Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University

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

2. Pediatric Imaging BJ Casey, Ph.D., Sackler Professor and Director Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University

3. Functional changes with development MRI fMRI DTI Structure Function Connectivity A B C For recent reviews: Casey, Tottenham, Liston & Durston (2005). Trends in Cognitive Science Casey, Galvan & Hare (2005). Current Opinions in Neurobiology Amso & Casey (in press). Current Directions in Psychological Science

4. Magnetic Resonance Imaging (MRI) of the Developing Human Brain A B C Diffusion Tensor Imaging (DTI) to track strengthening of connectivity of fiber tracts with development Structural MRI to track changes in size and shape of neuroanatomical structures with development Functional MRI (fMRI) to track changes in brain and behavior with development Casey et al 2005 Current Opinions in Neurobiology

8. Pediatric Issues(Precision of Measurement) • Hemodynamic Response • Spatial Normalization • Age-Appropriate Tasks • Behavioral Performance Differences

9. Time courses are similar for children and adults Kang et al, Neuroimage 2003

10. Common Stereotactic Space There are only small differences between adults and children in sulcus location Burgund et al Neuroimage 2002

11. Age Appropriate Paradigms What is changing with development? -behavioral level -neural level

12. Immature cognition is characterized by greater susceptibility to interference Ability to suppress inappropriate thoughts and actions in favor of appropriate ones (cognitive control). - adjust/alter thoughts and actions when predictions are violated (flexible rules use, E. Miller) Casey et al. 2000, 2002, 2005a, b,c

13. Spiderman NoGo Task “Try to catch Spiderman, but no, no, never catch the Green Goblin or you’ll be sorry!” Shultz, et al. 2003

25. Recruitment of Prefrontal Cortex across age Casey et al. 1997 JCN

26. Dorsolateral PFC Activity 1800 1500 1200 900 600 300 0 * Volume of Activity Children Adults Casey et al. 1997 * p < .05

27. Age vs Performance • Correlation of age and performance with brain activity • Partial out age and performance

28. Prefrontal Activity as a function of Age 2400 2000 1600 1200 800 400 Volume of Activation in MFG (mm3) 7 8 9 10 11 12 21 Age in Years Adapted from Casey et al., 1997 JoCN

29. Neuroanatomical correlates of go no/go performance Sackler Institute Durston et al (2002) Developmental Science

30. Age vs Performance • Correlation of age and performance with brain activity • Partial out age and performance • Assumes linearity

31. Age vs Performance • Correlation of age and performance with brain activity • Partial out age and performance • Assumes linearity • Parametric manipulation of task difficulty

32. Parametric Manipulation: vary # of preceding Gos before a NoGo Level 1 Level 2 Level 3 Time Ventral Prefrontal Activity during Go/Nogo Task Behavioral Performance during Go/Nogo Task Adults Children Adults Children Number of False Alarms % MR Signal Change 1 3 5 1 3 5 1 3 5 1 3 5 number of go trials preceding a nogo trial number of go trials preceding a nogo trial

33. Parametric Manipulation:vary # of preceding Gos before a NoGo Level 1 Level 2 Level 3 Time Ventral Prefrontal Activity during Go/Nogo Task Behavioral Performance during Go/Nogo Task Adults Children Adults Children Number of False Alarms % MR Signal Change 1 3 5 1 3 5 1 3 5 1 3 5 number of go trials preceding a nogo trial number of go trials preceding a nogo trial

34. Age vs Performance • Correlation of age and performance with brain activity • Partial out age and performance • Assumes linearity • Parametric manipulation of task difficulty • Matching performance (pre and post scan)

35. Performance over Time 100 - 80 - 60 - Adults Children Percent Accuracy 1 2 3 4 5 Runs Adapted from Thomas et al 1999

36. Age vs Performance • Correlation of age and performance with brain activity • Partial out age and performance • Assumes linearity • Parametric manipulation of task difficulty • Matching performance (pre and post scan) • Ages differ with time on task (pre-matching)

37. Area is active regardless of age or performance Activity differs as a function of performance rather than age Activity differs as a function of age, regardless of performance Schlaggar et al 2002

38. Area is active regardless of age or performance Activity differs as a function of performance rather than age Activity differs as a function of age, regardless of performance Schlaggar et al 2002

39. Area is active regardless of age or performance Activity differs as a function of performance rather than age Activity differs as a function of age, regardless of performance Schlaggar et al 2002

40. What is changing with development? Diffuse/focal Progressive/Regressive Brown et al 2005 Neuroimage

41. Cortical Changes with development on a variety of cognitive control tasks Casey et al. 2005 TICS

42. Longitudinal Study (7-12 years) Cortical regions that are recruited more (in red) and less (in blue) with development Sackler Institute, Cornell Medical Durston et al in press Dev Science

43. Longitudinal fMRI in typical development (Whole brain analyses based 21 scans) Within Ss Analysis Between Ss Analysis Between Ss Analysis at different ages of different ages of same ages Durston et al. in press Developmental Science Durston et al in press Dev Science

44. Fine-tuning of neural systems with development MRI fMRIDTI Structure Function Connectivity A B C

45. Developmental Differences in Frontostriatal structure Basal Ganglia Prefrontal Cortex Sowell et al., 1999

46. Developmental Differences in Frontostriatal Activity Prefrontal Cortex Basal Ganglia Neuroimage 2002 Dev Science 2002

47. Developmental Differences in Frontostriatal Activity

48. Development of Frontal and Posterior Tracts • Preliminary data suggest dissociation between allelic variants in dopamine genes expressed predominantly in prefrontal cortex and basal ganglia, respectively. 750 700 650 Mean Dav Children Adults Brightness corresponds to the relative anisotropy and color is direction of greatest diffusion (red = right-left, green = anterior-posterior, blue = superior-inferior). Boxes representing prefrontal white matter ROIs Mean prefrontal white matter Dav in children (7-10 years old) and adults (22-31 years old). Average diffusion is 7.7% lower in adults than in children (t = 3.17, p<.01).

49. Task Specific Connectivity Liston et al. submitted

50. Prefrontal Cortex Striatum Fiber tracts connecting Prefrontal and striatum