Repetitive TMS Effects on Autonomic Balance in Children with Autism

Background:  

Autism is a pervasive developmental disorder marked by difficulty in social interaction, impairments or lack of communication, and restricted range of interests. In addition, many children with autism exhibit symptoms associated with autonomic dysfunctions, which are presented as abnormalities in regulation of blood pressure, temperature, heart rate, and other body functions by the autonomic nervous system (ANS).  The main findings of autonomic abnormalities studies in Autism Spectrum Disorders (ASD) point at reduced baseline parasympathetic activity in association with evidence of increased baseline sympathetic tone resulting in an autonomic imbalance, which negatively affects physiological functions and manifests in alterations of various electrophysiological measures.

Objectives:  

The aim of the study was to investigate electrophysiological measures reflecting ANS activity in two cohorts of children with ASD during 12 and 18 weekly sessions of low frequency repetitive Transcranial Magnetic Stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC). The underlying hypotheses were: (1) low frequency (0.5 Hz) rTMS over the prefrontal cortex lowered ANS hyper-activation in children with autism through activation of frontal inhibitory tone controlling ANS, and (2) lower ANS arousal post-TMS will be manifested as a decrease of skin conductance level (SCL), heart rate (HR), and increased HR variability and in improvement of behavioral evaluation scores.

Methods:  

We investigated autonomic activity in 30 children with ASD during 12 sessions of rTMS and 18 children with ASD during 18 sessions of rTMS over DLPFC. Physiological activity measures such as skin conductance level (SCL), heart rate (HR), HR variability (HRV) were recorded during rTMS sessions with a C-2 J&J Engineering Inc. physiological monitoring system.  Behavioral evaluations were conducted using the Aberrant Behavior Checklist (ABC) and the Repetitive Behavior Scale (RBS-R).

Results:  

Post-12 rTMS measurements showed a decrease of low frequency (LF) component of HRV with statistical significant changes in HR regression and standard deviation of HR, though without any significant changes in SCL. Post 18 session rTMS outcomes showed slower heart rate accompanied by increase of high frequency (HF) component of HRV (as indicated by R-R intervals of ECG), higher deviation of R-R, and lower LF/HF ratio.

Conclusions:  

Our findings show reduced sympathetic activation after rTMS resulting in lower HR predominantly through withdrawal of sympathetic tone (LF of HRV) and increase of parasympathetic cardiac neural control activity post 12 rTMS sessions. Neuromodulation using prolonged 18 session rTMS course in children with ASD resulted in a more pronounced HR slowing, a higher power of HF of HRV and time domain measures of HRV.  Behavioral evaluations based on ABC and RBS-R scores showed similar improvements in 12 and 18 sessions of rTMS.  Low frequency rTMS activates inhibitory tone of the frontal cortex resulting in a lower excitation of the ANS probably through inhibitory fronto-limbic circuits.