Beatriz Luna, PhDBeatriz Luna, PhD

Laboratory of Neurocognitive DevelopmentLaboratory of Neurocognitive Development

University of PittsburghUniversity of Pittsburgh

Vulnerabilities in Neurocognitive Vulnerabilities in Neurocognitive Processes in AdolescenceProcesses in Adolescence

• Exogenous– Elicited by “external” guides

• External Stimuli, Emotional States– Not guided by a planned response – Reflexive Behavior

• Endogenous– Voluntary– Guided by internal plans– Overrides exogenously-guided behavior– Cognitive Control of Behavior / Decision Making– Can be adult like in adolescence

Control of Behavior

Conclusions: Adolescence

• Adolescents can demonstrate adult-level cognitive control of behavior– Behavioral Studies

• Brain mechanisms that support adult-level behavior in adolescence are immature– fMRI studies

• Adolescent cognitive control of behavior is immature and vulnerable to error – Conclusions

Brain Maturation in Adolescence

Synaptic Pruning Myelination

• Improved Brain Function– Increased efficiency of local computations– Increased speed of neuronal transmission

• Voluntary Response Inhibition (Paus 1990, Levin 1991, Ridderinkhof 1997, Fischer 1997, Munoz 1998, Luna 2004)

• Working Memory (Zald 1998, Demetriou 2002, Luna 2004)

Cognitive Development: Core Processes

Oculomotor Studies of Cognition

• Direct Measure of Cognitive Control– Minimal strategy formation

• Well-delineated Neural System– Anatomically & Physiologically

• Simple Cognitive Tasks– Appropriate for Developmental Studies

Behavioral Studies

• 245 subjects• 8-30 yo (93 Female/152 Males)

• Tasks– Speed of Processing– Response Inhibition– Working Memory

Methods

Child Development 2004

Direct current electro-oculography (EOG) -24 deg

-16 deg-8 deg

8 deg16 deg

24 deg

1 meter0 deg

Darkened Room

20

Central Fixation (1.5-2.5s)

Saccade to Target (1.5s)

-30 -20 -10 0 10 20 30

Degrees of Visual Angle

Visually Guided Saccades

Saccade

Illuminated TargetsCorrect Gaze Location

Non-visible Target Locations

Antisaccade Task

Central Fixation

Saccade away fromPeripheral Target

-24 -16 - 8 0 8 16 24

Degrees of Visual Angle

Feedback

Illuminated TargetsCorrect Gaze Location

1.5

sec

1.5

sec

3 -

5 se

c

19

ODR/Memory Guided Saccade Task

Central Fixation

Target Location to be Remembered

-27 -18 - 9 0 9 18 27

Degrees of Visual Angle

Delay Period

Saccade to Remembered Location

Feedback

Illuminated Targets

Correct Gaze Location

1.5-

2.5s

0.1

s1,

2,4,

8 s

1.5

s2.

0 s

Speed of Processing

Response Inhibition

Working Memory

Visually Guided Saccades

Voluntary Response Inhibition

Working Memory: Accuracy

Initial SaccadeFinal Saccade

Conclusions

• Cognitive control of behavior matures in adolescence

• What develops is the sophistication of responses not the appearance of an ability

Brain Imaging Studies

Capillary Bed

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baseline

activation

fMRI

Response Inhibition

MR Imaging Methods:

• Subjects (N=36)– 8-13y (N=11)– 14-17y (N=15)– 18-30y (N=10)

• fMRI Studies – 3.0 Tesla GEMS scanner– Gradient-Echo EPI, TR = 5000– In-plane resolution 3.125 mm2 – 23 - 3 mm slices, 2 mm gap– Standard anatomic imaging (SPGR)

Antisaccades

36 sec.

36 sec. 36 sec.

•Tasks Repeated for 7.5 cycles

Prosaccades

Antisaccade Trial

Fixation

Prosaccade Trial

Fixation

Antisaccade: Block Design

15

Adults > Adolescents and Children

Children AdultsAdolescents

FEF

Sup Coll

Lat Cer

R L

PEF

14

Adolescents and Children > Adults

Children AdultsAdolescents

R L

DLPFC

PPC

13

Response Inhibition: Planning

Event Related Antisaccades

Prosaccade Trials

Antisaccade Trials

+Saccade

+Cue

+

Fixation

+ +

10

Preparation to Inhibit a Response:

Children AdultsAdolescents

FEF

R L

9

Antisaccade Preparation: FEF

ChildrenAdolescentsAdults

• Adolescents, like children, do not reach adult-level activation for correct responses.• Adolescents, like adults, do show a second peak of activation.

7

-0.6

-0.4

-0.2

0

0.2

0.4

0.6

0.8

1

1 2 3 4 5 6 7 8 9 10 11

TR (2.5 sec)

% S

ign

al C

ha

ng

e

Preparation to Inhibit a Response:

Children AdultsAdolescents

R L

9

VLPFC

DLPFC

-0.3

-0.1

0.1

0.3

0.5

0.7

1 3 5 7 9 11

TR (2.5sec)

%S

ign

al C

ha

ng

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Antisaccade Preparation: DLPFC

•Adolescents, like children, show a delayed peak of activation.•Adolescents, like adults, show a similar magnitude of activation.

ChildrenAdolescentsAdults

6

Conclusions: Response Inhibition

• Maturation is characterized by the emergence of an integrated collaborative brain system.

• Adolescents are not as efficient at activating brain regions supporting response planning

• Adolescents compensate for immature brain systems by recruiting PFC

12

Working Memory

Methods: ODR task

Saccade

VGS TrialsWorking Memory Trials

time Saccade

Delay 4s

+

+

Cue 75 ms

+

Fix 2425 ms

Memory Guided

30 sec.

30 sec. 30 sec.

•Tasks Repeated for 10.5 cycles

Visually Guided

15

+

Fix 1250 ms

Working Memory

Basal Ganglia: Caudate & Putamen

DLPFC

Superior Temporal Gyrus

Children Adolescents Adults

Working Memory:Encoding and Maintenance

Methods: ODR task

+ +

Saccade

Fix 1250 ms

Saccade

Jittered 2.5-12.5s

Spatial Working Memory Trials

VGS Trials

Baseline

time Delay 2.5 or 10

+

+

Cue 75 ms

+

Fix 2425 ms

Prefrontal Cortex: Maintenance

2.5s Delay

BA9

Children8-12yo

Adolescents13-17yo

Adults18-30yo

10s Delay

BA9

BA10

PFC supports WM maintenance and is on line at all ages

Hippocampus: Encoding

Children8-12yo

Adolescents13-17yo

Adults18-30yo

2.5s Delay

10s Delay

•The hippocampus supports encoding and is only recruited by adults

Conclusions: Working Memory

• Adolescents are not efficient at recruiting regions that support encoding information in working memory.

12

Take Home Message

• While adolescents behave similarly to adults the brain processes supporting cognitive control of behavior are not mature

• Adolescence is a still unstable stage that is vulnerable to immature processing

2

Why?

• Adolescence is a crucial and necessary period of plasticity when brain circuitry and behavior is beginning to be established.

• Risk-taking behavior and novelty seeking may provide a mechanism for increasing exposure to the environment necessary for successful sculpting of the system.

end

Laboratory of Neurocognitive Development

Dr. Miya AsatoDr. Suzy Scherf

Matt Costello MA

Chuck Geier MA

Melanie Wilds BA Emi Yasui BA

Krista Garver BA

Dr. Bea Luna PI