Sackler Institute for Developmental Psychobiology

1
Sackler Institute for Developmental
Psychobiology Weill Medical College of Cornell Un
iversity
2
Insights into the Adolescent Brain
from Functional Neuroimaging Studies

BJ Casey, Ph.D., Sackler Professor and
Director Sackler Institute for Developmental P
sychobiology Weill Medical College of Cornell
University
3
Key Points

• Examine developmental progressions in terms of
  transitions into and out of adolescence rather
  than single snap shot in time
  
• Examine individual differences within a
  developmental stage in terms of potential risk
  and/or resilience factors.

4
Sackler Institute For Developmental
Psychobiology Weill Medical College of Cornell Un
iversity
Sackler Fellows Adriana Galvan (now at UCLA)
Todd Hare Rebecca Jones Conor Liston Fatima
Soloman Liat Levita Staff Sarah Getz and
Alex Millner Julie Spicer (now at Columbia)
Faculty Dima Amso Nim Tottenham Henning Voss
Sarah Durston (Utrecht) Inge-Marie Eigsti (U
Conn) Gary Glover (Stanford) Walter Mischel (Co
lumbia)
Funded in part by R01 MH63255, P50 MH62196, R21
DA15882, R01 DA018879, NSF 06-509, the Mortimer
D. Sackler family and Dewitt-Wallace Readers
Digest.
5
Overarching Question How is the brain changing
during adolescence that may explain behavioral
changes during this period?
6
Dramatic developmental changes in prefrontal and
subcortical regions during adolescence
(Sowell et al, 1999)
Subcortical limbic regions involved in
motivational behavior
Sowell et al 1999 Nature Neuroscience
7
Protracted Development of Prefrontal Control
Regions Earlier Development of Subcortical Limbic
Regions
Prefrontal Cortex
Functional Maturation
Adolescence
8
Protracted Development of Prefrontal Control
Regions Earlier Development of Subcortical Limbic
Regions
Limbic regions (accumbens)
Prefrontal Cortex
Functional Maturation
Adolescence
9
Assessment of Developmental Differencesin
Response to Rewarding Events

• Thirty-seven participants
• 12 adults (mean age25 years 6 female)
• 12 adolescents (mean age16 years 6 female)
• 13 children (mean age 9 years 7
  female)

Cue
Reward



10
(No Transcript)
11
(No Transcript)
12
(No Transcript)
13
(No Transcript)
14
(No Transcript)
15
Participants are faster on trials
that give the largest reward.
16
Imaging Results

Adolescents are similar to adults in volume of
accumbens activity BUT similar to children in pre
frontal activity.


17
Protracted development of the OFC relative to the
accumbens
4
3
2
Normalized Extent of Activity
1
0
-1
5 10 15 20
25
Age in years
-2
Galvan et al 2006 J Neuroscience
18
Neural recruitment differs by region for age
groupsand corresponds to enhanced activity in
the accumbens in adolescents.


Children
Adolescents
Peak MR
Signal Change
Adults
Nucleus Accumbens
Orbital Frontal Cortex
Volume of Activity



(mm3)
No of Interpolated Voxels
Nucleus Accumbens
Orbital Frontal Cortex
19
Different Developmental Trajectories
-Differential development of subcortical relative
to prefrontal control regions may explain
increased engagement in high risk, incentive
driven behaviors.
accumbens/amygdala prefrontal cortex
20
Individual variability in accumbens activity
across development
2
1
MR Signal Change
0
-1
Age (years)
21
Accumbens activity is correlated with risky
behavior
Galvan et al 2006 Developmental Science
22
Impulsive and risky behavior
Increased risking taking behavior in adolescence
may be related to differential development of
limbic subcortical vs. cortical control regions.
Developmental changes may be exacerbated by
individual differences in tendency to engage in
risky behavior.
accumbens prefrontal cortex
23
Is there a similar pattern in the amgydala to
negative events?
Monk et al 2003 Neuroimage
24
Emotional Go/Nogo Task
500 ms
2000 - 14,500 ms
500 ms
500 ms
Hare et al 2005 Bio Psychiatry
25
Enhanced activity in amygdala in
adolescents relative to children adults
when approaching negative information
10 15 20
25 30

• Age in Years

26
Emotional Reactivity to Empty Threatinitial
reactivity versus sustained reactivity
Early Trials Middle Trials Late
Trials
early
middle
late
27
Habituation of Amygdala Response to empty threat
related to Trait Anxiety(i.e., decrease in
activity from early to late trials)
Trait Anxiety Score
Sustained amygdala activity (late - early trials)
28
Functional Connectivity Between Prefrontal
Regions and Amygdala is associated
withHabituation of Amygdala Response

29
Conclusions
Changes in behavior during adolescence paralleled
by differential development of subcortical limbic
regions relative to prefrontal control regions.
Individual differences in responses to positive
or negative events, together with these
developmental changes may put certain teens at
risk for poor outcomes.
accumbens/amygdala prefrontal cortex
30
Imaging the Adolescent Brain Groovy
31
Sackler Institute for Developmental
Psychobiology Weill Medical College of Cornell Un
iversity