general introduction to functional mri - neurometrika€¦ · 17-10-2001 · neuroanatomy...

The MGH/MIT/HMS Athinoula A. Martinos Center Robert SavoyHyperVision, Inc.

Introduction to Physics, Physiology, Data Analysis, and

Experimental Design in fMRIfrom a Behavioral Science Perspective

Robert Savoy

General Introduction toFunctional MRI

A Broad Perspective 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 UniversityHyperVision, Inc, Lexington, MA

<[email protected]>



Before we start on fMRI design...

A few words about the “Big” issues

A few words MultiModal 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

Levels of ExplanationData SeparationAlgorithmic Separation



Approaches to Understanding the Human Brain

• Neurochemistry• Neuroanatomy• Neurophysiology

• Single and Multiple Cell Recordings

• Columnar Wiring• Brain Mapping• Psychology• Sociology

Levels of ExplanationData SeparationAlgorithmic Separation



MultiModal Imaging

DOTNIRS

PET

MEGEEG

Optical Microscopy

Intracranial Electrodes

TMSMRS

DTIDSI

High FieldMultiChannel

phMRI MRIComputational Neuroanatomy

functionalMRI

(a view oriented around MRI)



DOTNIRS

PET

MEGEEG

Optical Microscopy


TMSMRS

DTIDSI



functionalMRI

MultiModal Imaging and Approaches to Understanding the Human Brain

• Brain Mapping

• Psychology

• Sociology

• Neurophysiology• Single and Multiple

Cell Recordings

• Neuroanatomy

• Columnar Wiring

• Neurochemistry



MultiModal Imaging and Approaches to Understanding the Human Brain

• Brain Mapping

• Psychology

• Sociology

• Neurophysiology• Single and Multiple

Cell Recordings

• Neuroanatomy

• Columnar Wiring

• Neurochemistry

DOTNIRS

PET

MEGEEG

Optical Microscopy


TMSMRS

DTIDSI



functionalMRI



We will focus on fMRI, but...

Levels of ExplanationData Separation

Algorithmic Separation

PET

MEGEEG

Optical Microscopy


TMS

DOTNIRS

MRS

DTIDSI


phMRI MRI

Computational Neuroanatomy

functionalMRI

Integration Across ModalityAcross Function

Unity through Topic Simultaneous Data Acquisition

Ultimate Unity through Conceptual Integration and

Modeling of Brain Function



On to an introduction specific to Functional MRI


Personal Introduction• Thanks to many people...• My Eclectic background; Exptl. Psych.; Vision• General interests: 70% out? Integrating FNI data

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 Goals of this Workshop


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


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


NMR

MRI ExperimentalTask

ComparingBrains

Psycho-physiological

Laboratory

Data Analysis

Computersfor

Everything

Practicalities

Animal Brain MappingClinical Applications

Partial List of Other Modalities:Direct Stimulation • DOT • EEG • ERP

Lesions • MEG • Optical • PETStructural MRI • TES • TMS

FunctionalNeuroanatomy

Hemodynamics

ComputationalNeuroanatomy


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?


NMR

MRI ExperimentalTask

ComparingBrains

Psycho-physiological

Laboratory

Data Analysis

Practicalities

FunctionalNeuroanatomy

Hemodynamics

ComputationalNeuroanatomy

ExperimentalDesign


Basics of Functional MRI• Hemodynamics

• Roy and Sherrington• History• BOLD / Flow


First Examples with Humans


Basics of Functional MRI• Hemodynamics

• Roy and Sherrington• History• BOLD / Flow

• Instrumental Source of the Data• NMR• MRI• Contrast• Flexibility of Tool

"Inject Signal" (90° saturation rf-pulse)

Maximum Signal(minimal contrast)

Time

No Signal(no contrast)

8 Magnetic Fields and Relaxation


MRI In a SlideMRI in a Slide:

8 Magnetic Fields and Relaxation

01

x y z

12

■ To Obtain the NMR Signal: Three Magnetic Fields µ The magnetic field of a nucleus with spin B The main magnetic field, used to align nuclei B The radio-frequency field, used to flip nuclei

■ Relaxation: Two ways for the signal to go away T Longitudinal: The nuclei re-align with B T Transverse: The nuclei get out-of-phase

■ To Select Slices and Make Images: Three More Fields G , G , G The gradient fields

■ Shim Fields To make better images■ Shielding Fields To protect us from all of the above!

0


Singal Decays Expontntially

Signal decays exponentially

MaximumSignal Fading... Fading... Gone


Time


Different Rates of Decay


Time

Rate of decay varies across voxels


Faces Contrast for fMRIImage contrast varies with time


Maximum Signal(minimal contrast)

Time

No Signal(no contrast)

MaximumSignal

Time

(Little Contrast)

"Inject Signal"

(90° saturation rf-pulse)

MinimumSignal

(No Contrast)

IntermediateSignals

(Useful Contrasts)

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: signal decreases; imaging artifacts appear


Proton Density; T1-Weighted; T2-Weighted; MRA

contrast enhanced; 95%

dc

a b


Basics of Functional MRI

• Combining Hemodynamics and MRI

• Hemodynamics• Roy and Sherrington• History• BOLD / Flow

• Instrumental Source of the Data• NMR• MRI• Contrast• Flexibility of Tool


The Chain of IdeasIncreased Neural Activity

Increased Local Cerebral Blood Flow

Decreased DeoxyhemoglobinConcentration in Veins (BOLD)

Change in Magnetic Susceptibility

Change in NMR Signal


Deoxygenated blood attenuates signalin T2

*-weighted MR images

MRI volume element

O2

Figure from Rick Hoge


Decrease of Venous DeoxyhemoglobinConcentration During Increased Perfusion

O2

Figure from Rick Hoge


Close up on a few hydrogen nuclei, the Larmor frequencies of each, and how they add up

MRI volume element

O2

+ =

+ =


Basic Time Course of the Hemodynamic Response

Hemodynamic Delay and Dispersion

Neuronal Response

Time

Stimulus

1 sec

6-8 sec

Hemodynamic Response


20

20 seconds (60 - ε) seconds

ε =1000 msec

100 msec34 msec

Time (seconds) 8010 50

-0.5

0

0.5

1

1.5

2

2.5

15 20 25 30 35

PercentIncreasein MR Signal

Strength

1000 msec100 msec34 msec

Peak

Duration of Response to Very Brief Stimuli


Stimulus Duration: black: grey: white

Consisent latency (2 sec) to onset ofMR response

-0.5

0

0.5

1

1.5

2

2.5

15 20 25 30 35

PercentIncreasein MR Signal

Strength


Peak

Duration of Response to Very Brief Stimuli


Stimulus Duration: black: grey: white

Consisent latency (~2 sec) to onset ofMR response

Time (seconds)


Functional MRI is Complicated• Technology is Complicated

• Roy and Sherrington quotation


On the Regulation of the Blood-Supply of the BRAINC.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.


On the Regulation of the Blood-Supply of the BRAINC.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.



• Roy and Sherrington quotation • Good written resources are available (e.g., textbooks on fMRI)


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.


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. IadecolaNature 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.



• Link between neural activity and hemodynamics

• Experimental Design: A variety of techniques




Neuronal Response

Time

Stimulus

1 sec

6-8 sec



Neuronal Response

Stimulus

34-38 sec


30 sec Time


Buckner: Blocked/Spaced/RapidBlocked versus Mixed-Trial Paradigm

BLOCKED:

SPACED MIXED TRIAL:

RAPID MIXED TRIAL:




Neuronal Response

Time

Stimulus

1 sec

6-8 sec


b

a


Buckner: Blocked/Spaced/RapidBlocked versus Mixed-Trial Paradigm

BLOCKED:

SPACED MIXED TRIAL:

RAPID MIXED TRIAL:


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.


SPM: Statistical Parametric Mapping. (From the Department of Cognitive Neurology)



• 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


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 implieslimits and opportunities.


This concludes...

general introduction to functional mri - neurometrika€¦ · 17-10-2001 · neuroanatomy...

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