Enhancing Implicit Mentalizing in Autism Spectrum Disorder with Theta-burst stimulation of the Right Temporoparietal Junction: A Randomized Sham-controlled Double-blind Crossover Study

Abstract Theory of mind (ToM), the ability to attribute mental states to oneself and others, is impaired in individuals with autism spectrum disorder (ASD). The right temporoparietal junction (TPJ) is a key brain region in ToM with altered activity in ASD. Theta-burst stimulation is a non-invasive brain stimulation method that can be used to modulate cortical activity.The present study investigated the impact of theta-burst stimulation on the rTPJ on implicit mentalizing and egocentric bias in children and adolescents with high-functioning ASD. Out of the 17 initially recruited subjects, 12 completed three sessions of continuous theta-burst stimulation (cTBS), intermittent theta-burst stimulation (iTBS), and sham stimulation in a randomized order. Immediately after each stimulation session, cognitive correlates of ToM including implicit mentalizing and egocentric bias were evaluated using a computerized test. Both cTBS and iTBS significantly improved implicit mentalizing with a large effect size compared to sham stimulation, with cTBS being more effective than iTBS. However, the analysis showed no effect of stimulation on egocentric bias. The main limitation of this study was the small sample size, which may limit the generalizability of the findings. The findings suggest that theta-burst stimulation improves theory of mind in ASD and highlights the causal relationship between the rTPJ and implicit mentalizing in this population. The rTPJ may be a potential target for improving implicit mentalizing ability in autism and other disorders with impaired ToM.