International Meeting for Autism Research (May 7 - 9, 2009): Abnormal Functional Connectivity during Emotional Face Processing Is Associated with Neural Abnormalities in the Amygdala in Autism Spectrum Disorders

Abnormal Functional Connectivity during Emotional Face Processing Is Associated with Neural Abnormalities in the Amygdala in Autism Spectrum Disorders

Saturday, May 9, 2009: 1:00 PM
Northwest Hall Room 5 (Chicago Hilton)
N. M. Kleinhans , Radiology, University of Washington, Seattle, WA
C. Johnson , Nursing, University of Washington, Seattle, WA
T. L. Richards , Radiology, University of Washington, Seattle, WA
J. Greenson , University of Washington, Seattle, WA
E. H. Aylward , Radiology, University of Washington, Seattle, WA
G. Dawson , Autism Speaks; Department of Psychiatry, UNC Chapel Hill, Chapel Hill, NC
Background:

Difficulty evaluating and interpreting facial expressions has been reported in autism spectrum disorders (ASD) and is thought to be associated with amygdalar abnormalities. Despite numerous brain imaging studies of amygdala response to emotional faces in ASD, the relationship between the integrity of the neural tissue and neural functioning of the amydgala has not been previously assessed.

Objectives:

Functional magnetic resonance imaging (fMRI) and proton magnetic resonance spectroscopy (MRS) were used to explore the neural basis of abnormal emotional face processing in ASD.

Methods:

MRS and fMRI data were collected within the same scanning session. During fMRI scanning, 29 individuals with ASD and 25 normal controls viewed Ekman faces depicting fear or anger. Subjects were instructed to select which of two faces at the bottom of the screen portrayed the same emotion as the face at the top of the screen. The control condition consisted of a simple shape-matching task. The left amygdala was used as the seed region for the functional connectivity analyses. A physiological interaction approach was utilized to identify regions that showed stronger connectivity during the emotional face processing task compared to the shape matching task. MRS was used to measure n-acetyl aspartate (NAA), creatine/phosphocreatine (Cre), and choline/choline containing compounds (Cho) in the left amygdala. Automated tissue segmentation on the MRS voxel yielded percent white matter, gray matter, and CSF. Metabolite levels were normalized to 100% brain tissue by controlling for percentage of CSF within the voxel.

Results:

For the comparison of emotional faces vs. shapes, controls evidenced significantly stronger connectivity between the amygdala and right fusiform gyrus and the amygdala and left prefrontal cortex. The ASD group showed significantly increased connectivity between the amygdala and the occipital lobe (BAs 17, 18, and 19). Functional connectivity analyses were also conducted with the metabolite concentrations entered as independent variables. Percentage of gray matter within the MRS voxel was entered as a covariate in the analyses. For the ASD group, greater functional connectivity from the amygdala to the right fusifrom gyrus and right prefrontal cortex was associated with higher concentrations of Cre. Increased functional connectivity from the amygdala to the right fusiform, left hippocampus, left prefrontal cortex, and bilateral occipital cortex was associated with higher concentrations of NAA. No significant correlations between functional connectivity and Cho concentrations were observed.

Conclusions:

Overall, these findings indicate that individuals with ASD exhibit reduced connectivity to prefrontal regions and the fusiform face area and increased connectivity to primary and secondary visual cortices during socioemotional processing. The correlation between metabolite levels (NAA and Cre) and functional connectivity between the amygdala and cortical regions suggests that abnormal connectivity in ASD may be associated with neuronal impairments related to the integrity and energetic status of the cells. Other possible underlying neuronal abnormalities such as gliosis or chronic inflammation are less likely to contribute to abnormal connectivity given the current findings.

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