Amygdala Hyperconnectivity during Adaptive Executive Control of Social Information Processing in Autism Spectrum Disorders (ASD) Children

Background:  

Social communication, an area of impairment in ASD, involves dynamic interaction between social information processing (e.g., eye gaze) and flexible executive control of actions in the service of goals.  We have reported that ASD children engage a more widespread network of regions connected to the amygdala during executive control of social cues in a novel Stroop-like interference task, suggesting difficulty suppressing emotional reactivity during executive control (Murphy et al., 2012).  Here, we examine context-adaptation reflecting dynamic executive control of social cues, manifested in trial-to-trial adjustments in control evoked by variable proportion of incongruent and congruent trials – higher adjustment is needed in a block of 25% incongruent and 75% congruent trials relative to a block with 75% incongruent and 25% congruent trials.  Such adaptive executive control is reflective of real-world social interaction.

Objectives:  

To examine amygdala functional connectivity during adaptive executive control of socially significant information processing in 7-14 year-old ASD and control children.

Methods:  

Imaging was performed at 3T in 73 children (age, gender, and IQ matched 38  ASD, 35 controls) during 2 runs of the Stroop-like task requiring a left/right handed response to the direction indicated by a word (LEFT or RIGHT) positioned on the nasion of faces appearing in color with neutral facial expression.  Across trials, eye-gaze direction varied such that relative to the target word, it was either congruent (leftward gaze and “LEFT” word) or incongruent (leftward gaze and “RIGHT” word).  Unbeknownst to the subjects, the proportion of incongruent (I) and congruent (C) trials varied across blocks (25I-75C%; 50I-50C%; 75I-25C%) with jittered trials within blocks to allow selective averaging of incongruent and congruent trials.

Images were slice-time and motion-corrected, normalized and resliced to 3mm, smoothed with 8mm FWHM and using stringent motion-criteria retained 38 children (16 ASD, 22 controls).  Functional connectivity was analyzed using psychophysiological interaction in SPM8, for right and left amygdala ROIs based on the AAL brain atlas, separately for Incongruent and congruent trials.  Regions showing differences between ASD and control groups for 25I-75C% vs. 75I-25C% contrast were identified with a whole-brain ANOVA in SPM 8 (p < .05 Monte Carlo corrected; p<.001, k=24 voxels).

Results:  

Performance was slower for incongruent than congruent trials indicating interference suppression associated with greater executive control.  Interference was higher for 25I-75C% relative to 75I-25C% blocks but did not differ by group.  For both left and right amygdala, connectivity was greater in ASD than control children for incongruent trials, with right superior temporal sulcus and precuneus, important for gaze processing. Additionally, left amygdala also had greater connectivity with bilateral supplementary motor and striatal regions, involved in response inhibition and superior and inferior parietal cortex involved in spatial attention. Connectivity for congruent trials did not differ between groups for the left amygdala, but was greater with the left lingual gyrus, a visual processing region in ASD than control children.

Conclusions:  

These findings draw attention to hyperconnectivity of the amygdala with striatal and temporo-parietal regions as loci of network disturbances contributing to social interaction difficulties in ASD.