Toshimitsu Musha

A comparative study of synchrony measures for the early diagnosis of Alzheimer's disease based on EEG.

It is well known that EEG signals of Alzheimers disease (AD) patients are generally less synchronous than in age-matched control subjects. However, this effect is not always easily detectable. This is especially the case for patients in the pre-symptomatic phase, commonly referred to as mild cognitive impairment (MCI), during which neuronal degeneration is occurring prior to the clinical symptoms appearance. In this paper, various synchrony measures are studied in the context of AD diagnosis, including the correlation coefficient, mean-square and phase coherence, Granger causality, phase synchrony indices, information-theoretic divergence measures, state space based measures, and the recently proposed stochastic event synchrony measures. Experiments with EEG data show that many of those measures are strongly correlated (or anti-correlated) with the correlation coefficient, and hence, provide little complementary information about EEG synchrony. Measures that are only weakly correlated with the correlation coefficient include the phase synchrony indices, Granger causality measures, and stochastic event synchrony measures. In addition, those three families of synchrony measures are mutually uncorrelated, and therefore, they each seem to capture a specific kind of interdependence. For the data set at hand, only two synchrony measures are able to convincingly distinguish MCI patients from age-matched control patients, i.e., Granger causality (in particular, full-frequency directed transfer function) and stochastic event synchrony. Those two measures are used as features to distinguish MCI patients from age-matched control subjects, yielding a leave-one-out classification rate of 83%. The classification performance may be further improved by adding complementary features from EEG; this approach may eventually lead to a reliable EEG-based diagnostic tool for MCI and AD.

EEG filtering based on blind source separation (BSS) for early detection of Alzheimer's disease

OBJECTIVEnDevelopment of an EEG preprocessing technique for improvement of detection of Alzheimers disease (AD). The technique is based on filtering of EEG data using blind source separation (BSS) and projection of components which are possibly sensitive to cortical neuronal impairment found in early stages of AD.nnnMETHODSnArtifact-free 20s intervals of raw resting EEG recordings from 22 patients with Mild Cognitive Impairment (MCI) who later proceeded to AD and 38 age-matched normal controls were decomposed into spatio-temporally decorrelated components using BSS algorithm AMUSE. Filtered EEG was obtained by back projection of components with the highest linear predictability. Relative power of filtered data in delta, theta, alpha 1, alpha 2, beta 1, and beta 2 bands were processed with Linear Discriminant Analysis (LDA).nnnRESULTSnPreprocessing improved the percentage of correctly classified patients and controls computed with jack-knifing cross-validation from 59 to 73% and from 76 to 84%, correspondingly.nnnCONCLUSIONSnThe proposed approach can significantly improve the sensitivity and specificity of EEG based diagnosis.nnnSIGNIFICANCEnFiltering based on BSS can improve the performance of the existing EEG approaches to early diagnosis of Alzheimers disease. It may also have potential for improvement of EEG classification in other clinical areas or fundamental research. The developed method is quite general and flexible, allowing for various extensions and improvements.

Slowing and Loss of Complexity in Alzheimer's EEG: Two Sides of the Same Coin?

Medical studies have shown that EEG of Alzheimers disease (AD) patients is “slower” (i.e., contains more low-frequency power) and is less complex compared to age-matched healthy subjects. The relation between those two phenomena has not yet been studied, and they are often silently assumed to be independent. In this paper, it is shown that both phenomena are strongly related. Strong correlation between slowing and loss of complexity is observed in two independent EEG datasets: (1) EEG of predementia patients (a.k.a. Mild Cognitive Impairment; MCI) and control subjects; (2) EEG of mild AD patients and control subjects. The two data sets are from different patients, different hospitals and obtained through different recording systems. The paper also investigates the potential of EEG slowing and loss of EEG complexity as indicators of AD onset. In particular, relative power and complexity measures are used as features to classify the MCI and MiAD patients versus age-matched control subjects. When combined with two synchrony measures (Granger causality and stochastic event synchrony), classification rates of 83% (MCI) and 98% (MiAD) are obtained. By including the compression ratios as features, slightly better classification rates are obtained than with relative power and synchrony measures alone.

Blind Source Separation and Sparse Bump Modelling of Time Frequency Representation of Eeg Signals: New Tools for Early Detection of Alzheimer’s Disease

The early detection of Alzheimers disease (AD) is an important challenge. In this paper, we propose a novel method for early detection of AD using only electroencephalographic (EEG) recordings for patients with mild cognitive impairment (MCI) without any clinical symptoms of the disease who later developed AD. In our method, first a blind source separation algorithm is applied to extract the most significant spatiotemporal uncorrelated components; afterward these components are wavelet transformed; subsequently the wavelets or more generally time frequency representation (TFR) is approximated with sparse bump modeling approach. Finally, reliable and discriminant features are selected and reduced with orthogonal forward regression and the random probe methods. The proposed features were finally fed to a simple neural network classifier. The presented method leads to a substantially improved performance (93% correctly classified - improved sensitivity and specificity) over classification results previously published on the same set of data. We hope that the new computational and machine learning tools provide some new insights in a wide range of clinical settings, both diagnostic and predictive

Early detection of alzheimer’s disease by blind source separation, time frequency representation, and bump modeling of EEG signals

The early detection Alzheimer’s disease (AD) is an important challenge. In this paper, we propose a novel method for early detection of AD using electroencephalographic (EEG) recordings: first a blind source separation algorithm is applied to extract the most significant spatio-temporal components; these components are subsequently wavelet transformed; the resulting time-frequency representation is approximated by sparse “bump modeling”; finally, reliable and discriminant features are selected by orthogonal forward regression and the random probe method. These features are fed to a simple neural network classifier. The method was applied to EEG recorded in patients with Mild Cognitive Impairment (MCI) who later developed AD, and in age-matched controls. This method leads to a substantially improved performance (93% correctly classified, with improved sensitivity and specificity) over classification results previously published on the same set of data. The method is expected to be applicable to a wide variety of EEG classification problems.

Quantifying statistical interdependence by message passing on graphs---part ii: Multidimensional point processes

Stochastic event synchrony is a technique to quantify the similarity of pairs of signals. First, events are extracted from the two given time series. Next, one tries to align events from one time series with events from the other. The better the alignment, the more similar the two time series are considered to be. In Part I, the companion letter in this issue, one-dimensional events are considered; this letter concerns multidimensional events. Although the basic idea is similar, the extension to multidimensional point processes involves a significantly more difficult combinatorial problem and therefore is nontrivial. Also in the multidimensional case, the problem of jointly computing the pairwise alignment and SES parameters is cast as a statistical inference problem. This problem is solved by coordinate descent, more specifically, by alternating the following two steps: (1) estimate the SES parameters from a given pairwise alignment; (2) with the resulting estimates, refine the pairwise alignment. The SES parameters are computed by maximum a posteriori (MAP) estimation (step 1), in analogy to the one-dimensional case. The pairwise alignment (step 2) can no longer be obtained through dynamic programming, since the state space becomes too large. Instead it is determined by applying the max-product algorithm on a cyclic graphical model. In order to test the robustness and reliability of the SES method, it is first applied to surrogate data. Next, it is applied to detect anomalies in EEG synchrony of mild cognitive impairment (MCI) patients. Numerical results suggest that SES is significantly more sensitive to perturbations in EEG synchrony than a large variety of classical synchrony measures.

Improving the Specificity of EEG for Diagnosing Alzheimer's Disease

Objective. EEG has great potential as a cost-effective screening tool for Alzheimers disease (AD). However, the specificity of EEG is not yet sufficient to be used in clinical practice. In an earlier study, we presented preliminary results suggesting improved specificity of EEG to early stages of Alzheimers disease. The key to this improvement is a new method for extracting sparse oscillatory events from EEG signals in the time-frequency domain. Here we provide a more detailed analysis, demonstrating improved EEG specificity for clinical screening of MCI (mild cognitive impairment) patients. Methods. EEG data was recorded of MCI patients and age-matched control subjects, in rest condition with eyes closed. EEG frequency bands of interest were θ (3.5–7.5u2009Hz), α1 (7.5–9.5u2009Hz), α2 (9.5–12.5u2009Hz), and β (12.5–25u2009Hz). The EEG signals were transformed in the time-frequency domain using complex Morlet wavelets; the resulting time-frequency maps are represented by sparse bump models. Results. Enhanced EEG power in the θ range is more easily detected through sparse bump modeling; this phenomenon explains the improved EEG specificity obtained in our previous studies. Conclusions. Sparse bump modeling yields informative features in EEG signal. These features increase the specificity of EEG for diagnosing AD.

Quantifying statistical interdependence, part iii: N > 2 point processes

Stochastic event synchrony (SES) is a recently proposed family of similarity measures. First, “events” are extracted from the given signals; next, one tries to align events across the different time series. The better the alignment, the more similar the N time series are considered to be. The similarity measures quantify the reliability of the events (the fraction of “nonaligned” events) and the timing precision. So far, SES has been developed for pairs of one-dimensional (Part I) and multidimensional (Part II) point processes. In this letter (Part III), SES is extended from pairs of signals to N > 2 signals. The alignment and SES parameters are again determined through statistical inference, more specifically, by alternating two steps: (1) estimating the SES parameters from a given alignment and (2), with the resulting estimates, refining the alignment. The SES parameters are computed by maximum a posteriori (MAP) estimation (step 1), in analogy to the pairwise case. The alignment (stepxa02) is solved by linear integer programming. In order to test the robustness and reliability of the proposed N-variate SES method, it is first applied to synthetic data. We show that N-variate SES results in more reliable estimates than bivariate SES. Next N-variate SES is applied to two problems in neuroscience: to quantify the firing reliability of Morris-Lecar neurons and to detect anomalies in EEG synchrony of patients with mild cognitive impairment. Those problems were also considered in Parts I and II, respectively. In both cases, the N-variate SES approach yields a more detailed analysis.