid, sites which are frequently used as references for the SEP. It is important that investigators using these cephalic references to study the middle- and long-latency peaks of the SEP be aware of this activity as it will distort SEPs recorded from single sites and the SEP scalp topography, distortions which could unnecessarily complicate their interpretation.     

Nonlinear terms produced by passing amplitude-modulated sinusoids through a hair cell transducer function

We derive mathematically the output of Corey and Hudspeth's hair cell transducer function for the following cases: (1) the input is a single carrier whose output is modulated by the sum of two sinusoids; (2) the input is the sum of two carriers, each of which is amplitude-modulated by a single sinusoid. The theoretical results are similar to the results of an experiment in which field potentials were recorded from the human scalp while one ear was stimulated with auditory waveform (1) and with auditory waveform (2) of the cases above.     

Refractoriness of sural nerve in humans

High-frequency stimulation of peripheral nerve bundles is frequently used in clinical tests and physiologic experiments to study presynaptic and postsynaptic effects. To understand the postsynaptic effects, it is important to ensure that each pulse in the train is equally effective in stimulating the presynaptic nerve bundle; however, the optimal interpulse interval (IPI) and the stimulus intensity at which each pulse is equally effective in stimulating the same number of axons are not known. The magnitude of the compound action potential produced by each pulse in a train was tested on the sural nerve of 4 healthy human subjects. The stimulus train (2-4 pulses) was applied to the sural nerve at the lateral malleolus, and neural responses were recorded from just below the knee. With 2-pulse trains, families of curves between IPIs (1-6 ms) and normalized amplitudes of the second response were plotted for different stimulus intensities. Visual inspection of the data showed that the curves fell into 2 groups: with stimulus intensities <2.5x perception threshold (Th), the test response appeared partially at longer IPIs, whereas with stimulus intensities >=3x Th, partial recovery of the test response was earlier. The interval for complete recovery was statistically the same for low- and high-intensity stimulation. With more than 2 pulses in a stimulus train (IPI = 5 ms), the amplitude of the compound action potential (CAP) was not affected significantly. These results are important in understanding both the presynaptic and postsynaptic responses when presynaptic axon bundles are stimulated at high frequencies.     

New method for quantitative evaluation of esophageal sensibility

A method for quantitating esophagus sensibility by an electric stimulation test is described. Square stimulus waveform at different voltages and durations were transmitted to the esophagus, three series of electric stimuli being used in successive durations (0.5, 1, 2, 4, 8 and 16 ms); in each series the voltage discharge was increased progressively from 0 mV, until the subject noted the first sensation. This procedure was carried out at all esophageal levels. The following parameters were analyzed: sensitive threshold along the esophagus; the relation of threshold sensibility (mV) duration of stimulus (ms), and reobase and cronaxia for each esophageal level. At all esophageal levels, the sensitive threshold was regular and coherent; in the middle esophagus a zone was found having higher sensitive threshold than the proximal and distal esophageal zones. The relationship between sensitive threshold and inverse of the stimulus duration indicated that esophageal sensibility follows the basic law of excitation of WEISS, at least with this type of stimulus, reobase and cronaxia being representative of the sensibility threshold along the esophagus. Quantitative esophageal sensibility, therefore is concluded to be particularly suited to evaluation by electric stimulation.