Tubers Affecting the Fusiform Face Area Are Associated with Autism Diagnosis

Abstract

Objective: Tuberous sclerosis complex (TSC) is associated with focal brain "tubers" and a high incidence of autism spectrum disorder (ASD). The location of brain tubers associated with autism may provide insight into the neuroanatomical substrate of ASD symptoms. Methods: We delineated tuber locations for 115 TSC participants with ASD (n = 31) and without ASD (n = 84) from the Tuberous Sclerosis Complex Autism Center of Excellence Research Network. We tested for associations between ASD diagnosis and tuber burden within the whole brain, specific lobes, and at 8 regions of interest derived from the ASD neuroimaging literature, including the anterior cingulate, orbitofrontal and posterior parietal cortices, inferior frontal and fusiform gyri, superior temporal sulcus, amygdala, and supplemental motor area. Next, we performed an unbiased data-driven voxelwise lesion symptom mapping (VLSM) analysis. Finally, we calculated the risk of ASD associated with positive findings from the above analyses. Results: There were no significant ASD-related differences in tuber burden across the whole brain, within specific lobes, or within a priori regions derived from the ASD literature. However, using VLSM analysis, we found that tubers involving the right fusiform face area (FFA) were associated with a 3.7-fold increased risk of developing ASD. Interpretation: Although TSC is a rare cause of ASD, there is a strong association between tuber involvement of the right FFA and ASD diagnosis. This highlights a potentially causative mechanism for developing autism in TSC that may guide research into ASD symptoms more generally.

Reply to “Is There an Association between Tuber Involvement of the Fusiform Face Area in Autism Diagnosis?”

“…We thank Weiner and Willbrand for their interest in our recent work 1 . We commend their focused analysis relating the location of tubers associated with diagnosis of autism spectrum disorder (ASD) in our paper 2 to visually selective regions in the right temporal lobe, including the right fusiform face area (FFA). They note a spatial offset between the voxel‐wise lesion symptom mapping (VLSM) peak derived from tuber locations and the FFA as defined by functional neuroimaging.…”