Transcranial Magnetic Stimulation Questions:
Brain Anatomy Questions:
Transcranial Magnetic Stimulation Answers:
Basically, a TMS device allows a trained physician to use an electromagnet to noninvasively stimulate the brain of a patient. A rapidly changing magnetic field created by a magnetic coil causes weak electric currents in the brain through electromagnetic induction. By stimulating different areas of the cortex, it is possible to elicit a therapeutic response. For example, studies have shown that applying stimulation to the left prefrontal cortex increases activity below the stimulation site and produces a statistically significant reduction in depressive symptoms. TMS can currently target sites in the brain to within a few millimeters.
TMS is short for transcranial magnetic stimulation. rTMS, which is a newer form of TMS, stands for repetitive transcranial magnetic stimulation. rTMS improves on TMS by allowing for multiple magnetic pulses per second. The word “transcranial” simply refers to the fact that the magnetic field passes noninvasively through the head and no surgery is required.
TMS was developed in England and is currently being actively investigated at major universities throughout the world such as Harvard, Yale, Georgetown University Medical Center, The Medical University of South Carolina, Stanford University, Helsinki University Central Hospital, and the University of Sydney.
Transcranial Magnetic Stimulation clinical trials are currently enrolling subjects at nearly 100 locations around the United States and abroad. These studies can be found by a search at http://www.clinicaltrials.gov/ and are investigating TMS’s ability to treat numerous conditions. It is best to consult with your doctor in order to get a referral for most medical trials, but in many cases you can contact the research team directly via information provided on clinicaltrials.gov. Here is a small sample of the many studies currently underway:
In 2002, Health Canada approved TMS as a treatment for medication-resistant depression. Since that time, [Elata is currently researching this information] number of patients have been treated.
In America, in late 2008, the FDA cleared NeuroStar TMS therapy for the treatment of depression.
A 30-minute session is estimated to cost around $300.
TMS is frequently mentioned in the news. There have been recent articles in Time Magazine, New Scientist, The New York Times, MSNBC, Newsweek and the BBC. The MIT Technology Review has also written a summary of TMS. It is widely looked upon as having great potential to improve the quality of the lives of many who are currently suffering from mental illnesses. As the science improves over time, it is likely that TMS will be receiving more attention from the public news media.
From time to time TMS creates a flurry of excitement in the media. One example was in May 2007 when the University of Wisconsin announced that they were able to induce oscillations in the brain which appeared to be equivalent to slow wave sleep. While they were only able to do this in subjects who were already asleep, it is possible that TMS may one day be turned into a method for helping people have a good night’s rest.
TMS was introduced in the mid 1980s. It is generally agreed to be free from side effects when proper procedures are followed. Over the years since introduction, safety guidelines have been developed which minimize risks. The main complaint from a small percentage of patients is headache during and immediately following the stimulation session. This can be alleviated with over-the-counter pain medications such as aspirin or ibuprofen. It is believed that these headaches are caused by the inadvertent stimulation of nearby muscle groups, which results in tension headaches. Another common problem is ringing in the ears caused by the noise of the stimulating coil, so earplugs are typically worn during the procedure.
Seizures are the major possible risk associated with TMS, although they have only been encountered in several patients thus far. While TMS safety guidelines established in 1993 and revised in 1996 go a long way to reducing the chances of seizure, the possibility still exists. It is therefore necessary that TMS laboratories and physicians be prepared to deal with diagnosing and treating a seizure. All seizures thus far have been experienced either during or immediately following TMS treatment, during which time a patient should be closely monitored by the attending physician.
Patients can hear a loud clicking noise when the magnetic pulse is applied, so earplugs are normally worn to avoid discomfort. There is also a tingling sensation which can be felt in the scalp to a greater or lesser degree by patients. It is rarely uncomfortable. Some patients even report that they become so accustomed to the feeling that they can tell when the physician is stimulating the correct spot.
TMS is a noninvasive method of stimulating the brain through the use of magnetic fields. The stimulation coil does not make contact with the patient’s head as it induces a weak electrical current in the brain through electromagnetic induction. TMS has not been shown to cause memory loss or loss of consciousness. It does not require anesthesia nor does it cause seizures. TMS undoubtedly has a superior side effect profile to ECT. ECT was developed in the 1940s and 50s, albeit with later refinements, while TMS was invented in the mid-1980s.
According to The International Society for Transcranial Stimulation, in an article ‘Managing the Risks of Repetitive Transcranial Stimulation’ published in CNS Spectrums, “The long-term risks of rTMS are not known. However, the limited data available at this time (2002) from repeated application of high intensity, time-varying magnetic fields to humans, as in magnetic resonance imaging, do not suggest that they are significant.”
A number of studies have been conducted:
‘The clinical effectiveness and cost of repetitive transcranial magnetic stimulation versus electroconvulsive therapy in severe depression: a multicentre pragmatic randomised controlled trial and economic analysis.’
The results of comparative studies are mixed. Undoubtedly ECT remains a very effective treatment for depression. Peter Doskoch writes, “Indeed, if only a third of depressed individuals who would normally receive ECT turn out to benefit from rTMS, Dr. Janicak noted, ‘that would still be a significant advantage in our ability to manage severe depression’ and would ‘avoid many of the complications associated with ECT.’” Dr. Janicak is a Professor of Psychiatry at Rush University in Chicago Illinois and has authored several papers on TMS in medical journals such as Clinical Neurophysiology and Biological Psychiatry.   
Despite the many uses of brain imaging technologies such as MRI, they are unable to show causality. That is, they can show which areas of the brain are active in subjects performing tasks, but they cannot show that those areas are necessary to perform a task. The old saying “correlation is not causation” is quite true here. TMS can be used to selectively and temporarily introduce “noise” into targeted brain areas. The introduction of these signals will allow scientists to conduct experiments which will enable them to form and test hypotheses regarding the function of specific brain regions. This information, collected from healthy volunteers, will help to develop cures for diseases. It may also help philosophers and ethicists to further understand the nature of intelligence and consciousness.
TMS is currently being studied as a potential treatment for many disorders including depression, schizophrenia, posttraumatic stress disorder, obsessive-compulsive disorder, migraine headaches, autism, stroke, and chronic neuropathic pain. Numerous studies have been published in peer reviewed journals which indicate that TMS is even useful in treating cases of depression which are untreatable with any other therapy. Some have called TMS a “life saver.”
When used as a treatment for depression, TMS typically takes several weeks to work. But results are sometimes experienced after only one session.
Many (50-80%) patients with schizophrenia experience auditory hallucinations. The Yale Department of Psychiatry has conducted trials where an area of the brain above and behind the left ear was stimulated. “Patients showed improvement following active stimulation that exceeded … the placebo form of stimulation…. 53% of patients experienced at least a 50% reduction in their voices compared to 18% of patients receiving the placebo…”   
Early on in TMS research, it was shown that patients with motor neuron disease exhibited different response times as compared to normal individuals when their motor cortex was stimulated. TMS has been called a “quick and definitive” test for MND in a 2006 Time Magazine article on the topic. It is possible to detect MND this way, up to a year before it can be diagnosed using traditional methods. Early intervention may then be feasible to help patients in their fight against this disease.
Multiple studies have shown that TMS can be used to help rehabilitate stroke patients. Specifically, stroke victims regained motor performance and accuracy more readily when their motor cortexes were magnetically stimulated with TMS.
In 1831, Michael Faraday discovered the principle of electromagnetic induction. This phenomenon allows for the induction of current through the use of a changing magnetic field. It was already known, thanks to Galvani’s experiments of the 1700s, that the nervous system had an electrical component. For decades in the early 1900s, physiological experiments were done using huge magnetic coils. Although the state-of-the-art in electromagnets at the time was very crude, investigators managed to produce subtle psychological effects in test subjects. These experiments led to an eventual breakthrough where it was finally possible to stimulate the human eye into seeing phosphenes – the sensation of light. It was in 1985 that magnetic stimulation finally entered the clinic through the work of P.A. Merton at the National Hospital in London. Since then, advances in capacitors and other electronic components have made precise repetitive TMS possible. In 1987, the IEEE awarded the Prize for Innovation to the developers of the British group from the University of Sheffield which developed TMS.
In 2006, Professor Snyder of the Australian National University in Canberra published research in the journal Perception entitled “Savant-like numerosity skills revealed in normal people by magnetic pulses.” The paper begins by explaining that some autistics have mathematical abilities which far surpass those of most people. By stimulating the left anterior temporal lobe, the researchers were able to temporarily induce some surprising abilities in people who were not autistic. These test subjects were far more likely than their non-stimulated counterparts to be able determine the number of dots flashed on a computer screen. Such studies will allow scientists to understand not only the autistic brain but the non-autistic brain as well.
It has also been shown (as mentioned in New Scientist) in May of 2007 by Fortunato Battaglia at the City University of New York that stimulating the brains of mice can cause neuron growth, a process referred to as neurogenesis. It is possible that this phenomenon can be used to treat patients who are currently suffering with Alzheimer’s.
Throughout the history of medicine, it has been very difficult to study the brain at a functional level. Until very recently, scientists were only able to understand which areas of the brain played specific roles by studying patients who had suffered brain injury either through accident or disease. TMS changes all of this. It is now possible to create temporary and artificial anomalies in the brain by inducing a small current in finely controlled areas with the use of the TMS coil. By targeting areas, researchers can deduce which parts of the brain are responsible for different types of cognition. For example, in 2002, Marie-Hélène Grosbras and Tomáš Paus from McGill University published an article in the Journal of Cognitive Neuroscience where they are able to slow down a visual attention task by stimulating a part of the brain known to be involved in eye movements.
While Elata is not associated with any for-profit corporations, the following is a list of companies working to develop TMS:
Brainsway - http://www.brainsway.com/ (In 2007, awarded the UK’s Medical Futures Innovation Award for the most promising new treatment in the category of Mental Health and Neuroscience)
MagVenture - http://www.magventure.com/ (Manufactures the MagPro R30 which is approved by the FDA for use in the US when used to stimulate peripheral nerves and muscle)
Magstim - http://www.magstim.com/ (Hosted the “Summer School on TMS in Cognition” with Professor Vince Walsh, of the Institute of Cognitive Neuroscience and the Department of Psychology, University College London)
Neotonus - http://www.neotonus.com/home/index.htm
Neuronetics - http://www.neuronetics.com/ (Published in June of 2007 in Biological Psychiatry, the “largest conducted… first-ever international, multicenter, randomized, placebo-controlled, triple-blinded clinical trial with TMS Therapy”)
Nexstim - http://www.nexstim.com/
Researchers have developed criteria for controlled studies using sham equipment and placebo stimulation methodology. They recognize the need to avoid stimulation of the cortex while providing the subject with the illusion of stimulation by creating noises and scalp sensations which would be felt under actual conditions, while pretending to use a TMS coil. There are many different sham coils available which allow for studies to be ran with a control condition, which is very important in proving the effects of TMS.
All TMS studies must pass through an institutional review board before they are allowed to take place. The aim of this board is to protect the rights and welfare of study participants with special attention paid to ethical issues. Subjects are provided with informed consent and are permitted to leave the trial at any time if they wish. Informed consent is defined as a subject having an understanding of the study as well as all relevant facts and their implications.
In the US, Institutional Review Boards are governed by Title 45 CFR (Code of Federal Regulations) Part 46.
According to a paper in The Lancet, “Alternative projections of mortality and disability by cause 1990-2020: Global Burden of Disease Study”, depression will be the second leading cause of disability worldwide. Drug resistant, or refractory depression, occurs in up to 30% of cases. These patients have often tried every currently available pharmaceutical intervention and are still unable to return to a normal and healthy life. It is in these cases, estimated at around 4 million in the US alone, that TMS presents the possibility for greatest benefit.
Brain Anatomy Answers:
The cerebral cortex is the outermost layer of the brain, measuring 2-4mm thick. It is important in many functions, ranging from memory to emotion and is larger in humans as compared to other animals.
The motor cortex, as its name suggests, is pivotal in motor functions. It is part of the cerebral cortex. Early TMS research revealed that stimulating the motor cortex can cause the conduction of nerve impulses to the spinal cord. The motor cortex is currently used as a gauge to determine the appropriate strength of TMS pulses in a given subject. Researchers will stimulate the motor cortex and check for muscle movement. They will then note the setting required to induce this muscle movement, and use a lower setting (sub-motor threshold) to stimulate other parts of the brain as required by the study/treatment protocol. This is an important safety practice which greatly reduces the risk of seizures.
 Marcello Massimini, Fabio Ferrarelli, Steve K. Esser, Brady A. Riedner, Reto Huber, Michael Murphy, Michael J. Peterson, Giulio Tononi. (2007) ‘Triggering sleep slow waves by transcranial magnetic stimulation.’ Proceedings of the National Academy of Sciences of the United States of America, 104(20):8496-501.
 Belmaker B, Fitzgerald P, George MS, Lisanby SH, Pascual-Leone A, Schlaepfer TE, Wassermann E. (2003) ‘Managing the risks of repetitive transcranial stimulation.’ CNS Spectrums, 8(7):489.
 McLoughlin DM, Mogg A, Eranti S, Pluck G, Purvis R, Edwards D, Landau S, Brown R, Rabe-Heskith S, Howard R, Philpot M, Rothwell J, Romeo R, Knapp M. (2007) ‘The clinical effectiveness and cost of repetitive transcranial magnetic stimulation versus electroconvulsive therapy in severe depression: a multicentre pragmatic randomised controlled trial and economic analysis.’ Health Technology Assessment, 11(24):1-54.
 Eranti S, Mogg A, Pluck G, Landau S, Purvis R, Brown RG, Howard R, Knapp M, Philpot M, Rabe-Hesketh S, Romeo R, Rothwell J, Edwards D, McLoughlin DM. (2007) ‘A randomized, controlled trial with 6-month follow-up of repetitive transcranial magnetic stimulation and electroconvulsive therapy for severe depression.’ The American Journal of Psychiatry, 164(1):73-81.
 Grunhaus L, Schreiber S, Dolberg OT, Polak D, Dannon PN. (2003) ‘A randomized controlled comparison of electroconvulsive therapy and repetitive transcranial magnetic stimulation in severe and resistant nonpsychotic major depression.’ Biological Psychiatry, 53(4):324-31.
 Janicak PG, Dowd S, Rado J, Welch MJ, Fogg L, O'Reardon J, Avery D, Coffey CE, Sampson S, Boutros N. (2007) ‘Repetitive transcranial magnetic stimulation versus electroconvulsive therapy: efficacy of treatment in nonpsychotic patients with depression.’ The American Journal of Psychiatry, 164(7):1118; author reply 1118-9.
 O'reardon JP, Solvason HB, Janicak PG, Sampson S, Isenberg KE, Nahas Z, McDonald WM, Avery D, Fitzgerald PB, Loo C, Demitrack MA, George MS, Sackeim HA. (2007) ‘Efficacy and Safety of Transcranial Magnetic Stimulation in the Acute Treatment of Major Depression: A Multisite Randomized Controlled Trial.’ Biological Psychiatry.
 Martis B, Alam D, Dowd SM, Hill SK, Sharma RP, Rosen C, Pliskin N, Martin E, Carson V, Janicak PG. (2003) ‘Neurocognitive effects of repetitive transcranial magnetic stimulation in severe major depression.’ Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology, 114(6):1125-32.
 Janicak PG, Dowd SM, Martis B, Alam D, Beedle D, Krasuski J, Strong MJ, Sharma R, Rosen C, Viana M. (2002) ‘Repetitive transcranial magnetic stimulation versus electroconvulsive therapy for major depression: preliminary results of a randomized trial.’ Biological Psychiatry, 51(8):659-67.
 Hoffman, R.E., Boutros, N.N., Hu, S., Berman, R,M., Krystal, J.H., Charney, D.S. (2000) ‘Transcranial magnetic stimulation and auditory hallucinations in schizophrenia.’ Lancet, 355: 1073-1075.
 Hoffman, R.E., Hawkins, K.A., Gueorguieva, R. Boutros, N.N., Rachid, F., Carroll, K., Krystal, J.H. (2003) ‘Transcranial magnetic stimulation of left temporoparietal cortex and medication-resistant auditory hallucinations.’ Archives of General Psychiatry, 60: 49-56.
 Hoffman, R.E., Gueorguieva, R., Hawkins, K.A., Varanko, M., Boutros, N.N., Wu, Y.-T., Carroll, K., Krystal, J.H.. (2005) ‘Temporoparietal transcranial magnetic stimulation for auditory hallucinations: safety, efficacy and predictors in a fifty patient sample.’ Biological Psychiatry; 58:97-104.
 Robert M. Sapolsky. (2001) ‘Depression, antidepressants, and the shrinking hippocampus.’ Proceedings of the National Academy of Sciences of the United States of America, 98(22): 12320–12322.
 Leo RJ, Latif T. (2007) ‘Repetitive transcranial magnetic stimulation (rTMS) in experimentally induced and chronic neuropathic pain: a review.’ The Journal of Pain: Official Journal of the American Pain Society, 8(6):453-9.
 Snyder A, Bahramali H, Hawker T, Mitchell DJ. (2006) ‘Savant-like numerosity skills revealed in normal people by magnetic pulses.’ Perception, 35(6):837-45.
 Domenica Crupi, New York, NY, Hoau-Yan Wang, M. Felice Ghilardi, Angelo Quartarone, Messina, Italy, Fortunato Battaglia, New York. (2007) ‘rTMS, Stem Cells and Synaptic Plasticity.’ American Academy of Neurology, Poster Sessions: Neural Repair / Rehabilitation.
 Grosbras MH, Paus T. (2002) ‘Transcranial magnetic stimulation of the human frontal eye field: effects on visual perception and attention.’ Journal of Cognitive Neuroscience, 14(7):1109-20.
 Murray CJ, Lopez AD. (1997) ‘Alternative projections of mortality and disability by cause 1990-2020: Global Burden of Disease Study.’ The Lancet, 349(9064):1498-504.