Impaired Spatial Cognition and
Differences in Brain Connections
Naomi Goodrich-Hunsaker, Ph.D., Postdoctoral Scholar &
Ali Izadi, Graduate Student
Chromosome 22q11.2 Deletion Syndrome Family Meeting
March 10, 2013, MIND Institute, Sacramento, CA
Visuospatial Attention
•
The ability to actively direct attention to the appropriate
location of a visual stimulus
Visuospatial Attention
•
The ability to actively direct attention to the appropriate
location of a visual stimulus
•
Guiding our attention to a stimulus in space is the basis
of how we interact with our environment
Visuospatial Attention
•
The ability to actively direct attention to the appropriate
location of a visual stimulus
•
Guiding our attention to a stimulus in space is the basis
of how we interact with our environment
Visuospatial Attention in Children
with 22q Deletion Syndrome
Previous studies have shown that children with 22q demonstrate
difficulties in spatially based orienting
Visuospatial Attention in Children
with 22q Deletion Syndrome
Previous studies have shown that children with 22q demonstrate
difficulties in spatially based orienting
This may be due to altered structure of the brain and how each side
communicates with the other
(corpus callosum)
Visuospatial Attention in Children
with 22q Deletion Syndrome
Previous studies have shown that children with 22q demonstrate
difficulties in spatially based orienting
This may be due to altered structure of the brain and how each side
communicates with the other
(corpus callosum)
Study Design
Purpose:
•
To characterize and compare visuospatial impairments in
kids with 22q who have changes in brain structure
•
Communication between each side of the brain
•
Looking at gender and age in development
Study Design
Purpose:
•
To characterize and compare visuospatial impairments in
kids with 22q who have changes in brain structure
•
Communication between each side of the brain
•
Looking at gender and age in development
How to measure visuospatial impairments:
•
Using behavioral tasks:
Line bisection and landmark tasks
Study Design
Purpose:
•
To characterize and compare visuospatial impairments in
kids with 22q who have changes in brain structure
•
Communication between each side of the brain
•
Looking at gender and age in development
How to measure visuospatial impairments:
•
Using behavioral tasks:
Line bisection and landmark tasks
How to measure brain structure changes:
•
Using MRI imaging:
DTI fiber tractography
Participants
106 total participants (ages 7-15, average = 12.1 years)
•
•
77 participants with 22q
•
Ages 7-15, average = 11.9 years
•
42 males, 35 females
29 typically developing participants
•
Ages 7-15 average = 10.6 years
•
14 males, 15 females
Line Bisection Task
•
Children manually bisect a printed line
Line Bisection Task
•
•
Children manually bisect a printed line
Measures the ability to accurately respond to a
stimulus presented in space - spatial attention
Line Bisection Task
•
•
Children manually bisect a printed line
•
Typically developing right handed children
bisect lines slightly to the left
Measures the ability to accurately respond to a
stimulus presented in space - spatial attention
Line Bisection Task
•
•
Children manually bisect a printed line
•
Typically developing right handed children
bisect lines slightly to the left
•
Right hemisphere of brain is more tuned for
spatial attention, but focuses more on what you
see on the left - “right side neglect”
Measures the ability to accurately respond to a
stimulus presented in space - spatial attention
‣
Common clinical bed-side task used to
measure stroke impairments in one side of
the brain
Line Bisection Task
•
•
Children manually bisect a printed line
•
Typically developing right handed children
bisect lines slightly to the left
•
Right hemisphere of brain is more tuned for
spatial attention, but focuses more on what you
see on the left - “right side neglect”
Measures the ability to accurately respond to a
stimulus presented in space - spatial attention
‣
Common clinical bed-side task used to
measure stroke impairments in one side of
the brain
Results - Overall Group
Differences
Right side
35
30
●
TD (n=29)
22q (n=77)
25
20
Left side
Distance
15
10
5
0
−5
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−10
−15
−20
Left Hand
Right Hand
Results - Overall Group
Differences
Right side
35
30
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TD (n=29)
22q (n=77)
25
20
Left side
Distance
15
10
5
0
−5
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−10
−15
−20
Left Hand
Right Hand
When marking a printed line, children with 22q show greater leftward offsets
than typically developing children indicating impaired spatial accuracy.
Results - Age and Gender
Differences
35
30
25
20
●
●
Younger TD, n= 14
Older TD, n= 15
Younger 22q, n= 27
Older 22q, n= 34
Distance
15
10
5
0
−5
−10
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−15
−20
TD
22q
Results - Age and Gender
Differences
35
30
25
20
●
●
Younger TD, n= 14
Older TD, n= 15
Younger 22q, n= 27
Older 22q, n= 34
•
Distance
15
10
5
0
−5
−10
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−15
−20
TD
22q
Older kids are more
accurate, marking
closer to the center
of the line in both
22q and TD groups
Results - Age and Gender
Differences
35
30
●
●
25
20
Younger TD, n= 14
Older TD, n= 15
Younger 22q, n= 27
Older 22q, n= 34
•
Distance
15
10
5
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0
−5
−10
−15
−20
TD
35
30
25
20
●
●
22q
Male TD, n= 14
Female TD, n= 15
Male 22q, n= 33
Female 22q, n= 28
Distance
15
10
5
0
−5
−10
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●
−15
−20
TD
22q
Older kids are more
accurate, marking
closer to the center
of the line in both
22q and TD groups
Results - Age and Gender
Differences
35
30
●
●
25
20
Younger TD, n= 14
Older TD, n= 15
Younger 22q, n= 27
Older 22q, n= 34
•
Older kids are more
accurate, marking
closer to the center
of the line in both
22q and TD groups
•
No difference
between the way
males and females
mark the line
Distance
15
10
5
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●
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●
●●
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●
●
0
−5
−10
−15
−20
TD
35
30
25
20
●
●
22q
Male TD, n= 14
Female TD, n= 15
Male 22q, n= 33
Female 22q, n= 28
Distance
15
10
5
0
−5
−10
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−15
−20
TD
22q
Landmark Task
•
Children are asked to determine whether a pre-bisected mark is correctly
placed closer to the left or right side
Landmark Task
•
Children are asked to determine whether a pre-bisected mark is correctly
placed closer to the left or right side
•
Bisection marks (Kermit the frog) are pre-placed at different locations on
the line including at the midpoint and leftward/rightward positions
Landmark Task
•
Children are asked to determine whether a pre-bisected mark is correctly
placed closer to the left or right side
•
Bisection marks (Kermit the frog) are pre-placed at different locations on
the line including at the midpoint and leftward/rightward positions
•
Separates motor and perceptual components in the ability to determine
the spatial location (left/right) of a marked line
Landmark Task
•
Children are asked to determine whether a pre-bisected mark is correctly
placed closer to the left or right side
•
Bisection marks (Kermit the frog) are pre-placed at different locations on
the line including at the midpoint and leftward/rightward positions
•
Separates motor and perceptual components in the ability to determine
the spatial location (left/right) of a marked line
•
Typically developing children make more errors in judging the left/right
location of the mark as it gets closer to the “uncertainty zone” in the
middle
Landmark Task
•
Children are asked to determine whether a pre-bisected mark is correctly
placed closer to the left or right side
•
Bisection marks (Kermit the frog) are pre-placed at different locations on
the line including at the midpoint and leftward/rightward positions
•
Separates motor and perceptual components in the ability to determine
the spatial location (left/right) of a marked line
•
Typically developing children make more errors in judging the left/right
location of the mark as it gets closer to the “uncertainty zone” in the
middle
Results - Overall Group
Differences
100%
●
TD (n=26)
22q (n=45)
●
Percent Error
80%
●
●
60%
●
40%
●
●
20%
●
●
0%
−16
●
●
●
●
●
●
−12
●
−8
−4
0
Distance
4
8
12
●
●
16
Results - Overall Group
Differences
100%
●
TD (n=26)
22q (n=45)
●
Percent Error
80%
●
●
60%
●
40%
●
●
20%
●
●
0%
−16
●
●
●
●
●
●
−12
●
−8
−4
0
4
8
12
●
●
16
Distance
Children with 22q make more errors determining the leftward/rightward
location of the mark compared to typically developing children
Results - Overall Group
Differences
100%
●
TD (n=26)
22q (n=45)
●
Percent Error
80%
●
Guessing
●
60%
●
40%
●
●
20%
●
●
0%
−16
●
●
●
●
●
●
−12
●
−8
−4
0
4
8
12
●
●
16
Distance
Children with 22q make more errors determining the leftward/rightward
location of the mark compared to typically developing children
Results - Overall Group
Differences
100%
●
TD (n=26)
22q (n=45)
●
Percent Error
80%
●
Guessing
●
60%
●
40%
●
●
20%
●
●
0%
−16
●
●
●
●
●
●
−12
●
−8
−4
0
4
8
12
●
●
16
Distance
Children with 22q make more errors determining the leftward/rightward
location of the mark compared to typically developing children
“Guessing Distance” - Age and
Gender Differences
Older TD
(n=14)
Younger TD
(n=19)
Older 22q
(n=23)
Younger 22q
(n=29)
16 14 12 10 8 6
Left Side
4
2
2
4
6
8 10 12 14 16
Right Side
“Guessing Distance” - Age and
Gender Differences
Older TD
(n=14)
Younger TD
(n=19)
Older 22q
(n=23)
Younger 22q
(n=29)
16 14 12 10 8 6
Left Side
4
2
2
4
6
8 10 12 14 16
Right Side
•
Kids with 22q show
more variability in
distances at which they
guess location of mark
•
Performance improves
in older children in both
22q and TD groups
“Guessing Distance” - Age and
Gender Differences
Older TD
(n=14)
Younger TD
(n=19)
Older 22q
(n=23)
Younger 22q
(n=29)
16 14 12 10 8 6
Left Side
4
2
2
4
6
8 10 12 14 16
Right Side
TD Group
Male TD
(n=15)
Female TD
(n=19)
22q Group
Male 22q
(n=19)
Female 22q
(n=33)
−16−14−12−10 −8 −6 −4 −2
Left Side
2
4
6
8 10 12 14 16
Right Side
•
Kids with 22q show
more variability in
distances at which they
guess location of mark
•
Performance improves
in older children in both
22q and TD groups
“Guessing Distance” - Age and
Gender Differences
Older TD
(n=14)
Younger TD
(n=19)
Older 22q
(n=23)
Younger 22q
(n=29)
16 14 12 10 8 6
Left Side
4
2
2
4
6
8 10 12 14 16
Right Side
TD Group
•
Kids with 22q show
more variability in
distances at which they
guess location of mark
•
Performance improves
in older children in both
22q and TD groups
•
Males tend to guess
when mark is closer to
middle compared to
females with 22q
different
developmental
trajectory
Male TD
(n=15)
Female TD
(n=19)
-
22q Group
Male 22q
(n=19)
Female 22q
(n=33)
−16−14−12−10 −8 −6 −4 −2
Left Side
2
4
6
8 10 12 14 16
Right Side
•
Males and females
perform similarly in TD
group
Behavioral Tasks Summary
•
In both line bisection and landmark tasks, typically developing children perform
more accurately than children with 22q
-
Impairments are more pronounced on left side
Behavioral Tasks Summary
•
In both line bisection and landmark tasks, typically developing children perform
more accurately than children with 22q
•
Impairments are more pronounced on left side
Both tasks demonstrate improvements in performance with age for both
diagnosis groups
Behavioral Tasks Summary
•
In both line bisection and landmark tasks, typically developing children perform
more accurately than children with 22q
-
Impairments are more pronounced on left side
•
Both tasks demonstrate improvements in performance with age for both
diagnosis groups
•
Gender may play a potential role in task performance
-
females with 22q possibly demonstrate slower developmental
trajectory than males
Behavioral Tasks Summary
•
In both line bisection and landmark tasks, typically developing children perform
more accurately than children with 22q
-
Impairments are more pronounced on left side
•
Both tasks demonstrate improvements in performance with age for both
diagnosis groups
•
Gender may play a potential role in task performance
-
females with 22q possibly demonstrate slower developmental
trajectory than males
Diffusion Tensor Imaging (DTI)
•
DTI indirectly visualizes fiber tracts of the
brain through the ability of water to diffuse
multi-directionally
Diffusion Tensor Imaging (DTI)
•
DTI indirectly visualizes fiber tracts of the
brain through the ability of water to diffuse
multi-directionally
“In a glass of water, the motion of the water
molecules is completely random and is limited
only by the boundaries of the container”
- Isotropic
- (Hagmann 2006)
Diffusion Tensor Imaging (DTI)
•
DTI indirectly visualizes fiber tracts of the
brain through the ability of water to diffuse
multi-directionally
“In a glass of water, the motion of the water
molecules is completely random and is limited
only by the boundaries of the container”
- Isotropic
- (Hagmann 2006)
Diffusion Tensor Imaging (DTI)
•
DTI indirectly visualizes fiber tracts of the
brain through the ability of water to diffuse
multi-directionally
“In a glass of water, the motion of the water
molecules is completely random and is limited
only by the boundaries of the container”
- Isotropic
- (Hagmann 2006)
•
The difference is that in the brain there are
many boundaries, therefore water molecules
move preferentially in the direction of fibers
where they are less hindered
- Anisotropy
Diffusion Tensor Imaging (DTI)
•
DTI indirectly visualizes fiber tracts of the
brain through the ability of water to diffuse
multi-directionally
“In a glass of water, the motion of the water
molecules is completely random and is limited
only by the boundaries of the container”
- Isotropic
- (Hagmann 2006)
•
The difference is that in the brain there are
many boundaries, therefore water molecules
move preferentially in the direction of fibers
where they are less hindered
- Anisotropy
Diffusion Tensor Imaging (DTI)
•
DTI indirectly visualizes fiber tracts of the
brain through the ability of water to diffuse
multi-directionally
“In a glass of water, the motion of the water
molecules is completely random and is limited
only by the boundaries of the container”
- Isotropic
- (Hagmann 2006)
•
The difference is that in the brain there are
many boundaries, therefore water molecules
move preferentially in the direction of fibers
where they are less hindered
- Anisotropy
Corpus Callosum
•
Midline region that connects each
hemisphere of the brain
Corpus Callosum
•
Midline region that connects each
hemisphere of the brain
Corpus Callosum
•
Midline region that connects each
hemisphere of the brain
•
Represents a superhighway for
communication between the two
sides
Corpus Callosum
•
Midline region that connects each
hemisphere of the brain
•
Represents a superhighway for
communication between the two
sides
Results
TD
Results
TD
22q
Results
TD
22q
Preliminary 22q callosal tractography shows irregularities in callosal morphology
and fiber distributions
- It simply looks different ?!
DTI and Corpus Callosum:
Current Work
We have seen:
•
Kids with 22q have altered corpus callosum
morphology, differing in both size and shape
•
Fiber tracts show changes in shape and display
sparsity in various regions
DTI and Corpus Callosum:
Current Work
We have seen:
•
Kids with 22q have altered corpus callosum
morphology, differing in both size and shape
•
Fiber tracts show changes in shape and display
sparsity in various regions
We are currently studying:
•
Quantitative differences in fiber tracts
•
Correlations with gender and age
•
Differences in functional anisotropy (changes in
preferential movement of water molecules)
DTI and Corpus Callosum:
Current Work
We have seen:
•
Kids with 22q have altered corpus callosum
morphology, differing in both size and shape
•
Fiber tracts show changes in shape and display
sparsity in various regions
We are currently studying:
•
Quantitative differences in fiber tracts
•
Correlations with gender and age
•
Differences in functional anisotropy (changes in
preferential movement of water molecules)
Conclusions
Conclusions
Inference #1:
✓ Kids with 22q perform poorly in landmark and line
bisection behavioral tasks compared with TD
-
Impairments are reduced with age
Impairments are more evident on left side task performance
females with 22q may have more pronounced impairments
than males
Conclusions
Inference #1:
✓ Kids with 22q perform poorly in landmark and line
bisection behavioral tasks compared with TD
-
Impairments are reduced with age
Impairments are more evident on left side task performance
females with 22q may have more pronounced impairments
than males
Inference #2:
✓ DTI tractography demonstrates alterations in corpus
callosum structure and fiber distributions in kids with 22q
Conclusions
Inference #1:
✓ Kids with 22q perform poorly in landmark and line
bisection behavioral tasks compared with TD
-
Impairments are reduced with age
Impairments are more evident on left side task performance
females with 22q may have more pronounced impairments
than males
Inference #2:
✓ DTI tractography demonstrates alterations in corpus
callosum structure and fiber distributions in kids with 22q
Conclusion:
‣
Visuospatial impairments observed in children with 22q may be
caused by changes in brain development. The observed behavioral
impairments may also vary with both age and gender
Acknowledgements
Tony Simon
Nina Cung
Margie Cabaral
Andrea I. Quintero
Ling M. Wong
Joshua R. Cruz
Bella McLennan
Heather Shapiro
Thank You Participants!!!