A quarterly publication of the Autism Research Institute

The Autism Research Review International is quarterly publication of the Autism Research Institute

Fall, 2017 | Number 4, Volume 31

New research points to role of RCrusI in autism symptoms, hints at possible treatment

New research reveals that a specific part of the cerebellum plays a key role in autism spectrum disorders (ASD) and suggests that neuromodulation of this area may help treat the social deficits of individuals with the condition. 

Catherine Stoodley, Peter Tsai, and their colleagues focused on an area of the cerebellum called the Tsai and colleagues say neuromodulation of the cerebellum may be a promising therapy for social problems in ASD. Right Crus I (RCrusI). While abnormalities in this area are consistently reported in ASD, the researchers say that the contribution of RCrusI dysfunction to ASD has been unclear. 

In their study, the researchers established that in both humans and mice, the Right Crus I is functionally connected to multiple brain networks. “Given the extensive functional connectivity of RCrusI,” they say, “the structural and functional abnormalities in RCrusI often reported in ASD could have wide-ranging impacts on the function of multiple, distributed cortical regions implicated in ASD.” The researchers also found that in neurotypical adults, neuromodulation via transcranial direct current stimulation (tDCS) altered functional connectivity in cerebellar-cerebral networks associated with ASD. 

Using a mouse model of autism, the researchers found that structural connectivity between the RCrusI and the cortex’s inferior parietal lobule (IPL) was atypical in these mice. They also analyzed data from a large sample of children with ASD and found that the children exhibited abnormalities in functional RCrusI-IPL connectivity. 

“The left IPL is believed to integrate visuospatial, motor, and cognitive information,” the researchers say, “and it has been shown to be critical for imitating and interpreting the gestures of others. These functions are consistent with evidence that children with ASD struggle to efficiently integrate visual information to guide skilled behaviors, which is necessary for both imitation and normal social interaction and may be critical to the development of core ASD symptoms.” 

Additionally, the researchers determined that disrupting RCrusI function in normal mice resulted in impaired social interaction and abnormal repetitive behaviors. Finally, they found that stimulation of the RCrusI in the “autistic” mice improved social behavior but not repetitive behaviors. 

Tsai comments that the limited effects of neuromodulation may indicate that additional parts of the cerebellum are involved, or that there is a restricted time in which to correct repetitive behaviors. However, he notes that neuromodulation restored social behaviors even in adult mice. Tsai says, “Our findings have prompted new thoughts on how the cerebellum may be involved in autism and most importantly suggest that the cerebellum could be a therapeutic target for treatment.” The researchers note that the RCrusI is a more accessible target for brain stimulation than other autism-related networks that are deep within the brain. However, they caution that the safety of cerebellar neuromodulation for individuals with ASD needs to be tested, although the intervention is already used in treating schizophrenia.


Citations

“Altered cerebellar connectivity in autism and cerebellar-mediated rescue of autism-related behaviors in mice,” Catherine J. Stoodley, Anila M. D’Mello, Jacob Ellegood, Vikram Jakkamsetti, Pei Liu, Mary Beth Nebel, Jennifer M. Gibson, Elyza Kelly, Fantao Meng, Christopher A. Cano, Juan M. Pascual, Stewart H. Mostofsky, Jason P. Lerch, and Peter T. Tsai, Nature Neuroscience, Vol. 20, No. 12, December 2017, 1744-51. Address: Catherine Stoodley, Department of Psychology and Center for Behavioral Neuroscience, American University, Washington, DC, [email protected]

—and— 

“Autism therapy: Social behavior restored via brain stimulation,” news release, UT Southwestern Medical Center, December 13, 2017.