TMS-Based Neuromodulation Improves Functional Measures of Information Processing and Behavioral Responses in Autism Spectrum Disorder

Background:

The study is based on an underlying neuropathology model of autism which emphasizes minicolumnar pathology and lateral inhibition deficits resulting in behavioral and executive dysfunctions. We proposed that neuromodulation based on low frequency repetitive Transcranial Magnetic Stimulation (rTMS) will enhance lateral inhibition through activation of inhibitory double bouquet interneurons and will be accompanied by improvements in the prefrontal executive functions. In addition we proposed that rTMS will improve cortical excitation/inhibition ratio and result in changes manifested in electrocortical responses such as event-related potentials (ERP) and evoked and induced EEG gamma oscillations during cognitive tests.

    Objectives:

TMS offers a noninvasive method for altering excitability of the neural circuits and induction of  functional reorganization in the  cortex. We reported earlier positive effects of  rTMS in autism spectrum disorders (ASD)  in our pilot studies using shorter 6- and 12-session long  rTMS courses.  Along with traditional behavioral evaluations in current study we used ERPs and induced gamma responses power and coherence in a visual oddball task with illusory Kanizsa figures. Wee compared clinical, behavioral and elecotrocortical (ERP, single trial EEG) outcomes in 2 groups of children with autism (TMS, wait-list group). We predicted that 18 session long course in ASD patients will have better behavioral and ERP/EEG outcomes as compared to age- and IQ-matched wait-list ASD group.

    Methods:

We used 18 sessions of 1Hz rTMS applied bilaterally over the dorso-lateral prefrontal cortex (DLPFC) in 20 individuals with ASD (11-21 yrs old).  The wait-list group was comprised of 20 age-matched subjects with ASD tested twice. Both TMS, and wait-list (WTL)  groups were assessed at (1) the initial baseline using clinical behavioral questionnaires ( i.e., Aberrant Behavior Checklist [ABC], and Repetitive Behavior Scale-Revised [RBS-R]) and during  performance on visual oddball task with Kanizsa illusory figures, and (2) post completion of 18 sessions of  TMS (or wait period). 

     Results:

Post-TMS evaluations showed decreased irritability and hyperactivity on the ABC, and decreased stereotypic behaviors on the RBS-R. Following rTMS course we found decreased magnitude of the frontal N100 ERP component and evoked gamma power to non-targets, and shorter of the fronto-central P2a and  P3a ERPs and reduced induced gamma oscillation power to non-targets in TMS group as compared to the WTL. These ERP changes along with increased P3b and enhanced induced gamma oscillations (higher power,  phase coherence) to targets are indicative of more efficient processing of information post-treatment. Enhanced information processing was also reflected in such behavioral response measures as reaction time (RT) and error rate.

    Conclusions:

These results could be considered as a replication of our prior studies using shorter rTMS course. Collected data support our concept that rTMS improves executive functioning as evidenced by normalization of ERP and EEG responses and  behavioral reactions during executive function test, and also by improvements in clinical behavioral evaluations. The study links behavioral, clinical, and ERP/EEG responses during cognitive tests and TMS outcomes with an underlying developmental neuropathology model derived from investigations in our laboratory.