Novel Neuromodulation Therapy Integrating rTMS and Neurofeedback for the Treatment of Autism Spectrum Disorders

Background: Autism spectrum disorder (ASD) is a pervasive developmental disorder characterized by deficits in social interaction, language, stereotyped behaviors, and restricted range of interests. Based on neuropathological findings from our laboratory we proposed that repetitive transcranial magnetic stimulation (rTMS) could offer a therapeutic intervention targeting some of the described pathology. Our initial studies used 6, 12, and 18 sessions of slow frequency (0.5-1.0 Hz) rTMS over the dorso-lateral prefrontal cortex (DLPFC) with positive behavioral and electrophysiological results in children with ASD. Specifically we reported improvements in behavioral and executive functioning using electrocortical measures. In this study we probe the synergistic effects of neurofeedback in combination with rTMS.

Objectives: To study the combined effects of 18 sessions of low frequency rTMS over DLPFC with the prefrontal EEG biofeedback (neurofeedback -NFB) to prolong and/or reinforce TMS-induced EEG changes using a post-TMS EEG operant conditioning paradigm. The underlying hypotheses were that: (1) the combination of rTMS with neurofeedback would result in a synergistic outcome as compared to TMS-alone, and that (2) bothTMS-only and TMS+NFB would improve executive functions in autistic patients as compared to the waitlist control group.

Methods: The pilot trial recruited 54 children with ASD (mean age 14.2 yrs). Outcome measures included behavioral evaluations (Aberrant Behavior Checklist, repetitive Behavior Scale, Social Responsiveness Scale, etc.) and psychophysiological tests (e.g., visual oddball test with EEG recording). For the main goal of the study, we used 18 sessions of rTMS-only (TMS, N=17), 18 sessions of rTMS followed by prefrontal biofeedback combination (TMS+NFB, N=18) and waitlist (WL, N=19, 3-6 moths between tests) groups to examine effects on EEG, event-related potentials (ERP), and other functional and behavioral clinical outcomes.

Results: Behavioral, EEG and ERP outcomes were collected in pre- and post-treatment tests in all 3 groups. Results of the study support our hypotheses by demonstrating the positive effects of combined TMS+BFB neurotherapy as compared to TMS-only.  Both TMS groups showed significant improvements in behavioral and functional outcomes as compared to the children in the wait-list group. Follow-up assessments in both treatment groups (6-9 months post-treatment) are underway to assess the longitudinal stability of the findings and the need for booster sessions.

Conclusions: Our preliminary results are supportive of the hypothesis that combined rTMS and neurofeedback neuromodulation has longer lasting effects than rTMS alone. There have been no major side effects of the reported therapy and it has proven safe to apply in young children. Transcranial magnetic stimulation is the only treatment alternative, as of present, that targets some of the pathology observed in ASD.