Sonia Poltoratski Vanderbilt University fMRI. crippling depression unbridled joy intro psych what is...
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Sonia Poltoratski Vanderbilt University fMRI
Sonia Poltoratski Vanderbilt University fMRI. crippling depression unbridled joy intro psych what is BOLD? data analysis...is the wild wild west knowledge
crippling depression unbridled joy intro psych what is BOLD?
data analysis...is the wild wild west knowledge brain pictur e
Slide 3
Outline: MR Physics BOLD signal Basics of Analysis Evolution
Good & Bad Practices
Slide 4
MR Physics MR in humans = proton nuclear magnetic resonance,
which detects the presence of hydrogen nuclei Since the single
proton of hydrogen in unbalanced, normal thermal energy causes it
to spin about itself electron + - proton
Slide 5
Spins The protons positive charge generates an electrical
current In a magnetic field, this loop current induces torque,
called the magnetic moment () The protons odd-numbered atomic mass
gives it an angular momentum (J) proton + + + + + + + + + + J
Slide 6
Net magnetization (M) Negligible under normal conditions
Slide 7
magnetic field B0B0
Slide 8
Proton Precession Spinning objects respond to applied forces by
moving their axes perpendicular to the applied force
Slide 9
Proton Precession Spinning objects respond to applied forces by
moving their axes perpendicular to the applied force magnetic field
precession axis spin axis
Slide 10
Proton Precession magnetic field parallel state (low energy
level) anti-parallel state (high energy level)
Slide 11
Net Magnetization (M) magnetic field M longitudinal
transverse
Slide 12
Net Magnetization (M) Increasing magnetic field increase in net
magnetization magnetic field strength energy high energy state low
energy state E The Zeeman Effect
Slide 13
Signal Generation magnetic field B 0 photons: electromagnetic
fields oscillating at the resonate (Larmor) frequency of hydrogen
excitation B 1
Slide 14
Signal Generation: Net M magnetic field B 0 excitation B 1 M
flip angle
Slide 15
Signal Reception magnetic field B 0 decaying, time-varying
signal that depends on the molecular environment of the spins
reception
Slide 16
Signal Reception T 1 recovery (longitudinal relaxation):
Individual spins return to their low-energy state, and net M
becomes again parallel to the main field T 2 decay (transverse
relaxation): Immediately after excitation, spins precess in phase
This coherence is gradually lost Images depict the spatial
distribution of these properties - BOLD
Slide 17
T1 Relaxation Times Fat Grey Matter CSF White Matter
Slide 18
T2 Decay Times Fat White Matter Grey Matter CSF
Slide 19
Image Formation Magnetic gradient: spatially varying magnetic
field Adding a second gradient field causes spins at different
locations to precess at different frequencies in a predictable
manner Paul C. Lauterbur and Sir Peter Mansfield at the 2003 Nobel
Prize Ceremony
Slide 20
Image Formation longitudinal magnetization transverse
magnetization acquired MR signal in k- space 2D MR image slice
excitation 2D spatial encoding 2D inverse Fourier transform
Slide 21
Slice Excitation slice direction resonant frequency vs.
position
Slide 22
Slice Excitation slice direction frequency range of RF pulse
excited slice resonant frequency vs. position when gradient is
applied
Slide 23
Spatial Encoding A gradient field that differs along two
dimensions results in a unique frequency assigned to each location
in the space, influencing the locations spin phase Phase encoding
gradient: turned on before data acquisition so that spins
accumulate differential phase offset over space Frequency encoding
gradient: turned on during data acquisition so that the frequency
of spin precession changes over space Resulting data is in units of
spatial frequency, which can be converted into units of distance
via inverse Fourier transform Echo Planar Imaging (EPI) allows us
to collect an entire imagine in milliseconds, either following 1
excitation (single-shot) or several (multi-shot) 2D
Slide 24
T1-Weighted ImageT2-Weighted Image
Slide 25
Pop Quiz! MRI data acquisition The experimental data were
collected at the Vanderbilt University Institute for Imaging
Science using a 3T Philips Intera Achieva MRI scanner with an
eight-channel head coil. The functional data were acquired using
standard gradient-echo echoplanar T2*-weighted imaging with 28
slices, aligned approximately perpendicular to the calcarine sulcus
and covering the entire occipital lobe as well as the posterior
parietal and posterior temporal cortex (TR, 2 s; TE, 35 ms; flip
angle, 80; FOV, 192 x 192; slice thickness 3 mm with no gap;
in-plane resolution, 3 x 3 mm). In addition to the functional
images, we collected a T1-weighted anatomical image for every
subject (1 mm isotropic voxels). A custom bite bar system was used
to minimize the subjects head motion. Keitzmann, Swisher, Konig,
& Tong (2012)
Slide 26
Pop Quiz! MRI data acquisition The experimental data were
collected at the Vanderbilt University Institute for Imaging
Science using a 3T Philips Intera Achieva MRI scanner with an
eight-channel head coil. The functional data were acquired using
standard gradient-echo echoplanar T2*-weighted imaging with 28
slices, aligned approximately perpendicular to the calcarine sulcus
and covering the entire occipital lobe as well as the posterior
parietal and posterior temporal cortex (TR, 2 s; TE, 35 ms; flip
angle, 80; FOV, 192 x 192; slice thickness 3 mm with no gap;
in-plane resolution, 3 x 3 mm). In addition to the functional
images, we collected a T1-weighted anatomical image for every
subject (1 mm isotropic voxels). A custom bite bar system was used
to minimize the subjects head motion. Keitzmann, Swisher, Konig,
& Tong (2012)
Slide 27
Outline: MR Physics BOLD signal Basics of Analysis Evolution
Good & Bad Practices
Slide 28
BOLD signal Blood-Oxygen-Level-Dependent Contrast (Thulborn et
al., 1982; Ogawa, 1990) Oxygenated Hemoglobin Diamagnetic (no
unpaired electrons or magnetic moment) Deoxygenated Hemoglobin
Paramagnetic (significant magnetic moment) 20% greater magnetic
susceptibility, which impacts T2 decay
Slide 29
BOLD signal Blood-Oxygen-Level-Dependent Contrast (Thulborn et
al., 1982; Ogawa, 1990) Oxygenated Hemoglobin Diamagnetic (no
unpaired electrons or magnetic moment) Deoxygenated Hemoglobin
Paramagnetic (significant magnetic moment) 20% greater magnetic
susceptibility, which impacts T2 decay The more deoxygenated blood
is present, the shorter the T2 Difference emerges at ~ 1.5T
Slide 30
Ogawa (1990) Blood oxygen content in rodents reflected in
T2-weighted images Metabolic demand for oxygen (confirmed by
concurrent EEG) is necessary for BOLD contrast During an MRI
experiment with an anesthetized mouse, I saw most of the dark lines
disappear when the breathing air was switched to pure O 2 in order
to rescue the mouse as it appeared to start choking. This
observation rang a bell.
Slide 31
fMRI vs. Other Methods log size log time brain map column layer
neuron dendrite synapse millisecond second minute hour day MEG
& ERP Optical Imaging TMS fMRI PET Induced Lesions Natural
Lesions Multi-unit recording Single Unit Patch Clamp Light
Microscopy
Slide 32
Outline: MR Physics BOLD signal Basics of Analysis Evolution
Good & Bad Practices
Slide 33
Voxels 1mm x 1mm x 1.5mm voxels7mm x 7mm x 10mm voxels (Smith,
2004)
Slide 34
Preprocessing Stages Slice-timing correction: correcting for
differences in acquisition times within a TR Motion correction:
re-alignment of images across the session Spatial smoothing:
blurring of neighboring data points, akin to low-pass
filtering.
Slide 35
Preprocessing Stages Mean intensity adjustment: normalization
of signal to account for global drifts over time Temporal high-pass
filtering: removal of low-frequency drifts in time course
Slide 36
Hemodynamic Response Function percent MR signal change time (s)
stimulus peak initial dip undershoot -10 -5 0 5 10 15 20 25
Slide 37
Modeling the Waveform HRF block design fit this model to the
time series of each voxel
Slide 38
General Linear Modeling Y = X. + observed data at a single
voxel design matrix estimated parameters error test if the slope of
is different from zero
Slide 39
t stat at each voxel anatomical scan image = my FFA!
Slide 40
Outline: MR Physics BOLD signal Basics of Analysis Evolution
Good & Bad Practices
Slide 41
Nature (2012)
Slide 42
Voxel Resolution Kanwisher, McDermott, & Chun (1997): 3.25
x 3.25 x 6 mm McGugin et al. (2013): 1.25 x 1.25 x 1.25 mm
Slide 43
TR Duration (Tong Lab data) 7Tesla, TR = 200ms (not my)
unpublished data removed for web use
Slide 44
Outline: MR Physics BOLD signal Basics of Analysis Evolution
Good & Bad Practices
Slide 45
The Seductive Allure of Neuroimaging (Weisberg et al., J Cog
Neuro 2008) Non-experts judge explanations with neuroscience
information as more satisfying than explanations without
neuroscience, especially bad explanations.
Slide 46
The Nader Effect
Slide 47
Slide 48
Pitfalls in fMRI Study Design What is your contrast? What
conclusions can we draw from fMRI activation? Statistical Analysis
vs
Slide 49
Correcting for Multiple Comparisons (Bennett et al. 2010)
Slide 50
Puzzlingly High Correlations in fMRI Studies of Emotion,
Personality, & Social Cognition Vul et al. (2009) Noticed R
> 0.8 correlations, seemingly higher than possible under
constraints of fMRI and variability of personality measures
Non-independence error: Selecting a small number of voxels based on
some trait Only reporting the correlation of the trait to those
voxels 54% of surveyed papers, including those published in
Science, Nature, and Neuron Voodoo Correlations in Social
Neuroscience
Slide 51
Pitfalls in fMRI Study Design What is your contrast? What
conclusions can we draw from fMRI activation? Statistical Analysis
Correction for Multiple Comparisons Independently-selected ROIs
Software & Human Error Act carefully and critically at all
stages of fMRI research!
Slide 52
The Finer Things in fMRI Event-Related Design fMRI-A:
Adaptation Multi-Voxel Pattern Analysis
Slide 53
Event Related Design Allows us to mix events of different
types, avoiding effects related to blocking Events can be
categorized or defined post-hoc based on subjects responses In slow
ERD, the BOLD response is allowed to return to baseline between
events block design event-related design
Slide 54
Rapid Event Related Design events: individual HRFs: summed
HRFs: (BAD)
Slide 55
Rapid Event Related Design events: individual HRFs: summed
HRFs: (GOOD) jittered order & ISI
Slide 56
fMRI-A: Adaptation 1. Neuronal population is adapted by
repetition of a stimulus 2. Some property of the stimulus is
changed 3. Recovery from adaptation is assessed: Signal remains
adapted = neurons are invariant Signal recovers = neurons are
sensitive to the changed property (Grill-Spector & Malach,
2001) The resolution of fMRI makes it difficult to distinguish
between homogenous and heterogenous populations:
Slide 57
Example: Face Viewpoint Invariance Adapt to identical
viewChange the property of interest (Grill-Spector & Malach,
2001) In both cases, signal is reducedIn (L) case, signal
recovers
Multi-Voxel Pattern Analysis AKA: fMRI decoding, MVPA,
multivariate analysis In univariate analysis described so far, we:
Assume independence of each voxel Test whether each voxel responds
more to one condition than the other MVPA is designed to test
whether 2+ conditions can be distinguished based on activity
pattern in a set of voxels Critically, MVPA can sometimes identify
differences in conditions when average activity is equal (review:
Pratte & Tong, 2012)
Slide 60
Multi-Voxel Pattern Analysis (review: Norman et al., 2006)
a.Subjects view stimuli from two categories & feature selective
voxels are selected b.Data is divided into training and test runs;
Training voxel patterns are decomposed and tagged by category
c.Training runs are input to a classifier function d.The classifier
defines a multi- dimensional decision boundary, and category
membership for the test run is predicted