Modeling to Improve DBS

Deep brain stimulation (DBS) in Parkinson’s disease is an effective treatment for advanced PD. Yet there is great heterogeneity in individual responses, ranging from a 11 to 70% improvement in motor symptoms. Patient-specific computational models provide the means to study the effects of DBS by understanding how stimulation currents spread and impact different areas of the brain, which may in turn have differing effects on movement.

PhD candidate in Neuroscience Emily Lecy worked on a project called “Computational Models of the Direct and Indirect Basal Ganglia Pathways to Optimize Deep Brain Stimulation in Parkinson’s Disease” as a UMII-MnDRIVE PhD Graduate Assistant. This project aimed to develop a pipeline to understand how pallidal DBS impacts the striato-pallidal pathways of the brain (which are thought to have a direct influence on movement), design DBS parameters which preferentially activate the direct pathway (thought to facilitate movement) over the indirect pathway (thought to suppress movement) and measure the outcomes of these stimulation settings in those with PD through quantitative movement tasks. 

Ms. Lecy did this research under the supervision of MSI PIs Matthew Johnson (professor, Biomedical Engineering) and Colum MacKinnon (professor, Neurology). She used MSI resources for the project.

Over the course of this grant, the following has been completed.

• A computational modeling pipeline was created that includes both the direct and indirect striato-fugal pathways. Within these pathways, axons were created to have twists and turns which mimic axons seen through histological tracing studies (see figure).
• The computational model was fit to a multi-objective particle swarm optimization algorithm, which creates stimulation parameters that optimize the activation of the direct pathway relative to the indirect pathway.

The model will soon be used to design stimulation parameters which preferentially activate the direct pathway, thus possibly promoting movement. These settings will be tested in individuals with PD, and movement will be quantitatively assessed to see if pathway activation influences improves performance.

This award supported numerous posters and talks, including:

• Poster Presentation: Novel patient-specific computational modeling of pallidal deep brain stimulation for Parkinson’s Disease. University of Minnesota Neuromodulation Symposium, Minneapolis, MN, March 2022.
• Oral Presentation: Pathway Activation Differs Between Dorsal and Ventral Stimulation of the Human Globus Pallidus, Graduate Program in Neuroscience Colloquium, May 2023.
• Poster Presentation: Novel patient-specific computational modeling of pallidal deep brain stimulation for Parkinson’s Disease, an improved approach. University of Minnesota Neuromodulation Symposium, Minneapolis, MN, March 2023.

The UMII-MnDRIVE Graduate Assistantship program supported U of M PhD candidates pursuing research at the intersection of informatics and any of the five MnDRIVE areas: 

• Robotics
• Global Food
• Environment
• Brain Conditions
• Cancer Clinical Trials

This project was part of the Brain Conditions MnDRIVE area.

The Graduate Assistantship program has been converted to the Data Science Initiative-MnDRIVE Graduate Assistantship program. Research supported by the program is at the intersection of data science and the five MnDRIVE areas. Proposals must align with one of three data science tracks: Foundational Data Science; Digital Health and Personalized Health Care Delivery; and Agriculture and the Environment. The deadline for the program beginning in the Spring Term 2025 is 5 pm CDT, October 4, 2024.

Image description: Representations of pathways included in the pallidal DBS modeling pipeline, with the direct basal ganglia pathway is shown in green, and indirect shown in blue. The full-scale models contain 250 - 1200 axons per pathway, populations were determined via histological tracings from non-human primates (A. Parent et al., 2000; A. Parent & Hazrati, 1995b, 1995a; Sato et al., 2000). (A) Internal axons that traverse through nuclei of interest. These axons have random curvature that is created based on parameters that mirror non-human primate single axon reconstructions (Lévesque & Parent, 2005; M. Parent et al., 2001; Sato et al., 2000). (B) Capsular axons, representative of 3 sub-tracts which project different areas of cortex (motor, premotor, and supplementary motor area). Full scale models show overlapping of these three tracts on the anterior posterior axis. Single axons were chosen in this figure based on anatomical relevance to portray that although the tracts overlap, they have an anterior to posterior order of supplementary motor, premotor, and primary motor cortex (Petersen et al., 2019). Figures are oriented anatomically: anterior (A), posterior (P), medial (M), lateral (L), dorsal (D), ventral (V).