Distinct Neural Signatures in Social Brain Circuitry in Female Children with ASD

Background: Autism spectrum disorder (ASD) affects 1 in 189 girls in the United States and is characterized by pervasive deficits in social communication. Due to the greater incidence of ASD in males, the vast majority of research into the behavioral and brain bases of autism have relied on data collected predominantly from male participants. Unfortunately, this has precluded a comprehensive understanding of autism in females, which is critical for developing autism treatment approaches for girls. Of particular interest is that, on average, females with ASD have greater social communication abilities compared to males. This result is consistent with the hypothesis that females with ASD are “protected” from more severe forms of social dysfunction.

Objectives: Here, the goal of our work is to provide important new information regarding the behavioral and neural profiles of girls with ASD with a focus on identifying brain circuitry which are intact relative to boys with ASD.

Methods: We examined the integrity of brain systems underlying a critical aspect of social function that is impaired in ASD: the processing of human voices. Specifically, we examined intrinsic functional connectivity of the voice-selective brain network, anchored in bilateral superior temporal sulcus, in a group of 13 girls with ASD (7-12 y/o) and a comparison group of 13 boys with ASD matched on age, IQ, motion, and ADOS Social Affect. We are also analyzing similar brain and behavioral data from the ABIDE-2 dataset and vocal task-based brain imaging data previously collected by our group.

Results: Preliminary data provide evidence for differential recruitment of voice processing, reward, and affective brain systems in females with ASD. Consistent with a previous study (Abrams et al, PNAS, 2013), boys with ASD showed hypo-connectivity of the extended voice-selective network, which includes reward and salience regions. Strikingly, girls with ASD show hyper-connectivity within this network: connectivity in females with ASD exceeded both males with ASD as well as TD boys and girls.

Conclusions: Results suggest that girls with ASD show a distinct neural signature characterized by hyper-connectivity of the extended voice-selected network, and provide preliminary evidence that increased connectivity of voice-reward circuitry may serve as a neuroprotective mechanism for females with ASD. Findings provide new and important information regarding social brain circuitry in girls with ASD, and may contribute to the development of new approaches for identifying and treating affected girls.