Locked-in Intact Functional Networks in Children with Autism Spectrum Disorder: A Case-Control Study

• Main Authors: Andrew R. Pines, Bethany Sussman, Sarah N. Wyckoff, Patrick J. McCarty, Raymond Bunch, Richard E. Frye, Varina L. Boerwinkle
• Format: Article
• Language: English
• Published: MDPI AG 2021-08-01
• Series: Journal of Personalized Medicine
• Subjects: autism spectrum disorder; locked-in network syndrome; resting-state functional magnetic resonance imaging; temporal lobe epilepsy
• Online Access: https://www.mdpi.com/2075-4426/11/9/854

Resting-state functional magnetic resonance imaging (rs-fMRI) has the potential to investigate abnormalities in brain network structure and connectivity on an individual level in neurodevelopmental disorders, such as autism spectrum disorder (ASD), paving the way toward using this technology for a personalized, precision medicine approach to diagnosis and treatment. Using a case-control design, we compared five patients with severe regressive-type ASD to five patients with temporal lobe epilepsy (TLE) to examine the association between brain network characteristics and diagnosis. All children with ASD and TLE demonstrated intact motor, language, and frontoparietal (FP) networks. However, aberrant networks not usually seen in the typical brain were also found. These aberrant networks were located in the motor (40%), language (80%), and FP (100%) regions in children with ASD, while children with TLE only presented with aberrant networks in the motor (40%) and language (20%) regions, in addition to identified seizure onset zones. Fisher’s exact test indicated a significant relationship between aberrant FP networks and diagnosis (<i>p =</i> 0.008), with ASD and atypical FP networks co-occurring more frequently than expected by chance. Despite severe cognitive delays, children with regressive-type ASD may demonstrate intact typical cortical network activation despite an inability to use these cognitive facilities. The functions of these intact cognitive networks may not be fully expressed, potentially because aberrant networks interfere with their long-range signaling, thus creating a unique “locked-in network” syndrome.