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Original Investigation |

Atypical Cross Talk Between Mentalizing and Mirror Neuron Networks in Autism Spectrum Disorder

Inna Fishman, PhD1; Christopher L. Keown, MS1; Alan J. Lincoln, PhD2; Jaime A. Pineda, PhD3; Ralph-Axel Müller, PhD1
[+] Author Affiliations
1San Diego State University, San Diego, California
2Alliant International University, San Diego, California
3University of California San Diego, La Jolla, California
JAMA Psychiatry. 2014;71(7):751-760. doi:10.1001/jamapsychiatry.2014.83.
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Importance  Converging evidence indicates that brain abnormalities in autism spectrum disorder (ASD) involve atypical network connectivity, but it is unclear whether altered connectivity is especially prominent in brain networks that participate in social cognition.

Objective  To investigate whether adolescents with ASD show altered functional connectivity in 2 brain networks putatively impaired in ASD and involved in social processing, theory of mind (ToM) and mirror neuron system (MNS).

Design, Setting, and Participants  Cross-sectional study using resting-state functional magnetic resonance imaging involving 25 adolescents with ASD between the ages of 11 and 18 years and 25 typically developing adolescents matched for age, handedness, and nonverbal IQ.

Main Outcomes and Measures  Statistical parametric maps testing the degree of whole-brain functional connectivity and social functioning measures.

Results  Relative to typically developing controls, participants with ASD showed a mixed pattern of both over- and underconnectivity in the ToM network, which was associated with greater social impairment. Increased connectivity in the ASD group was detected primarily between the regions of the MNS and ToM, and was correlated with sociocommunicative measures, suggesting that excessive ToM-MNS cross talk might be associated with social impairment. In a secondary analysis comparing a subset of the 15 participants with ASD with the most severe symptomology and a tightly matched subset of 15 typically developing controls, participants with ASD showed exclusive overconnectivity effects in both ToM and MNS networks, which were also associated with greater social dysfunction.

Conclusions and Relevance  Adolescents with ASD showed atypically increased functional connectivity involving the mentalizing and mirror neuron systems, largely reflecting greater cross talk between the 2. This finding is consistent with emerging evidence of reduced network segregation in ASD and challenges the prevailing theory of general long-distance underconnectivity in ASD. This excess ToM-MNS connectivity may reflect immature or aberrant developmental processes in 2 brain networks involved in understanding of others, a domain of impairment in ASD. Further, robust links with sociocommunicative symptoms of ASD implicate atypically increased ToM-MNS connectivity in social deficits observed in ASD.

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Figure 1.
Within-Group Functional Connectivity Maps for Mirror Neuron System (MNS) (Top Panel) and Theory of Mind (ToM) (Bottom Panel) Seeds

Results of the within-group (autism spectrum disorder [ASD], typically developing [TD]; P < .05, corrected) analyses obtained for each MNS and ToM seed (top and bottom panels, respectively) are presented in a conjunction view. Seed regions of interest are presented on the axial slices on the left (red dots reflect the actual size of the spherical regions of interest). Inflated maps were generated using Surface Mapping with Analysis of Functional NeuroImages (SUMA, http://afni.nimh.nih.gov/afni/suma). L indicates left; laIPS, left anterior intraparietal sulcus (Talairach coordinates −40, −40, 45); lpSTS, left posterior superior temporal sulcus (−50, −55, 10); lPMC, left premotor cortex (–40, 5, 40); lTPJ, left temporal-parietal junction (−50, −55, 25); mPFC, medial prefrontal cortex (0, 50, 20); PC, precuneus; PCC, posterior cingulate cortex (0, −60, 40); R, right; raIPS, right anterior intraparietal sulcus (40, –40, 45); rpSTS, right posterior superior temporal sulcus (50, −55, 10); rPMC, right premotor cortex (40, 5, 40); and rTPJ, right temporal-parietal junction (50, −55, 25).

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Figure 2.
Regions Exhibiting Group Differences (Autism Spectrum Disorder [ASD] vs Typically Developing [TD]) in Functional Connectivity (FC) and the Relationship Between FC and Clinical Severity in the ASD Group

A, Clusters of significantly different FC (P < .05, corrected) in participants with ASD relative to the TD participants are illustrated for the theory of mind (ToM) seeds. The scatterplot on the right shows the relationship between the ToM–mirror neuron system (MNS) overconnectivity (average z scores for all between-network region of interest pairs) and social symptomatology measured by the Autism Diagnostic Interview–Revised (ADI-R) Social scores (Spearman r25 = 0.58, P = .003). B, Clusters of significantly different FC (P < .05, corrected) in the subset of 15 participants with ASD and Autism Diagnostic Observation Schedule (ADOS) Communication + Social (CS) of 10 or greater and 15 matched TD participants. All depicted ToM and MNS seeds yielded overconnected clusters (ASD > TD). The scatterplot on the right shows the relationship between the ToM-MNS overconnectivity (average z scores for all between-network region of interest pairs) and social symptoms measured by the ADI-R Social scores (Spearman r15 = 0.56, P = .04). Increasing ADI-Social values indicate greater social impairment. lTPJ indicates left temporal-parietal junction; L, left; mPFC, medial prefrontal cortex; PC, precuneus; PCC, posterior cingulate cortex; raIPS, right anterior intraparietal sulcus, R, right; and rTPJ, right temporal-parietal junction.

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