Consistency of the auditory evoked response: the presence of aberrant responses and their effect on N100 localization

The structure and distribution of the sources underlying the generation of evoked potentials (EPs) is often very complex. In an effort to improve localization accuracy of the auditory N100 (negative response occurring around 100ms poststimulus) component, we analyzed 13 datasets of single-trial EPs obtained from normal subjects using an iterative independent component analysis procedure which allowed us to detect a clear N100 component in each single trial and to study gross changes in component morphology across trials. We found that single-trial N100 amplitude was most often negative in polarity, as expected, but occasionally exhibited a marked reversal to become positive. The average N100, however, showed the typical negative polarity, in all subjects. Based on this observation, we separated the processed single trials in two groups of typical and aberrant responses, and from each group, we computed a partial EP that was used to localize the underlying intracranial sources. Additionally, we localized the classical ensemble average EP. Before processing, the N100 sources were identified correctly in the primary auditory cortex in only four datasets, while after processing, all 13 datasets yielded correct localizations, and the confidence volume of the sources improved by about 80%. Further analysis demonstrated that in nine datasets the improvement was mostly due to the typical responses, while the aberrant responses had an antagonistic effect. Our results suggest that aberrant responses should not be included in source localizations, especially when EEG-based brain mapping is intended as a clinical tool.     

Analyses of single-trial N1 amplitude and latency variability and their influence on the average evoked potential

Sixteen adult subjects listened to tone pips superimposed on Bach concertos and either attended to the tones or to the music. Auditory evoked potentials (EPs) were recorded to the tones in both conditions from C3 and C4 each referenced to linked ears. Although the expected Condition X Hemisphere interaction was not found, a main effect for Condition showed that N1 amplitude in the average EPs (AEPs) was greater in the Tones condition. P2 showed no significant main effects or interactions. The AEP was used as a template to identify N1 in each single-trial wave form. The difference in AEP amplitude between conditions was subsequently found to be due primarily to enhanced N1 amplitude in the single-trial wave forms, and not to a decrease in latency variability. This template-matching procedure appears to be a valid method for identifying N1 in single-trial wave forms based on the following findings: (1) multiple regression analyses demonstrated that 90-99% of the variance of the amplitude of N1 in the average EP could be accounted for by a weighted linear combination of single-trial amplitude and latency variability; (2) the values of the correlation coefficients between the AEP template and the single-trial EPs were generally very high, averaging approximately +0.91; (3) the distributions of the latency of N1 in the single-trial EPs were not flat as would be expected if random noise were being identified as N1.     

Single-trial event-related potentials with wavelet denoising.

The application of a recently proposed denoising implementation for obtaining event-related potentials (ERPs) at the single-trial level is shown. We study its performance in simulated data as well as in visual and auditory ERPs. For the simulated data, the method gives a significantly better reconstruction of the single-trial event-related responses in comparison with the original data and also in comparison with a reconstruction based on conventional Wiener filtering. Moreover, with wavelet denoising we obtain a significantly better estimation of the amplitudes and latencies of the simulated ERPs. For the real data, the method clearly improves the visualization of both visual and auditory single-trial ERPs. This allows the calculation of better averages as well as the study of systematic or unsystematic variations between trials. Since the method is fast and parameter free, it could complement the conventional analysis of ERPs.     

Interhemispheric Transfer in Normals and Acallosals: Latency Adjusted Evoked Potential Averaging

Interhemispheric transfer time (IHTT) can be estimated from visual evoked potentials (EPs). Latency adjusted averaging (LAA) produces EPs which have enhanced components. LAA also provides estimates of EP latency variance and signal-to-noise ratio (S/N). LAA was tested in analysis of EP-IHTT in normal and acallosal subjects. It was hypothesized that in normals S/N and latency variance would reveal signal degradation resulting from interhemispheric transfer. LAA in normals replicated IHTT findings for both P1 and N1 latency. Latency variance did not increase for cross-callosal measures, whereas the S/N measure showed significant EP degradation due to callosal transfer. EPs from five subjects with callosal absence (two commissurotomy; two complete and one partial callosal agenesis) showed significantly larger than normal latency variability, as well as decreased S/N ratios, for cross-hemisphere visual EPs. Results support the value of LAA in EP research on adequacy of hemispheric interactions in clinical populations.     

The effect of the phase of prestimulus alpha activity on the averaged visual evoked response.

The relationship between the latencies and amplitudes of the N1 and P2 components of the averaged visual evoked potential (EP) and the phase of the alpha activity immediately preceding the time of the stimulus, has been investigated in 7 male subjects. Low intensity flashes, delivered randomly between 2 and 6 whole seconds, were used as the stimuli. The phase angle of the EEG at the moment of stimulation was computed for all trials containing more than 100 microV2 of prestimulus alpha power. The single trials were grouped into 8 classes on the basis of the phase angle value, and averaged EPs for each individual were computed from these groups. In addition, averaged EPs were computed in 3 ways: (1) a grand average consisting of all artifact-free trials, (2) an 'alpha average' consisting of all trials containing more than 100 microV2 of prestimulus alpha power, and (3) a 'non-alpha average' consisting of all trials with less than 100 microV2 of prestimulus alpha power. Each of these 3 averages were cross-correlated with the phase-selective averages. It was found that the particular N1 component assessed in this experiment may possibly be entrained alpha activity, and that the measured P2 component is not an alpha process, yet it is influenced by the amount of prestimulus alpha activity.     

Cerebral evoked potentials after rectal stimulation.

We obtained reproducible cortical evoked potentials (EPs) in response to electrical stimulation of the rectum with 1 Hz frequency. We found 2 distinctly different EPs in response to rectal stimulation. In 5 females, the EP had an early onset latency (mean 26 msec) with multiple positive and negative peaks. In 10 females, the EP had a later onset latency (mean 52 msec) and a trifid configuration, having a very prominent negative peak. The early onset EPs after rectal stimulation appeared very similar to the wave form of the cortical EPs recorded after pudendal nerve stimulation. Finding similar interpeak latencies in the early onset EP after rectal stimulation and the EP after pudendal nerve stimulation suggests that either the same pathway was used or that rectal stimulation also stimulated the pudendal nerve. It appears that we stimulated visceral afferents when we recorded late onset EPs, because the large EP amplitude declined rapidly with faster stimulation rates and also with greater number of averaging, and the sensation threshold was very unstable, all different to somatosensory EPs.     

独立分量分析结合小波去噪算法提取诱发电位信号的仿真实验

采用结合独立分量分析和小波去噪算法的方法提取诱发电位信号。首先使用扩展信息最大的独立分量分析算法分析仿真的脑电信号,分离出诱发电位信号,自发脑电信号,肌电干扰与高斯噪声,然后使用小波阀值收缩算法滤除诱发电位信号中残留的一些高频噪声。仿真实验表明,基于独立分量分析的算法可以将混合在诱发电位信号中的干扰信号分离开来,而结合方法的提取结果在波形、相关系数指标等方面均优于单独使用独立分量分析算法的提取结果,这为实际临床应用中诱发电位的有效提取提供了思路。     

Evoked potential correlates of psychosis

Evoked potential (EP) correlates of several psychiatric disorders were investigated by applying a comprehensive EP procedure to 102 psychiatric patients and 28 nonpatients. EPs to left and right median nerve shocks, visual pattern flashes, and auditory clicks were recorded from one EOG and 14 monopolar scalp derivations. Nine age- and sex-matched groups were compared to yield the following main results: (i) EPs of overtly psychotic patients (schizophrenics, depressives, manics) differed markedly from normal, while those of patients without overt psychosis (neurotics, personality disorders, latent schizophrenics) did not; in the overtly psychotic, later EP events (100 msec or more poststimulus) were attenuated. (ii) EPs of neurotic depressives differed greatly from those of psychotic depressives. (iii) A somatosensory negative peak occurring 60-msec poststimulus (N60) was more posteriorly distributed in chronic schizophrenics (paranoid, undifferentiated) than in any other subject group. The attenuated later EP activity associated with overt psychosis was interpreted as a concomitant of cognitive (attention?) impairment, rather than of emotional disturbance.     

Pain related cerebral potentials: late and ultralate components

Brief CO2 laser radiant heat pulses activate both A delta- and C-fibres. In the evoked potential (EP) late and ultralate components can be seen as correlates of first and second pain. Usually the ultralate EP appears to be suppressed. It could be uncovered by a preferential A-fibre block, and in two neurological patients with tabes dorsalis and with a polyneuropathy involving myelinated fibre loss. Due to a strong latency jittering the shape of the ultralate component is distorted in the conventional average. Latency corrected averaging, adaptive filters or parametric spectral estimators are needed to analyze these EP components. As a result the filtered ultralate waveforms look very similar to the late EP components. Clinical application of CO2 laser EPs promises to nonivasively assess A delta- and C-fibre function.     

Pre-attentive information processing and impulsivity in bipolar disorder

Early responses to stimuli can be measured by sensory evoked potentials (EP) using repeated identical stimuli, S1 and S2. Response to S1 may represent efficient stimulus detection, while suppression of response to S2 may represent inhibition. Early responses to stimuli may be related to impulsivity. We compared EP reflecting stimulus detection and inhibition in bipolar disorder and healthy controls, and investigated relationships to impulsivity. Subjects were 48 healthy controls without family histories of mood disorder and 48 with bipolar disorder. EP were measured as latencies and amplitudes for auditory P50 (pre-attentional), N100 (initial direction of attention) and P200 (initial conscious awareness), using a paired-click paradigm, with identical stimuli 0.5 s apart. Impulsivity was measured by questionnaire and by laboratory tests for inability to suppress responses to stimuli or to delay response for a reward. Analyses used general linear models. S1 amplitudes for P50, N100, and P200, and gating of N100 and P200, were lower in bipolar disorder than in controls. P50 S1 amplitude correlated with accurate laboratory-task responding, and S2 amplitude correlated with impulsive task performance and fast reaction times, in bipolar disorder. N100 and P200 EP did not correlate with impulsivity. These findings were independent of symptoms, treatment, or substance-use history. EPs were not related to questionnaire-measured or reward-based impulsivity. Bipolar I disorder is characterized by reduced pre-attentional and early attentional stimulus registration relative to controls. Within bipolar disorder, rapid-response impulsivity correlates with impaired pre-attentional response suppression. These results imply specific relationships between ERP-measured response inhibition and rapid-response impulsivity.     

Pre-attentive information processing and impulsivity in bipolar disorder

Early responses to stimuli can be measured by sensory evoked potentials (EP) using repeated identical stimuli, S1 and S2. Response to S1 may represent efficient stimulus detection, while suppression of response to S2 may represent inhibition. Early responses to stimuli may be related to impulsivity. We compared EP reflecting stimulus detection and inhibition in bipolar disorder and healthy controls, and investigated relationships to impulsivity. Subjects were 48 healthy controls without family histories of mood disorder and 48 with bipolar disorder. EP were measured as latencies and amplitudes for auditory P50 (pre-attentional), N100 (initial direction of attention) and P200 (initial conscious awareness), using a paired-click paradigm, with identical stimuli 0.5 s apart. Impulsivity was measured by questionnaire and by laboratory tests for inability to suppress responses to stimuli or to delay response for a reward. Analyses used general linear models. S1 amplitudes for P50, N100, and P200, and gating of N100 and P200, were lower in bipolar disorder than in controls. P50 S1 amplitude correlated with accurate laboratory-task responding, and S2 amplitude correlated with impulsive task performance and fast reaction times, in bipolar disorder. N100 and P200 EP did not correlate with impulsivity. These findings were independent of symptoms, treatment, or substance-use history. EPs were not related to questionnaire-measured or reward-based impulsivity. Bipolar I disorder is characterized by reduced pre-attentional and early attentional stimulus registration relative to controls. Within bipolar disorder, rapid-response impulsivity correlates with impaired pre-attentional response suppression. These results imply specific relationships between ERP-measured response inhibition and rapid-response impulsivity.     

Validity of spectral analysis of evoked potentials in brain research

The averaged electronencephologram (EEG) response of the brain to an external stimulus (evoked potential, EP) is usually subjected to spectral analysis using the fast Fourier transform (FFT), especially to discover the relation of cognitive ability to so-called brain dynamics. There is indeed a discrepancy between these two systems, because the brain is a highly complex nonlinear system, analyzed by a linear system (FFT). We present in this work some inaccuracies that occurred when EPs are subjected to spectral analysis, using a model signal. First of all, the EP power spectra depended upon the number of samples used for averaging; the input EP (model signal) and the output EP (from the system) seemed to be similar in forms, but they exhibited completely different spectral power curves. It was concluded that the spectral analysis of evoked responses by using FFT (linear system analysis) in relation to brain (highly complex nonlinear system) may mislead neuroscientists.     

Brief Communication VALIDITY OF SPECTRAL ANALYSIS OF EVOKED POTENTIALS IN BRAIN RESEARCH

The averaged electronencephologram (EEG) response of the brain to an external stimulus (evoked potential, EP) is usually subjected to spectral analysis using the fast Fourier transform (FFT), especially to discover the relation of cognitive ability to so-called brain dynamics. There is indeed a discrepancy between these two systems, because the brain is a highly complex nonlinear system, analyzed by a linear system (FFT). We present in this work some inaccuracies that occurred when EPs are subjected to spectral analysis, using a model signal. First of all, the EP power spectra depended upon the number of samples used for averaging; the input EP (model signal) and the output EP (from the system) seemed to be similar in forms, but they exhibited completely different spectral power curves. It was concluded that the spectral analysis of evoked responses by using FFT (linear system analysis) in relation to brain (highly complex nonlinear system) may mislead neuroscientists.     

Bimodal evoked potentials during long-term therapy with conventional or slow release preparations of carbamazepine and valproic acid in children and adolescents with epilepsy

The measurement of evoked potentials (EPs) may be particularly useful in clinical neuropharmacology for investigation of drug effects of afferent nerve conduction within CNS. The study aims at estimating the long term effects of conventional or slow release formulation (CR) of carbamazepine (CBZ) and valproid acid (VPA) on visual (VPA) and brainstem auditory (BAEP) evoked potentials. Investigation covered 125 patients 8 to 18 years old to whom both formulations of CBZ or VPA were administered in monotherapy. Everyone received a drug dosage which gave an adequate therapeutic plasma concentration and satisfactory seizure control. Antiepileptic drugs (AEDs) plasma levels were measured by means of fluorescence polarization immunoassay method aided of TDx Analyzer (Abbott, Diagnostic). EPs were registered by means of Multiliner (Toennies, Germany). A pattern of reversal stimulation for VEP was used. The latencies of N75, P100, N145 as well as interpeak amplitudes of N75/P100, P100/N145 were evaluated. The following BAEP parameters were considered: morphology of the potential, absolute latencies of waves I, III, V and I-III, III-V, I-V. EP were always performed in the same conditions and with the same equipment for the epileptic and control groups. The obtained values were compared with age-matched control group. The following BAEP abnormalities were observed: prolonged absolute latencies of waves I, III, V as well as prolonged IPLs I-III. The BAEP V/I amplitude ratio and morphology of the waves were normal in all patients. The VEPs abnormalities manifested as prolongation of P100 or N145 latencies and reduction of amplitudes N75/P100, P100/N145. Results of these electrophysiological studies with CBZ and VPA demonstrate that EP are sensitive, noninvasive reflectors of AEDs effects within the CNS.     

Denoising improves visualization of evoked potentials with limited number of trials

Ensemble averaging is typically used to enhance the signal to noise ratio (SNR) of event related potentials (ERPs). This approach has the disadvantage of extending the recording time. We present an alternative approach to achieve SNRs similar to the ones obtained with ensemble averaging but with fewer trials. Single trial ERPs were denoised by using a wavelet denoising technique. With simulated ERPs we compared the performance obtained with the standard and denoised averages by quantifying the root-mean-square-error (RMSE) between ensemble averages obtained with and without denoising. Denoising decreased the RMSE, giving similar values to the ones obtained with the standard averages but with less than half the number of trials. RMSEs were comparable for larger number of trials, thus showing that denoising did not introduce spurious distortions to the ERPs. Wavelet denoising proved to be an efficient technique to improve evoked potential SNRs. It is useful in clinical settings, where recordings may be constrained by the limited capability to obtain a sufficient number of trials.     

Real-time intraoperative monitoring during neurosurgical and neuroradiological procedures

A real-time intraoperative evoked potential (EP) monitoring system is described and evaluated. Unique features include (1) online artifact rejection to reduce noise contamination, (2) optimum digital filtering to improve the signal-to-noise ratio of the EP signal, (3) statistically defined confidence intervals to determine significant EP peak latency deviations, and (4) sliding windows of EP subaverages of various sizes to minimize feedback time to the surgeon. The reliability and validity of this system were determined by comparison with conventional intraoperative EP averaging and by examining the correlation of EP parameter changes with concurrent surgical and radiological manipulations. This system was clearly superior to conventional averaging systems. Reliable EPs could be obtained from neurologically compromised patients within the electrically hostile operating room environment, in cases in which conventional averaging failed to extract a stable EP signal. EP update times of 10-20 s were quite common and allowed direct moment-to-moment correlations with surgical and radiological events. Case histories are presented that show the utility of this system for aiding in the prevention of neurological complications. This utility is examined for neurosurgical and neuroradiological procedures involving spinal cord, brainstem, midbrain, and cortical structures, and affecting the somatosensory, motor, auditory, and visual system pathways.     

Analysis and visualization of single-trial event-related potentials

In this study, a linear decomposition technique, independent component analysis (ICA), is applied to single-trial multichannel EEG data from event-related potential (ERP) experiments. Spatial filters derived by ICA blindly separate the input data into a sum of temporally independent and spatially fixed components arising from distinct or overlapping brain or extra-brain sources. Both the data and their decomposition are displayed using a new visualization tool, the "ERP image," that can clearly characterize single-trial variations in the amplitudes and latencies of evoked responses, particularly when sorted by a relevant behavioral or physiological variable. These tools were used to analyze data from a visual selective attention experiment on 28 control subjects plus 22 neurological patients whose EEG records were heavily contaminated with blink and other eye-movement artifacts. Results show that ICA can separate artifactual, stimulus-locked, response-locked, and non-event-related background EEG activities into separate components, a taxonomy not obtained from conventional signal averaging approaches. This method allows: (1) removal of pervasive artifacts of all types from single-trial EEG records, (2) identification and segregation of stimulus- and response-locked EEG components, (3) examination of differences in single-trial responses, and (4) separation of temporally distinct but spatially overlapping EEG oscillatory activities with distinct relationships to task events. The proposed methods also allow the interaction between ERPs and the ongoing EEG to be investigated directly. We studied the between-subject component stability of ICA decomposition of single-trial EEG epochs by clustering components with similar scalp maps and activation power spectra. Components accounting for blinks, eye movements, temporal muscle activity, event-related potentials, and event-modulated alpha activities were largely replicated across subjects. Applying ICA and ERP image visualization to the analysis of sets of single trials from event-related EEG (or MEG) experiments can increase the information available from ERP (or ERF) data.     

N100 evoked potential latency variation and startle in schizophrenia

The contribution of evoked potential (EP) latency jitter, a measure of CNS temporal variability, on startle and EP gating defects in schizophrenic subjects has not been characterized. The amplitude of the N100/P200 EP complex (peak to trough) derived using a time-locked averaging procedure, N100 EP latency jitter derived from single trial analysis, acoustic startle response and clinical symptoms were measured in 51 schizophrenic subjects. N100 latency jitter was inversely correlated with N100/P200 EP amplitude in both cross-sectional and longitudinal analysis. Subjects with elevated EP gating ratios (>0.5) had similar latency jitter values for initial (S1) and test (S2) stimuli, while subjects with a low gating ratio (0-0.5) had a lower level of S1 latency jitter. Temporal variability thus plays a significant and complex role in previously reported sensory gating deficits in schizophrenic subjects.     

Single-trial analysis of auditory evoked potentials improves separation of normal and schizophrenia subjects

ObjectiveIn this study, we employed iterative independent component analysis of single-trial auditory evoked responses to identify features of the P50 and N100 components that provide maximum separation between normal controls and schizophrenia subjects and compared the results against classical ensemble averaging.MethodWe analyzed data from 13 schizophrenia and 20 normal control subjects. Responses were obtained in a paired-stimulus paradigm, in which an auditory stimulus S₁ is followed by an identical S₂. The amplitude and latency of the P50 and N100 components in response to the S₁ and S₂ stimuli were measured in each single trial and used as features to classify the responses into two groups. Several methods were used for classification, while their performance was quantified in a 10-fold stratified cross-validation approach.ResultsWe found that normal controls tended to respond earlier and their individual responses had significantly higher amplitude (p < 0.01) and significantly less latency variability (p < 0.01) compared to schizophrenia patients. The S₁ latency was the most significant discriminatory feature (p < 0.01) followed by S₂ latency (p < 0.01). The S₂ amplitude, though relatively larger in normal subjects (p < 0.05), was the least discriminatory feature. Classification based on single-trial analysis yielded 100% accuracy, while the classical ensemble averaging yielded only a maximum of 76% accuracy.ConclusionsOur results demonstrate that single-trial analysis can accurately separate schizophrenia patients from normal controls and suggest that inter-trial variability plays a significant role in information processing in the human brain.SignificanceThe proposed technique may have a significant impact as a clinical tool in the quest for identifying physiological markers of schizophrenia.     

Prognostic significance of SSEP,BAEP and serum S-100B monitoring after aneurysm surgery

OBJECTIVE: Changes in evoked potentials (EPs) and increased levels of S-100B protein were used to identify cerebral ischemia or glial damage and to predict neurological outcome in aneurysm patients. MATERIAL AND METHODS: Somatosensory evoked potentials and Brainstem auditory-evoked potentials, and serum S-100B protein were simultaneously investigated pre- and postoperatively over a period of 10 days in 43 patients with 47 aneurysms (six in the posterior fossa). RESULTS: The EP scores showed a strong correlation with the clinical outcome. Sensitivity was 73%, and specificity 81%. Pathological S-100B levels >0.5 mg/l were equal in predictive values (correct positive eight, false positive six, correct negative 26, false negative three). Initially increased S-100B levels, long-lasting S-100B elevation, and secondary increasing S-100B values correlated with an unfavorable outcome. High peak S-100B values correlated with bad EP scores at discharge. EP deterioration was the first indicator anticipating S-100B elevation and clinical deterioration in five patients. There was a good correlation between pathological S-100B values or EP findings and infarction on CT scan. CONCLUSIONS: Both EPs and S-100B protein showed a comparable high predictive value for outcome. S-100B reflects the extent of primary brain damage after subarachnoid hemorrhage and time course of ongoing secondary brain damage. Evoked potentials assess the functional integrity and tended to react earlier than S-100B protein before definitive structural damage occurred.