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Practical Biomedical Signal Analysis Using MATLAB®, Second

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Katarzyna J. Blinowska, Jarosław Żygierewicz
 Practical Biomedical
Signal Analysis Using
MATLAB®
Second Edition

Katarzyna J. Blinowska, Jarosław Żygierewicz

MATLAB ® is a trademark of The MathWorks, Inc. and is used with permission. The MathWorks
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Contents

About the Series xi

Preface xiii

List of Abbreviations xv

1 A Short Introduction to MATLAB R 1

1.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.2 Where Is Help? . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.3 Vectors and Matrixes . . . . . . . . . . . . . . . . . . . . . . 1
1.4 Matrix Operations . . . . . . . . . . . . . . . . . . . . . . . . 2
1.4.1 Algebraic Operations . . . . . . . . . . . . . . . . . . . 2
1.4.2 Matrix Indexing . . . . . . . . . . . . . . . . . . . . . 3
1.4.3 Logical Indexing . . . . . . . . . . . . . . . . . . . . . 4
1.4.4 Example Exercise . . . . . . . . . . . . . . . . . . . . . 5
1.5 Conditionals . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
1.6 Loops . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
1.7 Scripts and Functions . . . . . . . . . . . . . . . . . . . . . . 6
1.8 Working with Binary Files . . . . . . . . . . . . . . . . . . . 7
1.8.1 Saving to and Loading from Binary Files . . . . . . . 7
1.8.2 Saving and Loading Signals Using .mat Files . . . . . 9
1.8.3 Exercises . . . . . . . . . . . . . . . . . . . . . . . . . 9
1.8.3.1 Unknown Data Type . . . . . . . . . . . . . 9
1.8.3.2 Unknown Number of Channels . . . . . . . . 10

2 Introductory Concepts 11
2.1 Stochastic and Deterministic Signals, Concepts of Stationarity
and Ergodicity . . . . . . . . . . . . . . . . . . . . . . . . . . 11
2.2 Discrete Signals . . . . . . . . . . . . . . . . . . . . . . . . . 14
2.2.1 The Sampling Theorem . . . . . . . . . . . . . . . . . 14
2.2.1.1 Aliasing . . . . . . . . . . . . . . . . . . . . . 15
2.2.2 Quantization Error . . . . . . . . . . . . . . . . . . . . 17
2.3 Linear Time Invariant Systems . . . . . . . . . . . . . . . . . 18
2.4 Duality of Time and Frequency Domains . . . . . . . . . . . 21
2.4.1 Continuous Periodic Signal . . . . . . . . . . . . . . . 22
2.4.2 Infinite Continuous Signal . . . . . . . . . . . . . . . . 22
2.4.3 Finite Discrete Signal . . . . . . . . . . . . . . . . . . 23

v
vi Contents

2.4.4 Basic Properties of Fourier Transform . . . . . . . . . 23

2.4.5 Power Spectrum: The Plancherel Theorem and Parse-
val’s Theorem . . . . . . . . . . . . . . . . . . . . . . . 24
2.4.6 Z -Transform . . . . . . . . . . . . . . . . . . . . . . . 25
2.4.7 Uncertainty Principle . . . . . . . . . . . . . . . . . . 26
2.5 Hypotheses Testing . . . . . . . . . . . . . . . . . . . . . . . 28
2.5.1 The Null and Alternative Hypothesis . . . . . . . . . . 28
2.5.2 Types of Tests . . . . . . . . . . . . . . . . . . . . . . 28
2.5.3 Multiple Comparisons Problem . . . . . . . . . . . . . 29
2.5.3.1 Correcting the Significance Level . . . . . . . 31
2.5.3.2 Parametric and Non-Parametric Statistical
Maps . . . . . . . . . . . . . . . . . . . . . . 31
2.5.3.3 False Discovery Rate . . . . . . . . . . . . . 32
2.6 Surrogate Data Techniques . . . . . . . . . . . . . . . . . . . 33

3 Single Channel (Univariate) Signal 35

3.1 Filters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
3.1.1 Designing Filters . . . . . . . . . . . . . . . . . . . . . 37
3.1.2 Changing the Sampling Frequency . . . . . . . . . . . 41
3.1.3 Matched Filters . . . . . . . . . . . . . . . . . . . . . . 42
3.1.4 Wiener Filter . . . . . . . . . . . . . . . . . . . . . . . 42
3.2 Probabilistic Models . . . . . . . . . . . . . . . . . . . . . . . 43
3.2.1 Hidden Markov Model . . . . . . . . . . . . . . . . . . 43
3.2.2 Kalman Filters . . . . . . . . . . . . . . . . . . . . . . 45
3.3 Stationary Signals . . . . . . . . . . . . . . . . . . . . . . . . 48
3.3.1 Analytic Tools in the Time Domain . . . . . . . . . . 48
3.3.1.1 Mean Value, Amplitude Distributions . . . . 48
3.3.1.2 Entropy and Information Measure . . . . . . 48
3.3.1.3 Autocorrelation Function . . . . . . . . . . . 49
3.3.2 Analytic Tools in the Frequency Domain . . . . . . . 50
3.3.2.1 Estimators of Spectral Power Density Based
on Fourier Transform . . . . . . . . . . . . . 50
3.3.2.2 Choice of Windowing Function . . . . . . . . 51
3.3.2.3 Parametric Models: AR, ARMA . . . . . . . 56
3.4 Non-Stationary Signals . . . . . . . . . . . . . . . . . . . . . 64
3.4.1 Instantaneous Amplitude and Instantaneous Frequency 64
3.4.2 Analytic Tools in the Time-Frequency Domain . . . . 66
3.4.2.1 Time-Frequency Energy Distributions . . . . 66
3.4.2.2 Time-Frequency Signal Decompositions . . . 69
3.4.3 Cross-Frequency Coupling . . . . . . . . . . . . . . . . 86
3.4.3.1 Models of Phase-Amplitude Coupling . . . . 87
3.4.3.2 Evaluation of Phase-Amplitude Coupling . . 88
3.5 Non-Linear Methods of Signal Analysis . . . . . . . . . . . . 93
3.5.1 Lyapunov Exponent . . . . . . . . . . . . . . . . . . . 95
3.5.2 Correlation Dimension . . . . . . . . . . . . . . . . . . 95
Contents vii

3.5.3 Detrended Fluctuation Analysis . . . . . . . . . . . . . 97

3.5.4 Recurrence Plots . . . . . . . . . . . . . . . . . . . . . 98
3.5.5 Poincaré Map . . . . . . . . . . . . . . . . . . . . . . . 99
3.5.6 Approximate, Sample, and Multiscale Entropy . . . . 99
3.5.7 Limitations of Non-Linear Methods . . . . . . . . . . . 101

4 Multiple Channels (Multivariate) Signals 103

4.1 Cross-Estimators: Cross-Correlation, Cross-Spectra, Coherence 103
4.2 Multivariate Autoregressive Model (MVAR) . . . . . . . . . 106
4.2.1 Formulation of MVAR Model . . . . . . . . . . . . . . 106
4.2.2 MVAR in the Frequency Domain . . . . . . . . . . . . 108
4.3 Measures of Directedness . . . . . . . . . . . . . . . . . . . . 108
4.3.1 Estimators Based on the Phase Difference . . . . . . . 108
4.3.2 Causality Measures . . . . . . . . . . . . . . . . . . . . 109
4.3.2.1 Granger Causality . . . . . . . . . . . . . . 109
4.3.2.2 Granger Causality Index and Granger-Geweke
Causality . . . . . . . . . . . . . . . . . . . . 110
4.3.2.3 Directed Transfer Function . . . . . . . . . . 111
4.3.2.4 Partial Directed Coherence . . . . . . . . . . 115
4.3.2.5 Directed Coherence . . . . . . . . . . . . . . 116
4.4 Non-Linear Estimators of Dependencies between
Signals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118
4.4.1 Kullback-Leibler Entropy, Mutual Information . . . . 118
4.4.2 Transfer Entropy . . . . . . . . . . . . . . . . . . . . . 119
4.4.3 Generalized Synchronization and Synchronization
Likelihood . . . . . . . . . . . . . . . . . . . . . . . . . 121
4.4.4 Phase Synchronization (Phase Locking Value) . . . . . 122
4.4.5 Testing the Reliability of the Estimators of
Directedness . . . . . . . . . . . . . . . . . . . . . . . 123
4.5 Comparison of the Multichannel Estimators of Coupling be-
tween Time Series . . . . . . . . . . . . . . . . . . . . . . . . 125
4.5.1 Bivariate versus Multivariate Connectivity Estimators 125
4.5.2 Linear versus Non-Linear Estimators of Connectivity . 127
4.5.3 The Measures of Directedness . . . . . . . . . . . . . . 128
4.6 Multivariate Signal Decompositions . . . . . . . . . . . . . . 129
4.6.1 Principal Component Analysis (PCA) . . . . . . . . . 129
4.6.1.1 Definition . . . . . . . . . . . . . . . . . . . . 129
4.6.1.2 Computation . . . . . . . . . . . . . . . . . . 129
4.6.1.3 Possible Applications . . . . . . . . . . . . . 130
4.6.2 Independent Components Analysis (ICA) . . . . . . . 130
4.6.2.1 Definition . . . . . . . . . . . . . . . . . . . . 130
4.6.2.2 Estimation of ICA . . . . . . . . . . . . . . . 131
4.6.2.3 Computation . . . . . . . . . . . . . . . . . . 132
4.6.2.4 Possible Applications . . . . . . . . . . . . . 132
viii Contents

4.6.3 Common Spatial Patterns . . . . . . . . . . . . . . . 133

4.6.4 Multivariate Matching Pursuit (MMP) . . . . . . . . . 134

5 Application to Biomedical Signals 137

5.1 Brain Signals . . . . . . . . . . . . . . . . . . . . . . . . . . . 137
5.1.1 Generation of Brain Signals . . . . . . . . . . . . . . . 139
5.1.2 EEG/MEG Rhythms . . . . . . . . . . . . . . . . . . 140
5.1.3 EEG Measurement, Electrode Systems . . . . . . . . . 143
5.1.4 MEG Measurement, Sensor Systems . . . . . . . . . . 145
5.1.5 Elimination of Artifacts . . . . . . . . . . . . . . . . . 145
5.1.6 Analysis of Continuous EEG Signals . . . . . . . . . . 149
5.1.6.1 Single Channel Analysis . . . . . . . . . . . . 150
5.1.6.2 Mapping . . . . . . . . . . . . . . . . . . . . 151
5.1.6.3 Connectivity Analysis of Brain Signals . . . . 152
5.1.6.4 Influence of Volume Conduction on Connec-
tivity Measures . . . . . . . . . . . . . . . . . 156
5.1.6.5 Graph Theoretical Analysis . . . . . . . . . . 157
5.1.6.6 Sleep EEG Analysis . . . . . . . . . . . . . . 160
5.1.6.7 Analysis of EEG in Epilepsy . . . . . . . . . 169
5.1.6.8 EEG in Monitoring and Anesthesia . . . . . 178
5.1.7 Analysis of Epoched EEG Signals . . . . . . . . . . . 179
5.1.7.1 Analysis of Phase-Locked Responses . . . . . 182
5.1.7.2 In Pursuit of Single Trial Evoked Responses 189
5.1.7.3 Applications of Cross-Frequency Coupling . . 194
5.1.7.4 Analysis of Non-Phase-Locked Responses . . 196
5.1.7.5 Analysis of EEG for Applications in Brain-
Computer Interfaces . . . . . . . . . . . . . . 215
5.1.8 fMRI Derived Time Series . . . . . . . . . . . . . . . . 218
5.1.8.1 Relation between EEG and fMRI . . . . . . 221
5.1.9 Near-Infrared Spectroscopy Signals . . . . . . . . . . . 225
5.2 Heart Signals . . . . . . . . . . . . . . . . . . . . . . . . . . 231
5.2.1 Electrocardiogram . . . . . . . . . . . . . . . . . . . . 231
5.2.1.1 Measurement Standards . . . . . . . . . . . . 231
5.2.1.2 Physiological Background and Clinical Appli-
cations . . . . . . . . . . . . . . . . . . . . . 232
5.2.1.3 Processing of ECG . . . . . . . . . . . . . . . 235
5.2.2 Heart Rate Variability . . . . . . . . . . . . . . . . . . 241
5.2.2.1 Time-Domain Methods of HRV Analysis . . 242
5.2.2.2 Frequency-Domain Methods of HRV Analysis 243
5.2.2.3 Non-Linear Methods of HRV Analysis . . . . 244
5.2.3 Fetal ECG . . . . . . . . . . . . . . . . . . . . . . . . 251
5.2.4 Magnetocardiogram and Fetal Magnetocardiogram . . 253
5.2.4.1 Magnetocardiogram . . . . . . . . . . . . . . 253
Contents ix

5.2.4.2 Fetal MCG . . . . . . . . . . . . . . . . . . . 257

5.2.5 Ballistocardiogram, Seismocardiogram, Photoplethys-
mogram . . . . . . . . . . . . . . . . . . . . . . . . . . 258
5.2.5.1 Wearable Devices . . . . . . . . . . . . . . . 259
5.3 Electromyogram . . . . . . . . . . . . . . . . . . . . . . . . . 261
5.3.1 Measurement Techniques and Physiological Background 261
5.3.2 Quantification of EMG Features . . . . . . . . . . . . 265
5.3.3 Decomposition of Needle EMG . . . . . . . . . . . . . 266
5.3.4 Surface EMG . . . . . . . . . . . . . . . . . . . . . . . 269
5.3.4.1 Surface EMG Decomposition . . . . . . . . . 270
5.4 Acoustic Signals . . . . . . . . . . . . . . . . . . . . . . . . . 278
5.4.1 Phonocardiogram . . . . . . . . . . . . . . . . . . . . . 278
5.4.2 Otoacoustic Emissions . . . . . . . . . . . . . . . . . . 281
5.5 Multimodal Analysis of Biomedical Signals . . . . . . . . . . 286

Bibliography 289

Index 349
About the Series

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xi
xii About the Series

The International Organization for Medical Physics

The International Organization for Medical Physics (IOMP) represents over
18,000 medical physicists worldwide and has a membership of 80 national
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Individual medical physicists of all national member organizations are also
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Preface

This book is intended to guide all those working in the field of biomedical
signal analysis and application, particularly for graduate students, researchers
at an early stage of their career, industrial researchers, and people interested
in the development of signal processing methods. The book is different from
other monographs, which are usually collections of papers written by several
authors. We tried to present a coherent view of various signal processing meth-
ods in the context of their application. Not only do we wish to present the
current techniques of biomedical signal processing, but we also want to pro-
vide guidance on which methods are appropriate for the given task and given
kind of data.
One of the motivations for writing this book was the longstanding ex-
perience of the authors in reviewing manuscripts submitted to journals and
conference proceedings, which showed how often the signal processing meth-
ods are misused. Quite often, sophisticated, but at the same time non-robust
and prone to systematic errors, methods are applied for the tasks where more
straightforward methods would work better. In this book, we aim to show the
advantages and disadvantages of different techniques in the context of their
applications.
In the first part of the book, we describe the methods of signal analysis, in-
cluding the most advanced and new approaches, in an easy and accessible way.
We illustrate them with MATLAB R Live Scripts. We omitted proofs of the
theorems when necessary, sending the reader to the more specialized mathe-
matical literature. To make the book a practical tool, we refer to MATLAB R
routines when available and to the software freely available on the Internet.
In the second part of the book, we describe the application of the methods
presented in the first part of the book to the different biomedical signals: elec-
troencephalogram (EEG), electrocorticogram (ECoG), event-related potential
(ERP), electrocardiogram (ECG), heart rate variability signal (HRV), elec-
tromyograms (EMG), magnetoencephalograms (MEG), magnetocardiograms
(MCG), phonocardiograms (PCG), and otoacoustic emissions (OAE).
In this second edition, we also address the analysis of fMRI (BOLD) and
functional near-infrared spectroscopy (fNIRS) time series. We discuss new
topics that gained interest in recent years, namely, phase-amplitude coupling,
wearable devices, multimodal signal analysis, and brain-computer interfaces.
Major updates concern multiple channel analysis and connectivity measures.
We included a short introduction presenting the basic syntax and functionality
relevant to signal processing for those new to MATLAB.

xiii
xiv Preface

Different approaches to solving particular problems are presented to

indicate which methods seem to be most appropriate for a given application.
Possible pitfalls, which may be encountered in applying the specific method-
ology, are pointed out.
We hope that this book will be a practical help to students and researchers
in choosing the appropriate methods, designing their own, and adding new
value to the growing field of biomedical research.
You can access MATLAB scripts and data in the support material section
at: www.routledge.com/9781138364417