Over the last few weeks we’ve shared a patient’s account of his experience with deep brain stimulation (DBS) and answered your questions about the current state of this therapy for the motor symptoms of Parkinson’s disease (PD). For DBS, a surgeon implants a thin electrode into the brain, targeting motor circuits that are not functioning properly. Small electrical pulses from a device similar to a cardiac pacemaker block the signals that cause some Parkinson's motor symptoms. While DBS is not suitable for all patients, for those who are good candidates, the procedure can significantly improve quality of life.
However, researchers believe they can improve the technology and thereby daily living for patients. Currently DBS stimulates continuously, rather than only when it’s needed. A personalized approach — stimulating when symptoms are bad and easing off when things are good — could alleviate some problems that patients have with this therapy.
The Michael J. Fox Foundation is supporting research by Coralie de Hemptinne, PhD, and Philip Starr, MD, PhD, from the University of California, San Francisco, toward that goal. Their team is working to record and characterize activity in the cortex (outer layer of the brain) with and without DBS to eventually program the system to turn on or off as needed. Coralie chatted with FoxFeed about her research:
MJFF: How does DBS treat the motor symptoms of PD?
Coralie de Hemptinne: It is still actually not entirely known. We know that it can work pretty well, but we do not know how it works. In order to have normal movement, different parts of the brain need to be able to adjust their activity patterns and communicate with one another. One way this happens is with periods of high synchronization across regions and periods without synchronization. In movement disorders, it seems like the brain is stuck in a state of very high synchronization, which prevents flexibility and neural patterns, and thus constrains movement. One way that DBS might work is to disrupt this excessive synchrony so that more normal neural patterns can resume.
MJFF: Tell us about your first project funded by the Foundation, which sought to understand more about the DBS effect.
CDH: Our hypothesis was that DBS would reduce excessive synchronization observed in movement disorder patients. Therefore, we recorded the brain activity of PD patients during DBS surgery through a strip of electrodes that we placed at the surface of the brain (cortex). We found that when stimulation was off, cortical activity of PD patients was characterized by excessive synchronization that was reduced when we turned the DBS on. When we turned it off again, the excessive synchronization returned.
MJFF: So your hypothesis was proven correct?
MJFF: Your new project will record cortical activity with DBS with an implanted device. Why do you feel you need a longer recording?
CDH: The problem with recording only in surgery is that we are very limited. We can only record for 10 to 15 minutes, and, of course, we are in the operating room so we also have some logistic constraints. Also, after a patient has had the DBS hardware implanted, doctors try to determine the best settings to improve the symptoms. DBS has four stimulating contacts, so they can change the contacts, the voltage of the stimulation and the frequency and pulse width. Symptom improvement takes time, too. For example, with rigidity, one can see improvement pretty fast, but with tremor or bradykinesia, it is not always immediate. In the operating room (OR), we cannot test different settings because we are limited in time, so we pick one set of parameters and we can usually see some improvement, but it is not necessarily the best setting.
In order to improve DBS therapies, we need to better understand the effect of long-term stimulation using different settings. We should look carefully at which symptoms are improved and if the stimulation induces side effects. Another thing we can measure using long-term brain recordings is the effects of medication, which we cannot evaluate during the surgery. Even if patients have DBS, they often need medication, too, and the different effects of medication versus DBS on cortical function has not been well studied.
MJFF: Can you monitor changes in the DBS effect as an individual’s Parkinson’s progresses?
CDH: We know that even after DBS surgery, the underlying brain pathology in PD progresses. With long-term brain recording, we may better understand this progression. Also PD patients can have a lot of fluctuation in motor and non-motor symptoms, which can persist somewhat after DBS. So far DBS stimulates continuously, so even if the symptoms are not bad, the stimulation is the same, and when the symptoms are really bad, there is no change either. Ideally, DBS would modify the stimulation depending on the symptoms and related brain activity changes, but to do that we need to know how brain signals change when a patient is doing well versus when they have really bad symptoms. We need to better characterize what is happening with their symptoms and how DBS really affects each of these symptoms.
MJFF: Are there consequences of continuous stimulation?
CDH: Current DBS therapy requires a lot of trial-and-error programming and adjusting by a neurologist. Additionally, if you stimulate continuously, sometimes you do not achieve the maximum benefits and sometimes you can trigger some side effects such as dyskinesia, speech problems or depression. With DBS, you can improve the symptoms, but you can also worsen them. You have to find the good balance to just improve symptoms but not generate side effects. Intermittent stimulation based on brain signals could reduce side effects and prolong the device battery life.
MJFF: Your current study, funded by the Foundation, uses a new DBS device from Medtronic. Can you tell us about that?
CDH: The device stimulates like other current DBS devices, but in addition you can record brain activity. The pacemaker-like device in the patient’s chest is attached to two sets of electrodes. We are using one set of electrodes to stimulate the basal ganglia and record activity in that deep structure. The other electrodes will record cortical activity.
MJFF: Can you cross analyze the deep brain activity and the cortical activity?
CDH: Yes. That is the goal: to look at the brain activity from deep structures and cortical structures at the same time and compare them, because these structures are talking to each other to determine what movement has to be done. We want to know how they interact and what is abnormal in their interaction in people with movement disorders.
MJFF: How will what you learn translate to the development of tailored DBS?
CDH: The goal would be, now that we have this biomarker of disease state, which is this excessive synchrony, to use that to determine when to stimulate and how to stimulate. We need more data, but the goal is to have the patient implanted with the deep electrodes and the cortical electrodes and measure the level of synchrony in real time. As soon as the synchrony level crosses a threshold and becomes excessive, the DBS would stimulate. Synchronization should decrease and then the stimulation would cease. It would be great, too, to determine how to stimulate: which contact to use, which voltage to use. But we need much more data for that.
MJFF: How far out from this technology are we?
CDH: I hope that in the next five years we will have an automatic DBS device to determine when to trigger the stimulation or not. To determine exactly which settings, that will likely take more time.