10/1/2012

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ssss s
Xin Di, PhD
Suril Gohel
UMDNJ-New Jersey Medical school
Contents
An example data - by Dr. Yu-Feng Zang
Resting-state: eye open vs. eye close
Data analysis
Prepare Data for analysis
Preprocessing
Device and Employ methods to Test hypothesis
Local properties
Connectivity
Test the Hypothesis and nfer Results
Group inference
ExampIe data set
Eye open/Eye closed data from ND
(http://fcon_1000.projects.nitrc.org/indi/retro/BeijingEOEC.html)
24 Subjects
Eye open, 6min, 240 images
Eye close, 6min, 240 images
TR 2 second, Voxel size: 3.13.13.5 mm
Anatomical SPGR image (MPRAGE mage)
Specific to resting-state fMR
Similar to task fMR
Generally is not needed
Image preprocessing
Slice timing
Motion correction
Spatial processing
Spatial normalization
Spatial smoothing
Temporal processing
Noise removal
Filtering
Global ntensity
normalization/Global
Regression
TemporaI processing
Noise removal
Physiological noises
Head motion
Filtering
Usually 0.01 0.08 Hz
Global ntensity
normalization/Global
regression
Physiological noises
o Cardiac
o Respiratory
TemporaI processing
Noise removal
Physiological noises
Head motion
Filtering
Usually 0.01 0.08 Hz
Global ntensity
normalization/Global
regression
WM/CSF Signal
o High probability threshold
p > 0.99 not p > 0.5
o Use eroded WM/CSF masks
o Use unsmoothed fMR data
o Mean time course or principle
components (Chai et al., 2012)
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TemporaI processing
Noise removal
Physiological noises
Head motion
Filtering
Usually 0.01 0.08 Hz
Global ntensity
normalization/Global
regression
Head motion
o Six rigid-body motion
parameters (translation and
rotation)
o Or their derivatives??
TemporaI processing
Noise removal
Physiological noises
Head motion
Filtering
Usually 0.01 0.08 Hz
Global ntensity
normalization/Global
regression
Global ntensity
normalization/Global
Regression
Will introduce negative
correlations (Murphy et al.,
2009)
NEVER!
Time series preprocessing
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Raw time course Regress out covariates Band-pass filtering
First 5 PCs of WM First 5 PCs of CSF Motion parameters
Hypothesis
Experiment
Eye open vs. Eye close
Goal
Functional specification
Local properties
Functional integration
Connectivity
LocaI properties
Time-domain Properties
Standard deviation (Biswal et al., 2007)
Frequency-domain Properties
Amplitude of Low-Frequency Fluctuation (ALFF, Zang et al.,
2007)
Fractional Amplitude of Low-Frequency Fluctuation (fALFF, Zou
et al., 2008)
Homogenous Properties
Regional Homogeneity (ReHo, Zang et al., 2004)
Fractal Properties
Hurst exponent (Bullmore et al., 2004)
Measuring IocaI properties
ALFF (Zang et al., 2007)
Band-Pass Filtering
Fourier transform
Square root
Average across 0.01 - 0.08
Hz - ALFF
Divided by global mean
mALFF
Divided by whole spectrum -
fALFF (Zou et al., 2008)
Zang et al., 2007
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Measuring IocaI properties
ReHo (Zang et al., 2004)
Local similarity
Kendall's coefficient of
concordance (KCC)
==
( R
i
)
2
~ n( R)
2
1
12
K
2
( n
3
~ n)
7 19 27
CaIcuIating ALFF/fALFF/ReHo
Detrend
deal temporal filtering
(0.01-0.08 Hz)
Calculating
ALFF/mALFF
fALFF/mfALFF
ReHo/mReHo
Resting-State fMR Data Analysis
Toolkit (http://www.restfmri.net/)
mfALFF
mReHo
mALFF
SingIe subject maps
Eye open Eye close
Group inference
Whether the effects are
reliable across subject?
Whether the effects are
different between two
groups?
Whether the effects are
different between
conditions?
More than two
groups/conditions
One-sample t-test
Two-sample t-test
Paired t-test
(repeated measure) ANOVA
Group inference
Group differences
Covariates
Global scaling
Mask (absolute mask or
whole brain mask)
Design matrix
Groups Effects of no interest
Group inference
Within-subject effects
Covariates
Global scaling
Mask (absolute mask or
whole brain mask)
Design matrix
Conditions Subjects
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eye close
> eye open
eye open
> eye close
Group inference
mALFF mfALFF mReHo
p < 0.001, cluster level FDR p < 0.05
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p < 0.001
k > 10
Measuring connectivity
Functional connectivity
Correlation
Mutual information
Effective connectivity
Granger causality
Dynamic causal model
A B
A B
Measuring connectivity
RO-based analysis
Simple
Need strong hypothesis
Selectivity problem
?
Measuring connectivity
Seed-based correlation
Less strong hypothesis
Exploratory
Specificity
Correlation maps might be
affected by seed selection
?
Measuring connectivity
Spatial independent
component analysis (CA)
Pure data-driven
Complicated algorithm
Explaining the results with
caution
Seed-based correIation
Defining ROs
Local differences (ALFF differences.)
Structural (AAL, Brodmann's area.)
Previous study (Coordinates)
Meta-analysis (Activation likelihood estimation .)
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Seed-based correIation
Covariates
Motion parameters
(translation, rotation,
derivatives...)
White matter, CSF (mean,
PCA princomp)
Global signal (NEVER!)
High-pass filter (1/100 Hz)
Series correlation (AR(1)?)
Design matrix
Seed WM CSF Motion Constant
Left
Visual
Seed-based correIation
Right
Visual
PCC
Seed
Eye open Eye close
Single subject maps
eye close
> eye open
eye open
> eye close
Seed-based correIation
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L. visual seed R. visual seed PCC seed
p < 0.001, cluster level FDR p < 0.05
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Group level analysis
SpatiaI ICA
Melodic in FSL
GFT in MATLAB
ssues
Run CA together or
separately?
Number of components?
Cole et al., 2010
Left
Executive
Motor
Higher
Visual
Right
Executive
DMN 1
st
Visual
IC maps aItogether
Primary
visual C
IndividuaI IC Maps
Higher
visual C
DMN C
Eye open Eye close
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eye close
> eye open
eye open
> eye close
Condition differences
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1
st
Visual C Higher Visual C DMN C
p < 0.001, cluster level FDR p < 0.05
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ResuIts summary
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Convergent results in higher visual area
Higher ALFF Higher ReHo
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Higher connectivity
with right visual RO
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Primary Visual
C activity
Summary remarks
Design is simple. Analysis is flexible.
Take care of physiological noises
Reporting analysis procedures in detail
Be careful when using global signal regression
Take care of multiple comparison problem
Not only multiple voxels, but also multiple Cs, and multiple
seeds.
References
ALFF: Zang YF, He Y, Zhu CZ, Cao QJ, Sui MQ, Liang M, Tian LX, Jiang TZ, Wang YF, (2007).
Altered baseline brain activity in children with ADHD revealed by resting-state functional MR.
Brain Dev 29(2):83-91.
fALFF: Zou QH, Zhu CZ, Yang Y, Zuo XN, Long XY, Cao QJ, Wang YF, Zang YF, (2008). An
improved approach to detection of amplitude of low-frequency fluctuation (ALFF) for resting-state
fMR: fractional ALFF. J Neurosci Methods172(1):137-41.
Reho: Zang Y, Jiang T, Lu Y, He Y, Tian L, (2004). Regional homogeneity approach to fMR data
analysis. Neuroimage22(1):394-400.
Seed-based correlation: Biswal B, Yetkin FZ, Haughton VM, Hyde JS, (1995). Functional
connectivity in the motor cortex of resting human brain using echo-planar MR. Magn Reson
Med34(4):537-41.
Seed-based correlation: Cordes D, Haughton VM, Arfanakis K, Wendt GJ, Turski PA, Moritz CH,
Quigley MA, Meyerand ME, (2000). Mapping functionally related regions of brain with functional
connectivity MR imaging. AJNR Am J Neuroradiol 21(9):1636-44.
CA: Beckmann CF, DeLuca M, Devlin JT, Smith SM, (2005). nvestigations into resting-state
connectivity using independent component analysis. Philos Trans R Soc Lond B Biol Sci
360(1457):1001-13.