Abstract
Objective: To study the effect of directional deep brain stimulation (DBS) electrode configuration and vertical electrode spacing on the volume of tissue activated (VTA) in the globus pallidus, pars interna (GPi).Background: Directional DBS leads may allow clinicians to precisely direct current fields to different functional networks within traditionally targeted brain areas. Modeling the shape and size of the VTA for various monopolar or bipolar configurations can inform clinical programming strategies for GPi DBS. However, many computational models of VTA are limited by assuming tissue homogeneity.Methods: We generated a multimodal image-based detailed anatomical (MIDA) computational model with a directional DBS lead (1.5 mm or 0.5 mm vertical electrode spacing) placed with segmented contact 2 at the ventral posterolateral “sensorimotor” region of the GPi. The effect of tissue heterogeneity was examined by replacing the MIDA tissues with a homogeneous tissue of conductance 0.3 S/m. DBS pulses (amplitude: 1 mA, pulse width: 60 μs, frequency: 130 Hz) were used to produce VTAs. The following DBS contact configurations were tested: single-segment monopole (2B-/Case+), two-segment monopole (2A-/2B-/Case+ and 2B-/3B-/Case+), ring monopole (2A-/2B-/2C-/Case+), one-cathode three-anode bipole (2B-/3A+/3B+/3C+), three-cathode three-anode bipole (2A-/2B-/2C-/3A+/3B+/3C+). Additionally, certain vertical configurations were repeated with 2 mA current amplitude.Results: Using a heterogeneous tissue model affected both the size and shape of the VTA in GPi. Electrodes with both 0.5 mm and 1.5 mm vertical spacing (1 mA) modeling showed that the single segment monopolar VTA was entirely contained within the GPi when the active electrode is placed at the posterolateral “sensorimotor” GPi. Two segments in a same ring and ring settings, however, produced VTAs outside of the GPi border that spread into adjacent white matter pathways, e.g., optic tract and internal capsule. Both stacked monopolar settings and vertical bipolar settings allowed activation of structures dorsal to the GPi in addition to the GPi. Modeling of the stacked monopolar settings with the DBS lead with 0.5 mm vertical electrode spacing further restricted VTAs within the GPi, but the VTA volumes were smaller compared to the equivalent settings of 1.5 mm spacing.
Highlights
Deep brain stimulation (DBS) is an established therapy for treatment of advanced movement disorders including Parkinson’s disease, tremor, and dystonia
Studies showing significant improvement in bradykinesia with globus pallidus pars interna (GPi) DBS examined the location of the DBS lead within the pallidum and noted that superior outcomes were associated with active contacts located in the dorsal portion of the GPi near the medial medullary lamina (Bejjani et al, 1998; Krack et al, 1998; Yelnik et al, 2000)
When the active electrode was placed near the ventral posterolateral “sensorimotor” GPi, and at low current settings such as 1 mA current, the volume of tissue activated (VTA) produced by configurations 1, 2a, and 3 (Figure 1) were entirely within the GPi (Figure 3A)
Summary
Deep brain stimulation (DBS) is an established therapy for treatment of advanced movement disorders including Parkinson’s disease, tremor, and dystonia. In Parkinson’s disease, in addition to the subthalamic nucleus (STN), the posterolateral “sensorimotor” region of the globus pallidus pars interna (GPi) is targeted due to its larger size and demonstrated efficacy to improve tremor, bradykinesia, rigidity, and drug-induced dyskinesia (Bejjani et al, 1998; Williams et al, 2014; Mirza et al, 2017; Wong et al, 2019). It is likely that stimulation of this region near the medial medullary lamina activates GPi motor efferents, and axons passing through or adjacent to GPi (Parent et al, 1995; Sato et al, 2000). Many computational models of VTA are limited by assuming tissue homogeneity
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