Will humankind ever truly understand the mysteries of the brain, with all its impulses, complex galaxies of neurons and hidden memories? A treatment called Deep Brain Stimulation (DBS) seeks to unlock some of those secrets, effectively curing some of our race’s most horrendous diseases by simple targeted electrical pulses. While the science behind DBS is still largely nebulous, the results are staggering—here, two area doctors weigh in on Transcranial Magnetic Stimulation (TMS) for depression and DBS for Parkinson’s disease.

SRQ: In layman’s terms, how do both Transcranial Magnetic Stimulation (TMS) and Deep Brain Stimulation (DBS) work? Dr. Jordana Hollen, MD, ABPN (Board Certified Psychiatrist, Comprehensive MedPsych Systems): With TMS, there is an area in the brain that we are trying to reactivate. Instead of messing around with medications, where you have to worry about what neurotransmitter this medication is going to target, TMS targets all the neurotransmitters in that area and basically reactivates them—you don’t have to worry about if this patient going to respond to this, or have a side effect from that. That’s one of the major benefits of TMS—it targets all the neurotransmitters in the area that is responsible for depression in the brain. The dorsolateral prefrontal cortex on the left side is where you need to stimulate consecutively for depression to lift. There is a precise location that you target for depression (on the left side of the brain), and there is a precise location when treating someone for anxiety—called right-sided TMS. Treatment for anxiety and pain disorders like Fibromyalgia are still in clinical trials and not approved yet, so it’s not approved and covered by insurance, but we could treat someone for anxiety or pain if they wanted to come in self-pay. But we are getting a lot more people now because Medicare, BlueCross/BlueShield and all these major insurance companies are covering TMS, which is fantastic. People are getting better; I am seeing people getting better. Dr. Kenneth Vives, MD, FACS (Director of Advanced Neurosurgery, Sarasota Memorial Hospital): Deep brain stimulation works by providing electrical stimulation at very specific areas in the brain, allowing us to change the function of the network of neurons that causes Parkinson’s disease. The two main targets in the brain for Parkinson’s are the subthalamic nucleus and the thalamus. These are both part of the same network of neurons that are involved in initiation of movement and major motor functions. They are parts of the dopaminergic system of the brain—they connect to the dopaminergic system of the brain. The dopamine-producing neurons in another area of the brain called the substantia nigra create one of the main features of Parkinson’s disease—the loss of those neurons. So there’s this whole network of different neurons that include the subthalamic nucleus, the globus pallidus and the substantia nigra—we can take this network that’s not functioning and get it closer to normal by providing electrical stimulation in these areas.

Are these invasive procedures? Hollen: The beauty of TMS is that it’s not invasive at all and doesn’t require anesthesia. There is no memory loss. Some people say they had a little bit of a headache because it is a loud tapping, and then just take what you normally would for a headache, like Tylenol, just after treatment. Vives: DBS is an invasive procedure. We use specific techniques to target the areas of the brain and find the few millimeters of the brain that we need to get the electrode into. We listen to the firing patterns of the neurons in the areas and then place the permanent electrodes in the brain, which go through a hole in the skull. That is then connected to a wire that goes underneath the skin—all of this is underneath the skin—into the area just below the collarbone where we implant the generator that provides the electrical stimulation. This is needed for diseases like Parkinson’s, unlike TMS, because this goes very deep inside the brain;  it would be very hard to reach those areas with techniques that go over the skin like TMS. The pulse is also needed continuously (unlike TMS)—many patients with Parkinson’s, especially with some of the forms with the tremor, if the patients stop the stimulation their symptoms will come back relatively rapidly.

How severe do someone’s symptoms have to be to qualify for either treatment? Hollen: For TMS it depends. You have self-paid TMS and TMS paid for by insurance. Now it’s covered by insurance for major depressive disorder. It’s not covered for anxiety—you can treat people for anxiety, but not through insurance. For major depressive disorder we do about five to six weeks of treatment, five days a week. Major depressive disorder is when people have been fairly depressed for a while, not meeting criteria for just depressive disorder, but actual major depressive disorder. According to the DSM IV, major depressive disorder is characterized by depression for more than two weeks, a mood change from the person’s baseline, impaired function (social, occupational, educational) along with other specific symptoms like irritability, feelings of worthlessness and thoughts of suicide. To meet criteria for it to be covered through insurance, it has to be something where they have tried four anti-depressants, they have tried certain augmentation agents, they have been through therapy and their major depressive disorder has been refractory to both those medications and psychotherapy. I recommend that people getting TMS are also in psychotherapy; I find you can make the most movement with both. Some people come to me and say their goal is to get off of medication and that’s why they want TMS, and we can try that, but there may be a role for both—they may feel really good and no longer depressed at the end of the TMS, but may find that a maintenance medication is the best thing for them. The TMS will lift the major depressive episode, but then there is a role for mediation as well. But a lot of people also just can’t tolerate medications, and that is where TMS comes in; they may have so many side effects from medications or they just never had any benefits from any medication, and then they have TMS and it’s a wonderful thing. Vives: Anybody that is having motor symptoms that are interfering with their lives that are not able to be managed with medication are a candidate for having DBS surgery done. We call it medically refractory—when their neurologist has tried all the tricks they can with medication and the patient is still having symptoms. This could be somebody with early onset Parkinson’s or even someone in their 80s. We don’t screen specifically on age.

What does each treatment look like in terms of process? Hollen: The TMS treatment is 37 minutes. However, the very first treatment takes a bit longer because we are trying to find a very specific location. We find location first then we figure out what the dose or intensity will be for the treatment, specific to each person. To find the correct location, anatomically you use guidelines on the skull and the ears and the eyes. Based on these markers just by looking at someone’s face and skull, I determine where to begin. Then you turn the machine on, delivering pulses, while looking for movement in the hand, trying to find the patient’s motor strip. First you will get an arm movement, then pinky movement, and you’ll move down to the part of the brain called the cortical homunculus, which is a neurological “map” of the anatomical divisions of the body. As you move down the skull, each finger down the hand will jump—when we get to thumb, my technicians and I say it’s the stuff dreams are made of. That is the exact spot that you want. When you find thumb movement at a low frequency, you know you are at the right location. You don’t treat on the motor strip—it is just the set up. We then move 5.5 centimeters from that location to find a very specific spot on the brain. Location first, then intensity of dose (frequency) with a computer algorithm. Once we find it, the frequency is the same each time the patient comes in. Vives: For DBS, the surgery is done in two stages. We actually don’t turn on the stimulator until a few weeks after the surgery is done. Some patients will have a microlesional effect—when we put the permanent wire in, it can cause a decrease in symptoms just from its presence even without getting electrical stimulation, so the effects are confusing during that time in terms of figuring out how much stimulation they actually need. The second surgery is when we put the generator in. That’s about an hour-long, outpatient surgery under general anesthesia—because of the anesthesia, we don’t like to turn it on right then. The neurologist usually turns it on in the office one or two weeks after the second surgery. What patients experience is a little bit dependent on the reason why we put it in. We have patients that want to have their DBS treat a tremor, which usually gets better very quickly. We kind of know what to expect when we turn it on because of the testing we’ve done beforehand. For the stiffness and rigidity that comes with Parkinson’s, that often responds very quickly as well. Some patients have a problem called dyskinesia, where they have too much movement, and often times it is linked to their medication cycle. That takes longer to get under control; usually it will take a few months of programming and manipulating the patient’s medication. You have to remember that Parkinson’s is a progressive degenerative disorder. So over time—this is actually one of the nice things about using this stimulation because we can program it through the skin—the patient may require more stimulation. Hollen: Unlike DBS, TMS doesn’t provide continuous stimulation—while it’s non-invasive, you have to keep coming back for treatment. If you have someone come in and they want to feel better really quickly because they are so depressed, you have to make a decision and discuss the timing. TMS is a true commitment. You come in for five to six weeks, five times a week, and some people just aren’t able to do that; some people feel so poorly that they really can’t do that. They need to decide if it so acute—they aren’t eating, drinking and are suicidal—do they need to go and get Electroconvulsive therapy (ECT), or is it a situation where they really don’t want ECT because they don’t want the general anesthesia or the memory issues that come along with it. With TMS, you just come in and get your treatment and go back to work—you can drive yourself, et cetera. But, they have to decide if it is worth it to take on TMS—you really have to put in that time before you start to get better.

For both TMS and DBS, do patients have to re-up? How long do the effects last? Hollen: We don’t know for TMS. What we have seen are several different scenarios. I have had people go through only one course of treatment and I don’t see them again, and the major depression has been completely lifted. I have had people who respond marvelously and TMS is the only thing that will work for them. Sometimes they will come back to me because a life event happened—a break up, a death, a confluence of events—and they are prone to major depression in general, so it hits them again and they come back and have another round of TMS which works great; many people say it’s the only thing that works. I have seen people come back in three months for another round of treatment and hopefully that is it until the next event happens, but that could be 5, 10 or even 20 years down the line—hopefully never. I like treating my patients, but I like when I don’t see them again, when there are long intervals between treatments. Vives: With DBS, the stimulation is set to fire at a certain pattern. The patient can actually turn it off to save the battery life, on the generator itself. The patients that can, for instance, tolerate having it off while they are asleep, especially if they have a loved one that can help them turn it all back on in the morning, they can save the battery life. The battery life varies from patient to patient—on average it is about four years. When it dies, it’s a very quick, routine procedure under local anesthesia to switch out for a new generator. Since the stimulation is continuous, the effects should stay the same, unless the disease progresses and we need to up the frequency.

What does the future look like for these treatments? Hollen: TMS is a wonderful treatment that you used to need a lot of money to have, and now it’s already moving in the direction of being covered by insurance. I hope it moves toward being covered for more things like anxiety and migraines and even PTSD in clinical trials. And it is moving in that direction, to cover all types of psychiatric disorders. Vives: In terms of Parkinson’s and DBS, I think we are going to continue to see advances in the devices themselves, ones that can provide better stimulation and better control over time. The one we have now just provides stimulation; it doesn’t actually listen to anything else in the brain and make decisions about how to change the pattern of stimulation. We have already a couple of other things we use this for—it’s approved for treating essential tremor, another movement disorder, and it does great for those patients. We can also treat dystonia, which is another movement disorder characterized by slow, dragging movements or static contractions—it’s still considered somewhat experimental. The same for obsessive-compulsive disorder. It’s being tested for Alzheimer’s, enhancing memory circuits, and even high blood pressure and obesity. We’re looking at areas of the brain in order to change the overall physiology of the patient’s body. It’s a tool that you can imagine being used for all sorts of disorders, we just have to very carefully identify the circuits we need to stimulate in order to have good outcomes. In terms of the long-term for DBS and Parkinson’s disease, it’s a neurodegenerative disease where cells are lost, and there are a few different strategies that could potentially be used to keep that from happening if we can identify it early enough. There’s a lot of research into biomarkers and other ways we can identify the disease in patients earlier—we want to start slowing the progression of Parkinson’s. DBS is treating their symptoms but it’s not really changing the progression of the disease. Before I came here, I was involved in a lot of research looking at ways of doing this with gene therapy with the idea that there are growth factors that can help save and support the remaining dopaminergic neurons and help them perform better or even re-enervate areas where they had stopped sending signals. Dr. Jim Schumacher in town is looking at putting in stem cells and trying to get them to differentiate to reconstitute the populations of neurons that have been lost. One thing to note: when you think about when your brain was first forming, when these circuits first made their initial contacts, the geometry was very small. And now, in the adult brain, the geometry has grown over time and everything is very far away. You have to find some way of guiding, when you put new neurons there, creating functional connections to the correct areas. I think it is going to require a combination of techniques to be effective.


About Our Participants

Dr. Jordana Hollen, MD, ABPN is board-certified by the American Board of Psychiatry and Neurology. She graduated Phi Beta Kappa and with honors from the University of North Carolina at Chapel Hill. Dr. Hollen completed her residency in psychiatry from the University of Florida. She specializes in treating anxiety, depression, ADHD and mood disorders. She is ECT-trained and also specializes in Transcranial Magnetic Stimulation (TMS) treatment for depression. Comprehensive MedPsych Systems is one of the eight facilities providing TMS in the United States.

Dr. Kenneth Vives, MD, FACS earned his undergraduate degree in biochemical engineering at Rutgers University, and completed his medical degree and residency at Yale University. While at Yale, Dr. Vives had a combined general neurosurgery practice at Yale-New Haven Hospital. He served in sections of epilepsy and spine at Yale-New Haven Hospital for 10 years. He also served as director of stereotactic and functional neurosurgery, associate residency program director and director of neurotrauma during his tenure at Yale University School of Medicine. Dr. Vives is board-certified in neurological surgery as well as a fellow of the American College of Surgeons and a member of the American Society of Stereotactic and Functional Neurosurgery, American Epilepsy Society, Congress of Neurological Surgeons, American Association of Neurological Surgeons as well as the American College of Surgeons. Dr. Vives provides services in general neurosurgery including brain and spinal surgery with the addition of stereotactic and functional neurosurgery concentrating on surgery for Parkinson’s disease and epilepsy. He is currently the director of advanced neurosurgery at Sarasota Memorial Hospital.