Issues in Pediatric NeuroimagingIssues in Pediatric Neuroimaging

Kathleen M. Thomas, Ph.D.

Institute of Child Development

University of Minnesota

AcknowledgementsAcknowledgements

B. J. CaseyB. J. CaseyRonald E. DahlRonald E. DahlCharles A. NelsonCharles A. NelsonNeal D. RyanNeal D. RyanPaul J. WhalenPaul J. Whalen

Jane W. CouperusJane W. CouperusJennifer J. Grubba-DerhamJennifer J. Grubba-DerhamRuskin H. HuntRuskin H. HuntLisa RohrerLisa RohrerElise L. TownsendElise L. TownsendAngela TsengAngela TsengNathalie VizuetaNathalie Vizueta

Funding from: NIMH, NINDS, McKnight FoundationFunding from: NIMH, NINDS, McKnight Foundation

Face ProcessingFace Processing

IdentityIdentity EmotionEmotion Direction of gaze (intentions)Direction of gaze (intentions)

The “Specialness” of FacesThe “Specialness” of Faces

Newborn infants prefer to look at face-like objects over other objects.

Johnson & Morton, 1991

Holistic ProcessingHolistic Processing

Inversion EffectsInversion Effects

Inversion EffectsInversion Effects

Facial Emotion Processing in ChildrenFacial 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

0 45 87 129 171 213 255 300

* *

Time (seconds)

Stimuli

Thomas et al, 2001, Biological Psychiatry

fMRI of Facial Emotion in ChildrenfMRI of Facial Emotion in ChildrenfMRI of Facial Emotion in ChildrenfMRI of Facial Emotion in Children

(8-15 yrs) and adults

Y = -2 Y = -4

Left AmygdalaSubstantia Innominata/

Ventral Pallidum

Y = -2 Y = -4Fear vs. Fixation

Amygdala Response to FearAmygdala Response to Fear

Children Adults

Fear vs. NeutralP

erce

nt

MR

Sig

nal

Ch

ange

in L

eft

Am

ygd

ala

.2

.1

0

-.1

-.2

Group Differences in ActivityGroup Differences in ActivityGroup Differences in ActivityGroup Differences in Activity

Per

cen

t M

R S

ign

al C

han

geIn

Lef

t &

Rig

ht

Am

ygd

ala Fear 2 minus Fear 1 .3

.2

.1

0

-.1

-.2

-.3

Females Males

Gender Differences in HabituationGender Differences in Habituation

SummarySummary

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 LesionsBilateral Amygdala Lesions

Adolphs et al., 1999, Neuropsychologia

Face Emotion ProcessingFace 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 PhobiaSocial PhobiaSocial PhobiaSocial Phobia

Rauch et al, 2000, Biological Psychiatry

Masked Fear vs Masked HappyGroup Difference

Post-Traumatic Stress Disorder (PTSD)Post-Traumatic Stress Disorder (PTSD)Post-Traumatic Stress Disorder (PTSD)Post-Traumatic Stress Disorder (PTSD)

DeBellis et al. (2000)

Amygdala Size in Childhood AnxietyAmygdala Size in Childhood AnxietyAmygdala Size in Childhood AnxietyAmygdala Size in Childhood Anxiety

Right Amygdala

0.01

0.05

p value

Thomas et al, 2001, Arch Gen PsychiatryFear vs. Neutral

Anxious ChildrenAnxious ChildrenAnxious ChildrenAnxious ChildrenAnxious children showed differential right amygdala activation compared to non-anxious children

% S

igna

l Ch

ange

in R

. Am

ygda

la

Healthy Anxious Children Children (n=12) (n=12)

0.4

0.2

0

-0.2

-0.4

Relative Response to FearRelative Response to FearRelative Response to FearRelative 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

% S

igna

l Ch

ange

in R

. Am

ygda

la

•••• ••

•

•

••

-1.0

-.5

0

.5

1.0

1.5

0 10 20 30 40 50 60

r = 0.624p < 0.005

Correlation with Everyday AnxietyCorrelation with Everyday AnxietyCorrelation with Everyday AnxietyCorrelation with Everyday Anxiety

% S

igna

l Ch

ange

in R

. Am

ygda

la

Healthy Anxious Depressed Children Children Children (n=5) (n=5) (n=5)

.6

.3

0

-.3

-.6

Relative Response Relative Response in Anxiety & Depressionin Anxiety & DepressionRelative Response Relative Response in Anxiety & Depressionin Anxiety & Depression

Depressed girls showed no change in the right amygdala for fear faces compared to neutral faces.

Considerations in Pediatric ImagingConsiderations in Pediatric ImagingConsiderations in Pediatric ImagingConsiderations in Pediatric Imaging

Hemodynamic response Spatial normalization Behavioral task Interpreting developmental effects

Does the hemodynamic response differ Does the hemodynamic response differ between adults and children?between adults and children?Does the hemodynamic response differ Does the hemodynamic response differ between adults and children?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 Can we use a common stereotaxic space for adult and child data?space for adult and child data?Can we use a common stereotaxic Can we use a common stereotaxic space for adult and child data?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 differencesInterpreting developmental differencesInterpreting developmental differencesInterpreting 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

1800

1500

1200

900 600

300

0

Vol

ume

of A

ctiv

ity

*

* p < .05Casey et al. 1997

DLPFCChildren

Adults

Group Differences in Magnitude or Extent of ActivityGroup Differences in Magnitude or Extent of Activity

Correlation between Activity & Behavioral PerformanceCorrelation between Activity & Behavioral Performance

Casey et al., 1997

Group Differences in Activity-Behavior RelationshipGroup Differences in Activity-Behavior Relationship

0

5

10

15

20

25

30

0 500 1000 1500 2000

Volume of Orbitofrontal Activation in mm3

Nu

mb

er o

f F

alse

Ala

rms

500 1000 1500 2000 2500

35

0

Perinatal Insult Control40

r = -.28 r = -.41

Percent Change in MR Signal Intensity

Fal

se A

larm

s

Perinatal Insult

0

5

10

15

20

25

30

-1.0 -.60 -.40 -.20 .20 .40 .60 .80 1 2 3 40 0-.80

40

35

45

r = -.77 r = .12 r = .81p < .05 NS p < .0005

Control

Group Differences in Activity-Behavior RelationshipGroup Differences in Activity-Behavior Relationship

N-Back Spatial Working MemoryN-Back Spatial Working MemoryN-Back Spatial Working MemoryN-Back Spatial Working Memory

+

+

+

+

Trial 1

Trial 2

Trial 3

Trial 4

Time

Thomas et al, 1999

1 2 3 4 5

100 -

80 -

60 -

Runs

Per

cent

Acc

urac

y

Adults

Children

Equating Initial PerformanceEquating Initial PerformanceEquating Initial PerformanceEquating Initial Performance

Thomas et al, 1999

Brown et al, 2005

Teasing Apart Age Teasing Apart Age and Performanceand PerformanceTeasing Apart Age Teasing Apart Age and Performanceand 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

% M

R S

ign

al C

ha

ng

e

1 3 5 1 3 5

Ventral Prefrontal Activityduring Go/Nogo Task

Adults Children

number of go trials preceding a nogo trial1 3 5 1 3 5

Behavioral Performanceduring Go/Nogo Task

Adults Children

number of go trials preceding a nogo trial

nogo

nogo

nogo

go

go go go

go go go go go

Parametric ManipulationParametric Manipulation

Continuous Recognition Memory TaskContinuous Recognition Memory Task

New (Concrete)

New (Abstract)

Old (Abstract)

Lag 5

Lag 2

New (Concrete)

New (Abstract)

New (Concrete)

Old (Concrete)

New Old

Duration = 500 ms

ISI = 4000 ms

TR = 2000 ms

Lag 2

Lag 5

New (Concrete)

Old (Concrete)

Medial Temporal Lobe ActivityMedial Temporal Lobe Activity

R L R L

Adults 7-8 yr oldsNew > Old

Concrete > AbstractOld > New

Group Differences in ActivityGroup Differences in ActivityAdults

7-8 yr olds

AbstractConcrete

Adults ChildrenParietal Parietal

NewLag 2Lag 5

Adults ChildrenParietal Right Parietal

Electrophysiological DataElectrophysiological Data

Child

R

R

L

R

R

L

R

R

R

Source ModelSource ModelAdult

NewLag 2Lag 5

Adults ChildrenParietal Right Parietal

Adult Child

Source Timing AnalysesSource Timing Analyses