Center for Integrative Biomedical Computing

Collaborating Investigator(s): Michael Okun, MD, Kelly Foote, MD
Institution: University of Florida

Deep brain stimulation (DBS) is a therapy in which a surgically implanted system can provide relief from disabling symptoms for a variety of disorders. It is an FDA-approved therapy for the treatment of Parkinson's disease (PD) and essential tremor (ET). DBS can modulate several different circuits in the vicinity of the electrode, which in turn can induce therapeutic effects and/or side effects for a wide range of neurological disorders. The DBS community is challenged to understand both the motor and non-motor effects of DBS, and to create systems that improve symptoms and avoid side effects. The broad goals of this research group are:

  1. to develop technology with which to measure and improve quality of life for patients treated using DBS;
  2. to form a data repository of patient outcomes that enables analysis of much larger patient populations than would be possible in a single center or clinical trial; and
  3. to use this data to accurately predict who will respond to DBS and how treatment should be applied to achieve the best possible outcomes for future patients.

Drs. Okun and Foote are both full professors and are co-directors of the Center for Movement Disorders & Neurorestoration at the University of Florida; both are world experts in their fields. They currently lead a group that is at the forefront of using DBS to treat patients with a range of neurological conditions including movement disorders (e.g., PD, ET, dystonia), psychiatric disorders (e.g., depression, Tourette syndrome), and neurodegenerative disorders (e.g., Alzheimer's). Combined, they have over 300 peer reviewed publications and their center has several ongoing scientific studies and clinical trials.

The fundamental purpose of DBS is to modulate neural activity with applied electric fields, but few investigators have the tools to enable a quantitative understanding of how changes in lead location or stimulation settings will modify activity in different brain circuits. Recently a number of studies have documented the electric fields generated during DBS. The computational power and computer science skills necessary to effectively implement such models are not available at most DBS centers. Nonetheless, many practitioners now recognize the value of computational models and interactive visualization for guiding the clinical application of DBS, as well as providing a basis for novel scientific studies. In addition, the stakes are high for patients, many of whom have received life- changing improvements in treatment, but some of whom have accepted the risks of invasive brain surgery and have failed to benefit from it. We believe that these two factors form the foundation of the relationship between the TR&Ds and this DBP. In order to make the most of this relationship, new technologies are needed to provide:

  1. tools that are easy to use. In the best case, the TR&D will develop interfaces that greatly facilitate medical image management and registration.
  2. Tools with an intuitive interface. Mobile apps are particularly attractive in this regard, especially those that can be easily integrated into a clinical workflow.
  3. Tools that facilitate the dissemination of knowledge among centers.
  4. Quantification of uncertainty.

These technical developments will allow investigators to make much better use of data collected during standard care, and will further allow them to predict how to best treat each DBS patient based on information gathered from large populations of prior patients. The major technical innovation is in the integration of patient imaging, DBS settings, clinical outcomes, and novel statistical models that will enable quantification of the effects of DBS in such a way that will enable the prediction of outcomes, effect size, and uncertainty for future patients. These capabilities are relevant for many areas of neuromodulation beyond DBS and we will argue that these technologies are critical because, in contrast to pharmaceuticals, there currently is no well-defined concept of a dose in DBS or any other neuromodulation therapy.

This DBP relies on several enabling technologies provided by the CIBC. The Simulation & Estimation TR&D provides tools and expertise in bioelectric field modeling and neuron population modeling and expertise in integrating clinical outcome data into patient-specific computational models. The Visualization TR&D provides tools and expertise in interactive models on a variety of platforms including desktop applications and mobile platforms, and visualization of effect size and uncertainty. The ultimate goal is to translate the anticipated results into improving patient outcomes and identifying new therapeutic technologies.