New Research on Axon Targeting in Deep Brain Stimulation
Anodic Stimulation Misunderstood: Preferential Activation of Fiber Orientations with Anodic Waveforms in Deep Brain Stimulation
Daria Nesterovich Anderson1,2,†, Gordon Duffley1,2,†, Johannes Vorwerk, PhD2, Alan D. Dorval, PhD1, Christopher R. Butson, PhD1,2,3
1Department of Bioengineering, University of Utah, Salt Lake City, UT
2 Scientific Computing & Imaging (SCI) Institute, University of Utah, Salt Lake City, UT
3Departments of Neurology and Neurosurgery, University of Utah, Salt Lake City, UT
† indicates co-authors contributed equally to this work
Background: Activation of axons in Deep Brain Stimulation (DBS) can be predicted by the second difference of electric potential along an axon. We hypothesize that axons can be preferentially targeted based on fiber orientation with either cathodic or anodic stimulation, depending on the sign of the second difference along an axon.
Materials and Methods: We used bioelectric field and multicompartment NEURON models to explore preferential activation of axons based on second differences across different fiber orientations. Through the use of the Hessian matrix of the electric potential, we extracted information regarding fiber orientation and second differences from the principal eigenvectors and eigenvalues. We tested cathodic, anodic, and charge-balanced pulses to target neurons based on fiber orientation.
Results: Multicompartment NEURON models revealed that axons in the longitudinal and latitudinal directions on a spherical coordinate system have positive second differences around a cathode and are activated with cathodic stimulation. In contrast, orthogonal axons have positive second differences around an anode and are activated with anodic stimulation. Additionally, orthogonal axons are more excitable with anodic stimulation than longitudinal and latitudinal axons are with cathodic stimulation. In a clinical scenario, fiber pathways associated with clinical benefit can be targeted based on anodic stimulation with activation thresholds 50% of cathodic stimulation.
Conclusions: Different fiber orientations can be selectively targeted with simple changes to the stimulus waveform, and anodic stimulation preferentially activates orthogonal fibers at lower thresholds, which could be utilized to improve power consumption in DBS.
Funding: This work was supported by the National Science Foundation (NSF): US IGNITE – 10037840 under Dr. Christopher R. Butson; CAREER Award – 1351112 under Dr. Alan D. Dorval; and the Graduate Research Fellowship – 1256065 under Daria Nesterovich Anderson.