Transcranial Magnetic Stimulation: Historical Aspects

It seems to me that the last decade has seen a resurgence of interest about magnetism and its possible use as a therapeutic modality for a variety of health related disorders. The field itself is now called magnetic therapy or magnotherapy. A quick search on Google for magnotherapy brought 63,000 hits. One particular site says, “Magnotherapy is nothing new – it has been used for thousands of years to help relieve pain and accelerate the natural healing process” (http://www.magnetic-health.eu/?page_id=128). However, most early accounts, although widely circulated, remain unsubstantiated (e.g., Cleopatra using magnets to preserve her beauty).

The origin for magnetic therapy probably dates back to the 1700’s when Franz Mesmer proposed a theory of invisible forces that could be transferred between animal bodies. He called this putative transfer of energy “animal magnetism”. Several decades later, the English scientist Michael Faraday demonstrated the presence of a magnetic field around a conductor carrying direct current. Among many salient discoveries, Faraday is credited with the observation that a varying magnetic field (caused by connecting and disconnecting a battery) acting on a conductor, causes a potential difference or voltage across the same. This observation had many ramifications, one of which has been examining the possible effects of magnetic fields on the human body.

In terms of science it should be stressed that almost all of the veritable human research has been done using very high magnetic field strengths (e.g., 1-2 Tesla). The resultant magnetic field strength is similar to that of a Magnetic Resonance Imaging scanner and some 20,000 times the strength of the Earth’s magnetic field. The use of lesser strength magnetic fields, usually static, has led to many speculations often with little scientific backing. It is well known, for example, that hemoglobin (a major component of blood that carries oxygen), contains iron and exhibits magnetic properties. Contrary to assertions in layman’s publications the static fields used for magnotherapy are several orders of magnitude too weak to have an effect on blood flow. As a matter of fact, the energetic fields of such magnets is so weak that it dissipates quickly with distance making their effects almost null in living tissue. It is for this reason that in this blog we won’t address the therapeutic use of magnetic blankets, pillows, creams, etc. Most credible researchers consider their use as pseudoscience.

The early history of magnetic stimulation of the human body centered around the phenomena of phosphenes. A phosphene is the experience of seeing light flashes without light actually entering the eyes. Researchers in the early 1900’s built large coils capable of wrapping around the human head. The large currents in these coils (often requiring help from the electrical company) provoked the phenomena of phosphenes. For several decades research into phosphenes addressed the question of the possible anatomical culprit; whether phosphenes were engender by the occipital cortex or the retina? By way of contrast modern research has centered around the creation of virtual/transitory lesions in the central nervous system and its ability to recover or exhibit plasticity.

f_a_c_t__2__fun_with_phosphenes__by_jadedianna-d52r655

The modern era of research with Transcranial Magnetic Stimulation (TMS) came about in the mid 1980’s. Anthony Barker, working at the Royal Hallamshire Hospital in Sheffield, developed a machine capable of non-invasively changing the excitability of brain tissue. The machine required the use of modern capacitors (a storage container of electrical energy) capable of discharging a large voltage. The large voltage is required to provide a rapid surge in current in the stimulating coil. The trailbrazing path of the Hallamshire group is still present today and the offsprings of the original group are still pursuing innovative avenues of research (http://www.shef.ac.uk/neuroscience/psychiatry/research/techniques/tms).

The recent revival of interest in TMS is in many ways due to the work of the multifacted Mark George from the Medical University of South Carolina. Dr. George combined his training in Psychiatry and Radiology by pursuing the effects of TMS in major depression. In 2010, Dr. George gained the approval of the FDA to use this technique in treatment refractory depression. A NOVA documentary details Dr. George’s efforts to use TMS in psychiatry (http://www.pbs.org/wgbh/nova/body/mind-control-TMS.html).

My group had the original idea of treating autism spectrum disorders (ASD) individuals with TMS. The idea came from our results showing the presence of a defect in the inhibitory surround of modules that make for information processing in the cerebral cortex. I thought that low frequency TMS could help build the inhibitory surround of these structures (see previous blog: https://corticalchauvinism.com/2013/01/27/why-use-transcranial-magnetic-stimulation-tms-in-autism/). High frequency TMS would otherwise be contraindicated as it could provoke seizures in this patient population. Thus far other groups from Boston and Australia have reproduced our original findings. One of the more accomplished researchers in the field, Lindsay Oberman, just wrote a literature review on the subject.

s200_lindsay.obermanDr-Peter-Enticott_portrait-379x570

Lindsay Oberman and Peter Enticott working separately (and in 2 different countries) have been the motive force to many of the more recent studies detailing the effects of TMS in ASD.

The potential benefits of TMS in ASD have been publicized by John Elder Robison (author of Look Me in the Eye). John credits TMS as having had a life-changing effect on him: “I credit TMS with fundamentally altering the way I see and engage other people. My strong belief in the power of TMS is solidly based on my own experiences in the lab” (http://www.johnrobison.com/collaborations.php).

Thus far our group has had a good number of publications and book chapters on the subject. Overall we have treated close to 200 individuals with this technique. In May, 2 days before the International Meeting for Autism research, we will participate in an autism consensus conference where we will try to define how different groups may work together towards establishing a large enough ASD clinical trial to have TMS be considered for approval by the FDA. The conference was the brainchild of Ms. Kimberley Taylor. founder of the Clearly Present Foundation.

References

Oberman L, Rotenberg A, Pasccual-Leone A. Use of transcranial magnetic stimulation in autism spectrum disorders. JADD Epub ahead of print.

4 responses to “Transcranial Magnetic Stimulation: Historical Aspects

  1. One of the problems wit hthe research done so far it seems to me is the sample sizes were all very small, the use of waitlist controls instead of sham TMS and behavioral ratings of caretakers, which I know from personal experience aren’t terribly reliable. I’m notg sure why your group did not use sham TMS as a control (or maybe is not possible) and had
    the use of blind raters to evaluate the behavioral differences. Is your group planning to do future studies using this metholodlogy i hop so. Also TMS seems to just affect neurons rather than glial cells because I guess glia don’t have action potentials and I wonder if glia can be involved in the etiology of autism as well as neurons as there are far more glial cells than neurons and the germinal cells that don’t migrate correctly could become llet’s say astrocytes as well as neurons, so I guess there are many things I don’t understand. I hope at some point your group does studies with Sham TMS controls as well as blind observers to evalutae behavioral changes. blind rater

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  2. Thanks for the comments. All of the criticisms in regards to the limitations of the studies are appropriate. The group size of our current clinical trials includes only about 25 individuals with ASD. However, we see them several times per week and the whole trial takes about 3 months per participant. Just to say that in a mom and pop operation like ours (without support from our university or the federal government) it takes about 6 months of our time. We are hopeful that by combining the efforts of different groups, the total numbers may increase and we have the equivalent of a phase III trial for the FDA. We have a consensus meeting before IMFAR to discuss this possibility.

    We do have the sham coil (about $3,000 out of pocket). The first patient we had was able to differentiate the sham coil from the real coil (a failed attempt at a double cross over experiment). It wasn’t that the raters could not be kept blind, the difficulty was in keeping the patients blind! Again we hope that if given some support and having larger numbers we may be able to run a large trial with sham controls. However, thus far several groups have followed our lead and reported positive findings with rTMS in ASD.

    Although we have used several screening techniques, they were not restricted to caretaker screening tests. Recognizing that these and others were not meant to be severity dependent measures we introduced electrophysiological measurements. I think this was one of the better contributions that we made to the literature. After studying the error negativity wave and other measures of event related potentials we have been extremely enthusiastic in pursuing differences in gamma frequencies. We wrote a blog about this regard (https://corticalchauvinism.com/2013/02/14/autism-what-is-the-buzz-about-gamma/). At present we believe that gamma abnormalities are a core feature of autism and offer a severity dependent measure to judge outcome in different interventions.

    Maybe astrocyte have something to do with the pathology of ASD. Right now we can only pursue one thing at a time and rTMS seemed a good way of indirectly proving our ideas.

    You were silent for a long time. I was beginning to feel lonely 🙂

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  3. It’s really interesting to hear about a scientist’s account of transcranial magnetic stimulation. I’ve thought about signing my son up for TMS. He has autism, so I’ve been trying to find an effective treatment for his ASD. It’s really interesting how the low frequency of TMS could build different parts of the brain. I hope that I can sign my son up for TMS so that his ASD can finally be treated.

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