Diffusion Tensor Imaging in Autism Spectrum Disorders: Preliminary Evidence of Abnormal Neural Connectivity

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. Results All volumes of interest were regions of lower FA and were observed primarily in pericallosal regions and temporal lobes. As confirmed by tractography, affected white matter structures included 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.

Structural Neural Phenotype of Autism: Preliminary Evidence from a Diffusion Tensor Imaging Study Using Tract-Based Spatial Statistics

“…39 Moreover, previously published DTI studies lend support to abnormalities of the inferior fronto-occipital fasciculus in ASD. 15,17,21,23,40,41 In the present study, the right inferior fronto-occipital fasciculus was the most severely affected association tract, which suggests a potential mechanism for known impairments in facial emotion recognition in ASD.…”

“…10 Moreover, several DTI studies also have revealed abnormalities of the left superior longitudinal fasciculus in ASD. 17,20,23,41,44 Although the important role the left superior longitudinal fasciculus has in language processing has been known since the 19th century, the importance of this structure in the right hemisphere is emerging. Abnormalities of the right superior longitudinal fasciculus also have important implications for ASD due to its connection to the superior temporal sulcus, 42 a region well known for its role in processing biologic motion, which is abnormal in ASD.…”

“…17,23 The inferior fronto-occipital fasciculus is unique in that it connects all 4 major lobes of the brain, 24 potentially serving an important role in linking all the components in what is commonly called the "social brain" (Fig 1). Therefore, it is hypothesized that the neural phenotype in ASD consists of widespread impairments in long-range connections with higher aberrations seen in the inferior fronto-occipital fasciculus.…”

A network of genetic repression and derepression specifies projection fates in the developing neocortex

“…This role for Tbr1 in callosal development is also intriguing in the context of autism. Autistic patients seem to have callosal abnormalities (19)(20)(21)(22)(23)(24)(25)(26), and in this context it is relevant that Auts2, a gene associated with autism, is regulated by Tbr1, which in turn is regulated by Satb2, a callosal fate specification gene. Recent studies suggest that a mutation in CAv1/2 (an L-type calcium channel) that is associated with Timothy syndrome, a form of autism, results in lower numbers of Satb2-expressing cells and an increase in Ctip2-expressing cells (31).…”

“…The functional significance of this relationship has been puzzling because Tbr1 regulates corticothalamic identity, and there have been no reports of defects in corticothalamic tracts in autistic patients. However, imaging studies in patients with autism have revealed defects in callosal tracts (2,(19)(20)(21)(22)(23)(24)(25)(26). A recent publication highlights a deficit in long-range connections (such as callosal connections) and excess of short-range cortical connections in patients with autism spectrum disorder (27).…”