rTMS neuromodulation improves electrocortical functional measures of information processing and behavioral responses in autism

Abstract

Objectives: Reports in autism spectrum disorders (ASD) of a minicolumnopathy with consequent deficits of lateral inhibition help explain observed behavioral and executive dysfunctions. We propose 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 event-related potential (ERP) recorded during cognitive tests.Materials and Methods: Along with traditional clinical behavioral evaluations the current study used ERPs in a visual oddball task with illusory figures. We compared clinical, behavioral and electrocortical outcomes in two groups of children with autism (TMS, wait-list group). We predicted that 18 session long course in autistic patients will have better behavioral and ERP outcomes as compared to age- and IQ-matched WTL group. We used 18 sessions of 1 Hz rTMS applied over the dorso-lateral prefrontal cortex in 27 individuals with ASD diagnosis. The WTL group was comprised of 27 age-matched subjects with ASD tested twice. Both TMS and WTL groups were assessed at the baseline and after completion of 18 weekly sessions of rTMS (or wait period) using clinical behavioral questionnaires and during performance on visual oddball task with Kanizsa illusory figures.Results: Post-TMS evaluations showed decreased irritability and hyperactivity on the Aberrant Behavior Checklist (ABC), and decreased stereotypic behaviors on the Repetitive Behavior Scale (RBS-R). Following rTMS course we found decreased amplitude and prolonged latency in the frontal and fronto-central N100, N200 and P300 (P3a) ERPs to non-targets in active TMS treatment group. TMS resulted in increase of P2d (P2a to targets minus P2a to non-targets) amplitude. These ERP changes along with increased centro-parietal P100 and P300 (P3b) to targets are indicative of more efficient processing of information post-TMS treatment. Another important finding was decrease of the latency and increase of negativity of error-related negativity (ERN) during commission errors that may reflect improvement in error monitoring and correction function. Enhanced information processing was also manifested in lower error rate. In addition we calculated normative post-error treaction time (RT) slowing response in both groups and found that rTMS treatment was accompanied by post-error RT slowing and higher accuracy of responses, whereas the WTL group kept on showing typical for ASD post-error RT speeding and higher commission and omission error rates.Conclusion: Results from our study indicate that rTMS improves executive functioning in ASD as evidenced by normalization of ERP responses and behavioral reactions (RT, accuracy) during executive function test, and also by improvements in clinical evaluations.

Neuromodulation Integrating rTMS and Neurofeedback for the Treatment of Autism Spectrum Disorder: An Exploratory Study

“…The outcomes of behavioral evaluations using RBS-R (Bodfish, Symons & Lewis, 1999) and ABC (Aman and Singh, 1994) questionnaires show improvements in autism symptoms similar to those that we reported in our other study when 18 session long 1 Hz rTMS course was used in 27 children with ASD (Sokhadze et al, 2014). Psychophysiological outcomes of the study show significant changes in behavioral responses (motor response accuracy and post-error RT slowing) and both early and later-stage ERP indices of task-relevant signal processing as a result of 18 sessions of low frequency rTMS treatment over DLPFC combined with prefrontal neurofeedback training course in 20 children with ASD.…”

“…In typically developing children the fronto-central P3a occurs earlier in time as compared to parietal P300 (P3b), but in autistic subjects the P3a and P3b components were found to peak almost simultaneously over the frontal and parietal sites in a spatial attention test (Townsend et al 2001). One of the most important findings of current study was replication of the increase of ERN amplitude and shortened latency post-TMS reported in previous studies using 12 and 18 sessions of rTMS (Sokhadze et al 2012, 2014). …”

“…It was previous reported (Baruth et al 2010c; Sokhadze et al 2009ab) that individuals with ASD as compared to typical controls showed enhanced N200 to task irrelevant as compared to task relevant stimuli, and the finding that N200 became more negative to target Kanizsa figures and less negative to non-target distracters post-rTMS treatment indicates a trend to normalization of the response pattern pointing at an improved visual signal processing and a more effective discrimination of the target. We reported very comparable frontal ERP outcomes in our study on children with ASD enrolled in 18 session long TMS treatment course (Sokhadze et al 2014). …”

High-Frequency Stimulation at the Subthalamic Nucleus Suppresses Excessive Self-Grooming in Autism-Like Mouse Models

“…Another justification for this study is that uncovering potential DBS target sites using mouse models may provide further insight into the neural pathways that might regulate SIB, and could be amenable to focal non-invasive brain stimulation therapies. Along these lines, Sokhadze et al (2014) recently reported low-frequency repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex, which is inhibitory, suppressed stereotypic behavior in children with an ASD.…”

Brain Stimulation and Modulation for Autism Spectrum Disorder

“…In the comparison between 27 individuals with ASD treated with 18 session long course of 1 Hz rTMS applied over the dorsolateral prefrontal cortex and 27 age-matched subjects with ASD as control, rTMS improves executive functioning and clinical symptoms such as irritability, hyperactivity, and stereotypic behaviors in ASD [27]. It was proposed that extended dosing (i.e., 6,000 pulses) of high-frequency (i.e., 20…”