Download LEC2 Broad Perspective and fMRI Introduction

General Introduction to
Functional MRI
Introduction to Physics, Physiology,
Data Analysis, and
Experimental Design in fMRI
from a Behavioral Science Perspective
Robert Savoy
The MGH/MIT/HMS Athinoula A. Martinos Center
HyperVision, Inc.
Robert Savoy
Functional Magnetic Resonance Brain Imaging
First, a few words about keeping...
A Broad Perspective
Robert L. Savoy, Ph.D.
Athinoula A. Martinos Center for Biomedical Imaging
of the Massachusetts General Hospital
Harvard University
HyperVision, Inc, Lexington, MA
<[email protected]>
A Broad Perspective
Robert Savoy
Functional Magnetic Resonance Brain Imaging
Before we start on fMRI design...
A few words about the “Big” issues
A few words MultiModal Imaging
A Broad Perspective
Robert Savoy
Functional Magnetic Resonance Brain Imaging
Approaches to Understanding the
Digital Computer
• Quantum Mechanics
• Materials Science
• Components
• Resistors, Capacitors, Transistors, Diodes
• Chip Diagrams
• Local Counters, Flip-Flops
• Wiring
• Global Hardware Circuitry)
• Software
• Networks
A Broad Perspective
Levels of Explanation
Data Separation
Algorithmic Separation
Robert Savoy
Functional Magnetic Resonance Brain Imaging
Approaches to Understanding the
Human Brain
• Neurochemistry
• Neuroanatomy
• Neurophysiology
• Single and Multiple Cell Recordings
•
•
•
•
Columnar Wiring
Brain Mapping
Psychology
Sociology
A Broad Perspective
Levels of Explanation
Data Separation
Algorithmic Separation
Robert Savoy
Functional Magnetic Resonance Brain Imaging
MultiModal Imaging
(a view oriented around MRI)
Optical Microscopy
PET
High Field
MultiChannel
phMRI
MEG
EEG
MRI
Computational
Neuroanatomy
TMS
MRS
DTI
DSI
functional
MRI
DOT
NIRS
Intracranial Electrodes
A Broad Perspective
Robert Savoy
Functional Magnetic Resonance Brain Imaging
MultiModal Imaging and Approaches to
Understanding the Human Brain
• Neurochemistry
Optical Microscopy
• Neuroanatomy
• Neurophysiology
PET
• Single and Multiple
Cell Recordings
• Columnar Wiring
phMRI
• Brain Mapping
• Psychology
• Sociology
A Broad Perspective
High Field
MultiChannel
MEG
EEG
MRS
MRI
Computational
Neuroanatomy
TMS
DTI
DSI
functional
MRI
DOT
NIRS
Intracranial Electrodes
Robert Savoy
Functional Magnetic Resonance Brain Imaging
MultiModal Imaging and Approaches to
Understanding the Human Brain
• Neurochemistry
Optical Microscopy
• Neuroanatomy
• Neurophysiology
PET
• Single and Multiple
Cell Recordings
• Columnar Wiring
phMRI
• Brain Mapping
• Psychology
• Sociology
A Broad Perspective
High Field
MultiChannel
MEG
EEG
MRS
MRI
Computational
Neuroanatomy
TMS
DTI
DSI
functional
MRI
DOT
NIRS
Intracranial Electrodes
Robert Savoy
Functional Magnetic Resonance Brain Imaging
MultiModal Imaging and Approaches to
Understanding the Human Brain
• Neurochemistry
Optical Microscopy
• Neuroanatomy
• Neurophysiology
PET
• Single and Multiple
Cell Recordings
• Columnar Wiring
phMRI
• Brain Mapping
• Psychology
• Sociology
A Broad Perspective
High Field
MultiChannel
MEG
EEG
MRS
MRI
Computational
Neuroanatomy
TMS
DTI
DSI
functional
MRI
DOT
NIRS
Intracranial Electrodes
Robert Savoy
Functional Magnetic Resonance Brain Imaging
MultiModal Imaging and Approaches to
Understanding the Human Brain
• Neurochemistry
Optical Microscopy
• Neuroanatomy
• Neurophysiology
PET
• Single and Multiple
Cell Recordings
• Columnar Wiring
phMRI
• Brain Mapping
• Psychology
• Sociology
A Broad Perspective
High Field
MultiChannel
MEG
EEG
MRS
MRI
Computational
Neuroanatomy
TMS
DTI
DSI
functional
MRI
DOT
NIRS
Intracranial Electrodes
Robert Savoy
Functional Magnetic Resonance Brain Imaging
MultiModal Imaging and Approaches to
Understanding the Human Brain
• Neurochemistry
Optical Microscopy
• Neuroanatomy
• Neurophysiology
PET
• Single and Multiple
Cell Recordings
• Columnar Wiring
phMRI
• Brain Mapping
• Psychology
• Sociology
A Broad Perspective
High Field
MultiChannel
MEG
EEG
MRS
MRI
Computational
Neuroanatomy
TMS
DTI
DSI
functional
MRI
DOT
NIRS
Intracranial Electrodes
Robert Savoy
Functional Magnetic Resonance Brain Imaging
MultiModal Imaging and Approaches to
Understanding the Human Brain
• Neurochemistry
Optical Microscopy
• Neuroanatomy
• Neurophysiology
PET
• Single and Multiple
Cell Recordings
• Columnar Wiring
phMRI
• Brain Mapping
• Psychology
• Sociology
A Broad Perspective
High Field
MultiChannel
MEG
EEG
MRS
MRI
Computational
Neuroanatomy
TMS
DTI
DSI
functional
MRI
DOT
NIRS
Intracranial Electrodes
Robert Savoy
Functional Magnetic Resonance Brain Imaging
MultiModal Imaging and Approaches to
Understanding the Human Brain
• Neurochemistry
Optical Microscopy
• Neuroanatomy
• Neurophysiology
PET
• Single and Multiple
Cell Recordings
• Columnar Wiring
phMRI
• Brain Mapping
• Psychology
• Sociology
A Broad Perspective
High Field
MultiChannel
MEG
EEG
MRS
MRI
Computational
Neuroanatomy
TMS
DTI
DSI
functional
MRI
DOT
NIRS
Intracranial Electrodes
Robert Savoy
Functional Magnetic Resonance Brain Imaging
We will focus on fMRI, but...
Integration
Optical Microscopy
PET
High Field
MultiChannel
phMRI
MEG
EEG
MRI
Computational
Neuroanatomy
TMS
MRS
DTI
DSI
functional
MRI
DOT
NIRS
Intracranial Electrodes
Levels of Explanation
Data Separation
Algorithmic Separation
A Broad Perspective
Across Modality
Across Function
Unity through
Topic
Simultaneous Data Acquisition
Ultimate Unity through
Conceptual Integration and
Modeling of Brain Function
Robert Savoy
Functional Magnetic Resonance Brain Imaging
On to an introduction specific to
Functional MRI
A Broad Perspective
Robert Savoy
Personal Introduction
• Thanks to many people...
• My Eclectic background; Exptl. Psych.; Vision
• General interests: 70% out? Integrating FNI data
The Goals of this Workshop
Thorough introduction to the basics of the physics,
experimental psychology, data analysis, and
practical constraints underlying fMRI-based
research. Discussion of basic data analysis theory
and tools. Starting to think about your experiments.
The MGH/MIT/HMS Athinoula A. Martinos Center
HyperVision, Inc.
Robert Savoy
Why Is fMRI So Exciting?
• Repeated studies on single subjects
• Better temporal resolution than the nearest
non-invasive volumetric imaging alternative
• Better, and ever-improving, spatial resolution
==================================
• Large installed machine base
• Remarkably flexible tool at its core
• Potential for complementing other tools, with
greater temporal resolution
The MGH/MIT/HMS Athinoula A. Martinos Center
HyperVision, Inc.
Robert Savoy
Introduction to fMRI: Outline
• Set the Stage
History and Basics of Functional MRI
• Practical Issues
Functional MRI is Complicated
• Applications
Selected Examples
• Research Themes
Challenges in Human Brain Mapping
The MGH/MIT/HMS Athinoula A. Martinos Center
HyperVision, Inc.
Robert Savoy
Introduction to fMRI: Outline
• Set the Stage
History and Basics of Functional MRI
• Practical Issues
Functional MRI is Complicated
• Applications
Selected Examples
• Research Themes
Challenges in Human Brain Mapping
The MGH/MIT/HMS Athinoula A. Martinos Center
HyperVision, Inc.
Robert Savoy
Practicalities
NMR
MRI
Computers
for
Everything
Experimental
Task
Hemodynamics
Data Analysis
Animal Brain Mapping
Clinical Applications
Partial List of Other Modalities:
Direct Stimulation • DOT • EEG • ERP
Lesions • MEG • Optical • PET
Structural MRI • TES • TMS
The MGH/MIT/HMS Athinoula A. Martinos Center
Psychophysiological
Laboratory
Functional
Neuroanatomy
Comparing
Brains
Computational
Neuroanatomy
HyperVision, Inc.
Robert Savoy
What is the real challenge?
What is your question?
Why should I believe
your answer?
What is the nature of an
answerable question,
using fMRI?
What would that answer
look like?
The MGH/MIT/HMS Athinoula A. Martinos Center
HyperVision, Inc.
Robert Savoy
Practicalities
NMR
MRI
Psychophysiological
Laboratory
Experimental
Task
Hemodynamics
Data Analysis
Functional
Neuroanatomy
Comparing
Brains
Experimental
Design
The MGH/MIT/HMS Athinoula A. Martinos Center
Computational
Neuroanatomy
HyperVision, Inc.
Robert Savoy
Basics of Functional MRI
• Hemodynamics
• Roy and Sherrington
• History
• BOLD / Flow
The MGH/MIT/HMS Athinoula A. Martinos Center
HyperVision, Inc.
Robert Savoy
First Examples with Humans
The MGH/MIT/HMS Athinoula A. Martinos Center
HyperVision, Inc.
Robert Savoy
Basics of Functional MRI
• Hemodynamics
• Roy and Sherrington
• History
• BOLD / Flow
• Instrumental Source of the Data
• NMR
8 Magnetic Fields and Relaxation
• MRI
• Contrast
• Flexibility of Tool
Maximum Signal
(minimal contrast)
No Signal
(no contrast)
"Inject Signal"
(90° saturation rf-pulse)
The MGH/MIT/HMS Athinoula A. Martinos Center
Time
HyperVision, Inc.
Robert Savoy
MRI in a Slide:
MRI
In
a
Slide
8 Magnetic Fields and Relaxation
■
■
■
■
■
To Obtain the NMR Signal: Three Magnetic Fields
 µ
The magnetic field of a nucleus with spin
 B0
The main magnetic field, used to align nuclei
 B
1 The radio-frequency field, used to flip nuclei
Relaxation: Two ways for the signal to go away
 T1
Longitudinal: The nuclei re-align with B0
 T
2 Transverse: The nuclei get out-of-phase
To Select Slices and Make Images: Three More Fields
 G
The gradient fields
x, G y, G z
Shim Fields
To make better images
Shielding Fields To protect us from all of the above!
The MGH/MIT/HMS Athinoula A. Martinos Center
HyperVision, Inc.
Robert Savoy
Signal decays exponentially
Maximum
Signal
Fading...
Fading...
Gone
Singal Decays Expontntially
Time
"Inject Signal"
(90° saturation rf-pulse)
The MGH/MIT/HMS Athinoula A. Martinos Center
HyperVision, Inc.
Robert Savoy
Rate of decay varies across voxels
Different Rates of Decay
"Inject Signal"
(90° saturation rf-pulse)
The MGH/MIT/HMS Athinoula A. Martinos Center
Time
HyperVision, Inc.
Robert Savoy
Image
contrast
varies
with
time
Faces Contrast for fMRI
Maximum
Signal
(Little Contrast)
Intermediate
Signals
(Useful Contrasts)
Maximum Signal
(minimal contrast)
(90° saturation rf-pulse)
(90° saturation rf-pulse)
(No Contrast)
No Signal
(no contrast)
"Inject Signal"
"Inject Signal"
Minimum
Signal
Time
Time
So, we must WAIT for dephasing to occur, in order
to get T2 or T2* contrast.
But while we are waiting, various bad things
happen:
imaging artifacts
appear
The MGH/MIT/HMS Athinoula A. Martinos
Centersignal decreases;
HyperVision, Inc.
Robert Savoy
Proton Density; T1-Weighted;
T2-Weighted; MRA
contrast enhanced; 95%
The MGH/MIT/HMS Athinoula A. Martinos Center
a
b
c
d
HyperVision, Inc.
Robert Savoy
Basics of Functional MRI
• Hemodynamics
• Roy and Sherrington
• History
• BOLD / Flow
• Instrumental Source of the Data
• NMR
• MRI
• Contrast
• Flexibility of Tool
• Combining Hemodynamics and MRI
The MGH/MIT/HMS Athinoula A. Martinos Center
HyperVision, Inc.
Robert Savoy
The Chain of Ideas
Increased Neural Activity
Increased Local Cerebral Blood Flow
Decreased Deoxyhemoglobin
Concentration in Veins (BOLD)
Change in Magnetic Susceptibility
Change in NMR Signal
The MGH/MIT/HMS Athinoula A. Martinos Center
HyperVision, Inc.
Robert Savoy
Deoxygenated blood attenuates signal
in T2*-weighted MR images
O2
Figure from Rick Hoge
MRI volume element
The MGH/MIT/HMS Athinoula A. Martinos Center
HyperVision, Inc.
Robert Savoy
Decrease of Venous Deoxyhemoglobin
Concentration During Increased Perfusion
O2
Figure from Rick Hoge
The MGH/MIT/HMS Athinoula A. Martinos Center
HyperVision, Inc.
Robert Savoy
Close up on a few hydrogen nuclei, the Larmor
frequencies of each, and how they add up
+=
O2
+=
MRI volume element
The MGH/MIT/HMS Athinoula A. Martinos Center
HyperVision, Inc.
Robert Savoy
Basic Time Course of the
Hemodynamic Response
Hemodynamic Delay and
Dispersion
Stimulus
1 sec
Time
Neuronal Response
Hemodynamic
Response
6-8 sec
The MGH/MIT/HMS Athinoula A. Martinos Center
HyperVision, Inc.
Robert Savoy
1000 msec
ε =
20 seconds
10
100 msec
34 msec
20
(60 -
ε) seconds
50
Time (seconds)
80
2.5
Consisent latency
(2 sec)
(~2
sec)totoonset
onsetofof
MR response
2
1.5
Stimulus Duration
1000 msec : black
100 msec : grey
34 msec : white
Peak
Percent
Increase 1
in MR
Signal 0.5
Strength
0
-0.5
Duration of Response
to Very Brief Stimuli
34 msec
100 msec
1000 msec
15
20
The MGH/MIT/HMS Athinoula A. Martinos Center
Time 25
(seconds)
30
HyperVision, Inc.
35
Robert Savoy
Functional MRI is Complicated
• Technology is Complicated
• Roy and Sherrington quotation
The MGH/MIT/HMS Athinoula A. Martinos Center
HyperVision, Inc.
Robert Savoy
On the Regulation of the Blood-Supply of the BRAIN
C.S. Roy and C.S. Sherrington Journal of Physiology 11, 85 (1890)
In modern English:
We think different investigators get
contradictory results because the technology
for measuring cerebral hemodynamics is
complicated.
The MGH/MIT/HMS Athinoula A. Martinos Center
HyperVision, Inc.
Robert Savoy
On the Regulation of the Blood-Supply of the BRAIN
C.S. Roy and C.S. Sherrington Journal of Physiology 11, 85 (1890)
One of the marked characteristics of the literature dealing with the
cerebral circulation is, we think, the contradictory nature of the
results which have been obtained by different investigators.
There is no reason, we imagine, for doubting that the cause of these
discrepancies is to be found in the great difficulty of avoiding the
sources of error which plentifully surround the subject, and in
overcoming certain technical difficulties which we shall presently
have to refer to. The ease with which one can obtain results upon
certain points, on taking up the subject, is itself, we believe, apt to
make the inquirer careless in controlling sources of error, which, it
may be noted, are some of them not at first sight obvious. We must
on this account say more about the technology of our subject than
would be necessary were the subject a simpler one.
The MGH/MIT/HMS Athinoula A. Martinos Center
HyperVision, Inc.
Robert Savoy
Functional MRI is Complicated
• Technology is Complicated
• Roy and Sherrington quotation
• Good written resources are available (e.g., textbooks on fMRI)
The MGH/MIT/HMS Athinoula A. Martinos Center
HyperVision, Inc.
Robert Savoy
Functional MRI is Complicated
• Technology is Complicated
• Link between neural activity and hemodynamics
• Still not well-understood
• Possible role of dopamine
• Latest work with monkeys and fMRI + invasive recording
• “Initial Dip”; Post-Stimulus Undershoot; Arteries, Veins &
Capillaries
• Models (Buxton; Mandeville & Weisskoff; Hoge)
• Recent Book: Functional Magnetic Resonance Imaging:
Principles and Techniques, by Richard Buxton, Cambidge Univ.
Press (2001). Strong emphasis on the connection between basic
physiology and the MR physics.
The MGH/MIT/HMS Athinoula A. Martinos Center
HyperVision, Inc.
Robert Savoy
Tightening the Links
• Regulation of the cerbral microcirculation during neural activity: is nitric oxide
the missing link? by C. Iodecola.
Trends in Neuroscience, 16 (6), 206 (1993)
• Neurogenic control of cerebral microcirculation: is dopamine minding the store?
by C. Iadecola
Nature Neuroscience, 1 (4), 263 (1998)
• Neurophysiological investigation of the basis of the fMRI signal. by N.K.
Logothetis, et al.
Nature, 412, 150 (2001)
• Imaging function in the working brain with fMRI. by R.S. Menon. Current
Opinion in Neurobiology, 11, 630 (2001)
This is still a controversial area. SEE FOR EXAMPLE a recent article
by Devor, et al.:
The Journal of Neuroscience, December 31, 2008 • 28(53):14347–14357
Chapter 6 in the Huettel textbook is good general introduction.
The MGH/MIT/HMS Athinoula A. Martinos Center
HyperVision, Inc.
Robert Savoy
Functional MRI is Complicated
• Technology is Complicated
• Link between neural activity and hemodynamics
• Experimental Design: A variety of techniques
The MGH/MIT/HMS Athinoula A. Martinos Center
HyperVision, Inc.
Robert Savoy
Basic Time Course of the
Hemodynamic Response
Hemodynamic Delay and
Dispersion
Stimulus
1 sec
Hemodynamic Delay and
Dispersion
Stimulus
Time
Neuronal Response
Hemodynamic
Response
Time
30 sec
Neuronal Response
Hemodynamic Response
34-38 sec
6-8 sec
The MGH/MIT/HMS Athinoula A. Martinos Center
HyperVision, Inc.
Robert Savoy
Blocked versus Mixed-Trial Paradigm
Buckner: Blocked/Spaced/Rapid
BLOCKED:
SPACED MIXED TRIAL:
RAPID MIXED TRIAL:
The MGH/MIT/HMS Athinoula A. Martinos Center
HyperVision, Inc.
Robert Savoy
Blocked versus Mixed-Trial Paradigm
Buckner: Blocked/Spaced/Rapid
BLOCKED:
SPACED MIXED TRIAL:
RAPID MIXED TRIAL:
The MGH/MIT/HMS Athinoula A. Martinos Center
HyperVision, Inc.
Robert Savoy
Blocked versus Mixed-Trial Paradigm
Buckner: Blocked/Spaced/Rapid
BLOCKED:
SPACED MIXED TRIAL:
RAPID MIXED TRIAL:
The MGH/MIT/HMS Athinoula A. Martinos Center
HyperVision, Inc.
Robert Savoy
Basic Time Course of the
Hemodynamic Response
Hemodynamic Delay and
Dispersion
a
Stimulus
1 sec
Time
Neuronal Response
Hemodynamic
Response
6-8 sec
The MGH/MIT/HMS Athinoula A. Martinos Center
b
HyperVision, Inc.
Robert Savoy
Blocked versus Mixed-Trial Paradigm
Buckner: Blocked/Spaced/Rapid
BLOCKED:
SPACED MIXED TRIAL:
RAPID MIXED TRIAL:
The MGH/MIT/HMS Athinoula A. Martinos Center
HyperVision, Inc.
Robert Savoy
Functional MRI is Complicated
• Technology is Complicated
• Link between neural activity and hemodynamics
• Experimental Design: A variety of techniques
• Data Analysis: Endless time sink
• 5+1 Lectures by Doug Greve on Data Analysis
• The saga of Michael Chee
• Recent (2009) controversy in the literature, based on statistics:
Nature News: Published online 13-Jan-2009: “Brain imaging studies
under fire” by Alison Abbott”, based on paper by Vul, et al.: “Voodoo
Correlations in Social Neuroscience” Perspectives on Psychological
Science 23-Dec-2008. Not to mention the saga of the dead salmon
brain activations (Bennett, et alia, OHBM Poster, June 2009.
The MGH/MIT/HMS Athinoula A. Martinos Center
HyperVision, Inc.
Robert Savoy
SPM: Statistical Parametric Mapping. (From the Department of Cognitive Neurology)
The MGH/MIT/HMS Athinoula A. Martinos Center
HyperVision, Inc.
Robert Savoy
Functional MRI is Complicated
• Technology is Complicated
• Link between neural activity and hemodynamics
• Experimental Design: A variety of techniques
• Data Analysis: Endless time sink
• MR Physics and Hemodynamics, Experimental
Design, and Data Analysis are Tightly Coupled
The MGH/MIT/HMS Athinoula A. Martinos Center
HyperVision, Inc.
Robert Savoy
Functional MRI is Complicated
•
•
•
•
•
Technology is Complicated
Link between neural activity and hemodynamics
Experimental Design: A variety of techniques
Data Analysis: Endless time sink
MR Physics and Hemodynamics, Experimental
Design, and Data Analysis are Tightly Coupled
• Each part of the chain implies
limits and opportunities.
The MGH/MIT/HMS Athinoula A. Martinos Center
HyperVision, Inc.
Robert Savoy
This concludes...
The MGH/MIT/HMS Athinoula A. Martinos Center
HyperVision, Inc.
Robert Savoy