Pam Harrison

May 18, 2016

BALTIMORE ― Evidence continues to accumulate that repetitive transcranial magnetic stimulation (rTMS), known to be successful in the treatment of refractory depression, can target and partially ameliorate core features of autism spectrum disorder (ASD).

In a session held at the International Meeting for Autism Research (IMFAR) 2016 that focused largely on the therapeutic use of TMS in ASD, Manuel Casanova, MD, professor of biomedical sciences, University of South Carolina School of Medicine, in Greenville, reported on the use of low-frequency rTMS in children and adolescents to enhance cortical inhibition.

As Dr Casanova pointed out, recent evidence suggests that symptoms of autism spectrum disorder (ASD) may arise from an increased ratio of cortical excitation to inhibition, and low-frequency (≤1 Hz) rTMS has been shown to increase inhibition of stimulated cortex by the activation of inhibitory circuits.

Patients younger than 18 years were assessed for symptoms using neuropsychological questionnaires both at baseline and following repeated sessions of TMS.

Electroencephalographic (EEG) and event-related potential (ERP) measures were also recorded at baseline and following rTMS to assess treatment effects on selective attention and executive functioning, both of which are core impairments in individuals with ASD.

"We targeted the dorsolateral prefrontal cortex because it is heavily connected to other areas of the brain and its function appears to be affected in autism," Dr Casanova told Medscape Medical News.

"We thought that by targeting this area, we could modulate it [so that it approached] the normal range and that its connecting sites would follow suit."

Important Therapeutic Potential

The investigators found that both EEG and ERP measures of selective attention and executive functioning improved significantly following 6, 12, or 18 sessions of low-frequency TMS.

They also found that measures of irritability and repetitive or stereotypical behavior, as assessed through clinical behavioral questionnaires, improved significantly.

"We proceeded with caution, but the more sessions the individual had, the better the results," said Dr Casanova.

The investigators have now treated approximately 200 patients with rTMS, and they report no major adverse events from its use.

The team is currently following patients to see how long treatment effects last and whether combining rTMS with other techniques, such as neurofeedback, enhance treatment effects.

"Repeated TMS has the potential to become an important therapeutic tool in ASD and may play an important role in improving quality of life for these patients," Dr Casanova concluded.

Reduced Social Impairment

Other participants at the same session reported on studies that addressed specific deficits in ASD and the effects that rTMS might have on brain structure and function. Stephanie Ameis, MD, University of Toronto, Canada, and colleagues carried out a pilot study to see whether repeated use of the procedure could significantly improve executive function in high-functioning adolescents and young adults with ASD.

Repetitive TMS (20 Hz) was applied bilaterally to the dorsolateral prefrontal cortex. Twenty patients between 16 and 35 years of age received treatment 5 days per week for 4 weeks. There was also a sham control arm in the study.

"We have now completed year 1 of our 2-year clinical trial," Dr Ameis reported, "and 20 subjects have now successfully completed our study protocol."

During the first year of their trial, the investigators confirmed that rTMS is both feasible and well tolerated and that only transient and mild side effects were reported following the sessions.

Peter Enticott, PhD, Deakin University, Melbourne, Australia, in turn reported on two studies of whether bilateral high-frequency (5-Hz) stimulation of the dorsomedial prefrontal cortex, using a deeper coil to achieve deeper stimulation, could lead to favorable clinical and cognitive changes among high-functioning adults with ASD.

The first study involved 28 high-functioning adults with ASD who received deep rTMS or sham rTMS 5 days a week for 2 weeks.

The second study was an open-label trial involving a total of 20 adults with ASD who received 16 active treatments during a study interval of 4 weeks.

"In study one, there was a significant decrease in self-reported clinical ratings of social impairment for those given active [rTMS] but no change for participants allocated to sham stimulation," Dr Enticott reported.

In the second study, the investigators again observed a decrease in clinical ratings of social impairment.

"These data suggest deep rTMS has effects on neural networks that support the integration and understanding of social information," Dr Enticott noted.

Early Days

Commenting on the findings for Medscape Medical News, session discussant Stewart Mostofsky, MD, director, Center for Neurodevelopmental and Imaging Research, Kennedy Krieger Institute, Baltimore, Maryland, said scientists are in the very initial stages of exploring the potential promise of using brain stimulation techniques, including TMS among others, to help address behavioral difficulties in individuals with autism.

"I think that what was presented at the meeting represented some positive findings that revealed some initial promise," Dr Mostofsky said.

"But there is a lot of work to be done to try to better understand how this tool might be used to address not only the core features of autism but related behavioral problems that individuals with autism experience as well."

Although Dr Mostofsky acknowledged that in some of the studies, patients did show some progress in such indices as irritability and general life function, he pointed out, "None of the studies addressed core social communicative deficits.

"I think everybody sees TMS as an approach that has a lot of potential, but I also think it would be preemptive at this point to convey to the general public that this is an approach that shows a lot of promise for addressing the core features of autism," he said.

The investigators and Dr Mostofsky report no relevant financial relationships.

International Meeting for Autism Research (IMFAR) 2016: Abstracts 103.002, 103.003, and 103.004, presented May 12, 2016.

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