Combination of Repetitive Transcranial Magnetic Stimulation and Neurofeedback for Treatment of Autism: A Case Study

Background: In a recent experimental treatment trial we reported positive therapeutic effects of low frequency repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) in children with autism spectrum disorders (ASD). We have also found positive effects of electroencephalographic (EEG) biofeedback (neurofeedback) self-regulation training in behavioral and EEG outcomes in children with ASD. To evaluate the potential benefits of combining these two treatments, we completed a pilot study of rTMS with neurofeedback in a high functioning 13-year-old male with autism and an anxiety disorder.

Objectives: To determine if concurrent application of bilateral rTMS over DLPFC and self-regulation of prefrontal EEG activity results in improvements in behavior, performance on selective attention tests, and electrophysiological indices of attention.

Methods: The diagnosis of autism in the 13-year-old male was confirmed using DSM-IV criteria and ascertained with the Autism Diagnostic Interview -Revised.  Cognitive testing indicated Average intelligence and, based on psychiatric evaluation, he also met criteria for an obsessive compulsive disorder and generalized anxiety disorder that was being treated with Zoloft. Behavioral assessments using the Aberrant Behavior Checklist, Social Responsiveness Scale, and Repetitive Behavior Scale - Revised  were conducted before and after a 4 week long waiting (no-treatment) period. The patient was also tested using a selective audio-visual attention test (IVA+Plus, Brain Train) and a visual oddball test with event-related potential (ERP) recording. Following pre-treatment evaluation, the patient completed 12 weekly sessions of experimental treatment where 1 Hz  rTMS treatment (150 pulses, 90% of motor threshold, 6 left and 6 right DLPFC) was immediately followed by 25 min long prefrontal neurofeedback training. Neurofeedback was aimed at suppression of low frequency (delta, theta) and enhancement of high frequency (beta, gamma) EEG activity using visual and auditory feedback provided by a DVD controlled by EEG measures. Twelve sessions of combined rTMS and NFB were followed by post-treatment behavioral, neurocognitive, and ERP assessments. After 4 weeks the patient was invited for six additional sessions of bilateral DLPFC rTMS and NFB followed by completion of the same behavioral, neurocognitive, and neurophysiological assessment instruments. Long-term effects were determined by a follow-up evaluation three months after conclusion of the 18-session treatment.

Results: Experimental treatment using the combination of rTMS and NFB coresponded to improvements in behavior, sustained auditory and visual attention (IVA+Plus), and in enhanced magnitude of ERP measures for target stimulus processing in the visual oddball task.  The patient exhibited more pronounced positive changes on several ERP measures of attention than children with ASD undergoing only 12 sessions of rTMS without NFB.

Conclusions: This single case experimental study provides support for the combination of rTMS with neurofeedback to treat symptoms of autism presenting with a comorbid anxiety disorder.  Further investigation is warranted including combining these approaches with behavioral intervention strategies.