Single-trial latency variability does not contribute to fast habituation of the long-latency averaged auditory evoked potential in the albino rat

Fas habituation (FH) is defined as a general reduction in long-latency, vertex-recorded, averaged auditory evoked potential (AEP) amplitude that occurs in response to the second of a pair of acoustic stimuli. Our laboratory has been studying FH in a variety of human populations with different paradigms and has interpreted it to be a measure of neural attentional mechanism(s) and/or resource allocation related to the processing of cognitive information. We have also reported an analogous phenomenon in the rat. In the present investigation, we examined the relationship between FH (viz., averaged AEP component amplitude decrement) and the single-trial latency variability of the AEP peaks comprising that component. Specifically, AEPs were obtained to 60 paired-tone stimuli from unanesthetized and restrained albino rats previously implanted with chronic skull electrodes. Using a template-matching algorithm similar to that used by Michalewski et al. (Electroenceph. clin. Neurophysiol., 1986, 65:59–71), the latency variability for each animal was computed for the N1 and P2 peaks of the single-trial AEPs that were used to compose the averaged wave form. Findings indicated that (a) there was no difference in single-trial latency variability for these peaks either within or across tones, and (b) there was no relationship between single-trial latency variability for either the N1 or the P2 peaks and the overall peak-to-peak amplitude (N1-P2) of the averaged wave form in response to the second tone. Thus, FH of the N1-P2 (i.e. Peak 2) amplitude in the rat is not due to an increase in latency variability across tones.     

Estimation of single-trial multicomponent ERPs: Differentially variable component analysis (dVCA)

A Bayesian inference framework for estimating the parameters of single-trial, multicomponent, event-related potentials is presented. Single-trial recordings are modeled as the linear combination of ongoing activity and multicomponent waveforms that are relatively phase-locked to certain sensory or motor events. Each component is assumed to have a trial-invariant waveform with trial-dependent amplitude scaling factors and latency shifts. A Maximum a Posteriori solution of this model is implemented via an iterative algorithm from which the components waveform, single-trial amplitude scaling factors and latency shifts are estimated. Multiple components can be derived from a single-channel recording based on their differential variability, an aspect in contrast with other component analysis techniques (e.g., independent component analysis) where the number of components estimated is equal to or smaller than the number of recording channels. Furthermore, we show that, by subtracting out the estimated single-trial components from each of the single-trial recordings, one can estimate the ongoing activity, thus providing additional information concerning task-related brain dynamics. We test this approach, which we name differentially variable component analysis (dVCA), on simulated data and apply it to an experimental dataset consisting of intracortically recorded local field potentials from monkeys performing a visuomotor pattern discrimination task. AcknowledgementsThis work was supported by NIMH (MH64204 and MH42900), NSF (IBN0090717), ONR (N000149910062), T32M07288, NARSAD Young Investigator Award (KHK), NASA IDU/IS/CICT Program, and the NASA Aerospace Technology Enterprise.     

On the Agreement between Manual and Automated Methods for Single-Trial Detection and Estimation of Features from Event-Related Potentials

The agreement between humans and algorithms on whether an event-related potential (ERP) is present or not and the level of variation in the estimated values of its relevant features are largely unknown. Thus, the aim of this study was to determine the categorical and quantitative agreement between manual and automated methods for single-trial detection and estimation of ERP features. To this end, ERPs were elicited in sixteen healthy volunteers using electrical stimulation at graded intensities below and above the nociceptive withdrawal reflex threshold. Presence/absence of an ERP peak (categorical outcome) and its amplitude and latency (quantitative outcome) in each single-trial were evaluated independently by two human observers and two automated algorithms taken from existing literature. Categorical agreement was assessed using percentage positive and negative agreement and Cohen’s κ, whereas quantitative agreement was evaluated using Bland-Altman analysis and the coefficient of variation. Typical values for the categorical agreement between manual and automated methods were derived, as well as reference values for the average and maximum differences that can be expected if one method is used instead of the others. Results showed that the human observers presented the highest categorical and quantitative agreement, and there were significantly large differences between detection and estimation of quantitative features among methods. In conclusion, substantial care should be taken in the selection of the detection/estimation approach, since factors like stimulation intensity and expected number of trials with/without response can play a significant role in the outcome of a study.     

A fast and reliable method for simultaneous waveform, amplitude and latency estimation of single-trial EEG/MEG data

The amplitude and latency of single-trial EEG/MEG signals may provide valuable information concerning human brain functioning. In this article we propose a new method to reliably estimate single-trial amplitude and latency of EEG/MEG signals. The advantages of the method are fourfold. First, no a-priori specified template function is required. Second, the method allows for multiple signals that may vary independently in amplitude and/or latency. Third, the method is less sensitive to noise as it models data with a parsimonious set of basis functions. Finally, the method is very fast since it is based on an iterative linear least squares algorithm. A simulation study shows that the method yields reliable estimates under different levels of latency variation and signal-to-noise ratio?s. Furthermore, it shows that the existence of multiple signals can be correctly determined. An application to empirical data from a choice reaction time study indicates that the method describes these data accurately.     

Single-event-related potential analysis by means of fragmentary decomposition

 A recently developed fragmentary decomposition method is employed to analyse single-trial event-related potentials (ERPs), thereby extending the traditional method of averaging. Using a conventional auditory oddball paradigm with 40 target stimuli, single-trial ERPs in 40 normal subjects were analysed for midline scalp (Fz, Cz and Pz) recording sites. The normalization effect, reported in our previous study of eye blink EMGs and proposed to be a characteristic property of a wide class of non-stationary physiological processes, was found to apply to these single-trial ERPs. Fragmentary decomposition of single-trial ERPs may be regarded as re-statement of the normalization effect. This allows both pre-stimulus EEGs and post-stimulus ERPs to be regarded as overlapping generic mass potentials (GMPs), with a characteristic Gaussian amplitude spectrum. On theoretical and empirical grounds we uniquely deduce a model GMP using an introduced “bud” function, and physically support it by the resting and transient conditions. The model takes into account the shape of the component, which suggests a simple relationship between the peak latency and the time of the component onset. Given that GMPs may be manipulated and sorted out, we present principles of the fragmentary synthesis, i.e. probabilistic ERP reconstructions on the basis of individual and ensemble properties of its identified components. Summarizing the component quantification in the form of the dynamic model provides for the first time the opportunity to quantify all significant components in single-trial ERPs. This method of single-trial analysis opens up new possibilities of exploring the dynamical ERP changes within a recording trial, particularly in late component “cognitive” paradigms. Received: 29 August 2000 / Accepted in revised form: 5 February 2001     

Single-trial ERP evidence for the three-stage scheme of facial expression processing

Using a rapid serial visual presentation paradigm, we previously showed that the average amplitudes of six event-related potential (ERP) components were affected by different categories of emotional faces. In the current study, we investigated the six discriminating components on a single-trial level to clarify whether the amplitude difference between experimental conditions results from a difference in the real variability of single-trial amplitudes or from latency jitter across trials. It is found that there were consistent amplitude differences in the single-trial P1, N170, VPP, N3, and P3 components, demonstrating that a substantial proportion of the average amplitude differences can be explained by the pure variability in amplitudes on a single-trial basis between experimental conditions. These single-trial results verified the three-stage scheme of facial expression processing beyond multitrial ERP averaging, and showed the three processing stages of "fear popup", "emotional/unemotional discrimination", and "complete separation" based on the single-trial ERP dynamics.     

A comparison of different methods for estimating single-trial P300 latencies

Inferences from comparative analyses of reaction time and P300 latency are stronger when the various aspects of the distribution across trials are treated in the same way for both variables. To this end, a number of studies have resorted to estimation of P300 latency at the single-trial level. This report presents a comparative evaluation of two common methods for such single-trial analysis, i.e., peak-picking and template-matching. Both methods were applied to a representative set of real data, comprising different task conditions and two age groups. Relevant scoring parameters were varied: low-pass filter settings (down to 0.94 Hz) for peak-picking, template duration (250–970 msec) and use of covariance vs. correlation for template-matching, and use of a noise-range criterion for both methods. It is concluded that peak-picking with a 3.4 Hz filter, and template-matching using covariance and template duration between 600 and 800 msec, are best in terms of sensitivity and reliability, with peak-picking surpassing template-matching. Also, the marked increase in the number of rejected trials when the noise-range criterion was applied resulted in unwanted modulation of behavioral effects of task conditions and age groups.     

Neuromagnetic index of hemispheric asymmetry prognosticating the outcome of sudden hearing loss

The longitudinal relationship between central plastic changes and clinical presentations of peripheral hearing impairment remains unknown. Previously, we reported a unique plastic pattern of "healthy-side dominance" in acute unilateral idiopathic sudden sensorineural hearing loss (ISSNHL). This study aimed to explore whether such hemispheric asymmetry bears any prognostic relevance to ISSNHL along the disease course. Using magnetoencephalography (MEG), inter-hemispheric differences in peak dipole amplitude and latency of N100m to monaural tones were evaluated in 21 controls and 21 ISSNHL patients at two stages: initial and fixed stage (1 month later). Dynamics/Prognostication of hemispheric asymmetry were assessed by the interplay between hearing level/hearing gain and ipsilateral/contralateral ratio (I/C) of N100m latency and amplitude. Healthy-side dominance of N100m amplitude was observed in ISSNHL initially. The pattern changed with disease process. There is a strong correlation between the hearing level at the fixed stage and initial I/C(amplitude) on affected-ear stimulation in ISSNHL. The optimal cut-off value with the best prognostication effect for the hearing improvement at the fixed stage was an initial I/C(latency) on affected-ear stimulation of 1.34 (between subgroups of complete and partial recovery) and an initial I/C(latency) on healthy-ear stimulation of 0.76 (between subgroups of partial and no recovery), respectively. This study suggested that a dynamic process of central auditory plasticity can be induced by peripheral lesions. The hemispheric asymmetry at the initial stage bears an excellent prognostic potential for the treatment outcomes and hearing level at the fixed stage in ISSNHL. Our study demonstrated that such brain signature of central auditory plasticity in terms of both N100m latency and amplitude at defined time can serve as a prognostication predictor for ISSNHL. Further studies are needed to explore the long-term temporal scenario of auditory hemispheric asymmetry and to get better psychoacoustic correlates of pathological hemispheric asymmetry in ISSNHL.     

Analysis of phase-locking is informative for studying event-related EEG activity

 A new method is presented for quantitative evaluation of single-sweep phase and amplitude electroencephalogram (EEG) characteristics that is a more informative approach in comparison with conventional signal averaging. In the averaged potential, phase-locking and amplitude effects of the EEG response cannot be separated. To overcome this problem, single-trial EEG sweeps are decomposed into separate presentations of their phase relationships and amplitude characteristics. The stability of the phase-coupling to stimulus is then evaluated independently by analyzing the single-sweep phase presentations. The method has the following advantages: information about stability of the phase-locking can be used to assess event-related oscillatory activity; the method permits evaluation of the timing of event-related phase-locking; and a global assessment and comparison of the phase-locking of ensembles of single sweeps elicited in different processing conditions is possible. The method was employed to study auditory alpha and theta responses in young and middle-aged adults. The results showed that whereas amplitudes of frequency responses tended to decrease, the phase-locking increased significantly with age. The synchronization with stimulus (phase-locking) was the only parameter reliably to differentiate the brain responses of the two age groups, as well as to reveal specific age-related changes in frontal evoked alpha activity. Thus, the present approach can be used to evaluate dynamic brain processes more precisely. Received: 12 February 1996 / Accepted in revised form: 11 October 1996     

Heritable features of the auditory oddball event-related potential: peaks,latencies, morphology and topography

Baseline auditory ERP data from a larger study of the genetic determinants of the response to alcohol were collected from 59 monozygotic (MZ) twin pairs and from 39 same-sex dizygotic (DZ) twin pairs who drank socially. Three methods for measuring genetic influence on the ERPs were applied. First, based on maximum-likelihood estimates, the heritability of conventional peak amplitude and latency of N1 and P3 components was computed for each of 16 lead locations using tests of the significance of heritability based on intraclass correlations. P3 amplitude provided the strongest results, distributed symmetrically over caudal leads, and implied gene dominance as the mode of genetic transmission for the P3 component. A substantial genetic influence on N1 latency suggested a mixture of additive and dominance effects in the left fronto-temporal region. N1 amplitude measures trended towards significant heritability, but none was observed for P3 latency. The second method used the maximum of the cross-correlation function to compare wave form shape in a lead-by-lead analysis of data from cotwins. Genetic influence was apparent in both target and non-target ERP responses, with a fronto-central topography of significant results. The third method reduced all spatial and temporal ERP differences from a pair of twins to a single scalar number for each response. Distributions of this global measure revealed significant genetic influence on both non-target and target ERPs. A post hoc analysis of the effect of gender on the heritability of N1 or P3 peaks and latencies revealed no statistically significant observations in this sample of young adult twins.     

Automatic and effortful processes in auditory memory reflected by event-related potentials. Age-related findings

Mismatch negativity (MMN) and N2b were elicited during a selective dichotic-listening task in 16 young (Y), 16 middle-aged (M) and 19 elderly (E) subjects to evaluate automatic and effortful memory comparison of auditory stimuli. Sequences of standard (80%) and deviant (20%) tones were dichotically presented to subjects in two runs. In each run, subjects were instructed to give a button-press response to the deviant (target) tones in the ear designated as attended and to ignore the input to the other ear.Peak latencies, peak amplitudes and mean amplitudes were calculated for MMN and N2b components in each subject. MMN latency and amplitude were quite stable regardless of age, while N2b latency was significantly longer in M and E subjects than in Y subjects. These results are interpreted as reflecting that automatic processes of comparison in auditory memory of stimuli presented at short interstimulus intervals remain quite stable from 23 to 77 years of age; however, those requiring attentional effort decline with age.     

Task difficulty,probability, and inter-stimulus interval as determinants of P300 from auditory stimuli

The P300 event-related potential was elicited with auditory stimuli in 4 experiments which manipulated combinations of stimulus target probability (10% vs. 30%), task difficulty (easy vs. hard), and inter-stimulus interval (5 sec vs. 2 sec). P300 amplitude was smaller and peak latency longer for the more difficult relative to the easier tasks across experiments. Increases in stimulus target probability generally diminished P300 amplitude and shortened peak latency more for the easy relative to difficult task conditions. Increasing the number of non-target stimulus tones decreased P300 amplitude reliably, but increased latency only slightly. Task difficulty did not interact with variations in inter-stimulus interval which produced generally weak effects for both amplitude and latency. These findings suggests that P300 amplitude and latency obtained from auditory discrimination paradigms reflect processing difficulty independently of stimulus target probability unless differences in task requirements affect stimulus encoding.     

High-rate sequential sampling of auditory brain-stem and somatosensory evoked responses in hypoxia

We developed a high-rate sequential recording technique that allowed simultaneous measurements of both auditory brain-stem response (ABR) and somatosensory evoked potential (SEP) every 10 sec. Using this method, a transient increase in amplitude of all the ABR and SEP components in response to hypoxia in dogs could be detected. The increase in amplitude preceded the prolongation of latency. Our study showed that there were succesive changes of evoked potentials in response to hypoxia. A transient increase in amplitude is the first to occur, followed by a latency prolongation and an amplitude decrease for both ABRs and SEPs.     

A non-parametric approach for identifying differentially expressed genes in factorial microarray experiments

We introduce a non-parametric approach using bootstrap-assisted correspondence analysis to identify and validate genes that are differentially expressed in factorial microarray experiments. Model comparison showed that although both parametric and non-parametric methods capture the different profiles in the data, our method is less inclined to false positive results due to dimension reduction in data analysis.     

Dissociable Neural Response Signatures for Slow Amplitude and Frequency Modulation in Human Auditory Cortex

Natural auditory stimuli are characterized by slow fluctuations in amplitude and frequency. However, the degree to which the neural responses to slow amplitude modulation (AM) and frequency modulation (FM) are capable of conveying independent time-varying information, particularly with respect to speech communication, is unclear. In the current electroencephalography (EEG) study, participants listened to amplitude- and frequency-modulated narrow-band noises with a 3-Hz modulation rate, and the resulting neural responses were compared. Spectral analyses revealed similar spectral amplitude peaks for AM and FM at the stimulation frequency (3 Hz), but amplitude at the second harmonic frequency (6 Hz) was much higher for FM than for AM. Moreover, the phase delay of neural responses with respect to the full-band stimulus envelope was shorter for FM than for AM. Finally, the critical analysis involved classification of single trials as being in response to either AM or FM based on either phase or amplitude information. Time-varying phase, but not amplitude, was sufficient to accurately classify AM and FM stimuli based on single-trial neural responses. Taken together, the current results support the dissociable nature of cortical signatures of slow AM and FM. These cortical signatures potentially provide an efficient means to dissect simultaneously communicated slow temporal and spectral information in acoustic communication signals.     

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-trial detection for intraoperative somatosensory evoked potentials monitoring

Abnormalities of somatosensory evoked potentials (SEPs) provide effective evidence for impairment of the somatosensory system, so that SEPs have been widely used in both clinical diagnosis and intraoperative neurophysiological monitoring. However, due to their low signal-to-noise ratio (SNR), SEPs are generally measured using ensemble averaging across hundreds of trials, thus unavoidably producing a tardiness of SEPs to the potential damages caused by surgical maneuvers and a loss of dynamical information of cortical processing related to somatosensory inputs. Here, we aimed to enhance the SNR of single-trial SEPs using Kalman filtering and time–frequency multiple linear regression (TF-MLR) and measure their single-trial parameters, both in the time domain and in the time–frequency domain. We first showed that, Kalman filtering and TF-MLR can effectively capture the single-trial SEP responses and provide accurate estimates of single-trial SEP parameters in the time domain and time–frequency domain, respectively. Furthermore, we identified significant correlations between the stimulus intensity and a set of indicative single-trial SEP parameters, including the correlation coefficient (between each single-trial SEPs and their average), P37 amplitude, N45 amplitude, P37-N45 amplitude, and phase value (at the zero-crossing points between P37 and N45). Finally, based on each indicative single-trial SEP parameter, we investigated the minimum number of trials required on a single-trial basis to suggest the existence of SEP responses, thus providing important information for fast SEP extraction in intraoperative monitoring.     

Temporal integration in auditory sensory memory: neuromagnetic evidence

The cortical mechanisms of auditory sensory memory were investigated by analysis of neuromagnetic evoked responses. The major deflection of the auditory evoked field (N100m) appears to comprise an early posterior component (N100m^P) and a late anterior component (N100m^A) which is sensitive to temporal factors. When pairs of identical sounds are presented at intervals less than about 250 msec, the second sound evokes N100m^A with enhanced amplitude at a latency of about 150 msec. We suggest that N100m^A may index the activity of two distinct processes in auditory sensory memory. Its recovery cycle may reflect the activity of a memory trace which, according to previous studies, can retain processed information about an auditory sequence for about 10 sec. The enhancement effect may reflect the activity of a temporal integration process, whose time constant is such that sensation persists for 200–300 msec after stimulus offset, and so serves as a short memory store. Sound sequences falling within this window of integration seem to be coded holistically as unitary events.     

Estimation of the noise autocorrelation function in auditory evoked potential applications

This work presents a simple and accurate method to estimate the noise autocorrelation function in auditory evoked potential applications. It basically consists in applying a conventional correlation function estimator over the contaminated evoked potential signal processed by a comb filter. The main feature of the proposed technique is the possibility of obtaining information on large correlation lags without the need of extra time intervals, minimizing the estimation time. A theoretical analysis is provided showing that, under certain but achievable conditions, the correlation function of the processed signal approximates the real noise correlation function. Simulation results and an example with a single-trial evoked potential estimation technique illustrate the expected performance. The proposed method is of special interest to either single or small number of trials evoked potential estimation techniques in anaesthesia monitoring applications.