1. DBP: SIMULATION OF DEEP BRAIN STIMULATION
Michael Okun, MD (Neurologist)
Kelly Foote, MD (Neurosurgeon)
Co-directors
Center for Movement Disorders & Neurorestoration
University of Florida
Introduction and description/accomplishments of UFL DBS Center

2. DBS Overview Conventional 4 contact DBS Leads
Brief introduction to DBS: over 100k patients implanted, and over 150 open trials on clinicaltrials.gov. After initial success and FDA approval for treating PD and ET, a wide range of other indications are being considered. The biggest public health problem that is being evaluated for DBS is depression, but it is also being tested for epilepsy, Alzheimer’s disease, obsessive-compulsive disorder, dystonia and others.
Conventional 4 contact DBS
Leads
Wired Magazine, Issue 15.03, March 2007

3. Scientific Goals
Accurate, patient-specific, multi-scale bioelectric field models of neuromodulation therapy.
Deployment of mobile platform for DBS decision support.
Development of virtual DBS surgery platform.
Primary Tools

4. Recent Progress
2016
University of Utah Neuroscience Initiative awards a pilot grant to perform pre-operative imaging on Human Connectome PRISMA MRI scanners.
Andrea Brock, 4th year Neurosurgery resident, is using this data to identify circuits modulated during effective versus ineffective stimulation.

5. Recent Progress
Collaboration with Dr. Foote on 17T imaging of human basal ganglia in DBS patient
Bioengineering graduate student Katie Warthen is integrating imaging, field models and clinical DBS settings A P
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6. Recent Progress
International Neuromodulation Registry setup and received IRB approval in 2016.
BRAIN Initiative R24 submitted Jan 2017 to develop tools and informatics platform to support BRAIN studies
Internal advisory board includes faculty from SCI and Bioinformatics.
External advisory board:

7. Challenges & Future Directions
Near real-time, multi-scale bioelectric field modeling.
Integration of models with outcomes and imaging databases.
Growth of Infrastructure and methods to support population health studies in neuromodulation.

8. Clinical and Research Application of Transcranial Brain Stimulation
Shorten into and motivate it more with a clinical scenario, sudden death and ischemia.
Get to slide 4 in minute 3.
Alvaro Pascual-Leone, MD, PhD, Michael Fox, MD, PhD, Mark Halko, PhD
Beth Israel Deaconess Medical Center and Harvard Medical School

9. Motivation to Stimulate Cerebellum
Nearly all known networks of the brain have cerebellar nodes
Modified from Buckner et al 2011

10. TMS and Cerebellum
The cerebellum is known for motor function, yet TMS is more likely to impact non motor function (orange: hypothetical TMS coil position, blue/red/green motor areas)
Modified from Buckner et al 2011

11. TMS Position and Stimulation
Positions of model TMS coil locations that could impact cerebellum
Figure 2. Using finite element modeling, combined with resting state imaging, it is possible to localize the best location to position a coil to stimulate a cerebellar network node. Left: grid of potential stimulation sites tested in silico. Right: intensity of magnetic field reaching default network nodes from each site.
Stimulating just cerebellar nodes was observed to change connectivity between two other
default network nodes that were not directly stimulated themselves. Our design relies upon targeting
resting-state networks for stimulation, an advance over traditional scalp location based targeting, and we
leverage the distributed cortex-cerebellum connectivity to modulate entire networks [12].
Intensity of magnetic field reaching default network nodes from each candidate TMS site

12. Changing Network Functional Connectivity
Stimulation of ideal default network site changes default network functional connectivity
Default connectivity
Changes in connectivity
Modified from Halko et al 2014

13. Model predicts functional connectivity
A single subject model field was used to assess the magnitude of effect upon cerebellar network nodes for individual subjects (e.g. each individual subject has slightly different locations of their cerebellar network “nodes”, thus recieving slightly different magnitudes of magnetic field). This is contrasted with the magnitude of functional connectivity change observed after stimulation.

14. Michael Fox, MD PhD: Electrodes and Targets
Assistant Professor in Neurology
1) Two different electrode configurations used in the optimization. We note that head meshes in both configurations are identical except where the electrodes touch the scalp.
2) Cortical ROI derived from rsfMRI with SG as the seed point.

15. Results of Optimization
Current
E Field
Optimization results for 2 methods on 2 electrode configurations. First row panels show the optimized stimulus pattern of a given method on a given electrode configuration. Second row shows the electric field normal to the cortex. Third row shows ERNI on the cortex.
Error

16. Comparison of Approaches
Electrode Current
Optimization results for all four ROIs using two optimization criteria and two electrode configu- rations. Four cortical ROIs shown on the first column, with color representing positive (red) and negative (blue) correlation with four seed points: global pallidus pars internus (GPi), subthalamic nucleus (STN), subgenual cingulate (SG), and ventral intermediate nucleus (VIM). Each of the remaining panels shows both optimized electrode stimulus pattern and corresponding electric field component normal to the cortical surface. For better visibility, the electrodes with small currents in the optimal solution are not shown.
Our results suggest that using a larger array of smaller electrodes does not necessarily yield more targeted modulation. For example, when Ruffini et al.’s least squares optimization criterion is used (i.e. the goal is to minimize the ERNI), optimized 27 electrode stimulus patterns yielded on average 35% smaller ERNI than optimized 82 electrode stimulus patterns. On the contrary, when our optimization criterion is used (i.e. the goal is to maximize directional current density in the ROI), 82 electrodes yielded on average 85% higher directional current in the ROI than 27 electrodes. These results suggest that different optimization criteria might favor different electrode number, type, and locations.
Normal Cortical Field