Closing the Loop With Cortical Sensing: The Development of Adaptive Deep Brain Stimulation for Essential Tremor Using the Activa PC+S.

Deep Brain Stimulation (DBS) is an important tool in the treatment of pharmacologically resistant neurological movement disorders such as essential tremor (ET) and Parkinson's disease (PD). However, the open-loop design of current systems may be holding back the true potential of invasive neuromodulation. In the last decade we have seen an explosion of activity in the use of feedback to "close the loop" on neuromodulation in the form of adaptive DBS (aDBS) systems that can respond to the patient's therapeutic needs. In this paper we summarize the accomplishments of a 5-year study at the University of Washington in the use of neural feedback from an electrocorticography strip placed over the sensorimotor cortex. We document our progress from an initial proof of hardware all the way to a fully implanted adaptive stimulation system that leverages machine-learning approaches to simplify the programming process. In certain cases, our systems out-performed current open-loop approaches in both power consumption and symptom suppression. Throughout this effort, we collaborated with neuroethicists to capture patient experiences and take them into account whilst developing ethical aDBS approaches. Based on our results we identify several key areas for future work. "Graded" aDBS will allow the system to smoothly tune the stimulation level to symptom severity, and frequent automatic calibration of the algorithm will allow aDBS to adapt to the time-varying dynamics of the disease without additional input from a clinician. Additionally, robust computational models of the pathophysiology of ET will allow stimulation to be optimized to the nuances of an individual patient's symptoms. We also outline the unique advantages of using cortical electrodes for control and the remaining hardware limitations that need to be overcome to facilitate further development in this field. Over the course of this study we have verified the potential of fully-implanted, cortically driven aDBS as a feasibly translatable treatment for pharmacologically resistant ET.

A Pilot Study on Data-Driven Adaptive Deep Brain Stimulation in Chronically Implanted Essential Tremor Patients.

Deep brain stimulation (DBS) is an established therapy for Parkinson's disease (PD) and essential-tremor (ET). In adaptive DBS (aDBS) systems, online tuning of stimulation parameters as a function of neural signals may improve treatment efficacy and reduce side-effects. State-of-the-art aDBS systems use symptom surrogates derived from neural signals-so-called neural markers (NMs)-defined on the patient-group level, and control strategies assuming stationarity of symptoms and NMs. We aim at improving these aDBS systems with (1) a data-driven approach for identifying patient- and session-specific NMs and (2) a control strategy coping with short-term non-stationary dynamics. The two building blocks are implemented as follows: (1) The data-driven NMs are based on a machine learning model estimating tremor intensity from electrocorticographic signals. (2) The control strategy accounts for local variability of tremor statistics. Our study with three chronically implanted ET patients amounted to five online sessions. Tremor quantified from accelerometer data shows that symptom suppression is at least equivalent to that of a continuous DBS strategy in 3 out-of 4 online tests, while considerably reducing net stimulation (at least 24%). In the remaining online test, symptom suppression was not significantly different from either the continuous strategy or the no treatment condition. We introduce a novel aDBS system for ET. It is the first aDBS system based on (1) a machine learning model to identify session-specific NMs, and (2) a control strategy coping with short-term non-stationary dynamics. We show the suitability of our aDBS approach for ET, which opens the door to its further study in a larger patient population.

Automated Deep Brain Stimulation Programming for Tremor.

Deep brain stimulation (DBS) programming, the systematic selection of fixed electrical stimulation parameters that deliver maximal therapeutic benefit while limiting side effects, poses several challenges in the treatment of movement disorders. DBS programming requires the expertise of trained neurologists or nurses who assess patient symptoms according to standardized clinical rating scales and use patient reports of DBS-related side effects to adjust stimulation parameters and optimize therapy. In this paper, we describe and validate an automated software platform for DBS programming for tremor associated with Parkinson's disease and essential tremor. DBS parameters are changed automatically through a direct computer interface with implanted neurostimulators. Each tested DBS setting is ranked according to its effect on tremor, which is assessed using smartwatch inertial measurement unit data, and side effects, which are reported through a user interface. Blinded neurologist assessments showed the automated programming method performed at least as well as clinician mediated programming in selecting the optimal settings for tremor therapy. This proof of concept study describes a novel DBS programming paradigm that may improve programming efficiency and outcomes, increase access to programming outside specialty clinics, and aid in the development of adaptive and closed-loop DBS strategies.

Motor cortical decoding performance depends on controlled system order.

Recent advances in intracortical brain-machine interfaces (BMIs) for position control have leveraged state estimators to decode intended movements from cortical activity. We revisit the underlying assumptions behind the use of Kalman filters in this context, focusing on the fact that identified cortical coding models capture closed-loop task dynamics. We show that closed-loop models can be partitioned, exposing feedback policies of the brain which are separate from interface and task dynamics. Changing task dynamics may cause the brain to change its control policy, and consequently the closed-loop dynamics. This may degrade performance of decoders upon switching from manual tasks to velocity-controlled BMI-mediated tasks. We provide experimental results showing that for the same manual cursor task, changing system order affects neural coding of movement. In one experimental condition force determines position directly, and in the other force determines cursor velocity. From this we draw an analogy to subjects transitioning from manual reaching tasks to velocity-controlled BMI tasks. We conclude with suggested principles for improving BMI decoder performance, including matching the controlled system order between manual and brain control, and identifying the brain's controller dynamics rather than complete closed-loop dynamics.