1) How did you first become involved in TMS?
I first encountered TMS when I was doing a research fellowship in 1989 at University College London. I was doing brain imaging with PET and SPECT, and was interested in the brain regions involved in regulating emotion. When I saw John Rothwell [professor of neurophysiology at the Institute of Neurology at Queen Square, ed.] using TMS in his motor lab to study the motor system, I immediately wondered if we could use it to investigate brain circuits involved in emotion regulation, and perhaps even treat diseases like depression.
2) For you personally, what was your main reason for choosing to work with TMS?
Imaging alone was insufficient. Brain activity during a task or state could be due to the task or state, or could be the brain’s reaction to the core activity, or could be merely incidental. TMS seemed to offer a way to push and pull circuits and test out causality. And maybe if we were lucky, and we are, actually treat brain diseases that involve dysfunction in these circuits.
3) How was TMS perceived in the ‘early days’?
Back then all of these ideas were heretical – regional neuroanatomy of depression, brain basis of emotion egulation, non-invasively and without causing a seizure stimulating someone out of depression. I later did the first clinical work at the National Institutes of Health (NIH) in Washington, with Dr. Robert Post. The going was still rough as there was much skepticism – getting asked to leave an ECT meeting, and having my senior boss at the NIMH tell me I could not talk to the press about TMS as they did not want to ‘sully the NIH name.’
4) Seen in the infamous hindsight, what would have been especially nice to know back then?
The FDA was concerned about TMS causing a seizure and the potential effects of lots of pulses. They thus limited our early studies in terms of the intensity of stimulation. We underestimated the number of pulses needed, and the number of weeks we needed to stimulate. I wish we had been more aggressive in pushing the parameters of stimulation. I think we underdosed for well over a decade, and may be still underdosing.
5) What do you consider to be among the most profound discoveries made?
That it worked is truly amazing. We did double blind studies from the beginning, but I was always worried that the effects were not going to replicate for whatever reason. I was very pleased when Dr. Saxby Pridmore, whom I had never met and who was working in Tasmania, Australia, started replicating our results, and showing changes in a biomarker called the dexamethosone suppression test (DST) [DST is used to assess adrenal gland function by measuring how cortisol levels change in response to an injection of dexamethasone. In conditions such as depression, dexamethasone can prevent cortisol levels from going down, ed.].
6) Even though we are seeing very promising results, there are still some patients with MDD whose condition does not improve with TMS. Will it be possible for more patients to respond positively to the treatment?
I am an optimist. I am confident that we can and will continue to refine and improve TMS for treating depression, at least approaching the efficacy of ECT (60% remission). There are lots of candidate clues for improvement. It is important to remember that many of the methods we use now for treating depression were educated guesses that have not been fully explored. These involve total dose (number of stimuli), different dosing regimens (multiple daily rather than once daily), frequency matching to the individual, or frequencies like theta burst that may be more powerful at changing the brain, better targeting, or combining TMS with talking therapy or special medications. There is still a lot to work on. It would be unbelievable if our educated
guesses turned out to be the best solutions.
7) What, within the field of TMS research for the treatment of MDD, do you consider to be among the biggest challenges you are facing today?
TMS for treating depression, as we do it now, is terribly inefficient, requiring many hours in the TMS chair. We need to figure out how to reduce this inefficiency and thus make it less costly, both to patients, doctors, and insurers. Wouldn’t it be great if we could get 70% remission with only a few hours work?
8) With MagVenture’s recent FDA clearance for depression treatment, four FDA cleared systems are now available. What impact will this have in the US?
I think this is all good news. A rising tide floats all boats and we have lots of boats now. This means that not only one manufacturer has to do battle with insurance companies, but we now have a larger industry to fight these battles. I think this competition will drive down costs and spur competition and innovation.
9) Do you expect to see many new TMS treatments emerging in the next 10 years or so? Where do you see the most potential in terms of treatment?
There are lots of studies with TMS in almost every major brain disease. Some of the more promising areas currently are acute or chronic migraine, pain (either post-surgical or chronic), OCD, PTSD and addictions.
10) Can you tell a little about your current study with the U.S. Department of Veterans Affairs (VA)?
Cooperative Study Protocol #556 is chaired by Dr. Jerry Yesavage at the Stanford VA and designed to test whether prefrontal TMS works to treat depression in veterans. It is thus more ‘realistic’ than the pivotal NIH, Neuronetics and Brainsway trials, which were antidepressant medication free studies in patients without substantial comorbidities. The VA trial allows patients to stay on their medications, and many of them have PTSD and prior substance abuse. MagVenture won the competitive bid for the TMS device. We hope to complete enrollment in the late spring of 2016.
Dr. Mark George
Dr. Mark George received his medical degree from the Medical University
of South Carolina in Charleston. He was a Visiting Research Fellow
at the Institute of Neurology, University College London, England.
At the National Institute of Mental Health (NIMH) he was among the
first to work with functional imaging which led to his pioneering use of
TMS. Since then, he has worked continuously to grow the science of
TMS. In 1995 he moved back to Charleston and built the functional neuroimaging
division and brain stimulation laboratories, now known as the MUSC
Center for Advanced Imaging Research. In 2008, with the academic publishing
company Elsevier, Dr. George launched the journal Brain Stimulation:
Basic, Translational and Clinical Research in Neuromodulation, of
which he is also the editor-in-chief.
Dr. Mark George has received numerous awards, and published over 400
scientific articles or book chapters.