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, 16-35 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 completed year 1 of our 2-year clinical trial. 20 subjects have now successfully completed our study protocol. Over the past 12 months, we have demonstrated feasibility and tolerability of our rTMS protocol in HF-ASD, having successfully recruited ~2 HF-ASD subjects/month (total N=20) to our study, retaining 100% of randomized subjects, with only transient and mild side-effects reported following rTMS.

Conclusions:   At IMFAR 2016, 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.