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TMS and Autism

Transcranial magnetic stimulation (TMS) is a relatively recent technology that has been FDA-approved for the treatment of depression and migraine with aura. TMS uses a magnetic field to stimulate specific areas of the brain. In recent years, there has been interest in applying TMS to treat other conditions, including Autism Spectrum Disorder (ASD), on an experimental basis. The specific form of TMS that has been of most interest is called repetitive transcranial magnetic stimulation (rTMS)

The investigation of rTMS for people with ASD became more widely known following the 2016 publication of John Elder Robison’s account of his experience with the procedure. In his book, Switched On, Robison offers a fascinating story of the changes that he experienced following rTMS, including differences in what are thought to be core features of autism.

Following an initial session of rTMS Robison reported a powerful experience on his trip home, triggered by listening to music:

“My vision was crystal clear, my head was full of sound, and I felt totally alive. The sterile digitized songs on my iPod had come to life and the feeling was so magnificently overwhelming that I began to cry. Not because I was happy or sad, but because it was all so intense.” (p. xxi)

What makes Robison’s experience even more striking is that it was not expected. The research protocol in which he participated was intended to measure the impact of rTMS on object naming (Fecteau et al., 2011). When Robison reported to investigators the dramatic response to music, he says they responded: “’Very interesting. And unexpected.’ . . . they didn’t have any idea why the TMS would have awakened the musical vision. It hadn’t been part of their plan.” (p. 76)

The day after a second session of rTMS, Robison experienced a profound difference when interacting with others. Recounting an exchange with a customer at his car repair business, Robison wrote:

“Somehow I had read the expressions in her face and answered them instinctively – and correctly. Most people take such abilities for granted, but I had a lifetime of experience missing those cues and saying the wrong things – sometimes the worst possible things – in response to the logical words others spoke to me. . . . You are seeing into their souls, a little voice said. Just then, I felt another flood of emotion and I had to step outside as the wave washed over me. Human eyes had become windows, and the surge of emotion pouring from them was very powerful. And somehow my new ability felt completely instinctive and natural, as if it had been there forever.” (p. 113)

Not all of the effects experienced by Robison were positive. His sensitivity to others’ depression caused him significant distress; he maintains this was an important factor in the failure of his marriage. He became aware that others were responding to him negatively, causing immediate pain and the reflection that similar interactions, to which he had been oblivious in the past, had happened countless times. And he found that his re-consideration of the past, too often, “turned formerly good memories bad” (p. 211); he realized that some events and relationships that he had perceived positively now had a sinister or negative aspect.

The effects of rTMS, as reported in the literature, are generally short-lived, although as a treatment for depression, there is reasonable support that the intervention leads to remission rates significantly higher than a placebo procedure (Gaynes et al., 2014). The immediate effects that Robison experienced were also not all permanent; he records that some were gone the following day, and some faded over a period of several days. But he also found that the procedure produced changes that lasted for years; he felt that his enhanced emotional sensitivity allowed him to be more successful in personal and professional domains.

As the more striking effects (e.g., his markedly different experience of music) faded, Robison confronted the question of whether it is better to experience something remarkable and then lose it, or to never have the experience at all. This is a question that other TMS subjects have considered as well, some concluding that continued ignorance would have been preferable.

The scientific literature on the experimental use of rTMS in people with ASD has rarely investigated changes to core features of the condition (Oberman et al., 2016). As with the protocol that Robison participated in, reports in the literature describe efforts to target areas of the brain associated with, for the most part, more prosaic skills. Oberman writes:

“A variety of brain regions and symptom domains have been targeted including: dorsal lateral prefrontal cortex (DLPFC) to improve irritability, repetitive behaviors, and executive functioning, supplementary and primary motor cortices to improve motor behavior, medial prefrontal cortex to improve mentalizing, and premotor cortex to improve speech production and eye-hand coordination. . . . it is unlikely that therapeutic TMS would reverse multiple aspects of the ASD phenotype, rather, it may improve specific core or associated symptoms related to an alteration in the functioning of a specific cortical region or circuit.” (p. 190)

Research on TMS as a therapeutic intervention in ASD, at this point, is said to “provide preliminary support for further exploration . . . .” However, methodological issues with the research abound and “off-label clinical use of rTMS for therapeutic interventions in ASD without an investigational device exemption and outside of an IRB approved research trial is currently premature pending further, properly powered and well-controlled trials.” (Oberman et al., 2016; p. 195) It is, in other words, not ready for prime time. While John Elder Robison recounts amelioration of deficits generally thought to be core features of ASD, those changes appear to have been fortuitous anomalies; at this point it is not clear what regions of the brain should be targeted to produce such effects.

Another particularly thorny issue, with respect to even the experimental use of rTMS, has to do with the age of the subjects. The generally accepted principle with regard to the treatment of autism is that earlier intervention is better, but there are serious hesitations about applying TMS to a developing brain. While there have been studies involving children, Oberman notes that “the brain of a child is not simply a smaller version of an adult brain and . . . therapeutic interventions such as rTMS may have distinct, unpredictable, and potentially long-lasting effects on neurodevelopment.” (p. 198)

The history of the treatment of autism has offered multiple examples of apparently promising interventions that stimulate high interest but in the end fail to live up to their promise. One positive feature with respect to rTMS is that early reports have spawned a serious program of research that continues to generate instructive data. The technology, as applied to ASD, is not ready for use as a treatment intervention; while there have been compelling anecdotal accounts, the data are mixed. Nonetheless, there is hope that the on-going research will not only indicate whether rTMS can successfully treat features of ASD, but will also help us to learn more about the neurocognitive functioning of people with autism.

References

Fecteau,S., Agosta,S., Oberman, L., & Pascual-Leone, A. (2011). Brain stimulation over Broca’s area differentially modulates naming skills in neurotypical adults and individuals with Asperger’s syndrome. European Journal of Neuroscience, 34, 158–164. doi:10.1111/j.1460-9568.2011.07726.x

Gaynes, B.N., Lloyd, S.W., Lux, L., Gartlehner, G., Hansen, R.A., Brode, S., . . . Lohr, K.N. (2014). Repetitive transcranial magnetic stimulation for treatment-resistant depression: a systematic review and meta-analysis. Journal of Clinical Psychiatry, 75, 477–489. doi:10.4088/JCP. 13r08815

Oberman, L. M., McCracken, J. T., Pascual‐Leone, A., Rotenberg, A., Casanova, M. F., & Enticott, P. G. (2016). Transcranial magnetic stimulation in autism spectrum disorder: Challenges, promise, and roadmap for future research. Autism Research, 9, 184–203. doi:10.1002/aur.1567

Robison, J.E. (2016). Switched on: A memoir of brain change and emotional awakening. New York: Spiegel & Grau.

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