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Improving Deep Brain Stimulation to Treat Freezing of Gait

Improving Deep Brain Stimulation to Treat Freezing of Gait

While deep brain stimulation (DBS) is a powerful treatment for many people living with Parkinson’s, this therapy does not treat all the symptoms of PD and isn’t suitable for all patients. Earlier this year we launched a funding program to support projects that seek to improve DBS or to explore other neuromodulation techniques.

In DBS, a neurosurgeon implants a thin electrode into the brain, targeting motor and potentially other circuits that are not functioning properly. Small electrical pulses from a device similar to a cardiac pacemaker modulate the signals that cause some Parkinson's motor symptoms.

Dr. Michael S. Okun, co-director and professor of the Center for Movement Disorders and Neurorestoration at the University of Florida College of Medicine and national medical director for the National Parkinson Foundation, is the recipient of an MJFF grant to improve upon the current standards and to help more people with DBS therapy.

His project targets freezing of gait and uses an advanced approach, sending electrical impulses only when the brain needs them. Current DBS sends pulses continuously, which may result in side effects, may not adequately address freezing of gait and may burn the device’s battery at a rapid clip.

Dr. Okun spoke with us about his research:

MJFF: Does current DBS treat freezing of gait?

Dr. Michael Okun: People with gait disturbances frequently report inconsistent responses, no response and sometimes even worsening of freezing following DBS. The current technology works for people with Parkinson’s who have a good response to dopaminergic medications; DBS is very good at addressing tremor, “on/off” fluctuations and dyskinesia. Walking and balance dysfunction and freezing can be very disruptive for patients, and can lead to falls and injury, but the response to DBS has been disappointing. Gait can sometimes improve, especially if “on” time is enhanced by DBS; however gait and balance problems and freezing all tend to progress and become resistant to medications and to DBS.

MJFF: What is the aim of your project?

MO: We’re looking at a novel way to detect brain signals responsible for freezing and to modulate them with a technology we believe may be capable of breaking the freezing episodes.

We’re going to place DBS leads into parts of the brain called the globus pallidus interna (GPi) — a frequent target of DBS for Parkinson’s — and the pedunculopontine nucleus (PPN), which is a well-known locomotor center that has important connections relevant to walking.

We’re not putting in regular DBS devices. The technology we will use will allow us to measure something called local field potentials, where we can monitor, in real time, the electrical currents from both the GPi and the PPN, and more importantly sample the conversations going on between these regions. We believe there’s a network of activity that underpins gait dysfunction in Parkinson’s disease. In this project we are going to begin to get a picture of what the “brain freezing” network looks like.

MJFF: How will that help you develop a new kind of DBS?

MO: For the first several months after implantation we’re going to monitor and learn about these brain signals. In a controlled laboratory setting, we can set the device for closed-loop stimulation, meaning it only fires an electric impulse when the device sees the “freezing signal” in the brain. We think the GPi may be the gas pedal and the PPN may be the brake. So if someone freezes, we may need to take our foot off the gas and de-activate the brake. We’re going to explore different DBS stimulation paradigms to understand the signals, and then to modulate them and try to gain control of freezing symptoms.

MJFF: Why is closed-loop stimulation advantageous?

MO: No two people with Parkinson’s disease are alike. We need to understand what network signals change during individual symptoms, and then we need to deliver an efficient therapy “on demand” that will be appropriate for a particular symptom. We are entering the era of personalized medicine for Parkinson’s disease.

Freezing of gait is one disabling symptom of Parkinson’s disease, and we are hoping that the brain signals will reveal that it is a straightforward problem. If we can demonstrate that the application of these technologies works for freezing, perhaps we can take another step toward some of the more complex issues.

MJFF: How has MJFF played a role in your research?

MO: The partnership has been terrific. The Michael J. Fox Foundation understands the innovation that needs to happen to bring us cutting-edge technologies. We believe we have a very good idea and a lot of reason to believe we can make it work in people with PD. This is where MJFF has done a great job in allowing researchers like us to take a step closer to our dream, which in this case is a personalized approach to treating Parkinson’s disease.

Learn more about other research into closed-loop DBS.

Read more from Dr. Okun in his book on Parkinson’s treatment.

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