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

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

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

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

Holistic Processing

Inversion Effects

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

** Time (seconds) Stimuli Thomas et al, 2001, Biological Psychiatry fMRI of Facial Emotion in Children (8-15 yrs) and adults

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

Children Adults Fear vs. Neutral Percent MR Signal Change in Left Amygdala Group Differences in Activity

Percent MR Signal Change In Left & Right Amygdala Fear 2 minus Fear Females Males Gender Differences in Habituation

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

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

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

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

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

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

Right Amygdala 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

% Signal Change in R. Amygdala Healthy Anxious Children (n=12) (n=12) 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

Child Reported SCARED Score % Signal Change in R. Amygdala r = p < Correlation with Everyday Anxiety

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

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

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

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.

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

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

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?

Children Adults Volume of Activity * * p <.05 Casey et al DLPFC Children Adults Group Differences in Magnitude or Extent of Activity

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

Group Differences in Activity- Behavior Relationship Volume of Orbitofrontal Activation in mm 3 Number of False Alarms Perinatal Insult Control 40 r = -.28r = -.41

Percent Change in MR Signal Intensity False Alarms Perinatal Insult r = -.77r =.12 r =.81 p <.05NS p <.0005 Control Group Differences in Activity- Behavior Relationship

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

Runs Percent Accuracy Adults Children Equating Initial Performance Thomas et al, 1999

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

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

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

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

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

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

Child R R L R R L R R R Source Model Adult

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