Tubers Affecting the Fusiform Face Area Are Associated with Autism Diagnosis.

Researchers studied people with Tuberous Sclerosis Complex, a condition that causes brain lesions called 'tubers' and often leads to autism. They found that when these brain lesions affected a specific area called the fusiform face area (involved in recognizing faces), people were nearly 4 times more likely to have autism. This discovery helps us understand how brain differences might contribute to autism development.

This study examined 115 individuals with Tuberous Sclerosis Complex (TSC) to identify brain lesion locations associated with autism diagnosis. Researchers compared 31 participants with autism to 84 without autism, analyzing brain 'tubers' (focal lesions) across various regions. While no differences were found in overall tuber burden or in previously identified autism-related brain regions, advanced voxelwise analysis revealed that tubers affecting the right fusiform face area were significantly associated with autism diagnosis, increasing risk 3.7-fold. This finding suggests the fusiform face area may play a causative role in autism development within TSC and provides insights into potential neuroanatomical mechanisms underlying autism spectrum disorder more broadly.

Findings suggest the fusiform face area may be a critical region for autism development in TSC. This could inform targeted interventions and monitoring strategies for TSC patients with tubers in this region, and guide broader autism research into face processing and social cognition mechanisms.

Study limited to individuals with TSC, a rare condition, which may not generalize to broader autism population. Sample size of 31 autism cases is relatively small. Cross-sectional design cannot establish temporal causation between tuber location and autism development.

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. 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. 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.

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. ANN NEUROL 2023;93:577-590.