Thoughts on Transcranial Magnetic Stimulation and Autism

During the past few years a lot of interest has been generated regarding the possible use of Transcranial Magnetic Stimulation (TMS) as a therapeutic modality for autism spectrum disorder (ASD). The interest stems, in part, from a series of clinical trials conducted in my laboratory in which we used TMS in ASD as a way of correcting a dysfunctional cerebral cortex. Our first trial received the recognition of a EUREKA award from the National Institute of Mental Health. That initial study led us to roughly a decade of research on the subject.

Looking back at our efforts we have had 14 published clinical trials on over 200 patients. Each trial varied in terms of the parameters used for TMS and the particular outcome measures used to establish efficacy.  All of our subjects have been children, usually in the range of 8 to 18 years of age, with high-functioning autism. When dealing with children it is best to take “baby steps” and each change in our protocols has been tweaked so as to insure the safety of our patients. Thus far we have reported quantifiable improvements in several domains of behavior such as irritability and stereotypies. These improvements have been in the range of modest to moderate but still statistically significant overall. In addition, based on teachers’ questionnaires, we have also noted improvements in behavior at school. The latter finding makes a lot of sense as a child that is able to sit still, be attentive, and partake in required educational activities would do better at school than one who is irritable and/or distracted.  Furthermore, the procedure has been well tolerated and side-effects (e.g., headaches) have been minor and transitory. Positive results, when present, are not immediately seen and rely on the plasticity of the brain to correct itself.  Benefits appear to be transitory and, depending on the subject, last approximately 6 months. Booster treatment are necessary to maintain improvement, but each successive treatment appears to be spread further apart.

Based on our experience with TMS we have never seen or reported on a cure for ASD. Non-verbal patients remain non-verbal and any intellectual impairments remain unfazed.  Indeed, our experience with low functioning ASD individuals has been unrewarding. TMS may help correct functional deficits but not anatomical ones.  Cortical malformations and other developmental lesions which may be found in low functioning autistic individuals are not amenable to treatment with TMS.

A recent book by John Elder Robison entitled “Switched On” has idealized TMS treatment as a possible cure for autism. According to the narrative, TMS stimulation allowed John to gain empathy, to subconsciously color his experiences with emotional overtones, and to acquire theory of mind (i.e., he was able to better understand the intentions of others). These effects have been permanent, that is, without further need of booster shots. John participated in several studies at Harvard University none of which was a clinical trial. In the studies, single pulses of TMS were used as a way of investigating specific functions of the brain.  This type of TMS, single pulses, has no discernible effects outside the session of stimulation. Although John’s experiences were both emotional and personal they are best attributed to a placebo effect.

TMS remains an experimental tool in ASD. There haven’t been multicenter trials with large enough number of participants to prove its effectiveness and enable comparisons to other treatments.  Similarly, patients receiving TMS for ASD have not been followed for any considerable length of time. Thus far, the Food and Drug Administration(FDA) of the United States has not recognized the therapeutic value of TMS in ASD.

Properly designed trials will be of importance in order to judge the effectiveness of TMS. A major stumbling block to overcome is the fact that participating subjects can feel the effects of active TMS stimulation. The strong magnetic field not only stimulates the cerebral cortex but also the nerves of muscles in the scalp.  The resultant contraction of scalp muscles cause transitory headaches.  It is therefore difficult to blind participants as to whether they are receiving active stimulation or a sham condition.  Having knowledge of an active treatment, specially one with physical effects like muscle contractions, may promote a strong placebo response, just as in the case of John Robison.

Needless to say that much more research is needed in regards to TMS and ASD. In our laboratory we are presently trying to answer a few important questions.  First, why do ASD patients respond in markedly different ways to TMS, some improving while others remain impervious to the intervention?  In general, individuals with ASD have an imbalance in their autonomic system, i.e., the part of the nervous system that controls involuntary functions of the body such as heart rate. TMS is usually applied to areas of the frontal lobes that help regulate the autonomic system.  It seems likely that the improvements observed with TMS regarding irritability, anxiety and attention may be the result of modulating these key areas of the brain.  We are now interested in using measurements of autonomic reactivity (e.g., heart rate variability, galvanic skin response) as possible predictors of outcome for ASD.  Second, we have observed a synergistic effect when combining TMS with neurofeedback. It may be that a better therapeutic effect can be obtained when combining TMS, with other interventions, e.g., neurofeedback, drug therapy. Lastly, several of our clinical trials suggest that participating patients showed improvements in attentional control. Not surprisingly, this executive function is controlled by the frontal lobes. It may be that the improvements noted in our clinical trials may have been due to a subset of patients that had attention deficits.  If so, TMS therapy would best be served by targeting this subgroup of patients.

In summary, clinical trials using TMS in ASD have been few with modest to moderate results. Positive outcomes have been noted primarily in high functioning individuals. Despite the popular press, no reports of “cures” have been reported.  Well-designed large-scale clinical trials are still needed to judge the effectiveness of this intervention.  The few cases of seizures reported while using TMS should draw attention to the fact that we need to be cautious when treating ASD patients, a condition where one third of individuals suffer from epilepsy. In regards to TMS, be cautious of commercial enterprises charging a lot of money and offering cures or improvements of any or all autistic symptoms. Patients and their parents should be aware of the positives and negatives of TMS therapy before investing a significant portion of their financial resources to this intervention.

Addendum 3/1/17: In a previous year I had met with Lindsay Oberman who had clarified to me that none of the studies in which John Robison participated were clinical trials. My understanding was that John had received single stimulation in mechanistic studies designed to study brain plasticity. John clarified that none of these single-pulse studies had any effect on him. The study which had long lasting cognitive effect on John used 1 pulse per second for 30 minutes over Broca’s area. I appreciate John’s clarification. (I must clarify however, that I still believe that John’s effect were placebo induced- see comments below).

2 responses to “Thoughts on Transcranial Magnetic Stimulation and Autism

  1. Re: your addendum, does this change your conclusion that John Elder Robison’s improvement was “best attributed to a placebo effect”? When I heard him talk about his experience, it sounded as though it was something that he hadn’t expected to happen at all, which I thought ruled out the placebo effect as an explanation.

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    • Thank you for allowing me to expand. It does not change my mind in regards to the effect of his intervention. I have discussed this to some extent with John. When he received repeated stimulations, John reacted to the sham stimulation. Instead of directly placing the coil against the desired area, it was placed slanted so that it would do little in terms of stimulating the brain. The force of a magnetic field follows an inverse square law which would have minimized the strength of the same. Under normal circumstances TMS targets an area the size of a quarter and is only effective some for a depth of 2.5 cm, allowing only the stimulation of the crests of the cerebral cortex, not even the depth of the convolutions. The slanted wand would not have been able to focus a large enough area of any significant depth to have physiological effects. The other thing that I explained to John is that he received stimulations at the wrong place in the brain (Broca’s area) to have such dramatic effects on executive functions (like for example the dorsolateral prefrontal cortex). In addition, the TMS effects tend to be additive and in need of multiple sessions for them to take a hold, afterwards they tend to wash up with time and patients are in need of booster shots. John’s effects were immediate and have persisted over time. I attend a meeting where people are TMS users. Nobody and I mean nobody has seen effects like those reported by John. I must also point out that I also have many issues with the ways the studies at Harvard were conducted. Patients were reused in multiple studies (they were no longer naive) and they were encouraged to even talk to each other about their results. This environment may have promoted the placebo effects of any intervention.

      I must add that the whole reason for writing this blog was the request of one health professional and many patients who had attended centers where TMS was being commercialized as a treatment for ASD and using John’s book as evidence of effectiveness. The only thing that they took out of their participation was a major financial loss ($20,000 per month for 2 months not counting travel and lodging expenses). Unfortunately these centers are now becoming quite popular. As I said in my blog, I have not seen a cure or effects as dramatic as those of John in any patient, and we have the largest clinical experience on TMS in ASD reported in the literature.

      I am happy that John has had such a life altering effect by his intervention. I consider him a good friend. However, given all of the evidence, I would have to conclude that his experience can be primarily attributed to a placebo effect.

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