Patient-specific models of deep brain stimulation: influence of field model complexity on neural activation predictions

Abstract

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become the surgical therapy of choice for medically intractable Parkinson's disease. However, quantitative understanding of the interaction between the electric field generated by DBS and the underlying neural tissue is limited. Recently, computational models of varying levels of complexity have been used to study the neural response to DBS. The goal of this study was to evaluate the quantitative impact of incrementally incorporating increasing levels of complexity into computer models of STN DBS. Our analysis focused on the direct activation of experimentally measureable fiber pathways within the internal capsule (IC). Our model system was customized to an STN DBS patient and stimulation thresholds for activation of IC axons were calculated with electric field models that ranged from an electrostatic, homogenous, isotropic model to one that explicitly incorporated the voltage-drop and capacitance of the electrode-electrolyte interface, tissue encapsulation of the electrode, and diffusion-tensor based 3D tissue anisotropy and inhomogeneity. The model predictions were compared to experimental IC activation defined from electromyographic (EMG) recordings from eight different muscle groups in the contralateral arm and leg of the STN DBS patient. Coupled evaluation of the model and experimental data showed that the most realistic predictions of axonal thresholds were achieved with the most detailed model. Furthermore, the more simplistic neurostimulation models substantially overestimated the spatial extent of neural activation.

Keywords: Parkinson's disease; computational modeling; deep brain stimulation; neural activation.

Fig. 1. Patient-specific DBS model

(A) Sagittal view of the post-operative patient MRI with the patient-specific electrode location and trajectory determined by image-thresholding segmentation. Also shown is a white bounding box depicting the region of interest for panels B-F. (B) 3D nuclei placed within the same patient-specific modeling environment (thalamus – yellow volume; STN – green volume). (C) DTI tensors displayed as ellipsoids. The colors depict the individual fractional anisotropy values of the tensors (blue–0; red–1), while the shape describes both the magnitude and direction of water diffusion (spherical – isotropic; cylindrical – anisotropic). (D) Isolines depicting the potential distribution near the active contact 2 (blue – low voltage; red – high voltage). (E) 240 fiber trajectories within the IC (white lines), created using DTI tractography. (F) FEM voltage solutions impressed upon the 240 fibers after being stimulated with a −5 V cathodic stimulus at contact 3.

Fig. 2. DBS FEM comparison

The left column depicts voltage isolines generated at the peak of a −1 V cathodic stimulus pulse for each model variant. The isolines represent voltage values of −0.1 V to −0.01 V in 0.01 V increments. The right column depicts the corresponding simulated stimulus waveform for each model.

Fig. 3. Voltage-distance relationship

Model IC activation thresholds for each DBS FEM at each of the four contacts of the DBS electrode are plotted as a function of the closest distance from a given axon to the center of that specific stimulating electrode contact. Least-square fits of the voltage distance equation to the model data are overlaid on the plots.

Fig. 4. Comparison of model and experimental results

The top row depicts the anatomical model representation (thalamus – yellow volume; STN – green volume; activated IC axons – red). The bottom row displays the EMG time-triggered average signal for the triceps muscle (upper 95% confidence interval–red; average–green; lower 95% confidence interval–blue). (A) With stimuli delivered through contact 3, there were no fibers activated in Model V at −4 V, and the clinical EMG was also sub-threshold for activation. (B) At the clinical EMG threshold (−5 V) for the triceps muscle, 15% of the IC fibers were activated in Model V. (C) At a super-threshold EMG voltage of −6 V, 36% of the fibers were recruited in Model V.

Fig. 5. Sensitivity analysis

Contour maps depict the percentage of IC axons activated using Model IV (A) or Model V (B), while perturbating the location of contact 3 of the DBS electrode ± 1 mm (0.25 mm increments) in the mediolateral (x-axis) and anteroposterior (y-axis) directions. The black dot in the center of the image depicts the default electrode location.

Fig. A1. Characterizing the electrode-electrolyte interface voltage drop

(A) In vitro experimental setup showing the recording locations (red points) while stimulating with the Medtronic 3387 human DBS electrode. (B, C) Point-by-point comparison of the voltages recorded experimentally with the voltages predicted by the in vitro DBS FEM with a 42% voltage-drop at the electrode-electrolyte interface.