Abstract
Objective: This study indirectly tested the hypothesis that individuals with autism spectrum disorders (ASDs) have impaired neural connections between the amygdala, fusiform face area, and superior temporal sulcus, key processing nodes of the ‘social brain’. This would be evidenced by abnormalities in the major fibre tracts known to connect these structures, including the inferior longitudinal fasciculus and inferior fronto-occipital fasciculus.
Method: Magnetic resonance diffusion tensor imaging was performed on 20 right-handed males (ASD = 10, controls = 10) with a mean age 13.5 ± 4.0 years. Subjects were group-matched according to age, full-scale IQ, handedness, and ethnicity. Fractional anisotropy was used to assess structural integrity of major fibre tracts. Voxel-wise comparison of white matter fractional anisotropy was conducted between groups using ANCOVA adjusting for age, full-scale IQ, and brain volume. Volumes of interest were identified using predetermined probability and cluster thresholds. Follow-up tractography was performed to confirm the anatomic location of all volumes of interest which were observed primarily in peri-callosal regions and the temporal lobes.
Results: The regions of lower fractional anisotropy, as confirmed by tractography, involved the inferior longitudinal fasciculus/inferior fronto-occipital fasciculus, superior longitudinal fasciculus, and corpus callosum/cingulum. Notably, some volumes of interest were adjacent to the fusiform face area, bilaterally, corresponding to involvement of the inferior longitudinal fasciculus. The largest effect sizes were noted for volumes of interest in the right anterior radiation of the corpus callosum/cingulum and right fusiform face area (inferior longitudinal fasciculus).
Conclusions: This study provides preliminary evidence of impaired neural connectivity in the corpus callosum/cingulum and temporal lobes involving the inferior longitudinal fasciculus/inferior fronto-occipital fasciculus and superior longitudinal fasciculus in ASDs. These findings provide preliminary support for aberrant neural connectivity between the amygdala, fusiform face area, and superior temporal sulcus–temporal lobe structures critical for normal social perception and cognition.
Acknowledgements
We graciously thank Dr Robert Schultz, who kindly provided the data and computational resources necessary for our analysis and Dr Sarah Paterson, who assisted with the preparation of the manuscript. We would also like to acknowledge the help of Lawrence Win, Kenneth Rando, and Marcello DiStasio with data assembly. We gratefully acknowledge the effort and commitment of the participants and their families in this study.
Declaration of interest: We are thankful for the grant support we have received for this project from the National Institute of Child Health and Human Development (NICHD) Collaborative Programs of Excellence in Autism (CPEA) (U19-HD35482), the National Institute of Neurological Disorders and Stroke (NINDS) (R01-NS035193), and the General Clinical Research Centers (GCRC) (MO1-RR00125). This work was also supported, in part, by the American Psychiatric Institute for Research and Education/Eli Lilly and Company Psychiatric Research Fellowship and the ANA/Pfizer Fellowships in Clinical Practice from Pfizer's Medical and Academic Partnership program. The authors alone are responsible for the content and writing of the paper.