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fMRI
sequentially
or
Field of View (FOV): extent of the brain that is inside the image
Slice thickness
Matrix size:
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Module 4
Psychological inference
reverse inference
probability of observing an activity
Reverse inference: Can we infer a psychological state given the brain activity
when people make reverse inferences they assume that there is high positive predictive
value (PPV)
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For a brain activation to have high PPV it must have high sensitivity and high specificity
Compute its sensitivity, specificity and positive and negative predictive values
Require testing many tasks, contexts
estimating eect sizes and predictive accuracy
testing assumptions
comparing evidence for dierent theories
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longitudinal component: parallel to the magnetic field
transverse component: perpendicular to the magnetic field
in the absence of an external magnetic field there is no net magnetization. the nuclei of
magnetic atoms are randomly oriented
when placed in a strong magnetic field there is a net longitudinal magnetization in the direction
of the field
The nuclei precess about the filed with an angular frequency determined by the Larmor
frequency
A radio Frequency pulse is to used to align the phase and tip over the nuclei.
Longitudinal relaxation: The restoration of net magnetization along the longitudinal direction
as spins return to their parallel state
When the RF is removed the longitudinal magnetization grows back to its original size and the
transverse component decreases
Transverse relaxation: loss of net magnetization in the transverse plane due to loss of phase
coherence
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T2* : combined eect of T2 and local inhomogeneities in the magnetic field. used to image
brain function
magnetic field gradient: we sequentially control the spatial inhomogeneity of the magnetic field,
meaning that we slightly change the field
The measurements that we make are the Fourier transform of the image we would like to
reconstruct
the measurements are acquired in the frequency domain (k-space)
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the better the spatial resolution the more k-space measurements I need to make (e.g. for 64 x
64 resolution I need 4096 measurements, meaning that I need to change the values of kx and
ky 4096 times.
spiral
the measured k-space data is complex valued
K-space
data is acquired in the k-space. By application of the inverse fourier transform we acquire an
image
there is not an one-to-one relationship between image and k-space. So each individual point in
an image space depends on all the points acquired in the k-space
if we are interested in the relative contribution of the high versus the low frequency waves in
the k-space, we select for one of the two
high frequency parts oscillate quickly and are responsible for detail in the picture. they
represent small structures whose size is on the same order as the voxel size (tissue
boundaries)
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low frequency parts (center of k-space) give the contrast. They represent parts of the object
that change is a slow manner
oxyhemoglobin is diamagnetic
Active neurons increase blood flow< decrease in deoxy-hemo< increase T2* weighted image
peak BOLD 4-6 s after activation: over-compensation in blood flow dilutes the concentration
of deoxy-hemo and the BOLD signal increases
properties of HRF:
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but does not always reflect changes in neuronal activity: e.g .blood steal phenomena
Signal to noise ratio (SNR): the strength of a signal divided by an estimate of noise variability
Contrast-to-noise (CNR): The dierence between two signals divided by an estimate of noise
variability
ways of calculation
spatial SNR: mean intensity within signal area of interest () divided by standard
deviation outside signal area ().
spatial CNR : dierence in intensity between two tissue types divided by the variability
of measurements (1-2)/1,2
temporal SNR (or functional SNR): mean signal across time divided by variability (i.e.
standard deviation) across time. /
Temporal CNR (or signal sensitivity)
Scaling:
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depends on
2. acquisition parameters
3. tissue type
implications
refractory eects
saturation: reductions in amplitude of a response as a function of inter-stimulus
intervals
high frequency spikes
image distortions
periodic fluctuations
slow drift across time
1. acquisition
2. Analysis:
Issues to check:
1. coverage
2. RF noise and malformed images
3. Transient gradient artifacts/spikes
4. Ghosting
5. dropout
6. task-correlated movement
drift: slow changes in voxel intensity over time. low frequency noise
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main reason: scanner instabilities
but
aliasing: if TR is too low. periodic signals that occur more rapidly than the sampling rate will
often be aliased back to lower frequencies.
to avoid aliasing we must sample at least twice as fast as the fastest frequency in the signal
functional maps
functional column
large-scale networks
BOLD point-spread function: related to microvasculature bed area aected by local neuronal
activity and venous/arterial flow contributions
why?
artifacts
inter-subject normalization
spatial alignement
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hyper acuity: the patter of activity across voxels may contain more info than any one voxel
can sometimes detect functional topography even if voxels are not small enough
to fit within one functional area
even if neurons are randomly intermixed MVPA may still identify patterns that are dierentially
associated with each
the classification of neuronal activation for events types is still possible because patterns of
activation for events are uncorrelated
Temporal Resolution
limited in fMRI
onset: 2-3 s
Temporal hyperacuity:
E.g. examining brain activation upon presentation of famous vs non famous faces. We present
a block of famous faces and after a while a block of non famous faces
Rule of thumb: two condition block design with 16-20 sec blocks maximize power
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Goal: induce human subject to do or experience the psychological states you are studying
Considerations:
Predictability influences psychological state. the predictability of a stimulus influences
how fast someone responds to it
3. Participant strategy
dierent stimuli configurations aord dierent strategies. e.g stroop test: compatible
(the word and the colour are the same) vs
incompatible trials.
you can not block compatible and incompatible trials
E.g recall happy vs sad memories. people cant switch back and forth from sad faces
Kinds of Designs
Design
Trial Structure
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Basic principle: designing a study that is powerful for one purpose vs designing a study for
many purposes
1. within factors
2. within-levels of factors
within observed variables (e.g. peoples performance)
between-person variables:
between factors
between levels
between observed
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Examples
look at negative and neutral pictures
condition A: just look at them
condition B: look and reappraisal
Pure insertion principal: processes in complex conditions are simply added on top of
those in simpler, baseline conditions. Cognitive subtraction
E.g. brain- behavior correlation: correlate brain activity during A stimulus with
the level of the psychological state the stimulus is supposed to induced. E.g. brain activity
during reappraisal of negative stimuli vs level of psychological reappraisal.
Multiple subtraction: triangulate between event A and brain process by subtracting multiple
kinds of events
If the dierent conditions that we are subtracting o have the di
characteristics we can control for some of the drawbacks of pure
insertion.
E.g. compare brain activation at faces and brain activation with objects
and intact faces with scrubbed faces. this is to make sure that the FFA is
activated when someone sees a face and not other things
process overlap/dissociation
double dissociation: task A activates more than task B in one area and B
activated more than A in another area.
separate modifiability: task A activates one area but B not and vice versa
factorial design: view two factors at once and test of dissocciations in the area activated.
e.g task switching experiment:
factor 1: internal switch of attention between objects (2 levels)
factor 2: external switch of attention (2 levels)
2 x 2 factorial space
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enhance specificity
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2. check statistical assumptions and transform data to meet the assumptions
3. standardize the locations of brain regions across subjects to achieve validity and
sensitivity in group analysis
Steps:
principal component analysis
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Typically each slice is sampled at slightly dierent time points . e,g, the top of
the brain volume might be sample a second later than the bottom
slice time correction shifts each voxels time series so that they appear to have been sampled
simultaneously
slices 1, ,2 ,3 are
di time points
have di time
sampled at
so they
curves
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temporal interpolation: use info from near time points to estimate the amplitude of the MR
signal at the onset of each TR
use a linear, spline or sinc function
phase shift: slide the time course by applying a phase shift to the furrier transform of the time
course
Head motion:
when analyzing the time series associated with a voxel we assume that it depicts the same
region of the brain at every point
and some target image
it involves 6 variable parameters. 3 sets of translation in the x,y direction and 3 sets of rotations
(6 DOF).
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Warping
Transformations where the equations relating the coordinated of the image are non-linear
Co-registration
the functional and structural images do not have the same signal intensity in the same areas so
they cannot be subtracted
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the structural MRI image used in the coregistration is wrapped onto a template image
Talairach space
based on a single subject , on a single hemisphere
Montreal Neurological Institute: combination of many subjects but right handed only
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matched filter theorem: a filter that is matched to the signal will give optimum signal to noise
typically the amount of smoothing is chose airport and is idependent to the data
so
Non-stationary spatial Gaussian Markov random field
smoothing varies across space and time
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1. within subject
2. across subjects
do it in stages
The GLM approach treats the data as a linear combination of model functions (predictors) plus
noise (error)
the model functions have known shapes (lines, curve) but unknown amplitudes
simple regression
anova
Multiple regression
mixed eects/hierarchical
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in most cases there is a closed form solution while others require iterative solutions
Simple regression
one prediction one outcome
Step 1: specify the model: there is a linear relationship between the predictor and the outcome
Step 3: Statistical inference: test slope and get a p value: how likely is that i have observed this
slope under the null hypothesis
paired t test
each measure is not independent
from the previous one
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within subjects
between groups
do it in stages
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estimate of how large the dierence in activation is between famous and nonferrous
faces
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hemodynamic delay: BOLD responses are delayed and dispersed relative to neural activity
x (t)= v(h(t))
x(t): fMRI signal over time
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event-related design:
one regression for each condition
their average
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Contrast: linear combination of GLM parameters
T-contrast: single, planned contrast > t test
Specified by a vector of weights (c) so that cT= a scalar value
signed: positive and negative values
columns are applied independently
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factor 2
2. the scaling aects the magnitudes but not the inferences I make (t, p values)
Contrast weights must be
all participants. so no
runs
Exception: I can test the average of one or more conditions against the implicit
baseline
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2. HRF is correct
The HRF shape depends both on the vasculature and the time course of neuronal activity
bottom right:
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FIR model
and so on
so 4 predictors
1. accuracy(bias): can the model capture the true response without systematic
variance?
2. precision(variance): are the model parameters estimated with littles error variance?
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bias/variance tradeo
1. simple:
few parameters so high precisions
parameters are interpretable measures of neuroscientific interest
3. Accurate in ways that count:captures the true response amplitude int he
physiological range
Examples:
signal drift
physiological artifacts (e.g.
respiration)
head motion
Drift
slow changes in voxel-intensity over time
due to scanner instabilities
1 corresponds to task
2. baseline
Physiological Noise
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Respiration and heart beat give rise to periodic noise often alliased into task frequencies
the sampling rate must be twice as big as the frequency of the curve you seek to model
Head Motion
Basic motion correction in the pre-processing stages takes into account gross dierences bet
Scrubbing: drop images with high movement estimates. treat as missing data
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how to estimate ?
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GLM Estimation
t
the desired line is the line that makes the square of the residuals e1, e2, e3 as small as
possible
Q= (Y-X) (-)
taking the derivative with respect to and setting it to 0 gives us the normal equations:
XX(hat)=XY
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Properties:
that means that any other unbiased estimator of beta will have a larger variance that the OLS
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Noise Models
is not typically the identity matrix because fMRI data typically exhibit significant
autocorrelation caused by physiological noise and drift that has not bee appropriately modeled
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the autocorrelation is equal to 1 if the lag is 0. However if we have a lag of one time point the
autocorrelation is equal to and decays as we move further
Iterative Procedure
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Inference, Contrast and t-tests
After fitting the GLM we use the estimated parameters to determine whether there is significant
activation present in the voxel.
Contrasts
test whether linear combinations of parameters are significant
0 for 1
1 for 2
-1 for 3
in order to test the null hypothesis against the non null we use t statistics
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1. massive univariate approach: separate models are fixed to each voxel of the brain
Problems: many false alarms
Group-level
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Analysis I
Muti-level Analysis
fMRI experiments are often repeated for:
several runs in the same session
several sessions on the same subject
several subjects
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the most basic kind of group result is contrast values between task and control. Each dot is a
score for one subject
the spread between the dots reflects the variance of the data or the noise
Group Analysis II
Mixed-Eect Models
Hierarchical Models
a). measurement error
b) response magnitude
sex
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drug type
Random eects
subject
word (e.g. choose one positive words and one negative)
if eect is treated as fixed, error terms in model do not include variability across levels
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it assumed that the first level parameters are randomly sampled from a population of possible
regression parameters
Statistical techniques define the loss function that should be minimized in order to find the
parameters of interest
used techniques: minimize loss function, reduced minimized loss function
algorithms define the manner in which the chosen loss function is minimized
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1-2=0
Test statistic T :measures the compatibility between the null hypothesis and the data
P-value: probability that the test statistic would take a value as or more extreme than actually
observed if Ho is true
P(T>t| Ho)
Threshold u controls false positive rate at level
= P(T>|o)
The probability that the test statistic lies above that value is equal to value a
Errors:
1. Type I error: the null hypothesis is true but we mistakenly reject it (false positive)
Power of the test: probability that a hypothesis test will correctly reject a false null hypothesis
more than one hypotheses are performed so the the risk of making a single Type 1 error is
greater than the value for a single test.
the more tests one performs the greater the likelihood that he will perform a false positive
100.000 voxels with a 0.05 threshold will give us 5.000 false alarms
choosing a threshold is a balance between sensitivity (true positive) and specificity (true
negative)
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the probability of making one or more Type I errors in a family of tests under the null hypothesis
Bonferroni correction
In the FWER hypothesis, Ho states that there is no activation in any of the m voxels
If we reject a single voxel null hypothesis we reject the whole FWER hypothesis
we want to control the probability that any of the test statistics in any of the voxels is above
some value u
Bonferroni correction
m= total number of voxels
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if we have 10 hypothesis and we
want to control for the probability
that the sum of them is above 0.05
then we take the threshold for each
to be 0.005 (0.05/10)
it is based on approximating the distribution of the maximum statistic over the whole image
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has a Gaussian distribution at every point and every collection of points.
and so it is defined by its mean and covariance
approximate the upper tail of the maximum distribution which is the part needed to find
the appropriate thresholds and
account for spatial dependence
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no of holes
if we threshold at u=0.5 we get 27 bolbs (whites in the picture) and one hole (in one of the
bottom bolbs)
Euler characteristic =2
Euler characteristic=1
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Properties:
RFT assumptions
1. The entire image is either multivariate Gaussian or derived from multivariate Gaussian
images
2. The statistical image must be suciently smooth to approximate a continuous
random field
FWHM smoothness of 3-4 voxel sizes is preferable
FDR controls the proportion of false positives among all rejected tests
V: false positive
FWER=P(V>or = 1)
V: number of false positives
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FDR is 0 if R=0
A procedure controlling for FDR ensures that on average the FDR is no bigger than a prespecified rate q which lies between 0 and 1
anything below the black line is active and anything above is not active
Cluster-level inference
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combines info about the intensity (how big the t statistics are and how many voxels there are)
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Uncorrected thresholds: many studies use them especially when the sample size is small
because correcting for thresholds would decrease the power
Extent Threshold: use an arbitrary threshold and retain clusters of k contiguous active voxels
(e.g. p<0.001, 10 contingent voxels)
but problematic because false-positives are contiguous regions of multiple voxels due to
smoothness
the thresholds used are the default ones in each package (!)
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x2 is the predicted signal upon presentation of nonsense stimuli
1 is the predictor estimate which tells you how much the bold signal in one voxel increases in
response to sentences
2 is the predictor estimate that tells you how much the signal increases in response to
nonsense words
1 and 2 are weighted meaning that if a voxel responds more to words that nonsense
stimulation 1 should be greater than 2
1. find beta weights that best approximate a voxels signal
the best approximation is the one with less error
2. compare the beta weights for dierent predictors (sentences vs nonsense words)
the design matrix
the BOLD signal
we look for beta weights that give the best approximation that is the one the minimizes the
sum of the squared errors
in the GLM we include as predictors : six predictors for head motion and predictors for time
derivatives that enable us to shift our approximation one time point back or forward.
that is because not all participants have the same hemodynamic function
GLM
2. run a GLM (with the signal and the design matrix as input)
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significant values are those that have t values that are not random
fewer voxels deemed active compared to average eect analysis. Why? because it takes into
account between subject-variability
Smoothing:
simple smoothing by mean: replace the values of 10 voxels by the mean value
with a Gauss kernel: weighted average for each voxel, in relation to the neighbors
RPV image: shows rebel per voxel= smoothness of data in each voxel
Convolusion of HDR:
canonical HRF: same for all brain regions
temporally basis function: dierent HRF for dierent brain regions
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in the GLM framework the convolution of the stimulus function with each basis function is a
column in the design matrix
Finite Impulse response: one HRF for each event type in each voxel
1. canonical HRF: fixed HRF
2. canonical HRF+ temporal derivative
3. canonical HRF+ temporal derivative+ dispersion derivative
4. FIR
5. smooth FIR
six. Inverse Logit Model
parametric modulation: a stimulus is parametrically varied across repetitions and this might
be reflected in the neuronal response. they are used to model trial to trial variation
temporal autocorrelation:
nearby time-points are positively correlated because of
physiological noise
drift
Modeling of noise:
AR (p)
ARMA (1,1):