1. Issues in Pediatric Neuroimaging Kathleen M. Thomas, Ph.D. Institute of Child Development University of Minnesota

2. Acknowledgements B. J. Casey Ronald E. Dahl Charles A. Nelson Neal D. Ryan Paul J. Whalen Jane W. Couperus Jennifer J. Grubba-Derham Ruskin H. Hunt Lisa Rohrer Elise L. Townsend Angela Tseng Nathalie Vizueta Funding from: NIMH, NINDS, McKnight Foundation

3. Face Processing Identity Identity Emotion Emotion Direction of gaze (intentions) Direction of gaze (intentions)

4. The Specialness of Faces Newborn infants prefer to look at face-like objects over other objects. Johnson & Morton, 1991

5. Holistic Processing

6. Inversion Effects

8. Facial Emotion Processing in Children Infants discriminate positive and negative facial expressions at least as young as 4 months of age Discrimination of emotions within valence categories appears to take longer to develop, extending well into childhood and even early adolescence

9. 0 45 87 129 171 213 255 300 ** Time (seconds) Stimuli Thomas et al, 2001, Biological Psychiatry fMRI of Facial Emotion in Children (8-15 yrs) and adults

10. Y = -2Y = -4 LeftAmygdala Substantia Innominata/ Ventral Pallidum Y = -2 Y = -4 Fear vs. Fixation Amygdala Response to Fear

11. Children Adults Fear vs. Neutral Percent MR Signal Change in Left Amygdala.2.1 0 -.1 -.2 Group Differences in Activity

12. Percent MR Signal Change In Left & Right Amygdala Fear 2 minus Fear 1.3.2.1 0 -.1 -.2 -.3 Females Males Gender Differences in Habituation

13. Summary The normal amygdala response to facial expressions differs across development Ambiguity hypothesis The amygdala response may differ between males and females These data do not address whether these changes are due to differences in bottom-up or top-down processing streams

14. Amaral et al., (2003) Adult lesions to the amygdala in non-human primates result in a lack of normal fear responses to threatening stimuli Bilateral Amygdala Lesions

15. Adolphs et al., 1999, Neuropsychologia Face Emotion Processing Brain Damaged Controls Bilateral Amygdala Lesions

16. Birbaumer et al. (1998) Social phobics show an enhanced amygdala response to neutral faces compared to non-phobic controls The amygdala response to odors (neutral, positive & negative) was no different for social phobics suggesting the effect is specific to face stimuli The two groups did not differ in their ratings of the valence or aversiveness of the faces or odors Social Phobia

17. Rauch et al, 2000, Biological Psychiatry Masked Fear vs Masked Happy Group Difference Post-Traumatic Stress Disorder (PTSD)

18. DeBellis et al. (2000) Amygdala Size in Childhood Anxiety

19. Right Amygdala 0.01 0.05 p value Thomas et al, 2001, Arch Gen Psychiatry Fear vs. Neutral Anxious Children Anxious children showed differential right amygdala activation compared to non-anxious children

20. % Signal Change in R. Amygdala Healthy Anxious Children (n=12) (n=12) 0.4 0.2 0 -0.2 -0.4 Relative Response to Fear Anxious children activated the right amygdala more for fear faces than neutral faces, unlike non- anxious children who showed significantly more activity for neutral faces

21. Child Reported SCARED Score % Signal Change in R. Amygdala -.5 0.5 1.0 1.5 0102030405060 r = 0.624 p < 0.005 Correlation with Everyday Anxiety

22. % Signal Change in R. Amygdala Healthy Anxious Depressed Children Children Children (n=5) (n=5) (n=5).6.3 0 -.3 -.6 Relative Response in Anxiety & Depression Depressed girls showed no change in the right amygdala for fear faces compared to neutral faces.

23. Considerations in Pediatric Imaging Hemodynamic response Spatial normalization Behavioral task Interpreting developmental effects

24. Does the hemodynamic response differ between adults and children? Richter, 2003

25. Kang et al., 2003 The time course and amplitude of the hemodynamic response in a simple visual-motor response task is similar in adults and 7-8 year old children.

26. Can we use a common stereotaxic space for adult and child data? Burgund et al, 2002

27. Individual sulci were located within 4 mm of one another between adults and 7-8 year old children. This difference is within the resolution of most functional MRI measurements. Burgund et al, 2002

28. Interpreting developmental differences Differences between age groups may include signal intensity (magnitude), extent of activity (volume), direction of effect, relation to behavior What does the group difference reflect?

29. Children Adults 1800 1500 1200 900 600 300 0 Volume of Activity * * p <.05 Casey et al. 1997 DLPFC Children Adults Group Differences in Magnitude or Extent of Activity

30. Correlation between Activity & Behavioral Performance Casey et al., 1997

31. Group Differences in Activity- Behavior Relationship 0 5 10 15 20 25 30 0500100015002000 Volume of Orbitofrontal Activation in mm 3 Number of False Alarms 50010001500 20002500 35 0 Perinatal Insult Control 40 r = -.28r = -.41

32. Percent Change in MR Signal Intensity False Alarms Perinatal Insult 0 5 10 15 20 25 30 -.60-.40-.20.20.40.60.80123400 -.80 40 35 45 r = -.77r =.12 r =.81 p <.05NS p <.0005 Control Group Differences in Activity- Behavior Relationship

33. N-Back Spatial Working Memory + + + + Trial 1 Trial 2 Trial 3 Trial 4 Time Thomas et al, 1999

34. 1 2 3 4 5 100 - 80 - 60 - Runs Percent Accuracy Adults Children Equating Initial Performance Thomas et al, 1999

35. Brown et al, 2005 Teasing Apart Age and Performance 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

36. % MR Signal Change 1 3 5 Ventral Prefrontal Activity during Go/Nogo Task Adults Children number of go trials preceding a nogo trial 1 3 5 Behavioral Performance during Go/Nogo Task Adults Children number of go trials preceding a nogo trial nogo go Parametric Manipulation

37. Continuous Recognition Memory Task Lag 2 Lag 5 New (Concrete) Old (Concrete)

39. Medial Temporal Lobe Activity RL R L Adults 7-8 yr olds New > Old

40. Concrete > Abstract Old > New Group Differences in Activity Adults 7-8 yr olds

41. Abstract Concrete Adults Children Parietal New Lag 2 Lag 5 Adults Children Parietal Right Parietal Electrophysiological Data

42. Child R R L R R L R R R Source Model Adult

43. New Lag 2 Lag 5 Adults Children Parietal Right Parietal Adult Child Source Timing Analyses