Closed-Loop Deep Brain Stimulation: Bidirectional Neuroprosthetics for Tremor and BCI

Thesis (Ph.D.)--University of Washington, 2016-06

Deep brain stimulation (DBS) has become a widely adopted method for treating a variety of neurological and movement disorders. However, current clinically deployed systems are open-loop and do not take into account the potentially intermittent nature of symptoms. By closing the loop with wearable sensors to directly sense symptoms such as tremor, we can determine not only when stimulation may be necessary but also estimate what intensity of stimulation should be used. By limiting stimulation to only the level needed, we can increase the battery life of the implanted devices and reduce exposure to unintended side-effects. To accomplish this, I have developed a mobile and wireless platform for investigating closed-loop DBS applications in ambulatory patients. The platform consists of a set of worn sensors communicating over Bluetooth to a host application running on a smartphone or PC. By taking advantage of sensed data including inertial measurements, electromyography(EMG) and local field potentials, host applications built on my research platform are capable of performing digital signal processing and data fusion in order to make control decisions. These control decisions can include enabling or disabling stimulation or modifying individual stimulation parameters (voltage, pulse width, frequency) in response to changes in neurological symptoms. These control decisions are then sent over Bluetooth to a Medtronic Nexus system which relays packets and control decisions to an implanted Activa PC or PC+S neurostimulator. By taking advantage of this real-time command link between the implanted device and the host application we can create a closed-loop DBS system for testing in human patients. To test this research platform, I have performed vanguard experimental work to use these closed-loop systems with both Essential Tremor and Parkinson's Disease patients. In Essential Tremor patients, I have used wearable inertial and EMG sensors to suppress kinetic tremor as the patient repeatedly performed a task that produced tremor. Two control methods were used with a patient at the University of Washington, one using an inertial-based tremor estimate to manipulate the stimulation amplitude and the second used EMG to selectively determine when clinical stimulation should be delivered. Additionally, by making use of the sensed neural data available from the Activa PC+S, we have been able to prototype brain-computer interface(BCI) tasks to teach the patient how to use motor imagery to control a cursor. In Parkinson's patients, I have developed systems to suppress rest tremor using both an inertial sensor and the beta-band sensed from the patient's subthalamic nucleus. Both of these systems were tested at Stanford University. This work represent some of the first experiments using where wearable sensors or neural-sensed signals have been used in this way with a fully implanted neural interface. As this project has moved forward it will allow for investigations into the clinical performance of long-term closed-loop deep brain stimulation and brain-computer interfaces. This future work will include developing system-identification experiments to develop models of symptom-stimulation relationships. This system modeling work will enable new patient-specific algorithms to be developed to improve the closed-loop DBS performance with either wearable sensor or neural sensing in the future. There is also a future opportunity to design a system that uses a BCI-triggered DBS algorithm to allow patients to use their BCI cursor control to manipulate their own stimulation level. The significance of this work will be in improving DBS patient quality of life through enabling DBS systems to provide selective therapeutic stimulation. This will allow implanted batteries to last longer or to be made smaller, and patients will only experience side-effects when the need their symptoms treated. The mobile systems I have developed will also be useful in expanding our understanding of neurological movement disorders treatable with DBS by providing consistent data collection and monitoring while patients continue their lives outside of the clinic or hospital. As these systems are clinically deployed, we anticipate that a large amount of valuable data will be obtained. This will facilitate dynamical modeling that will give new insight into the neurological basis of tremor and will expand the understanding of the underlying neural control problems that give rise to tremor disorders.