Ding Nie

A Method to Investigate Structural-Functional Correlations in the Default Mode and other

Networks: Applied to Schizophrenia

12/16/2009 1/22

Overview Motivation Default mode network Methods

Computing structural gray matter maps Computing functional maps using ICA Correlation analysis

Results ICA maps of interest Histogram of correlations Spatial map results

Discussion Future work

12/16/2009 2/22

Motivation

Structural magnetic resonance imaging (sMRI) and functional magnetic resonance imaging (fMRI) analyses are typically performed separately

Previous studies only examine the localized correlation between sMRI and fMRI

Previous research do not explore inter-correlations of structural & functional data across the whole brain

In our recent study we introduced methods to explore structural-functional correlations across the whole brain [1]

[1] A. Michael, S. Baum, T. White, O. Demirci, N. C. Andreasen, J. M. Segall, R. E. Jung, G. D. Pearlson, V. P. Clark, R. L. Gollub, S.

C. Schulz, J. Roffmann, K. O. Lim, B. C. Ho, H. J. Bockholt, and V. D. Calhoun, "Does Function Follow Form?: Methods to Fuse

Structural and Functional Brain Images Show Decreased Linkage in Schizophrenia," NeuroImage, In Press.

Main Result from that Study

In this study we investigated the interconnection of task-related fMRI data and gray matter volumes across the whole brain

Used GLM method to construct the task related functional activation map

From the histogram of structural-functional correlations it was seen that linkage between strucure and function was weaker in schizophrenia patients (SZ) than healthy controls (HC)

In this study we are interested in the structural linkages to the default mode network (DMN)

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Gray Matter Correlation with Sensory Motor Task (HC - SZ)

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Gray Matter Correlation with Sensory Motor Task

HC

SZ

-1.0 -0.8 -0.6 -0.4 -0.2 0.0 +0.2 +0.4 +0.6 +0.8 +1.0

Correlation

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(b)HC - SZ

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Gray Matter Correlation with Sensory Motor Task (HC - SZ)

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Gray Matter Correlation with Sensory Motor Task

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Gray Matter Correlation with Sensory Motor Task (HC - SZ)

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Gray Matter Correlation with Sensory Motor Task

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SZ

-1.0 -0.8 -0.6 -0.4 -0.2 0.0 +0.2 +0.4 +0.6 +0.8 +1.0

Correlation

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Gray Matter Correlation with Sensory Motor Task (HC - SZ)

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Gray Matter Correlation with Sensory Motor Task

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SZ

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Correlation

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(b)HC - SZ

12/16/2009 4/22

Default Mode Network (DMN)

Comprises regions more active during rest than during tasks

Thought as task-independent components and decreases in activity while the brain engages in a task

In this study we explore if structural-functional correlations differences exist between HC and SZ in the DMN

[2] Marcus E. Raichle, Ann Mary MacLeod, Abraham Z. Snyder, William J. Powers, Debra A. Gusnard, and Gordon L. Shulman, " A

default mode of brain function," Proc. Natl. Acad. Sci. U. S. A. 98, 676–682.

Methods Participants

Four different sites: IA, MA, MN, NM

sMRI Image Acquisition

fMRI Image Acquisition

n Age Education SES

HC 70 (50m, 20f) 34 ± 11 yrs 15 ± 3 yrs 2.4 ± 0.7

SZ 70 (57m, 13f) 35 ± 11 yrs 13 ± 3 yrs 2.7 ± 1.1

Scanner TR TE FOV Voxel

Siemens 1.5 T 12ms 4.76ms 161mm 0.63x0.63x1.5 mm3

12/16/2009 6/22

Scanner TR TE FOV Voxel Gap

Siemens 3 T 2s 30ms 22cm 3.4x3.4x4 mm3 1 mm

sMRI Preprocessing

sMRI Images brain tissue distribution

Gray matter (GM) White matter (WM) CSF

Template

Smooth Normalize

SPM used for preprocessing

12/16/2009 7/22

Find default mode

Motion Correction

1 2

Functional Images

Time 1 2 … 3

(secs)

Phase Fix

1 2 3

0s .66s .33s

Normalize

Template

Smooth

fMRI Preprocessing

group ICA used for preprocessing

Group ICA

84 81 78 75 72 69 66 63

60 57 54 51 48 45 42 39

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RL

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Scans

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nal U

nits

IC 11

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00.20.4

IC 12

-0.200.2

IC 17

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IC 18

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R L

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7.6 Scans

12/16/2009 8/22

fMRI Task

Novel (complex sound)

OFF (16s)

200ms

Standard (1 kHz)

Mean ISI = 1200ms

Target (1.2 kHz) (a) AOD

LEARN 5 3 6 1 9

4 * 7 * 9

* * 3 * *

3 2 8

…

3 6 1 9

+ 3

Encode (6s) Recognize (38s) Fixate

2s 1s

Or 1.1s 0.6-2.4s

4-20s

ON (38s)

(b) SIRP ON (16s) ON

Pitch

0.2s 0.5s

(c) SM

Novel (complex sound)

OFF (16s)

200ms

Standard (1 kHz)

Mean ISI = 1200ms

Target (1.2 kHz) (a) AOD

LEARN 5 3 6 1 9

4 * 7 * 9

* * 3 * *

3 2 8

…

3 6 1 9

+ 3

Encode (6s) Recognize (38s) Fixate

2s 1s

Or 1.1s 0.6-2.4s

4-20s

ON (38s)

(b) SIRP ON (16s) ON

Pitch

0.2s 0.5s

(c) SM

fMRI Independent components of a sensorimotor task

Sensorimotor: A motor response for a sensory stimulus

Sensory stimuli

Auditory tones

Eight different pitched tones

Ascending and descending

Motor response

Right thumb button Press

On-Off blocks (16s)

Sensorimotor Task Time Course

12/16/2009 1/22

Group ICA

Evaluate time course of the functional data

Use multiple regression to show the beta weights of each subject on each component and on the task time course

: time course for individual subjects

: time course for each component

Save the beta values in two 70×1 matrices of HC and SZ for each component of interest

1 1i i p pi iy x x [3] D. Kim, D. Mathalon, J. M. Ford, M. Mannell, J. Turner, G. Brown, A. Belger, R. L. Gollub, J. Lauriello, C. G. Wible, D. O'Leary, K.

Lim, S. Potkin, and V. D. Calhoun, "Auditory Oddball Deficits in Schizophrenia: An Independent Component Analysis of the fMRI

Multisite Function BIRN Study," Schizophr Bull, vol. 35, pp. 67-81, 2009.

12/16/2009 10/22

iyix

Beta-Structure Correlation Analysis How all voxels from sMRI correlate to each functional component

Threshold 91×109×91-voxel sMRI data using mask to exclude CSF, skull and non-brain region, reducing the number of voxels to N 199k voxels

The correlation matrix RSF is 1×N, N: # of brain voxels

Interpret the correlation matrix using histogram and spatial map

Compare this with previous results

RSF

cov( , )

i

ii

X B

X B

Voxels (N)

Sub

ject

sSu

bje

cts

Structure (S)Structure Voxels (N)

Beta Value (B)

i SF correlationiX

12/16/2009 11/22

sMRI-fMRI Correlation Histogram For each component of interest, draw the histogram of RSF for HC and SZ to

show the difference in each component

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N correlationsRSF

12/16/2009 12/22

sMRI-fMRI Correlation Spatial Map Each RSF contain number of elements equal to N (# of voxels)

Can be used to build a spatial map to see the spatial distribution of correlation

Compare the region with ICA results show the difference between HC and SZ

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N correlationsRSF

12/16/2009 13/22

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Task-Related Component

HC SZ HC-SZ -2.0

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Correlation with

task time Course

HC: p<1.2e-26

SZ: p<6.4e-25

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Default Mode 1

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Correlation with

task time Course

HC: p<3.2e-14

SZ: p<8.6e-09

HC SZ HC-SZ

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Default Mode 2

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Correlation with

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HC: p<3.2e-07

SZ: p<5.9e-04

HC SZ HC-SZ

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Another Component of Interest

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Correlation with

task time Course

HC: p<1.6e-06

SZ: p<1.4e-08

HC SZ HC-SZ

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Discussion: Histogram of Correlations

Individual histograms: HC & SZ, difference in all four components

Difference histogram

More negative correlations in SZ than HC; more positive correlations in HC than SZ: Task-related component Default mode 1 Another component of interest

Linkage between Gray matter and functional activity higher in HC than SZ : Default mode 2

12/16/2009 18/22

Discussion: Spatial Map Results

Spatial map shows HC has more positive regions than SZ in all four components

Regions in the cerebellum show more positive correlation in HC than SZ in three components: Task-related component Default mode 1 Another component of interest

The hot region in HC-SZ map does not overlap with functional brain region

12/16/2009 19/22

Preliminary Results: Brain Regions

Task-Related Component

Default Mode Component 1

Default Mode Component 2

Other Component of Interest

HC-SZ>0

Cerebellum Posterior Cerebellum Middle Parietal Lobe Anterior Cerebellum

Middle Occipital Lobe

Posterior Frontal Lobe Middle Frontal Lobe Posterior Cerebellum

Middle Frontal Lobe Anterior Temporal Lobe Posterior Occipital Lobe

Middle Temporal Lobe

Anterior Parietal

HC-SZ<0

Middle Cerebellum Middle Cerebellum Middle Temporal Lobe Middle Cerebellum

Middle Frontal Lobe Posterior Parietal Lobe Anterior Frontal Lobe

Posterior Frontal Lobe

12/16/2009 20/22

Future Works

Explore the effects of outliers in the subjects:

Bootstrap

Compute statistical significance of results

Identify differential brain regions and implication to

schizophrenia

Identify correlations with white matter

12/16/2009 21/22

Thank you!