Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University

1. Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University

2. 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

3. Key Points Examine developmental progressions in terms of transitions into and out of stages of development rather than single snap shot in time; Examine individual differences within a developmental stage in terms of potential risk and/or resilience factors.

4. 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

5. Overarching Question How is the brain changing during development that may explain behavioral changes, especially nonlinear ones?

6. 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

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 accumbens Prefrontal Cortex Functional Maturation Adolescence

9. Assessment of Developmental Differencesin Response to Rewarding Events • 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) Cue Reward = = =

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 prefrontal activity. *

17. Nucleus Accumbens Orbital Frontal Cortex Age (years) 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. 0.4 0.3 0.2 0.1 0 1000 800 600 400 200 0 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. Rate of Maturation Adolescence 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. 5 10 15 20 25 30 Individual variability in accumbens activity across development 2 1 % MR Signal Change 0 Age (years) -1

21. Accumbens activity is correlated with risky behavior Galvan et al 2006 Developmental Science

22. Rate of Maturation Adolescence Impulsive and risky behavior 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. accumbens prefrontal cortex

23. Protracted Development of Prefrontal Control Regions Earlier Development of Subcortical Limbic Regions amygdala Prefrontal Cortex Functional Maturation Adolescence

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 Age in Years 10 15 20 25 30

26. Emotional Reactivity to Empty Threat:initial reactivity versus sustained reactivity Early Trials Middle Trials Late Trials early middle late

27. Emotional Reactivity to Empty Threat:initial reactivity versus sustained reactivity Early Trials Middle Trials Late Trials early middle late

28. Emotional Reactivity to Empty Threat:initial reactivity versus sustained reactivity Early Trials Middle Trials Late Trials early middle late

29. 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)

30. Anxious Individual Less Anxious

31. Functional Connectivity Between Prefrontal Regions and Amygdala is associated withHabituation of Amygdala Response

32. Maturation Adolescence Conclusions 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. accumbens/amygdala prefrontal cortex