Department of Biomedical Engineering, University of Minnesota, Minneapolis, United States of America.
J Neural Eng. 2018 Oct;15(5):056029. doi: 10.1088/1741-2552/aad978. Epub 2018 Aug 10.
This study investigated stimulation strategies to increase the selectivity of activating axonal pathways within the brain based on their orientations relative to clinical deep brain stimulation (DBS) lead implants.
Previous work has shown how varying electrode shape and controlling the primary electric field direction through preclinical electrode arrays can produce orientation-selective axonal stimulation. Here, we significantly extend those results using computational models to evaluate the degree to which clinical DBS leads can direct stimulus-induced electric fields and generate orientation-selective activation of fiber pathways in the brain. Orientation-selective pulse paradigms were evaluated in conceptual models and in patient-specific models of subthalamic nucleus (STN)-DBS for treating Parkinson's disease.
Single-contact monopolar or two-contact bipolar stimulation through clinical DBS leads with cylindrical electrodes primarily activated axons orientated parallel to the lead. Conversely, multi-contact monopolar stimulation with a cathode-leading pulse waveform selectively activated axons perpendicular to the DBS lead. Clinical DBS leads with segmented rows of electrodes and a single current source provided additional angular resolution for activating axons oriented 0°, ±22.5°, ±45°, ±67.5°, or 90° relative to the lead shaft. Employing multiple independent current sources to deliver unequal amounts of current through these leads further increased the angular resolution of activation relative to the lead shaft. The patient-specific models indicated that multi-contact cathode configurations, which are rarely used in clinical practice, could increase activation of the hyperdirect pathway collaterals projecting into STN (a putative therapeutic target), while minimizing direct activation of the corticospinal tract of internal capsule, which can elicit sensorimotor side-effects when stimulated.
When combined with patient-specific tissue anisotropy and patient-specific anatomical morphologies of neural pathways responsible for therapy and side effects, orientation-selective DBS approaches show potential to significantly improve clinical outcomes of DBS therapy for a range of existing and investigational clinical indications.
本研究旨在探索基于大脑中轴突相对于临床深部脑刺激（DBS）植入物的方向来增加激活轴突通路的选择性的刺激策略。
先前的工作已经表明，通过临床前电极阵列改变电极形状并控制主要电场方向如何产生取向选择性轴突刺激。在这里，我们使用计算模型显著扩展了这些结果，以评估临床 DBS 导联在多大程度上可以引导刺激诱导的电场，并在大脑中产生纤维通路的取向选择性激活。在概念模型和用于治疗帕金森病的丘脑底核（STN）-DBS 的患者特定模型中评估了取向选择性脉冲方案。
通过具有圆柱形电极的临床 DBS 导联进行单接触单极或双接触双极刺激主要激活与导联平行的轴突。相反，具有阴极领先脉冲波形的多接触单极刺激选择性地激活与 DBS 导联垂直的轴突。具有分段电极排和单个电流源的临床 DBS 导联为激活与导联轴成 0°、±22.5°、±45°、±67.5°或 90°的轴突提供了额外的角分辨率。使用多个独立的电流源通过这些导联输送不等量的电流，进一步提高了相对于导联轴的激活角分辨率。患者特定模型表明，很少在临床实践中使用的多接触阴极配置可以增加投射到 STN 的直接通路侧支的激活（一个潜在的治疗靶点），同时最大限度地减少内囊的皮质脊髓束的直接激活，当刺激时，这可能会引起感觉运动副作用。
当与负责治疗和副作用的神经通路的患者特定组织各向异性和患者特定解剖形态学相结合时，取向选择性 DBS 方法有可能显著改善一系列现有和研究性临床适应症的 DBS 治疗的临床结果。
