Supplementary Materials: Williams et al

Neural response to faces in preadolescent children:

Because the neural response to emotional faces varies across development, we characterizedface responsive regions in our entire 8-12 year old sample. Among other regions, we found robust amygdala responses to faces (both fear and neutral) while controlling for group (Figure 2, Table S1; p < .05, corrected whole brain). Additional brain regions shown in Table S1 that responded to face stimuli in our preadolescent sample are consistent with studies of face viewing in adults and adolescents (for review seeFusar-Poli et al, 2009).

Table S1: Neural response to faces across all subjects

# Voxels / Peak Voxel / Hemisphere / Location
1551 / 38, -92, -6 / Right / Inferior Occipital Gyrus
702 / -22, -20, -18 / Left / Paraphippocampal Gyrus
554 / 24. -16, -18 / Right / Paraphippocampal Gyrus
397 / -42, -50, -30 / Left / Cerebellum
190* / -8, -74, 50 / Left / Precuneus
122 / 50, -52, 50 / Right / Inferior Parietal Lobule
87 / 32, -2, -42 / Right / Fusiform Gyrus
84 / 14, -84, -30 / Right / Cerebellum
78 / 34, 44, -10 / Right / Middle Frontal Gyrus

*Deactivation

Greater activation to fear versus neutral faces

To examine valence effects in our preadolescent sample, fear faces were compared with neutral faces. Similar to studies of adults and adolsecents(e.g. (Fusar-Poli et al, 2009) we found greater amygdala activation to fear relative to neutral faces (Supplemental Figure 1), as well as greater activation within regions of the fusiform gyrus and middle temporal gyrus (Table S2; p < 0.05, corrected whole brain). Amygdala activation to fear vs. neutral faces did not differ between AD children and controls (p=.39).

Table S2: Valence effect across all subjects, whole brain

# Voxels / Peak Voxel / Hemisphere / Location
264 / 46, -38, 2 / Right / Middle Temporal Gyrus
92 / -40, -54, -20 / Left / Fusiform Gyrus

Increased amygdala activation in AD children during uncertain anticipation relative to neutral anticipation

To test whether the increased amygdala activation observed in children with ADs in response to the Uncertain cue, relative to the certain Negative cue, was driven by response to uncertainty, we also compared the difference in Uncertain cues and certain Neutral cues between AD children and controls. Similar to the findings presented in Figure 3, when comparing AD children and controls for their difference in activation between the Uncertain andNeutral cues within the face-responsive amygdala region, children with ADs exhibited differential amygdala activation (Supplemental Figure 2, p < 0.05 corrected), further demonstrating the specific effect of uncertainty. Within the Uncertain cue condition, control children demonstrated significant deactivation (p < 0.005) that was absent in the anxiety disorder group (p = 0.54).

Increased amygdala response in AD children for neutral faces preceded by uncertain cues

To examine the specificity of the increased amygdala activation observed in AD children when viewing fear faces preceded by Uncertain cues versus fear faces that followed certain, Negative cues, we performed the same analysis using neutral faces. Similar to the finding for fear faces, relative to controls, AD children demonstrated enhanced amygdala reactivity to neutral faces that were preceded by an uncertain cue (Supplemental Figure 3).When viewing neutral faces preceded by the Uncertain cue, AD children had significant activation (p < 0.005) that was absent in the control group (p = 0.97).

AD children exhibit increased activation within other brain regions during uncertain anticipation

Exploratory whole brain analyses within the anticipation task uncovered additional regions that differed between AD and control children during uncertain anticipation, including portions of the left insula, cerebellum, and visual cortex (Supplemental Figure 4, TableS3).

Table S3: Increased activation during uncertain anticipation in children with ADs

# Voxels / Peak Voxel / Hemisphere / Location
209 / 4, -74, -14 / Right / Lingual Gyrus
103 / 22, -28, -26 / Right / Cerebellum/Fusiform Gyrus
99 / -36, 14, -6 / Left / Insula
77 / -26, -36, -38 / Left / Cerebellum

Reference:

Fusar-Poli P, Placentino A, Carletti F, Landi P, Allen P, Surguladze S, et al (2009). Functional atlas of emotional faces processing: a voxel-based meta-analysis of 105 functional magnetic resonance imaging studies. Journal of psychiatry & neuroscience : JPN34(6): 418-432.

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