Sackler Institute for Developmental Psychobiology
Weill Medical College of Cornell University
Insights into the Developing Brain
from Functional Neuroimaging Studies
BJ Casey, Ph.D.,
Sackler Professor and Director
Sackler Institute for Developmental Psychobiology
Weill Medical College
of Cornell University
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.
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
Overarching Question
How is the brain changing during development that may
explain behavioral changes, especially nonlinear ones?
Dramatic developmental changes in
prefrontal and subcortical regions
during adolescence
Focus has
typically been
on prefrontal
cortex (PFC)
(Sowell et al, 1999)
Subcortical regions including limbic (accubens) regions
Sowell et al 1999
Nature Neuroscience
Functional Maturation
Protracted Development of Prefrontal Control Regions
Earlier Development of Subcortical Limbic Regions
Prefrontal Cortex
Adolescence
Functional Maturation
Protracted Development of Prefrontal Control Regions
Earlier Development of Subcortical Limbic Regions
accumbens
Prefrontal Cortex
Adolescence
Assessment of Developmental Differences
in Response to Rewarding Events
Cue
• Thirty-seven participants
Reward
=
•12 adults (mean age:25 years; 6
female)
•12 adolescents (mean age:16 years;
6 female)
=
•13 children (mean age: 9 years;
7 female)
=
Participants are faster on trials
that give the largest reward.
Reaction Time
Small
Medium
Reaction time (msec)
650
Large
600
550
500
450
400
350
300
Run1
Run2
Run3
Run4
Run5
Imaging Results
Nucleus
Accumbens
800
BUT similar to
children in
prefrontal activity.
600
*
500
400
300
200
100
0
Children
Adolescents
Adults
Lateral Orbital Frontal Cortex
Volume of Activity
800
No. of
Adolescents are
similar to adults in
volume of
accumbens activity
No. of Voxels
700
700
600
500
400
300
200
*
100
0
C hildren
Adolescents
Adults
Protracted development of the OFC relative to
the accumbens
Normalized Extent of Activity
4
Nucleus Accumbens
3
Orbital Frontal Cortex
2
1
0
-1
5
-2
10
15
Age in years
20
25
Age (years)
Galvan et al 2006 J Neuroscience
Neural recruitment differs by region for age groups
and corresponds to enhanced activity in
the accumbens in adolescents.
*
*
0.3
Children
0.2
Adolescents
0.1
Adults
0
Nucleus Accumbens
Orbital Frontal Cortex
1000
terpolated Voxels
(mm3)
Peak % MR
Signal Change
0.4
800
600
400
200
Volume of Activity
*
*
*
Rate of Maturation
Different Developmental Trajectories
accumbens/amygdala
prefrontal cortex
Adolescence
-Differential development of
subcortical relative to
prefrontal control regions
may explain increased
engagement in high risk,
incentive driven behaviors.
Individual variability in accumbens activity
across development
% MR Signal Change
2
1
0
-1
5
10
15
20
Age (years)
25
30
Accumbens activity is correlated with
risky behavior
Galvan et al 2006 Developmental Science
Rate of Maturation
Impulsive and risky behavior
accumbens
prefrontal cortex
Adolescence
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.
Functional Maturation
Protracted Development of Prefrontal Control Regions
Earlier Development of Subcortical Limbic Regions
amygdala
Prefrontal Cortex
Adolescence
Emotional Go/Nogo Task
500 ms
2000 - 14,500 ms
500 ms
500 ms
Hare et al 2005 Bio Psychiatry
Enhanced activity in amygdala in
adolescents relative to children & adults
when approaching negative information
10
15
20
Age in Years
25
30
Emotional Reactivity to Empty Threat:
initial reactivity versus sustained reactivity
Early Trials
Middle Trials
1.0
.5
0.0
-.5
A
-1.0
T
-1.5
C
5
10
15
20
Age (years)
25
30
% BOLD Signal in the Amygdala
early
1.5
middle
1.0
.5
0.0
-.5
A
-1.0
T
-1.5
C
5
10
15
20
Age (years)
25
30
% BOLD Signal in the Amygdala
1.5
1.5
% BOLD Signal in the Amygdala
Late Trials
late
1.0
.5
0.0
-.5
A
-1.0
T
-1.5
C
5
10
15
20
Age (years)
25
30
Emotional Reactivity to Empty Threat:
initial reactivity versus sustained reactivity
Early Trials
Middle Trials
1.0
.5
0.0
-.5
A
-1.0
T
-1.5
C
5
10
15
20
Age (years)
25
30
% BOLD Signal in the Amygdala
early
1.5
middle
1.0
.5
0.0
-.5
A
-1.0
T
-1.5
C
5
10
15
20
Age (years)
25
30
% BOLD Signal in the Amygdala
1.5
1.5
% BOLD Signal in the Amygdala
Late Trials
late
1.0
.5
0.0
-.5
A
-1.0
T
-1.5
C
5
10
15
20
Age (years)
25
30
Emotional Reactivity to Empty Threat:
initial reactivity versus sustained reactivity
Early Trials
Middle Trials
1.0
.5
0.0
-.5
A
-1.0
T
-1.5
C
5
10
15
20
Age (years)
25
30
% BOLD Signal in the Amygdala
early
1.5
middle
1.0
.5
0.0
-.5
A
-1.0
T
-1.5
C
5
10
15
20
Age (years)
25
30
% BOLD Signal in the Amygdala
1.5
1.5
% BOLD Signal in the Amygdala
Late Trials
late
1.0
.5
0.0
-.5
A
-1.0
T
-1.5
C
5
10
15
20
Age (years)
25
30
Habituation of Amygdala Response
to empty threat related to Trait Anxiety
(i.e., decrease in activity from early to late trials)
Trait Anxiety Score
70
60
50
40
AGE_GRP
A
T
30
- 1 .5
- 1 .0
- .5
0 .0
.5
1 .0
Sustained amygdala activity
(late - early trials)
Anxious
Individual
Less
Anxious
% BOLD Signal in Amygdala (late - early)
Functional Connectivity Between Prefrontal
Regions and Amygdala is associated with
Habituation of Amygdala Response
1.0
.5
0.0
-.5
-1.0
-1.5
-.4
-.2
0.0
.2
lOFC-Amygdala Connectivity (z-score)
.4
Conclusions
Maturation
Differential development of
subcortical limbic regions relative
to prefrontal control regions during
adolescence are paralleled by
changes in behavior.
accumbens/amygdala
prefrontal cortex
Adolescence
Individual differences in responses
to positive or negative events,
together with these developmental
changes may put certain teens at
risk for poor outcomes.