Neuromodulation Therapy Integrating Prefrontal rTMS and Neurofeedback for the Treatment of Autism

Background: The study is based on an underlying neuropathological model of autism (Casanova et al. 2006) which emphasizes “minicolumnar” pathology and cortical lateral inhibition deficits  resulting in behavioral abnormalities and executive dysfunctions. We propose that neuromodulation based on repetitive Transcranila Magnetic Stimulation (rTMS) over prefrontal area will enhance lateral inhibition through activation of inhibitory double bouquet interneurons and will be accompanied by positive  EEG alteration that can be operantly conditioned using neurofeedback (NFB) training immediately after each rTMS session. In our studies using rTMS we demonstrated improvements in executive functions, as well as positive effects of prefrontal neurofeedback training in autism (Sokhadze et al., 2014; Wang et al., 2014). In the current study each rTMS session was followed by NFB, and this was predicted to result in  synergetic response.

Objectives: The overall aim of the study was to investigate behavioral responses, ERP indices of information processing, and coherence of induced gamma oscillations in children with autism enrolled either in 18 weekly sessions of combined rTMS -NFB training group or in the wait-list group.  The goal of our study was to investigate whether behavioral, EER and EEG indices, and behavioral evaluation outcomes  will show positive changes in the treatment group (N=20) as compared to wait-list group (N=22). 

Methods: We used 18 weekly sessions of 0.5 Hz rTMS bilaterally over dorsolateral prefrontal cortex  followed by  prefrontal neurofeedback  in 20 children with autism (14.9 yrs). Another group of children with autism (N=22, 15.6 yrs) was tested twice within 4 months. Baseline and post-treatment assessments used selective attention tests with EEG/ERP recording and behavioral evaluations (Aberrant Behavior Checklist [ABC] and Repetitive Behavior Checklist [RBS-R]).

Results: Post-TMS-NFB evaluations showed decreased irritability and hyperactivity on ABC, and decreased stereotypic and total repetitive behaviors scores on RBS.  The TMS-NFB group showed decrease of error rate (F=5.62, p=0.02).  Magnitude of the frontal N100 decreased, while amplitude of the P200 to target stimuli increased post-TMS-NFB. Similar effects were expressed as well in the parietal P3b. The treatment group showed increase coherence of induced gamma to targets between frontal and temporal sites (e.g., F3-T7, F=6.67, p=0.014). NFB sessions resulted in linear regression of the theta-to-beta ratio and increase of gamma power over 18 sessions of integrated treatment.

Conclusions: Improved clinical behavioral evaluation outcomes along with functional EEG/ERP measures post-TMS-NFB  are indicative of more efficient information processing post-treatment. The study represents a pilot translational clinical research exploration where rTMS and neurofeedback were combined, and treatment effects were compared with a wait-list group using clinical, behavioral and cognitive outcome measures.  Preliminary results are very encouraging and warrant further more rigorous randomized controlled clinical trials.

References: Casanova, M. F., et al. (2006). Abnormalities of cortical minicolumnar organization in the prefrontal lobes of autistic  patients. Clinical Neuroscience Reseacrh. 6:127-133.

Sokhadze, E. M. et al. (2014)  rTMS neuromodulation improves electrocortical functional measures of information processing and behavior in autism. Frontiers Systems Neuroscience. 8:134

Wang, Y., et al (2014) Prefrontal neurofeedback  training approaches in autism. NeuroRegulation 1:275-277.