Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, USA.
J Neural Eng. 2013 Aug;10(4):045005. doi: 10.1088/1741-2560/10/4/045005. Epub 2013 May 31.
Deep brain stimulation (DBS) near the pedunculopontine nucleus (PPN) has been posited to improve medication-intractable gait and balance problems in patients with Parkinson's disease. However, clinical studies evaluating this DBS target have not demonstrated consistent therapeutic effects, with several studies reporting the emergence of paresthesia and oculomotor side effects. The spatial and pathway-specific extent to which brainstem regions are modulated during PPN-DBS is not well understood.
Here, we describe two computational models that estimate the direct effects of DBS in the PPN region for human and translational non-human primate (NHP) studies. The three-dimensional models were constructed from segmented histological images from each species, multi-compartment neuron models and inhomogeneous finite element models of the voltage distribution in the brainstem during DBS.
The computational models predicted that: (1) the majority of PPN neurons are activated with -3 V monopolar cathodic stimulation; (2) surgical targeting errors of as little as 1 mm in both species decrement activation selectivity; (3) specifically, monopolar stimulation in caudal, medial, or anterior PPN activates a significant proportion of the superior cerebellar peduncle (up to 60% in the human model and 90% in the NHP model at -3 V); (4) monopolar stimulation in rostral, lateral or anterior PPN activates a large percentage of medial lemniscus fibers (up to 33% in the human model and 40% in the NHP model at -3 V) and (5) the current clinical cylindrical electrode design is suboptimal for isolating the modulatory effects to PPN neurons.
We show that a DBS lead design with radially-segmented electrodes may yield improved functional outcome for PPN-DBS.
在靠近脑桥被盖核（PPN）的地方进行深部脑刺激（DBS）被认为可以改善帕金森病患者药物难治性的步态和平衡问题。然而，评估这一 DBS 靶点的临床研究并未显示出一致的治疗效果，一些研究报告出现了感觉异常和眼球运动副作用。在 PPN-DBS 期间，脑干区域的空间和通路特异性调制程度尚不清楚。
在这里，我们描述了两个计算模型，用于估计人类和转化非人类灵长类动物（NHP）研究中 PPN 区域的 DBS 直接影响。三维模型是根据每个物种的分割组织学图像、多室神经元模型以及 DBS 期间脑干中电压分布的不均匀有限元模型构建的。
计算模型预测：（1）-3 V 单极阴极刺激可激活大多数 PPN 神经元；（2）两种物种的手术靶向误差仅为 1 毫米，就会降低激活选择性；（3）特别是，在 PPN 的尾部、内侧或前部进行单极刺激会激活相当一部分小脑上脚（在人类模型中高达-3 V 时的 60%，在 NHP 模型中高达 90%）；（4）在 PPN 的前部、外侧或前部进行单极刺激会激活相当大比例的内侧丘系纤维（在人类模型中高达-3 V 时的 33%，在 NHP 模型中高达 40%）；（5）目前的临床圆柱电极设计对于隔离对 PPN 神经元的调制效果不理想。
我们表明，具有径向分段电极的 DBS 引线设计可能会为 PPN-DBS 带来更好的功能效果。
