Depression: Collaborated Study of Epidural Prefrontal Cortical Stimulation
Guest: Dr. Istvan Takacs – Neurosurgery, MUSC
Host: Dr. Linda Austin – Psychiatry, MUSC
Dr. Linda Austin: Dr. Istvan Takacs is Professor in the Department of Neurosurgery here at the Medical University of South Carolina. Dr. Takacs, you recently collaborated with Dr. Nahas on a very exciting study. And we recorded another podcast with Nahas about that study, in which you implanted small electrodes on the brain surface of some very depressed individuals. Tell us about your role in the study.
Dr. Istvan Takacs: Well, some time back, it has been known to us, in neurosurgery, that stimulation of the cortical surface is clinically effective for pain conditions. The question then arose, if stimulation of the motor cortex; which is further back in the brain, is helpful in controlling the sensation of pain, could some other part of the brain’s surface be controlled with similar technology to achieve other ends? And, that’s how this took off.
Dr. Linda Austin: I see. So, I know Dr. Nahas has been working in this area for quite some time. How did the two of you begin to collaborate on that? How did that partnership develop?
Dr. Istvan Takacs: Well, I received my training at a neurosurgical center where minimally invasive and functional neurosurgical techniques were in the foreground. So, I have always had an interest in changing, or rewiring, the brain, not just excising the sick parts of the brain. And when I came here eight years ago, I was very interested in establishing a relationship with the Department of Psychiatry. And, luckily for me, the Department of Psychiatry, here, happened to be staffed with people who were also interested in technology. So, the ground was laid for a cooperation that at other academic centers is more like a chasm between the two departments. But here, we were of a similar mind. They had already done groundbreaking studies on vagus nerve stimulation for depression, a technology that had been employed in neurosurgery for the treatment of epilepsy prior to that. So, there was a history of adaptation of certain technologies to new concepts.
Dr. Linda Austin: Do you recall the first conversation you had with Dr. Nahas about this particular issue?
Dr. Istvan Takacs: It was several years ago; at least four or five years ago, when this idea was first thrown about.
Dr. Linda Austin: And, from your point of view, what was the most challenging aspect? We talked about this in another podcast. You drill four small burr holes in the skull, with the patients under light anesthesia, and then implant electrodes; small paddles, on the surface of the brain. From your side of it, what was the most challenging part?
Dr. Istvan Takacs: Well, the most challenging part is always, in broad terms, to turn concept into reality. You can always wish to have a certain electrode placed over a certain convolution of the brain, but then, actually, in practice, to make that happen, and be able to double check that you ended up where you intended to, to verify that you’re stimulating what you think you’re stimulating, there have to be some techniques worked out to verify localization. And we figured that out. That’s more, sort of, a Benjamin Franklin-like, common sense, issue, rather than workbench science.
We devised a routine. To write the protocol for how to do this, you need a script that’s, really, not different from the scripts that actors read from. We had to get the choreography of all of it right so that it was done in a reasonable amount of time, with as little discomfort for the patient as possible. So, there were some practical problems that, to me, being in the operating room, were a challenge, but that a lot of people don’t think about; just like you don’t think about camera angles when you go to the movies. You just want to enjoy the show.
Dr. Linda Austin: Just to back up for those who didn’t hear the other podcast, what you’re referring to is that after the patient is under light anesthesia, you apply the paddles, but then wake the patient up and ask them questions about what they’re feeling, to try to get a sense of whether you’ve actually applied the electrodes correctly.
Dr. Istvan Takacs: Yes. That is correct. What we also want to do is, at the very beginning, since this has never been done before, make sure that the currents applied to the brain surface don’t cause an immediate discomfort to the patient. That would take away the value of long-term treatment. So, initially, when the electrodes are first implanted, you increase the stimulation intensity to try to discern whether the patient has any sort of negative side effect from the stimulation.
We were fairly certain that, knowing the way that various talents of the brain are distributed on the brain surface, where we were stimulating, you would not get any strange sensations of a physical kind. But you always want to make sure that by applying a certain current, you’re not spreading too much current to adjacent parts of the brain, and inducing a seizure, or whatnot. So, the first application of currents, when the electrodes were in place, were done to make sure that we didn’t cause the patient any discomfort.
After that, a protocol had been devised by which certain stimulation parameters were changed in a stepwise fashion. And the patients were responding to questions and images shown to them on a computer screen; on a laptop that was placed in front of them. Their responses were logged and saved for future reference, once all the wounds were healed and the patients were under more normal outpatient conditions, so that all of this could be repeated and then carried forward with evermore stimulation parameters.
Dr. Linda Austin: I recall Dr. Nahas saying that one of the patients had a good response in the OR but did not have a good response to the long-term treatment, and vice-versa. Did that surprise you, that there was not a perfect correlation there? Do you see that with other similar kinds of procedures?
Dr. Istvan Takacs: I think when you have a sample size of five, anything can happen. With such a small number of patients, you can conceive of a situation where everybody is taking a good drug, but nobody is cured, just by statistical chance. So, if I was surprised by anything, it was that four out of five showed early signs of improvement. I’m also very well aware that the more patients you have, the more solid your statistics become, and the more solid your predictions about the future can be. Five patients, we were happy to get what we got.
Dr. Linda Austin: I bet. Are you excited about this technique?
Dr. Istvan Takacs: I’m very excited about this technique. It turns out that it’s much simpler, surgically, technically, to implant the cortical stimulator than to implant the deep brain stimulator, which is another technique that is being looked at in the treatment of psychiatric disease. And, if you’re not penetrating anything, your chances of hurting anything are much smaller.
The brain is like an onion, where the outer layers are evermore sophisticated compared to the inner layers. Many of the inner layers of the brain are just relay stations and integrating stations; almost like nodes in a telephone network, for things that are actually happening on the brain surface. So, what we’re doing on the brain surface is actually changing the way thoughts, or concepts, are shaped, rather than how or whether they’re transmitted from one node to another. So, if it’s a more sophisticated way to influence the brain and, at the same time, a safer way to influence the brain, it is, then, superior to other techniques. And again, with only five patients in the group, for now, you cannot condemn anything, or elevate anything to preeminence. But you can have hope, and, of that, we have plenty.
Dr. Linda Austin: Well, it’s a very thrilling step. I feel like I’m in the presence of somebody who has done something of historic significance. So, we’re very excited for you. We give you our deepest congratulations, and can’t wait to see what the next chapter of this research reveals.
Dr. Istvan Takacs: Thank you very much.
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