Clinical Trials of Deep Repetitive Transcranial Magnetic Stimulation (rTMS) to Bilateral Dorsomedial Prefrontal Cortex in Autism Spectrum Disorder

Background: Autism spectrum disorder (ASD) is characterised by impairments in social relating, which have been linked to abnormal activation within ‘social brain’ networks that include dorsomedial prefrontal cortex (dmPFC).  

 Objectives: Across two clinical trials, we investigated whether high-frequency (5 Hz) stimulation of bilateral dmPFC, using a deep rTMS coil to achieve the necessary depth of stimulation, could induce clinical, cognitive, and neurobiological changes among ‘high-functioning’ adults with ASD. 

Methods: Study One involved a randomised, sham- controlled clinical trial of deep rTMS to bilateral dmPFC in 28 adults with ASD. Participants received active or sham deep rTMS each weekday for two weeks. Clinical and cognitive assessments were conducted before, after, and one-month following the treatment phase. Study Two was an open-label study where 20 adults with ASD received 16 active treatments over 4 weeks. Participants underwent positron emission tomography (PET) to assess brain glucose metabolism before and after the treatment course, while clinical and cognitive assessments were conducted before, after, 1-month, 3-months, and 6- months following treatment. 

Results: In Study One, there was a significant decrease in self-reported clinical ratings of social impairment for those in the active condition, but no change for participants allocated to sham stimulation. In Study 2, there was again a decrease in clinical ratings of social impairment, and evidence for enhanced glucose metabolism (mid cingulum) following deep rTMS. 

Conclusions: These data provide preliminary support for the safety and efficacy of deep rTMS to dmPFC in ASD, and suggest effects on neural networks that support the integration and understanding of social information. The clinical significance of these findings will be explored.