Differences in Brain
Connections and Structures
Michelle Deng, Ph.D., Postdoctoral Scholar
Cognitive Analysis & Brain imaging Laboratory
MIND Institute
University of California, Davis
ymdeng@ucdavis.edu
Chromosome 22q11.2 Deletion Syndrome Family Meeting
April 15, 2012
Monday, April 16, 2012
Atypical brains in children with
22q11.2DS Und
erst
a nd
DIFF
the
ERE
NCE
S
Monday, April 16, 2012
•
Atypical brains in children with
22q11.2DS
Some brain structures enlarged or reduced compared to TD
Middle of
the brain
•
•
•
differences in
neural connectivity
reduce gyrification
& cortical thickness
...
Karayiorgou et al. (2010) Nature Reviews
Srivastava et al. (2011) Human Brain Mapping
Monday, April 16, 2012
Limbic System & Hippocampus
•
Important structure in the
limbic system, involved in:
!
!
!
•
Hippocampus
memory
spatial processing
emotional processing
Linked to general
intelligent level in children
Schumann, C. M. et al. (2007) Hippocampus
•
Hippocampal – prefrontal
functional connectivity
impairments in 22q11.2DS
mice model Sigurdsson et. al. (2010)
Nature
Courtesy, Dr. Arthur W. Toga, Laboratory of Neuro Imaging at UCLA
Monday, April 16, 2012
Limbic System & Hippocampus
the primary output of
connections from
Fornix
hippocampus
How can we measure it
in the brain ??
How about
the structural
connectivity?
Courtesy, Dr. Arthur W. Toga, Laboratory of Neuro Imaging at UCLA
Monday, April 16, 2012
Diffusion Tensor Imaging
H2 O
free
movement
Monday, April 16, 2012
directional
movement
“see” the tracts !
Diffusion Tensor Imaging
DTI color-map
Front-Back
Left-Right
Top-Bottom
DTI - measure the movement of water molecules,
an indirect way to “see” the brain white matter fibers
Monday, April 16, 2012
Define Fornix in Individual Brain
Front
back
Draw a front seed
AA
Monday, April 16, 2012
Draw a back seed
B
Find the Fornix Connections
Front
•
Calculated the most likely
100,000 connections between
the front-back seeds.
•
Picked the top most likely
1,000 connections (1%)
back
A
C
Monday, April 16, 2012
D
Front
back
Fornix - Connections
Left
Fornix
Type1
Type2
from the
Front Seed
from the
Back Seed
“perfectly”
connected
connecting the
front-back
seeds
Monday, April 16, 2012
“tangled” with neighbor
fibers
Fornix - Connections
Type2
Type1
L
R
TD
(n=38)
22q
(n=45)
TD
(n=38)
22q
(n=45)
Monday, April 16, 2012
28 (74%)
8 (21%)
2 (5%)
21 (47%)
12 (27%)
6 (13%)
24 (63%)
13 (34%)
1 (3%)
22 (49%)
9 (20%)
< 50%
< 30%
12 (27%)
How well the fibers are organized ?
•
How can we “see” and measure it in the brain ?
fractional
anisotropy
FA
RD radial diffusivity
directional
movement
Monday, April 16, 2012
“see” and measure
the integrity !
Averaged Fractional Anisotropy
0.6
22q n=39(L),n=43(R)
0.4
0.3
0.1
0.0
RD
Right
Left
1.6
22q n=39(L),n=43(R)
TD-Type1
TD-Type2
22q-Type1
22q-Type2
1.0
Averaged Radial Diffusivity
1.2
Less organized
fibers
0.6
0.6
0.8
0.8
1.0
1.2
1.4
TD (n=38)
Right
Averaged Radial Diffusivity
Averaged Radial Diffusivity
1.4
1.6
22q-Type1
22q-Type2
0.2
Averaged Fractional Anisotropy
0.4
0.3
0.2
0.0
0.1
Mean FA across the tract
Left
Mean RD across the tract
TD-Type1
TD-Type2
0.5
TD (n=38)
Averaged Fractional Anisotropy
0.5
0.6
FA
Fornix - Less organized in children with
22q11.2DS
Left
Monday, April 16, 2012
Right
Left
Right
Which specific regions ?
•
Can we “zoom in” to examine in detail which area less
organized?
•
front to back walk along the tract
cut into 45 pieces
Front
Monday, April 16, 2012
Back
A
B
Fractional Anisotropy Along the Trajectory
Fractional Anisotropy Along the Trajectory
Left Fornix (Anterior to Posterior)
0.8
0.7
Right Fornix (Anterior to Posterior)
TD (n=37)
0.8
22q (n=38)
Back
Front
FA value (weighted)
FA value (weighted)
0.6
0.5
0.4
0.3
0.5
0.4
0.3
0.2
0.2
0.1
0.1
5
10
15
20
25
30
35
40
0
45
5
10
15
steps along the trajectory (A->P)
C
20
25
30
35
40
45
steps along the trajectory (A->P)
D
Radial Diffusivity Along the Trajectory
Radial Diffusivity Along the Trajectory
Left Fornix (Anterior to Posterior)
2.5
Right Fornix (Anterior to Posterior)
TD (n=37)
2.5
22q (n=38)
2.0
TD (n=38)
22q (n=43)
2.0
RD um2/msec (weighted)
RD um2/msec (weighted)
22q (n=43)
0.7
0.6
0
TD (n=38)
1.5
1.0
1.5
1.0
0.5
0.5
5
10
15
20
25
30
steps along the trajectory (A->P)
Monday, April 16, 2012
35
40
45
5
10
15
20
25
30
steps along the trajectory (A->P)
35
40
45
Atypical Midline Structures
Cavum Septum Pellucidum (CSP)
Beaton et al., 2010
Monday, April 16, 2012
Atypical Midline Structures
Cavum Septum Pellucidum (CSP)
A
C
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)$"'$%&
Cavum Septum Pellucidum Volume
TD (n=72)
22q (n=79)
TD_M (n=33)
22q_M (n=43)
TD_F (n=39)
22q_F (n=36)
4
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#..&
B
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(/)#..&
)+0..&
!"#$%&'()*$+'$,-$.'/012$
1
)("*+%&
2
!"#$%&
3
+'"#!%&
log CSP Volume (in mm^3)
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+"$)%&
#*",+%&
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0
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Beaton et al., 2010
Monday, April 16, 2012
#)0..&
All
Male
Female
***
**
*
significant level: *** p<0.001; **p<0.01; * p<0.05
Atypical Midline Structures
Lateral Ventricles
5.0
5.5
Lateral Ventricular Volume
TD (n=74)
22q (n=80)
***
TD_M (n=34)
22q_M (n=45)
TD_F (n=40)
22q_F (n=35)
***
*
4.5
4.0
3.5
2.5
3.0
log Ventricular Volume (in mm^3)
***
All
Male
Female
significant level: *** p<0.001; **p<0.01; * p<0.05
Monday, April 16, 2012
Enlarged Ventricles with Age
Lateral Ventricle Volume and Age
45000
TD (n=72)
22q (n=78)
TD Male (n=32)
22q Male (n=44)
TD Female (n=39)
22q Female (n=33)
40000
35000
3
Ventricle Volume (in mm )
30000
25000
20000
15000
10000
5000
0
80
100
120
140
Age in month
Monday, April 16, 2012
160
180
200
80
100
120
140
160
180
200
80
100
120
140
Age in month
Age in month
Boys
Girls
160
180
•
Summary
Atypical hippocampal connections in children with 22q11.2DS
!
!
!
•
Atypical midline structures
!
!
!
!
•
less organized fornix
especially at the area connecting to hippocampus
varies a lot between children with 22q11.2DS
It d
epe
nds
enlarged CSP
...
enlarged lateral ventricles
varies a lot between children with 22q11.2DS
may influence the hippocampal connections
Not yet found strong functional implications from any single
component, BUT each of them has been commonly reported
in patients with schizophrenia.
Do these brain differences matter ??
Monday, April 16, 2012
Thanks !
All participants and their families!!
Tony Simon & the CABIL team
Brian A. Wandell
Naomi Goodrich-Hunsaker
Robert F. Dougherty
Margarita Cabaral
Michael Perry
David G. Amaral
Danielle Harvey
Kristopher Kalish
Owen Carmichael
Son Nguyen
Yuen Ting Chan, Erica
Monday, April 16, 2012
& the Stanford University
Vista Lab
http://white.stanford.edu/index.php