Switched On

NOTE: During the past few months I have been made aware that the link buttons at the end of my blogs do not provide a proper count for those who have shared the same through social media. I appreciate people emailing me about the problem; however, I am computer naïve and do not know how to correct the problem. Sorry

Switched On is the long awaited book of John Elder Robison’s personal experiences with Transcranial Magnetic Stimulation (TMS). John is a very talented individual within the autism spectrum who has been quite successful while partaking in diverse careers, e.g., guitar engineer, car mechanic, photographer. In the world of autism John is best known as both an author (Look Me in the Eyes) and Neurodiversity advocate. It is difficult to attend an autism related activity without his name being mentioned.

John has taken a “soft stance” on Neurodiversity, one that sees both gifts and disabilities for those within the spectrum while also accepting the benefits of research and therapy. The “hard stance” for other Neurodiversity individuals is that autism (and other mental conditions) falls within the normal variability of the human genome and thus, being normal, see no need for further research or treatment.

The book Switched On relates how sometime in 2008 John partook in a research study on TMS and autism directed by Alvaro Pascual-Leone from Harvard University. After one session of stimulations John felt an emotional upsurge that allowed him to perceive the world around him differently to what he was accustomed. His description suggests that TMS opened a floodgate of introspective thoughts as to his own emotional state and the people around him. He recalled past memories that seemingly persisted in his subconscious and now –after TMS- acquired a different meaning. According to John these changes have persisted and may account for some of the emotional highs and lows he has experienced over the last few years. On the positive side, as a photographer his compositions have acquired an individual artistic style that he and others seem to enjoy. John has also become more empathetic towards the plight of his customers as they bring their cars to his repair shop. Furthermore, his social skills have remarkably improved, especially in regards to the art of “small-talk”. On the negative side, John believes TMS made him more aware of the problems in his marriage and ultimately contributed to his divorce.

Transcranial Magnetic Stimulation is a technique that induces a current in a small area of the cerebral cortex. The equipment works in analogous fashion to an electrical generator where a changing magnetic field induces current in a wire. In the case of the brain, the machine (generator) provides the magnetic field and the wires are the projections of cells called neurons. A different technique called transcranial direct current stimulation uses a small amount of current (1-2 miliamperes) between scalp electrodes to change the state of brain activation.  In some chapter towards the end of Switched On TMS and tDCS are conflated.

The circuitry of tDCS is quite simple and can be easily assembled by the do-it-yourself community. I have questioned whether this technique is of any benefit and those using the same appear to lack sophistication in both electronics and neurosciences (see bit.ly/1P8Brqx). I usually say that the naivety of neuroscientists will be judged by the number of tDCS articles in their CVs. At present tDCS providers are targeting desperate parents of children with neurodevelopmental conditions and charging them money for therapies that have yet to be validated. TMS on the other hand depends on the discharge of a large current from a bank of supercapacitors into a coiled wire. The high current is very dangerous and requires the use of special switches and “bleeding” components. The circuitry required for TMS escapes the knowledge of the do-it-yourself community.

Switched On narrates the emotional liberation of John that occurred after TMS. However, an equally impressive story (in essence a subplot) is the lack of ethics of the people that conducted the TMS clinical trial wherein John participated. For purpose of the trial John helped recruit patients through his blog. John also gave lectures and narrated his personal observations that then became available to potential participants.  Moreover, the administrators of the trial instigated John to share his experiences with other participants and eventually altered the negative perspective of at least one of them. Later on John and other participants were recycled into other TMS trials. In one part of the book it is suggested that John may have participated simultaneously in more than one study. These patients were no longer naïve and their brains had already been changed by the initial bout of TMS stimulation. The results of these trials are tainted.

John’s trial was finally published in a third tier journal in 2011. The same provided results on a small population, only 10 patients. The study was not a treatment trial but one studying brain mechanisms engaging the formulation of words (object naming). The reasoning behind the experiment was never properly formulated and John recounts multiple sessions where the ideas ricocheted from corpus callosum projections to emotional reciprocity to mirror neurons.  At present the idea of a broken mirror system in autism has been debunked (see bit.ly/1M9F84T). Furthermore it is extremely naïve from a neurosciences perspective to take mirror neurons as the basis of a TMS experiment. Mirror neurons only constitute a minority of the cells at any given site.  Even when the proper site and depth can be stimulated any effects of TMS would be the result of the large majority of non-mirror neurons being activated (note: some of these cells have an anti-mirror neuron effect).

I personally take exception at the way the investigators changed experimental parameters from their first trial to those conducted more recently, and for which patients have apparently been recycled.  John participated and had good results with slow frequency stimulation but was bothered and claimed no similar beneficial effects from later interventions in which a very fast rate of stimulation (theta burst) was used. Theta bursts may shorten the time of stimulation from half an hour (with slow frequency) to only a couple of minutes. The shortened time is advantageous to the physician; however, a side-by-side comparison trial in ASD should have been attempted before completely shifting parameters. When dealing with patients, it is all about baby steps.

My group finished a treatment clinical trial on TMS and ASD in 2005 and was able to publish the results in the Journal of Autism and Developmental Disorders 3 years later. By 2008 we had concluded 2 additional trials and had already treated over 100 individuals in the autism spectrum.  More importantly the people at Harvard had a copy of our grant and preliminary results. Our next 2 studies were published in 2010. In all we have seen and reported on more patients than all other groups combined. Contrary to Harvard my group has concentrated on treatment efforts rather than studying potential mechanisms. We have reported beneficial reports on TMS and ASD but only in higher functioning individuals. One of my biggest regrets has been telling parents of lower functioning individuals that their child may not be able to participate in our trials as they may not comply with inclusionary/exclusionary criteria. This practice of warning patients has escalated  after Switched On was published.

I am extremely happy for the life altering experience that John has had. In addition publicizing his story has certainly brought a lot of needed publicity to the field. We conceived of TMS as being the first therapeutic intervention targeting the core pathology of the condition. Side effects are minimal. However, results vary from individual to individual. I have never seen results of the magnitude reported by John and they certainly have not been apparent immediately after stimulation.  TMS effects are cumulative and the brain has to remodel itself based on the magnetic pulses, a process that takes time. What I would try to avoid is having parents gain false hope and be the targets of unscrupulous commercial ventures targeting both their plight and pockets (see bit.ly/1qq6ytg).

4 responses to “Switched On

  1. Hi Manny,

    I never really considered whether there would be an ethical question having the same group of us take part in sequential trials. What did you see as wrong with that? From a participant point of view, why would we not want to keep volunteering for interesting studies?

    Also with respect to results I would point out that the most striking changes came a day after one TMS session, after the nigh too hallucination/dreams. I don’t know how to explain that – it certainly was not immediate.

    Was that effect a result of one stimulation, or did a series of stimulations tip some kind of balance in my head? I don’t know.

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    • I thought of an analogy to the recycling of patients that you would like. You can receive an electrolytic capacitor from the factory in its original non-charged state. Once you charge the capacitor it will never return to its original state (some charge will be kept in the dielectric). You can discharge the capacitor, it will just never be the same.

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  2. Hi John.

    Thanks for the comment. You always express yourself in a thoughtful manner which I appreciate.
    Recycling patients is definitely a major concern in clinical trials (I served for over 12 years in 2 different IRB committees). An exclusionary criteria for participating in multiple trials is usually indicated in the informed consent that you sign at the beginning of the trial. In the case of TMS the brain that you stimulate in one trial can’t be considered in its “primitive state” any longer. Also, there are questions about how to “fool” the patient in a blind trial if they are experienced with the zapping of an active coil. I doubt that Alvaro or anybody else acquired approval for “recycling” patients. I am also not aware if this has been reported in their publications.
    We have recycled patients in our trials but in reporting results of 6, 12 and 18 session trials. In essence they were participating in the same trial but we variously extended the number of sessions in the same.
    I am not sure how to explain the hallucinations. You also claimed dizziness, the same had a movement component and became more prominent when your eyes were closed- meaning it was vertigo maybe vestibular neuronitis. These potential side effects should have been investigated and reported as an adverse event to the IRB. Interesting to know whether they were actually reported to the IRB or in the articles.
    I am very happy with the results and positive life experience that you have had with TMS. I am less positive about the trial that you participated in, the results as they were reported, as well as on the possibility of commercial ventures making money out desperate parents.
    Looking forwards to seeing you again at IMFAR.

    Manny

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  3. As you point out, John Robison in promoting his book lead people to believe that this was a treatment study when in fact it was a measure of brain plasticity of certain areas of “asperger’s” individuals as compared to normal controls. Another problem with the research that you neglected to mention is that at least some members of the experimental group, included, not only John Elder Robison, a successful author and businessman, but also an orthopedic surgeon and a harvard educated financial analyst who claimed to be on the autism spectrum. This group certainly is not typical of any group of persons with autism spectrum disorders who mostly can’t work and obtain the level of success that these research subjects did.

    There is also the possibility that the effects John Robison felt were nothing more than a placebo which is certainly possible in research like this. It is a shame that people reading this book will get the idea that this is some sort of legitimate autism treatment.

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