Sackler Institute for Developmental Psychobiology

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Sackler Institute for Developmental
Psychobiology Weill Medical College of Cornell
University
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Pediatric Imaging
BJ Casey, Ph.D., Sackler Professor and
Director Sackler Institute for Developmental
Psychobiology Weill Medical College of Cornell
University
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Functional changes with development

MRI fMRI DTI Structure
Function Connectivity
A B C
For recent reviews Casey, Tottenham, Liston
Durston (2005). Trends in Cognitive
Science Casey, Galvan Hare (2005). Current
Opinions in Neurobiology Amso Casey (in
press). Current Directions in Psychological
Science
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Magnetic Resonance Imaging (MRI) of the
Developing Human Brain
A B C
Diffusion Tensor Imaging (DTI) to track
strengthening of connectivity of fiber tracts
with development
Structural MRI to track changes in size and shape
of neuroanatomical structures with development
Functional MRI (fMRI) to track changes in brain
and behavior with development
Casey et al 2005 Current Opinions in Neurobiology
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Pediatric Issues(Precision of Measurement)

• Hemodynamic Response
• Spatial Normalization
• Age-Appropriate Tasks
• Behavioral Performance Differences

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Time courses are similar for children and adults
Kang et al, Neuroimage 2003
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Common Stereotactic Space
There are only small differences between adults
and children in sulcus location
Burgund et al Neuroimage 2002
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Age Appropriate Paradigms

• What is changing with development?
• -behavioral level
• -neural level

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Immature cognition is characterized by greater
susceptibility to interference
Ability to suppress inappropriate thoughts and
actions in favor of appropriate ones (cognitive
control). - adjust/alter thoughts and actions
when predictions are violated (flexible rules
use, E. Miller)
Casey et al. 2000, 2002, 2005a, b,c
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Spiderman NoGo Task
Try to catch Spiderman, but no, no, never catch
the Green Goblin or youll be sorry!
Shultz, et al. 2003
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Recruitment of Prefrontal Cortex across age
Casey et al. 1997 JCN
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Dorsolateral PFC Activity
1800 1500 1200 900 600 300 0

Volume of Activity
Children Adults
Casey et al. 1997
p lt .05
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Age vs Performance

• Correlation of age and performance with brain
  activity
• Partial out age and performance

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Prefrontal Activity as a function of Age
2400 2000 1600 1200 800 400
Volume of Activation in MFG (mm3)
7 8 9 10 11 12
21 Age in Years
Adapted from Casey et al., 1997 JoCN
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Neuroanatomical correlates of go no/go performance
Sackler Institute Durston et al
(2002) Developmental Science
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Age vs Performance

• Correlation of age and performance with brain
  activity
• Partial out age and performance
• Assumes linearity

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Age vs Performance

• Correlation of age and performance with brain
  activity
• Partial out age and performance
• Assumes linearity
• Parametric manipulation of task difficulty

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Parametric Manipulation vary of preceding Gos
before a NoGo
Level 1 Level 2 Level 3
Time
Ventral Prefrontal Activity during Go/Nogo Task
Behavioral Performance during Go/Nogo Task
Adults Children
Adults Children
Number of False Alarms
MR Signal Change
1 3 5 1 3
5
1 3 5 1 3
5
number of go trials preceding a nogo trial
number of go trials preceding a nogo trial
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Parametric Manipulationvary of preceding Gos
before a NoGo
Level 1 Level 2 Level 3
Time
Ventral Prefrontal Activity during Go/Nogo Task
Behavioral Performance during Go/Nogo Task
Adults Children
Adults Children
Number of False Alarms
MR Signal Change
1 3 5 1 3
5
1 3 5 1 3
5
number of go trials preceding a nogo trial
number of go trials preceding a nogo trial
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Age vs Performance

• Correlation of age and performance with brain
  activity
• Partial out age and performance
• Assumes linearity
• Parametric manipulation of task difficulty
• Matching performance (pre and post scan)

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Performance over Time
100 - 80 - 60 -
Adults Children
Percent Accuracy
1 2 3 4 5
Runs
Adapted from Thomas et al 1999
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Age vs Performance

• Correlation of age and performance with brain
  activity
• Partial out age and performance
• Assumes linearity
• Parametric manipulation of task difficulty
• Matching performance (pre and post scan)
• Ages differ with time on task (pre-matching)

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Area is active regardless of age or
performance Activity differs as a function of
performance rather than age Activity differs
as a function of age, regardless of performance
Schlaggar et al 2002
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Area is active regardless of age or
performance Activity differs as a function of
performance rather than age Activity differs
as a function of age, regardless of performance
Schlaggar et al 2002
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Area is active regardless of age or
performance Activity differs as a function of
performance rather than age Activity differs
as a function of age, regardless of performance
Schlaggar et al 2002
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What is changing with development? Diffuse/focal
Progressive/Regressive
Brown et al 2005 Neuroimage
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Cortical Changes with development on a variety of
cognitive control tasks
Casey et al. 2005 TICS
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Longitudinal Study (7-12 years) Cortical regions
that are recruited more (in red) and less (in
blue) with development
Sackler Institute, Cornell Medical Durston et al
in press Dev Science
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Longitudinal fMRI in typical development (Whole
brain analyses based 21 scans)
Within Ss Analysis Between Ss Analysis
Between Ss Analysis at different ages of
different ages of same ages
Durston et al. in press Developmental Science
Durston et al in press Dev Science
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Fine-tuning of neural systems with development

MRI fMRI DTI Structure
Function Connectivity
A B C
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Developmental Differences in Frontostriatal
structure
Basal Ganglia Prefrontal Cortex
Sowell et al., 1999
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Developmental Differences in Frontostriatal
Activity
Prefrontal Cortex Basal Ganglia
Neuroimage 2002 Dev Science 2002
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Developmental Differences in Frontostriatal
Activity
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Development of Frontal and Posterior Tracts

• Preliminary data suggest dissociation between
  allelic variants in dopamine genes expressed
  predominantly in prefrontal cortex and basal
  ganglia, respectively.

750 700 650
Mean Dav
Children Adults
Brightness corresponds to the relative anisotropy
and color is direction of greatest diffusion (red
right-left, green anterior-posterior, blue
superior-inferior). Boxes representing prefrontal
white matter ROIs
Mean prefrontal white matter Dav in children
(7-10 years old) and adults (22-31 years old).
Average diffusion is 7.7 lower in adults than in
children (t 3.17, plt.01).
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Task Specific Connectivity
Liston et al. submitted
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Prefrontal Cortex Striatum Fiber tracts
connecting Prefrontal and striatum
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Frontostriatal connectivity correlated with
frontostriatal activity, especially in the
striatum.
PFC
Striatum
MR SIGNAL CHANGE
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• Frontostriatal connectivity in correlated with
  how well the individuals with ADHD performed the
  go/nogo task.

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In ADHD parents - as frontostriatal connectivity
increased - performance approached that of
parents w/o ADHD.
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Traditionally, the focus of biological research
on ADHD has been on neurotransmitters within
prefrontal circuitry like dopamine and
norepinephrine. The findings highlight the need
to also consider genetic and environmental
factors that may alter myelin and axonal
migration (e.g. neurotrophin factors and white
matter injury).
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Conclusions
The imaging data suggests a fine-tuning of neural
systems with development (MRI, fMRI and DTI).
Brain regions associated with more basic
functions such as sensorimotor processes, mature
first. This development is followed by
association areas involved in top-down control of
behavior (e.g., cognitive control and
frontostriatal circuitry). (shift from concrete
rule learning to flexible abstract)
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Sackler Institute For Developmental
Psychobiology Weill Medical College of Cornell
University
Faculty Dima Amso Matthew Davidson John
Fossella Nim Tottenham Henning Voss Sarah
Durston (Utrecht/Sackler) Richard Watts (New
Zealand) Gary Glover (Stanford)
Fellows Adriana Galvin Todd Hare Conor
Liston Sumit Niogi Staff Jason Buhle Marcella
Nurse
AcknowledgmentsWork funded in part by R01
MH63255, P50 MH62196, R01 DA018879, R21 DA15882
and the Mortimer Sackler family.