Repetitive Transcranial Magnetic Stimulation for Executive Function Deficits in Autism Spectrum Disorder and Effects on Brain Structure and Function

Background: There are no satisfactory treatments for executive functioning (EF) deficits that predict real-world disability and long-term morbidity in individuals with high functioning autism spectrum disorder (HF-ASD). Our randomized, double-blind, sham-controlled pilot study results suggest that four weeks of repetitive transcranial magnetic stimulation (rTMS) applied to dorsolateral prefrontal cortex (DLPFC) can significantly improve EF performance in adults with schizophrenia (Cohen’s d=0.91). As there may be overlapping etiology resulting in EF impairments in HF-ASD and in schizophrenia, the same biological treatments may improve performance deficits in both conditions.

Objectives: To complete a pilot study exploring the novel application of rTMS to DLPFC for treatment of EF deficits in adolescents and young adults with HF-ASD. This pilot study focuses on evaluating the feasibility of implementing our rTMS treatment protocol in HF-ASD. Our primary aims are to: (i) determine if our rTMS protocol can be successfully applied in people with HF-ASD, (ii) examine whether active rTMS improves EF performance in HF-ASD, and (iii) use structural and functional MRI in a pre/post design to identify mechanisms of treatment response. 

Methods: We are using a randomized, double-blind, sham-controlled design comparing active (20Hz) vs. sham rTMS applied 5 days per week for 4 weeks bilaterally to DLPFC in young people with HF-ASD (active, N=20 vs. sham, N=20, 16-25 years). Outcome measures of EF performance (measured using Cambridge Neuropsychological Test Automated Battery) are being evaluated before and after the 4-week intervention. Structural and functional neuroimaging measures (MRI/DTI/rs-fMRI and task-based fMRI) will also be acquired at baseline, and at the end of the 4-week rTMS trial in HF-ASD subjects to assess for biomarkers of treatment response.  

Results: We have now started recruitment for our clinical trial and have four subjects who have entered into our study protocol within a short period of time. Thus far, there is considerable interest among individuals with HF-ASD to enter into our study and initial participants are tolerating our protocol well. Over the next six months, we anticipate that twelve participants with ASD will have completed our study protocol.  

Conclusions: At IMFAR 2015, we will present our novel protocol, as well as preliminary data regarding the feasibility of implementing our study protocol in HF-ASD participants. In addition, we will present preliminary neuroimaging results including: associations between baseline measures of cognitive performance and DLPFC structure and DLPFC activation, as well as microstructure of white matter tracts connecting to the DLPFC.