Sackler Institute for Developmental PsychobiologyWeill Medical College of Cornell University

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

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

Subcortical regions including limbic (accubens) regions

(Sowell et al, 1999)

Focus has typically been on prefrontal cortex (PFC)

Sowell et al 1999Nature Neuroscience

Fun

ctio

nal M

atur

atio

n

Adolescence

Prefrontal Cortex

Protracted Development of Prefrontal Control RegionsEarlier Development of Subcortical Limbic Regions

Fun

ctio

nal M

atur

atio

n

Adolescence

accumbens

Prefrontal Cortex

Protracted Development of Prefrontal Control RegionsEarlier Development of Subcortical Limbic Regions

• 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

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.

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.

-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

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

-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

-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

Accumbens activity is correlated with risky behavior

Galvan et al 2006 Developmental Science

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

Fun

ctio

nal M

atur

atio

n

Adolescence

amygdala

Prefrontal Cortex

Protracted Development of Prefrontal Control RegionsEarlier Development of Subcortical Limbic Regions

500 ms

Emotional Go/Nogo Task

500 ms

500 ms2000 - 14,500 ms

Hare et al 2005 Bio Psychiatry

10 15 20 25 30

Enhanced activity in amygdala in adolescents relative to children & adults

when approaching negative information

Age in Years

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

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

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

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

AnxiousIndividual

LessAnxious

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

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