Fiber Activation by Bipolar Stimulation in Deep Brain Stimulation: A Patient Case Study

TL;DR

The findings of the study highlight that temporally static VTA models do not adequately describe the differences in the outcomes of bipolar stimulation settings with switched polarity, whereas neural fiber activation models hold potential in this regard.

Abstract

Deep Brain Stimulation (DBS) is a therapy widely used for treating the symptoms of neurological disorders. Electrical pulses are chronically delivered in DBS to a disease-specific brain target via a surgically implanted electrode. The stimulating contact configuration, stimulation polarity, as well as amplitude, frequency, and pulse width of the DBS pulse sequence are utilized to optimize the therapeutic effect. In this paper, the utility of therapy individualization by means of patient-specific mathematical modeling is investigated with respect to a specific case of a patient diagnosed with Essential Tremor (ET). Two computational models are compared in their ability to elucidate the impact of DBS stimulation on the dentato-rubrothalamic tract: (i) a conventional model of Volume of Tissue Activated (VTA) and (ii) a well-established neural fiber activation modeling framework known as OSS-DBS. The simulation results are compared with tremor measured in the patient under different DBS settings using a smartphone application. The findings of the study highlight that temporally static VTA models do not adequately describe the differences in the outcomes of bipolar stimulation settings with switched polarity, whereas neural fiber activation models hold potential in this regard. However, it is noted that neither of the investigated models fully accounts for the measured symptom pattern, particularly regarding a bilateral effect produced by unilateral stimulation.

Figures (5)

• Figure 1: DBS as a control system. The DBS system comprises the implanted pulse generator (IPG), the lead, and the connecting wire; the stimulation parameters serve as input. Patient symptoms are quantified for symptom severity assessment. The quantified symptoms are fed back to tune stimulation parameters in closed-loop DBS.
• Figure 2: Fiber activation for clinically active settings as given by OSS-DBS. Neural fibers intersecting the lead trajectory or encapsulation layer are labeled as damaged (green), whereas neuron models exhibiting induced firing are categorized as activated (red). Fibers not exhibiting activation are labeled as non-activated (white).
• Figure 3: (a) Visualization of a bipolar C3-, C4+ configuration for the lead. Cathodic contacts are highlighted in blue, and the anodic contact is represented in red. (b) DBS Lead placement relative to a segment of the fibertract, in this case, the ndDRTT. The blue shape represents the static VTA, while the intersection with the fiber tract is shown in red.
• Figure 4: Part of the 2D tremor signal trajectory (blue) under clinical DBS settings for the left hand. Black circles correspond to the upper bound of the radius of the predefined Markov states.
• Figure 5: Hand tremor distributions with DBS on and off. The on setting corresponds to the clinically used setting with both leads active. In both hands, the probability of large tremor amplitudes is significantly reduced under DBS. Tremor is more pronounced in the dominant left hand.