BJ Casey, Ph'D'

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Cognitive Neuroscience Studies of Human
Development
BJ Casey, Ph.D. Sackler Professor and
Director Sackler Institute for Developmental
Psychobiology Weill Medical College of Cornell
University
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Sackler Institute For Developmental
Psychobiology Weill Medical College of Cornell
University
Faculty Matthew Davidson (U Mass) Sarah
Durston (Utrecht) Inge-Marie Eigsti (U
Conn) Nim Tottenham Walter Mischel (Columbia)
Physicists Doug Ballon Gary Glover
(Stanford) Henning Voss
Graduate Students Adriana Galvan Todd Hare
Conor Liston Sumit Niogi Julie Spicer
(Columbia) Staff Jason Buhle Marcella Nurse
Acknowledgments Work funded in part by R01
MH63255, P50 MH62196, R01 DA018879, R21 DA15882
and the Mortimer D. Sackler family.
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CONVERGING METHODS
MRI-based morphometry Genotyping
Human Brain Development
EEG
ERP
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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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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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Cognitive Development
Immature cognition is characterized by
susceptibility to interference from competing
sources Ability to suppress inappropriate
thoughts and actions in favor of goal oriented
ones (i.e., cognitive control).
Casey et al. 2000, 2002, 2005
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Cognitive Development
Immature cognition is characterized by
susceptibility to interference from competing
sources Ability to suppress inappropriate
thoughts and actions in favor of goal oriented
ones in the presence of compelling incentives or
emotional contexts.
Casey et al. 2000, 2002, 2005
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Question What neural systems are changing
during development that underly changes in
cognitive control? 1) Development of Cognitive
Control and Underlying Circuitry 2)
Variability in Cognitive Control within Age
Groups 3) Impact of Developing Reward
Systems on Cognitive Control
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Developmental Differences in Frontostriatal
structure
Basal Ganglia Prefrontal Cortex
Sowell et al., 1999
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Gogtay et al 2004
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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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vPFC and ACC correlate with performance
Casey et al. 1997 JoCN
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Neuroanatomical correlates of go no/go performance
Durston et al (2002) Developmental
Science
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Developmental Differences in Prefrontal Activity
1800 1500 1200 900 600 300 0

Volume of Activity
Children Adults
p lt .05
Casey et al. 1997 JoCN
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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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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
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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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Cortical Changes with development on a variety of
cognitive control tasks
Casey et al. 2005 TICS
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Longitudinal Study (7-14 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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Question What neural systems are changing
during development that could explain increased
risk taking and lack of cognitive control? 1)
Fine-tuning of control systems parallels ability
to maintain goal-oriented behavior across
different contexts and time.
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Diffusion Tensor Imaging

MRI fMRI DTI Structure
Function Connectivity
A B C
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Frontostriatal Activity correlated with go/nogo
task performance
Prefrontal Cortex Basal Ganglia
Sackler Institute Durston et al Neuroimage
2002 Durston et al Dev Science 2002
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Developmental Differences in Frontostriatal
Activity
Liston et al (in press) Cerebral Cortex
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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).
Liston et al (in press) Cerebral Cortex
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Performance Specific Connectivity
Liston et al (in press) Cerebral Cortex
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Delay of Gratification Task
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Parametric Manipulation vary of preceding Gos
before a NoGo
Level 1 Level 2 Level 3
Time
Behavioral Performance during Go/Nogo Task
Adults Children
Number of False Alarms
MR Signal Change
1 3 5 1 3
5
number of go trials preceding a nogo trial
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Performance on Delay task at 4 years predicts
performance on Go/no task up to 20 years later.
p lt .05 p lt .01
Eigsti et al (2006) Psychological Science
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Question What neural systems are changing
during development that could explain increased
risk taking and lack of cognitive control? 1)
Fine-tuning of control systems parallels ability
to maintain goal-oriented behavior across
different contexts and time. 2) There are
individual differences in cognitive control that
can be measured early in development and may
serve as predictors of high risk adolescent
behaviors.
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Question What neural systems are changing
during development that could explain increased
risk taking and lack of cognitive control? 1)
Development of Cognitive Control and Underlying
Circuitry 2) Variability in Cognitive
Control within Age Groups 3) Impact of
Developing Reward Systems on Cognitive Control
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Protracted Development of Top Down Control Regions
PFC/ACC
Rate of Maturation
Adolescence
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Protracted Development of Top Down Control Regions
accumbens/amygdala
PFC/ACC
Rate of Maturation
Adolescence
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Influence of Reward on Behavior Distinct stimuli
associated with different magnitudes of reward
Cue
Fixation
Fixation
Response
Reward
ITI
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3
4
5
6
7
8
9 20
1
0
Time in seconds
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Ventral Striatum and OFC

• Across all subjects, the accumbens was most
  sensitive to the different reward values.

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Conjunction Analysis
Children Adolescent
Adult Overlap
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Developmental Differences in Extent of Activity



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Different Developmental Trajectories for
subcortical and cortical regions
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Developmental Differences in Magnitude of
Response to Varying Rewards
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Different Developmental Trajectories
-Different developmental trajectories of
subcortical and cortical regions may explain high
risk behavior -Individual differences in
recruitment of subcortical systems may be a
marker for increased risk.
accumbens/amygdala prefrontal cortex
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Conclusions 1) Fine-tuning of control systems
parallels ability to maintain goal-oriented
behavior. 2) There are individual differences in
this ability that can be measured early and may
predict elevated risk. 3) Different
developmental trajectories for cortical and
subcortical regions may underlie impulsive, high
risk behaviors during adolescence that exacerbate
individual differences in this ability.