Though TMS is a fairly new therapeutic tool, it has a long history. A history that started over 200 years ago with the discovery that electrical currents applied to animal and human nerves could induce automatic twitches of the muscle. Unfortunately, this ground breaking discovery was popularized not for its legitimate scientific value, but rather by charlatans who used this discovery to stage macabre demonstrations of deceased individuals “coming back to life” through the application of electrical current. Unfortunately, this early misuse of the power of electrical energy set the stage for skepticism and reasonable calls for caution from the medical and scientific community. That being said, one must not throw the baby out with the bathwater so to speak. Based on these early discoveries, we now know that the nervous system works via electrical currents and that nerves can be activated by inducing electrical currents via external stimulation. In fact, Neurologists commonly use direct electrical stimulation today to probe the functioning of the peripheral nervous system. The only problem with using external electrical stimulation to activate nerves, as anyone who has undergone an EMG study of the peripheral nervous system will attest, is that it is extremely uncomfortable. Additionally, peripheral nerves sit close to the surface of the skin, making them easily accessible. The central nervous system (specifically neurons in the brain), however, sit a centimeter or more under the surface of the scalp. Thus, neurons in the brain require a much larger amount of electricity in order be activated by external stimulation.
As a result of this inaccessibility, devices powerful enough to discharge the amount of electricity required to activate brain cells were not invented until 1937 when the first electroconvulsive therapy (ECT) device came onto the market. ECT was first developed by Italian Physicians Cerletti and Bini to treat the manic symptoms of schizophrenia. Unfortunately, like the discovery of electrical stimulation over 100 years prior, the use and misuse of ECT spread quicker than science could keep up with as practitioners were applying ECT for a range of neuropsychiatric conditions without real knowledge of how or why it may work nor regulatory oversight to limit its use. This gross overuse, especially on vulnerable populations such as inpatients in psychiatric facilities, and often without appropriate anesthesia, lead to widespread and serious adverse psychological and physical side effects and a strong negative public opinion toward the therapy (despite being highly effective for a number of disorders). It should be noted that ECT was developed before the FDA assumed regulatory control over emerging medical devices in the United States and was “grandfathered” in and it still operates outside of the purview of FDA regulation today. That being said, the public backlash to ECT and other such devices lead the FDA, in 1976, to be charged with the oversight of the cautious development and implementation of novel device-based therapies.
From ECT to TMS
So, how do we get from electrical to magnetic stimulation, or from ECT to TMS? The concept of inducing electricity from pulsed magnetic fields had actually been discovered prior to ECT, in the 1880’s by a physicist named Michael Faraday who discovered what is now known as “Faraday’s Law of electromagnetic induction.” Faraday observed that a pulse of electric current passing through a wire coil (such as a TMS coil) generates a magnetic field, which in turn can induce a secondary electrical current in a nearby conductor (such as the brain). Thus, it is the magnetic field that passes from the coil through the scalp, but electrical currents that do the stimulation. Notable here is that magnetic fields are much less painful than electrical fields and once inside the brain, the brain doesn’t have any pain receptors. So Faraday’s Law became the critical element enabling the development of TMS. It took 100 years, however, before the first TMS device was developed. Dr. Anthony Barker, a Physicist working at the Royal Hampshire Hospital designed the first TMS device in 1985. At first, this TMS device was developed to study the basic physiology of the brain by applying single pulses of TMS and observing behavior immediately after stimulation (for example stimulating motor areas of the brain and observing twitches in peripheral muscles). However, by the mid 1990’s clinical researchers at the National Institutes of Health wondered if repetitive application of TMS pulses may lead to an enduring change in the function of the neurons. Thus was the birth of therapeutic applications of repetitive transcranial magnetic stimulation or rTMS. The first therapeutic application that was trialed, and still the most studied today is treatment-resistant Major Depressive Disorder. A simple search of the literature results in over 1,000 published articles supporting the use of rTMS in depression. Despite the overwhelming evidence for the safety and efficacy of TMS for depression, and likely due to the missteps from ECT, it wasn’t for over a decade later, in 2008, that TMS was FDA cleared for treatment-resistant depression. Like ECT before it, and especially following its FDA clearance, clinics offering both on-label (for depression) and off-label therapies for a myriad of neurological and psychological pathologies have been opened world-wide.
The Future of TMS
With increasing numbers of individuals seeking TMS therapy, ensuring patients received the best possible treatment by a doctor well versed in both the appropriate methodology and all relevant device considerations, has become of paramount concern in the field. We do not want history to repeat itself. As I hope to discuss in upcoming blog entries, just because a specific set of parameters (e.g. high frequency stimulation of the left dorsolateral prefrontal cortex) works for depression, does not mean that this is the appropriate protocol for autism for example or PTSD. Just as one would not expect the same medication to work for all ailments, the same TMS protocol will also likely not be appropriate for all conditions. Like developing a new drug, we must consider dose (how much TMS to apply, how often, and at what frequency), localization (where in the brain do we stimulate and how do we define that region (structurally or functionally) and for what individuals (which conditions, what age range). Are there people that should not receive TMS where it may be more risky or counterindicated? There are many questions, but also an increasing number of clinical researchers dedicated to answering them. Though there is great promise in the use of TMS for a wide variety of neuropsychiatric disorders, we must be smart about how we apply it. TMS most certainly has the power to lead to a long-term change in brain network functioning. We just need to make sure that we know which “dysfunction” we are trying to remedy and whether this “remedy”, at the level of the brain network, has the potential to lead to a clinical benefit to the patient. More to come in the next blog entries on this and other relevant topics.