FM Huettel.

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FUNCTIONAL
Magnetic Resonance Imaging
SECOND EDITION

Scott A. Huettel
Brain Imaging and Analysis Center, Duke University

Allen W. Song
Brain Imaging and Analysis Center, Duke University

Gregory McCarthy
Yale University

Sinauer Associates, Inc • Publishers

Sunderland, Massachusetts U.S.A.

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Brief Contents

1 An Introduction to fMRI 1
2 MRI Scanners 31
3 Basic Principles of MR Signal Generation 57
4 Basic Principles of MR Image Formation 89
5 MR Contrast Mechanisms
and Pulse Sequences 121
6 From Neuronal to Hemodynamic Activity 159
7 BOLD fMRI: Origins and Properties 193
8 Signal, Noise, and Preprocessing
of fMRI Data 243
9 Experimental Design 293
10 Statistical Analysis: Basic Analyses 331
11 Statistical Analysis II: Advanced Approaches 377
12 Advanced fMRI Methods 419
13 Combining fMRI with other Techniques 443
14 The Future of fMRI: Practical
and Ethical Issues 485

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Contents

Preface xiii 2 MRI Scanners 31

1 An Introduction to fMRI 1
How MRI Scanners Work
Static magnetic field 32
Radiofrequency coils 35
Gradient coils 38
31

What Is fMRI? 3
Shimming coils 41
Measurement versus manipulation
Computer hardware and software 41
techniques 4
Experimental control system 43
BOX 1.1 WHAT IS FMRI USED FOR? 6 Physiological monitoring equipment 43
Key concept: contrast 9
Key concept: resolution 11 MRI Safety 44
Effects of static magnetic fields on human
History of fMRI 15
physiology 44
Early studies of magnetic resonance 15
BOX 2.1 OUTLINE OF AN FMRI
NMR in bulk matter: Bloch and Purcell 17 EXPERIMENT 45
The first MR images 18 Translation and torsion 49
Growth of MRI 21 Gradient magnetic field effects 50
BOX 1.2 THE NOBEL CONTROVERSY: Radiofrequency field effects 52
SCANNERS OR IMAGES? 22 Claustrophobia 53
Organization of the Textbook 24 Acoustic noise 54
Physical bases of fMRI 25 Summary 54
Principles of BOLD fMRI 25
Design and analysis of fMRI experiments 26 Suggested Reading 55
Applications and future directions 27 Chapter References 55
Summary 28
Suggested Reading 28
Chapter References 29

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viii Contents

4 Basic Principles of MR Image

Formation 89
CONCEPTUAL PATH 90
Slice Selection 91
Frequency Encoding 93
Phase Encoding 95

3 Basic Principles of MR Signal

Generation 57
Conceptual Path: Summary of Image
Formation 96
QUANTITATIVE PATH 97
CONCEPTUAL PATH 57
Nuclear Spins 59 Analysis of the MR Signal 97
BOX 4.1 AN EXAMPLE OF SPATIAL
Spins in an External Magnetic Field 60 ENCODING 98
Magnetization of a Spin System 62 Longitudinal magnetization (Mz) 101
Solution for transverse magnetization
Excitation of a Spin System and Signal (Mxy ) 102
Reception 64 The MR signal equation 105
Relaxation Mechanisms of the Slice Selection, Spatial Encoding, and
MR Signal 65 Image Reconstruction 106
Conceptual Summary of MR Signal Slice selection 106
Generation 67 Two-dimensional spatial encoding
(frequency and phase encoding) 109
QUANTITATIVE PATH 68 Relationship between image space and
Common Terms and Notations 68 k-space 113
Converting from k-space to image space 114
Nuclear Spins 69 3-D Imaging 117
Magnetic Moment 69 Potential Problems in Image
Angular Momentum 70 Formation 117
Spins in an External Magnetic Field 71 Summary 120
Spin precession 71 Suggested Reading 120
Energy Difference between Parallel
and Antiparallel States 74
Magnetization of a Spin System 75
Excitation of a Spin System and Signal
5 MR Contrast Mechanisms and
Pulse Sequences 121
Reception 77 Static Contrasts and Related Pulse
Spin excitation 78 Sequences 122
BOX 3.1 A QUANTITATIVE CONSIDERATION OF Proton-density contrast 123
THE ROTATING REFERENCE FRAME 80 T1 contrast 126
Signal reception 83 T2 contrast 129
T2* contrast 131
Relaxation Mechanisms of a Spin
Chemical contrast 132
System 85
Macromolecular contrast 133
The Bloch Equation for MR signal Motion Contrasts 135
generation 87
MR angiography 135
Summary 87 Diffusion-weighted contrast 138
Suggested Reading 88 BOX 5.1 DIFFUSION TENSOR IMAGING 140
Perfusion-weighted contrast 142

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Contents ix

Fast Imaging Sequences for fMRI

Echo-planar imaging 147
Spiral imaging 148
Signal recovery and distortion correction
147
7 BOLD fMRI: Origins and
Properties 193
for EPI and spiral images 152 History of BOLD fMRI 193
Discovery of BOLD contrast 194
Summary 154
The coupling of metabolism and
Suggested Reading 156 blood flow 196
Chapter References 157 BOX 7.1 PET IMAGING 197
The Growth of BOLD fMRI 201

6 From Neuronal to
Hemodynamic Activity 159
Contributing factors 201
Early fMRI studies 203
BOX 7.2 FUNCTIONAL STUDIES USING
CONTRAST AGENTS 204
Neuronal Activity 160 The BOLD Hemodynamic Response 208
Ion channels in neurons 162 BOX 7.3 NEURONAL ACTIVITY AND BOLD
Neurotransmitters and action potentials 163 FMRI 209
Cerebral Metabolism: Neuronal Energy The initial dip 211
Consumption 165 Spatial Resolution 214
Adenosine triphosphate (ATP) 166 Spatial specificity in the vascular system 216
The Vascular System of the Brain 168 What spatial resolution is needed? 219
Arteries, capillaries, and veins 170 Temporal Resolution of fMRI 220
Arterial and venous anatomy of the human What temporal resolution is needed? 223
brain 171 Effects of stimulus duration and timing 225
Microcirculation 172
Linearity of the Hemodynamic
Blood Flow 174 Response 229
Control of blood flow 175 Properties of a linear system 230
BOX 6.1 NEUROVASCULAR COUPLING AND Evidence for rough linearity 231
CONTROL OF BLOOD FLOW 176 Challenges to linearity 233
Effects of increased blood flow on fMRI-adaptation 235
capillaries 179
Summary 237
BOX 6.2 PRIMER ON NEUROANATOMY 182
Summary 190 Suggested Reading 238
Suggested Reading 190 Chapter References 239
Chapter References 191
Signal, Noise, and
8 Preprocessing of fMRI
Data 243
Understanding Signal and Noise 245
Signal and noise defined 245
BOX 8.1 TERMINOLOGY OF FMRI 246
Functional SNR 248
Effects of Field Strength on fMRI
Data 250
Field strength and raw SNR 251
Field strength and spatial properties of
activation 252
Challenges of high-field fMRI 254

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x Contents
Sources of Noise in fMRI 255
Thermal noise 256
System noise 258
Motion and physiological noise 259
Non-task-related neural variability 262
Behavioral and cognitive variability in task
performance 262
BOX 8.2 VARIABILITY IN THE HEMODYNAMIC
RESPONSE OVER SUBJECTS AND
SESSIONS 264
Preprocessing 267
Quality assurance 267
Slice acquisition time correction 269
Head motion: an overview 271
Prevention of head motion 274
Correction of head motion 276
Distortion correction 277
Functional–Structural Coregistration
and Normalization 280
Functional–structural coregistration
Spatial normalization 281
Temporal and Spatial Filtering
Temporal filtering 285
Spatial filtering 287
Summary 289
Suggested Reading 289
Chapter References 290
9 Experimental Design
Basic Principles of Experimental
293
Design 294
Setting Up a Good Research
Hypothesis 296
Are fMRI data correlational? 298
Confounding factors 299
Good Practices in fMRI Experimental
Design 302
Blocked Designs 303
Setting up a blocked design 304
BOX 9.1 BASELINE ACTIVATION IN FMRI 306
Advantages and disadvantages of blocked
designs 310
Event-Related Designs 313
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Principles of event-related fMRI 316
Advantages of event-related designs 319
BOX 9.2 EFFICIENT FMRI EXPERIMENTAL
DESIGN 320
Mixed Designs 325
Summary 327
Suggested Reading 327
Chapter References 328
10 Statistical Analysis: Basic
Analyses 331
Basic Statistical Tests 333
Contrasting experimental conditions:
the t-test 334
Comparing experimental and predicted
responses: correlation analyses 338
280 BOX 10.1 IDENTIFYING TASK-RELATED
PERIODICITY: FOURIER ANALYSES 341
284 Regression Analyses 343
The general linear model: an overview 343
Constructing a design matrix: regressors of
interest 345
Constructing a design matrix: nuisance
regressors 349
Modeling neuronal activity 351
Modeling hemodynamic convolution 352
Contrasts 354
Assumptions of the general linear
model 356
Corrections for Multiple
Comparisons 357
Calculating the significance threshold 358
Thresholding based on clusters of
activation 360
Estimating the number of independent
tests 361
Region-of-Interest Analyses 362
Intersubject Analyses 365
Group and parametric effects 367
Displaying Statistical Results 369
Summary 373
Suggested Reading 373
Chapter References 374
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Contents xi

11 Statistical Analysis II:

Advanced Approaches
Data Exploration Approaches 378
Principal components analysis (PCA) 378
Independent components analysis (ICA) 380
Partial least squares (PLS) 382
Between-Subjects Correlations:
Hyperscanning 384
Functional Connectivity Approaches
386
From coactivation to connectivity:
a conceptual overview 386
BOX 11.1 INTERSUBJECT CORRELATIONS IN FREE
VIEWING 387
Resting-state connectivity 391
Psychophysiological interactions 393
Inferring causality from fMRI data 394
Combining fMRI and DTI 399
Prediction Approaches 401
Predicting variation among individuals 402
BOX 11.2 REAL-TIME FMRI 403
Predicting variation in behavior 407
Pattern classification using machine learning
algorithms 408
Capabilities and challenges of fMRI pattern
classification 412
Summary 415
Suggested Reading 416
Chapter References 416
377 12 Advanced fMRI
Methods 419
Improved Spatial Resolution 420
MR microscopy 420
Parallel imaging 423
Parallel imaging with massive
coil arrays 425
Improved Temporal Resolution 426
Multiple-channel acquisition 427
Partial k-space imaging 427
Efficient k-space trajectories 430
Improved experimental designs 432
Improved Functional Resolution through
New Contrast Mechanisms 433
Temperature-dependent contrast 434
pH-dependent contrast 435
Ion-gated contrast 437
Neuronal magnetic field contrast 438
Lorentz effect contrast 439
Summary 440
Suggested Reading 441
Chapter References 441
13 Combining fMRI with other
Techniques 443
Cognitive Neuroscience 443
Strategies for research in cognitive
neuroscience 445
Manipulating Brain Function 446
Direct cortical stimulation 446
Functional consequences of direct cortical
stimulation 448
Transcranial magnetic stimulation (TMS) 450
Brain lesions 452
Combined lesion and fMRI studies 454
Probabilistic brain atlases 455
Brain imaging and genomics 457
Measuring Brain Function 458
Single-unit recording 458
BOX 13.1 ELECTROGENESIS 459
Limitations of single-unit recording 462
Properties of electrical field potentials 464
Localizing the neural generators of field
potentials 465

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xii Contents

14 The Future of fMRI: Practical

and Ethical Issues 485
Introduction 485
Interpreting and Presenting
fMRI Data 486
Coverage of fMRI research in the popular
media 487
Core principles for presenting fMRI
research 489
BOX 14.1 REVERSE INFERENCE 490
Conducting fMRI Research 494
Proposing and approving fMRI research 495
Intracranially recorded field potentials 466 Ensuring the confidentiality of
BOX 13.2 LOCALIZATION OF FUNCTION USING fMRI data 497
FIELD POTENTIAL RECORDINGS 468
BOX 14.2 INCIDENTAL FINDINGS IN FMRI
Scalp-recorded field potentials 470 RESEARCH 498
BOX 13.3 COMBINING FMRI AND EEG/ERP Safe conduct of fMRI studies 502
TECHNIQUES 472
Pregnancy testing in fMRI research 504
Magnetoencephalography 474
Using fMRI with non-human primates 476 Applying fMRI to New and Controversial
Topics 505
Summary 480
Reading minds 506
Suggested Reading 480 Identifying traits 509
Chapter References 481 The Future of fMRI Research (and your
role in it) 511
Summary 513
Suggested Reading 515
Chapter References 515
Glossary 517
Index 533

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