Transcranial Magnetic Stimulation – Where Physics Meets Psychiatry

November 5th, 2018

When I was sitting in my physics course during junior year of college, I never thought that the laws and theories I was learning while rolling my eyes because of course none of this would ever apply to my future, would have an impact on my career. Little did I know, that during my college years in the mid to late 1990’s, crucial research had just begun, and would intersect my path over 20 years later.  Approximately 200 years prior to my college years, it was discovered that neurons carry electrical energy. In 1780, Luigi Galvani discovered he could make the legs of a dead frog twitch by enervating it with an electric spark. This “galvanized” Mary Shelly to write Frankenstein, and 100 years after Galvani’s discovery, the English Physicist Michael Faraday created a magnetic field by running electricity through a coil. Then, 80 years after Faraday, research began that used magnetic fields to stimulate the human muscle. Twenty years later, Anthony Barker conducted the first transcranial magnetic stimulation (TMS) procedure in a human in 1985 using his “Sheffield Magnet,” the first TMS device. Here is where physics met brain.  

The alternating magnetic field will affect conductors in the vicinity of that field, even when the conductor is a neuron in the brain. Within 2 years of the first TMS device used, safety guidelines were released. Ten years later, a group of leading TMS authorities convened and published the first detailed safety and ethical guidelines for TMS in both clinical and laboratory settings, and also demonstrated its potential efficacy. This step helped to legitimize transcranial magnetic stimulation (TMS) as a safe and true area worthy of further research and was necessary to avoid the pitfalls of the unvetted longstanding practice of ECT (electroconvulsive therapy) which did not undergo these important steps prior to its widespread use for various disorders. So, TMS was found to be safe and effective, but for what?

Researchers in the field of psychiatry hypothesized that if an electromagnetic field can be used to create an action potential and thereby depolarize neurons, this in turn would send cascading signals throughout an entire circuit of neurons, triggering the secretion and modulation of various neurotransmitters within that circuit. In other words, could TMS do what systemic medications have been trying to do, but in a localized, focused treatment? If so, what psychiatric condition should be targeted first to investigate, and what area of the brain should be targeted? These three questions needed to be addressed before any progress could be made. Major depression was chosen as the target condition to investigate, given that millions of people are plagued by this disorder and its potential for lethality.

For years, pharmaceutical developers were trying to create antidepressants that would not be lethal in overdose and target various neurotransmitters. For example, the SSRIs, or selective serotonin reuptake inhibitors, the first of which was Prozac launched in 1980, were designed to be safe and not cause cardiotoxicity in overdose, as was the issue with the tricyclic antidepressants. The other issue with antidepressants, is that they target specific neurotransmitters, but many are involved with depression and anxiety symptoms. Therefore, it became evident that one medication, or monotherapy, was not going to be adequate in putting depression into remission, but multiple, or augmentation strategies.

This was how I was trained; if one medication does not achieve remission for the patient, but there is at least some improvement or response, then do not switch and start all over again. Instead, add, layer, augment with additional medications that work synergistically together. The downside is with various systemic medications at work, there are various potential side effects as well. Again, the question is posed, can TMS do what multiple medications do, but non-systemically?  

Mark George, MD and Alvaro Pascal-Leone, MD were two of the pioneers who spearheaded the mid 90’s research, and they continue to conduct significant TMS-related research today. Now that it was established, TMS was to be investigated for its use in the depressed patient, the above question was reiterated. Where to target the beam? Ideally, the target would be as superficial of a location as possible. This is because, as physics would have it, the deeper a magnetic beam goes, the more spread out it becomes, hence losing focality.

So what area of the brain is superficial but linked to the mesolimbic system, the striatum, the hippocampus, and other deep brain structures that are involved in depression? The answer: the dorsolateral prefrontal cortex, or DLPFC. This particular area is linked electrochemically to the deeper brain structures and this in turn translates to stimulation of all structures in the circuit.  You stimulate one, you stimulate them all, the domino effect. After 10 years and 90 clinical trials and several meta-analyses suggesting a moderate effect size, the first phase III, randomized, double-blind controlled multi-site study for the use of repetitive transcranial magnetic stimulation in treatment-resistant major depression was conducted by JP O’Reardon in 2007. The U.S. company Neuronetics, using their proprietary NeuroStar rTMS system, was a large part of these studies. Then in 2008, the FDA officially approved the use of Repetitive Transcranial Magnetic Stimulation (rTMS) therapy for treatment-resistant depression. Mark George, MD ran another large, NIMH-funded study that validated the initial safety and efficacy results in 2010. Eventually, in 2013, health insurance companies started to cover TMS therapy for their patients, giving more of the population the option of receiving TMS therapy after failing multiple medication trials.

In the end, the questions were answered. With consecutive and repetitive, stimulatory magnetic pulses over the dorsolateral prefrontal cortex, neuromodulation of that area and the connected areas can occur, leading to statistically significant improvement in depression symptoms. This begs the question, where else on the beam can TMS target and what else can benefit from this advanced technology. Future applications of TMS are currently under investigation. Various other companies have jumped into TMS technology, spring-boarding off of the NeuroStar FDA approval. Migraines, OCD, addiction, and other neuropsychiatric conditions such as Parkinson’s Disease, Autism and stroke, are other conditions that have the potential to be benefited by TMS technology. The possibilities are great and the potential number of people who can benefit from this method of non-invasive treatment is vast and inspiring and leaves me with much hope. I feel privileged to be able to now offer my own patients TMS as a treatment option, having become a certified TMS provider myself. I never would have thought that all of those theories and equations from the great minds of the 18th Century physicists, and studies conducted while I was in college would lead me down this career path. It’s as if I was pulled by a magnetic force…

If you or a loved one are looking for a safe alternative to electromagnetic treatment for depression in Miami, FL or any brain stimulation treatment for depression in Miami, FL, contact the team at SuccessTMS today!