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4th International Conference “Neural Networks and Expert Systems in Medicine and Healthcare” 20-22 June 2001, Milos Island, Greece NNESMED 2001 Independent Components Analysis of Single Trial CNV data J.H. Britton & B.W. Jervis Sheffield Hallam University Sheffield, UK ABSTRACT: Established techniques for the analysis of Event Related Potentials (ERPs) involve averaging of time-locked sections of the EEG signal over many trials to obtain the ERP waveform. Such techniques are necessary as single trial ERP signals are obscured by ongoing EEG activity, with signal to noise ratios below -10dB. The Independent Components Analysis (ICA) method is used to determine unknown source signals which have been transmitted through and linearly mixed in an unknown system to produce mixed output signals. ICA was applied to multi-channel CNV data in order to extract and analyse single trial ERP waveforms and their underlying source signals. Variations in the extracted single CNV waveform during the recording session were observed. Analysis of the underlying source signals suggests that these variations are the result of changes to the transmission path of the source signals. INTRODUCTION The aim of this study is to apply the Independent Components Analysis (ICA) method to event related potential (ERP) data in order to extract and analyse single trial ERP waveforms and their source signals. ERPs are electrical signals produced by the brain in response to stimuli or cognitive activity. They are usually obtained by averaging sections of EEG recorded during many repetitions (or trials) of a simple cognitive or motor task. Averaging over many trials is necessary because each single trial ERP is obscured by random fluctuations in the ongoing EEG. multi-channel ERP data to obtain the underlying source signals and single trial CNV waveforms. The study is based on the assumption that the signal recorded at each electrode is a linear combination of a number of unknown source signals. Many of these source signals may be produced by neural generators close to the surface of the scalp, and can be considered to represent EEG noise and artefacts unrelated to the ERP. However, it is likely that some of the source signals are produced by specific neural generators located in regions of the brain responsible for the production of the ERP. THEORY The use of cognitive and motor ERPs has been investigated as a means of diagnosing neurological disorders [1], [2]. Such studies have been held back by several factors. These include the limited volume of data collected from each individual (a single averaged ERP waveform) and practical difficulties associated with collecting ERPs from some patient groups. To overcome some of these difficulties, and provide new insights into the how ERPs change during a recording session, methods have been proposed for the extraction of single trial ERPs. Examples include Adaptive Multi-resolution Analysis [3] and Time Sequence Adaptive Filtering [4]. This study uses an ERP called the Contingent Negative Variation (CNV), which is generated by a cued reaction time task. Each CNV paradigm consists of a pair of tones (a warning tone and an imperative tone) separated by a fixed interval of 1 second. The participant is instructed to press a button as quickly as possible in response to the imperative tone. Typically at least 30 single CNV trials are averaged. Methods have been devised to determine unknown source signals which have been transmitted through and linearly mixed in an unknown system to produce mixed output signals (the measured signals). The determination of these source signals is known as blind source separation. ICA provides a method to achieve this. Here we apply the ICA method to The Infomax approach [5] to ICA was employed here. The unknown mutually time independent source signals s are linearly mixed by the mixing matrix A to produce the signals as measured x , see Figure 1. s1 s2 : A x1 W u1 x2 u2 : : : sn xn g(.) : : un y1=g1(u1) y2=g2(u2) : : yn=gn(un) Figure 1: Infomax ICA algorithm The aim is to find the unmixing matrix W A 1 which unmixes the x s to produce outputs u s . The infomax approach is to maximise the mutual information between the inputs x and the outputs y of the nonlinear functions g( u ). The g( u ) should be the cumulative probability density functions of the source signals. This also minimises the mutual information between the outputs y [6]. Further since the mapping between the u and the y is invertible the mutual information between the u is minimised. Thus the u W W T 1 1 2y x T produced by the CNV paradigm. A source signal was considered to be part of the CNV waveform if it fulfilled two criteria: The signal contained little or no energy before the warning stimulus and after the imperative stimulus The signal consisted of a single transient peak 6 15 4 Voltage (uV) 10 Voltage (uV) approximate the time independent source signals s according to the accuracy of the estimated weights in W . Maximisation of the mutual information was shown to equate to the maximisation of the entropy of the outputs y [5]. By maximising this entropy with respect to W an iterative algorithm was found for calculating W in terms of the incremental changes in the weights per iteration. This involved matrix inversion and the convergence time was decreased by introducing the natural gradient [7] . This algorithm applied to super-Gaussian sources. An extended algorithm was developed to include sub-Gaussian sources [8]. Thus for super-Gaussian sources with N inputs and N outputs: 5 0 -2 -5 0 1 (2) (3) The components of the source signals measured at the electrodes x c are given by: x c W 1u 2 Time (s) 3 -4 0 4 1 2 Time (s) 3 4 Figure 2: Underlying source signals identified using ICA. Left: ERP source signal. Right: noise source signal applies for the extended algorithm in which the – sign is associated with super-Gaussians and the + sign with subGaussians. The estimates of the source signals are: u Wx 0 (1) for a sigmoidal nonlinearity with g (u) (1 e u ) 1 , and W I tanhuuT uuT W 2 (4) When extracting ERP components rows of u which correspond with EEG or artefactual sources are set to zero. METHODS ERP data were digitally recorded (sampled at 125Hz) from a healthy subject using a montage of 25 equally spaced scalp recording electrodes, distributed symmetrically around the central - midline position (Cz). Linked mastoids were used as a reference, and two additional electrodes were positioned around the eyes to record the EOG. Each single trial recording started 1 second before the warning stimulus, and ended 2 seconds after the imperative stimulus, giving 4 seconds, or 500 data points for each channel. The data were pre-processed to correct for baseline drift, and low pass filtered to remove high frequency EEG energy. The remaining sources consisted of EEG noise and artefacts. For each single trial recording a small number of CNV source signals were identified. Figure 2 shows waveforms for one ERP source signal and one noise source signal. Denoised single trial CNV were obtained by setting rows of the source signal matrix that contained EEG and artefacts to zero, and multiplying the resulting matrix by the mixing matrix (the inverse of the unmixing matrix). The latency (relative to the onset of the warning stimulus) and peak voltage of the extracted CNV were analysed. The single trial CNV can be reconstructed at any of the 25 scalp electrodes used during the recording process. For the purposes of this study, the waveforms obtained at the central-midline position Cz will be used as the CNV is known to be most prominent at this point. The matrix of unmixed source signals produced by the ICA algorithm is ordered according to the variance in each source signal. Due to the random nature of the noise contaminating each trial, the ERP source signals occur on different rows of the matrix on each trial. To enable the ERP sources to be compared across trials, the rows of each source signal matrix were re-ordered according to the position in time of the peak voltage in each ERP source signal relative to the warning stimulus. Figure 3 shows the first 5 rows of the re-ordered source signal matrix for one single trial. 20 0 -20 20 1 3 1 3 1 3 1 3 0 The 25 scalp recordings and two EOG signals for a single trial (the mixed signals) were presented to the ICA algorithm as an N*M matrix where N is the number of data channels, and M is the number of points in each channel. This gave the unmixing matrix once the algorithm had converged. From this and the input signals, the source signals, their components at the electrodes, the individual ERPs at the electrodes, and the average of the ERPs at the electrodes over all trials were calculated. The original ICA algorithm was used [5] because the extended algorithm [8] resulted in incorrect ERP waveforms. For each single trial, 27 unmixed signals were plotted and inspected visually in order to identify those which were -20 20 0 -20 20 0 -20 20 0 -20 0 0.5 1 Time (s) 1.5 2 Figure 3: ERP source signals for trial 1 (warning stimulus at time t=0) Columns of each corresponding mixing matrix were similarly re-ordered to allow comparisons across trials. The mixing matrix for a single trial can be viewed as a set of filters through which all of the underlying source signals for that trial are passed to generate the measured mixed signals. One row of the mixing matrix combines all of the source signals to produce the measured signal at a single electrode. As the measured signal at the Cz electrode position is of interest, analyses of the mixing matrix have been carried out only on the corresponding row. 6 4 Voltage (uV) 2 The normalised cross-correlation coefficient at lag = 0, 12(0), between two waveforms x1 and x2 was calculated thus: 12 ( j ) r12 ( j ) 1 N 1 2 N 1 2 x 2 ( n) x1 (n) N n 0 n 0 (5) 1/ 2 0 -2 -4 -6 -8 -10 0 r12 1 N Figure 5: Average of extracted single trial CNVs at Cz (solid line) & average measured CNV at Cz (broken line). Warning stimulus at 1s, imperative stimulus at 2s N 1 x ( n) x n 0 1 2 ( n) 4 3 2 Time (s) 1 where (6) The cross-correlation coefficient between the extracted single trial CNV waveforms at Cz for trial number 1 and each subsequent trial was calculated. The cross-correlation coefficient between the row of the mixing matrix corresponding to the Cz electrode at trial number 1 and that of each subsequent trial was also calculated. The peak amplitude and latency (the time between the warning stimulus and the peak CNV amplitude) of each extracted single trial CNV at site Cz is shown in Figure 6. The CNV power for each extracted single trial CNV at site Cz is shown in Figure 7. 1.1 0 1 -10 Extracted single trial CNV waveforms 0.9 Latency (s) Peak amplitude (uV) RESULTS -20 -30 0.8 0.7 0.6 -40 Figure 4 shows an example set of single trial CNV waveforms extracted using the ICA technique reconstructed at the Cz electrode (the central-midline site). 5 10 0 0.5 -50 0 5 10 15 20 Trial number 25 30 0.4 0 5 10 15 20 Trial number 25 30 Figure 6: Voltage (upper left) and latency relative to warning stimulus (upper right) of extracted single trial CNV peak at Cz -20 -30 20 -5 15 -10 -40 -50 0 1 2 Time (s) 3 -15 0 4 1 2 Time (s) 3 4 10 5 10 5 RMS power (uV) Voltage (uV) Voltage (uV) 0 -10 5 0 0 Voltage (uV) Voltage (uV) 0 -5 0 5 10 15 20 Trial number 25 30 Figure 7: RMS power of extracted single trial CNV at Cz -5 -10 -10 -15 -15 0 1 2 Time (s) 3 4 -20 0 1 2 Time (s) 3 4 Figure 4: Single trial CNV waveforms at Cz. Warning stimulus at 1s, imperative stimulus at 2s It is seen in Figures 6 and 7 that the peak CNV amplitude, latency and the CNV RMS power vary significantly from trial to trial and do not appear to change systematically during the experimental session. Underlying source signals & mixing matrix The accuracy of the denoised signals can be estimated by comparing the average of the measured single trials with the average of the denoised single trials. Results show that the average of the denoised signals deviates little from the average of the recorded signals for each electrode site in the region where the ERP is located. Figure 5 shows the averaged noisy CNV recorded at Cz and the average of the extracted single trial CNV. All of the recorded single trial CNVs are made up of 3 to 5 source signals. Only small variations in the shape and position (relative to the warning stimulus) of these source signals are observed across the trials for which 5 source signals have been identified. In cases where there are less than 5 source signals, the waveforms have similar shape and latency to those observed when 5 sources are present, but one or more of the source waveforms seen when 5 sources are present are absent. Inspection of the denoised single trials shows significant trial to trial variations in the measured CNV for all trials. These variations are primarily the result of changes in the mixing matrix for each trial, as they are not reflected in the underlying source signals. The solid line in Figure 8 shows the correlation between the single trial CNV at Cz extracted for trial number 1 and each subsequent trial. The broken line in Figure 7 shows the correlation between the appropriate row of the mixing matrix for trial number 1 and each subsequent trial. were found to vary from trial to trial. These changes were not reflected in the underlying source signals, which suggests that trial to trial variations in the CNV are result of changes to the transmission path through which the underlying source signals propagate. Further work is necessary to extend the findings presented here and to apply the ICA method to a larger dataset. REFERENCES 1 1. Jervis, B. W., Saatchi, M. R., Allen, E. M., Hudson, N. R., Oke, S., and Grimsley, M., 1993, “Pilot study of computerised differentiation of Huntington's disease, schizophrenic, and Parkinson's disease patients using the Contingent Negative Variation”, Medical and Biological Engineering and Computing, 31, 31-38 2. Saatchi, M.R., and Jervis, B. W., 1991, “PC-based integrated system developed to diagnose specific brain disorders”, Computing Control Engineering Journal, 2, 61-68 3. Saatchi, M.R., Gibson, C., Rowe, J.W.K., and Allen, E.M., 1997, ‘Adaptive multiresolution analysis based evoked potential filtering’, IEE Procedings on Science & Measurement Technology, 144, 4, 149-155 4. Ferrara, E. R. and Widrow, B., 1981, “The time-sequenced adaptive filter” IEEE Transactions ASSP, 29, 3, 776-770 5. Bell A.J., and Sejnowski T. J., An InformationMaximisation Approach to Blind Separation and Blind Deconvolution, Neural Computation, 7, 1129-1159, 1995. 6. Nadal J.-P. and Parga N., Non linear neurons in the low noise limit: a factorial code maximises information transfer, Network, 5, 565-581, 1994. 7. Amari S., Cichocki A., and Yang H.H., A New Learning Algorithm for Blind Signal Separation, Advances in Neural Information Processing Systems, 8, 757-763, 1996. 8. Girolami M., and Fyfe C., Generalised Independent Component Analysis through Unsupervised Learning with Emergent Bussgang Properties, International Conference Neural Networks, 1788-1891, Houston, USA, 1997. Correlation coefficient 0.8 0.6 0.4 0.2 0 -0.2 -0.4 0 5 10 15 20 Trial number 25 30 Figure 8. Solid line: Correlation between extracted trial 1 and subsequent trials. Broken line: Correlation between mixing matrix row for trial 1 & all subsequent trials. It is seen in Figure 8 that the correlation between the mixing matrix row for trial 1 at Cz and the rows for subsequent trials follows a similar pattern to the correlation between the extracted single trial CNV waveforms. DISCUSSION Extracted single trial CNV Results suggest that the signals extracted using the ICA technique reflect the shape of the underlying single trial CNV. The similarity between the average of the recorded (noisy) single trials and that of the extracted single trials shows that the extracted single trial CNVs are not systematically distorted by the ICA method. The power, peak amplitude, and latency of the extracted CNV waveforms vary randomly across trials. Underlying source signals & mixing matrix Analyses of the unmixed source signals show that the CNV is made up of a small number of underlying sources which remain fairly constant during the course of the CNV experiment. Trial to trial variations in the measured signals are primarily the result of changes in the unmixing matrix. This suggests that trial to trial variations in the CNV are due to changes in the transmission path through which the underlying source signals are propagated to the scalp electrode recording positions. CONCLUSION ICA offers a means to identify the source signals underlying the CNV and extract single trial CNVs. The CNV waveforms