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Sackler Institute for Developmental PsychobiologyWeill Medical College of Cornell University
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BJ Casey, Ph.D., Sackler Professor and Director
Sackler Institute for Developmental Psychobiology
Weill Medical College of Cornell University
Insights into the Developing Brainfrom Functional Neuroimaging Studies
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Key Points
1) Examine developmental progressions in terms of transitions into and out of stages of development rather than single snap shot in time;
2) Examine individual differences within a developmental stage in terms of potential risk and/or resilience factors.
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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), especially in.the context of emotion or incentives.
Casey et al. 2000, 2002, 2005a, b,c
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Overarching Question How is the brain changing during development that may explain behavioral changes, especially nonlinear ones?
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Dramatic developmental changes in prefrontal and subcortical regions
during adolescence
Subcortical regions including limbic (accubens) regions
(Sowell et al, 1999)
Focus has typically been on prefrontal cortex (PFC)
Sowell et al 1999Nature Neuroscience
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Fun
ctio
nal M
atur
atio
n
Adolescence
Prefrontal Cortex
Protracted Development of Prefrontal Control RegionsEarlier Development of Subcortical Limbic Regions
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Fun
ctio
nal M
atur
atio
n
Adolescence
accumbens
Prefrontal Cortex
Protracted Development of Prefrontal Control RegionsEarlier Development of Subcortical Limbic Regions
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• Thirty-seven participants
•12 adults (mean age:25 years; 6 female)
•12 adolescents (mean age:16 years; 6 female)
•13 children (mean age: 9 years; 7 female)
Reward
=
=
Cue
=
Assessment of Developmental Differencesin Response to Rewarding Events
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Reaction Time
300
350
400
450
500
550
600
650
Run1 Run2 Run3 Run4 Run5
Reaction time (msec)
Small
Medium
Large
Participants are faster on trials that give the largest reward.
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Nucleus Accumbens
0
100
200
300
400
500
600
700
800
Children Adolescents Adults
No. of Voxels
Lateral Orbital Frontal Cortex Volume of Activity
0
100
200
300
400
500
600
700
800
Children Adolescents Adults
No. of
*
*
Imaging Results
Adolescents are similar to adults in volume of accumbens activity
BUT similar to children in prefrontal activity.
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-2
-1
0
1
2
3
4
Protracted development of the OFC relative to the accumbens
Nucleus Accumbens
Orbital Frontal Cortex
Age (years)
Nor
mal
ized
Ext
ent
of A
ctiv
ity
Age in years
Galvan et al 2006 J Neuroscience
5 10 15 20 25
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Neural recruitment differs by region for age groupsand corresponds to enhanced activity in
the accumbens in adolescents.
200
400
600
800
1000
No o
f In
terp
ola
ted
Voxels
(m
m3
) *
0
0.1
0.2
0.3
0.4
Nucleus Accumbens Orbital Frontal Cortex
Peak %
MR
S
ignal C
hang
e
* *
*
*Volume of Activity
Children
Adolescents
Adults
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-Differential development of subcortical relative to prefrontal control regions may explain increased engagement in high risk, incentive driven behaviors.
Rat
e o
f M
atur
atio
n
Adolescence
Different Developmental Trajectories
accumbens/amygdala
prefrontal cortex
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-1
0
1
2
5 10 15 20 25 30
Age (years)
% M
R S
ign
al C
han
ge
Individual variability in accumbens activity across development
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Accumbens activity is correlated with risky behavior
Galvan et al 2006 Developmental Science
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Differential development of limbic subcortical vs. cortical control regions may be related to increased risking taking behavior in adolescence.
Individual differences in tendency to engage in risky behavior may compound risk for poor outcomes during this developmental period.
Impulsive and risky behavior R
ate
of
Mat
urat
ion
Adolescence
accumbens
prefrontal cortex
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Fun
ctio
nal M
atur
atio
n
Adolescence
amygdala
Prefrontal Cortex
Protracted Development of Prefrontal Control RegionsEarlier Development of Subcortical Limbic Regions
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500 ms
Emotional Go/Nogo Task
500 ms
500 ms2000 - 14,500 ms
Hare et al 2005 Bio Psychiatry
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10 15 20 25 30
Enhanced activity in amygdala in adolescents relative to children & adults
when approaching negative information
Age in Years
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Emotional Reactivity to Empty Threat:initial reactivity versus sustained reactivity
Age (years)
30252015105
% BOLD Signal in the Amygdala
1.5
1.0
.5
0.0
-.5
-1.0
-1.5
A
T
C
Age (years)
30252015105
% BOLD Signal in the Amygdala
1.5
1.0
.5
0.0
-.5
-1.0
-1.5
A
T
C
Age (years)
30252015105
% BOLD Signal in the Amygdala
1.5
1.0
.5
0.0
-.5
-1.0
-1.5
A
T
C
early middle late
Early Trials Middle Trials Late Trials
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Emotional Reactivity to Empty Threat:initial reactivity versus sustained reactivity
Age (years)
30252015105
% BOLD Signal in the Amygdala
1.5
1.0
.5
0.0
-.5
-1.0
-1.5
A
T
C
Age (years)
30252015105
% BOLD Signal in the Amygdala
1.5
1.0
.5
0.0
-.5
-1.0
-1.5
A
T
C
Age (years)
30252015105
% BOLD Signal in the Amygdala
1.5
1.0
.5
0.0
-.5
-1.0
-1.5
A
T
C
early middle late
Early Trials Middle Trials Late Trials
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Emotional Reactivity to Empty Threat:initial reactivity versus sustained reactivity
Age (years)
30252015105
% BOLD Signal in the Amygdala
1.5
1.0
.5
0.0
-.5
-1.0
-1.5
A
T
C
Age (years)
30252015105
% BOLD Signal in the Amygdala
1.5
1.0
.5
0.0
-.5
-1.0
-1.5
A
T
C
Age (years)
30252015105
% BOLD Signal in the Amygdala
1.5
1.0
.5
0.0
-.5
-1.0
-1.5
A
T
C
early middle late
Early Trials Middle Trials Late Trials
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Sustained amygdala activity(late - early trials)
1.0.50.0- .5- 1.0- 1.5
70
60
50
40
30
AGE_GRP
A
T
Habituation of Amygdala Response to empty threat related to Trait Anxiety
(i.e., decrease in activity from early to late trials)
Tra
it A
nxie
ty S
core
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AnxiousIndividual
LessAnxious
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Functional Connectivity Between Prefrontal Regions and Amygdala is associated with
Habituation of Amygdala Response
lOFC-Amygdala Connectivity (z-score)
.4.20.0-.2-.4% BOLD Signal in Amygdala (late - early) 1.0
.5
0.0
-.5
-1.0
-1.5
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Differential development of subcortical limbic regions relative to prefrontal control regions during adolescence are paralleled by changes in behavior.
Individual differences in responses to positive or negative events, together with these developmental changes may put certain teens at risk for poor outcomes.
Mat
urat
ion
Adolescence
Conclusions
accumbens/amygdala
prefrontal cortex