Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, USA.
J Neural Eng. 2012 Aug;9(4):046005. doi: 10.1088/1741-2560/9/4/046005. Epub 2012 Jun 25.
Deep brain stimulation (DBS) in the ventral intermediate nucleus of thalamus (Vim) is known to exert a therapeutic effect on postural and kinetic tremor in patients with essential tremor (ET). For DBS leads implanted near the caudal border of Vim, however, there is an increased likelihood that one will also induce paresthesia side-effects by stimulating neurons within the sensory pathway of the ventral caudal (Vc) nucleus of thalamus. The aim of this computational study was to (1) investigate the neuronal pathways modulated by therapeutic, sub-therapeutic and paresthesia-inducing DBS settings in three patients with ET and (2) determine how much better an outcome could have been achieved had these patients been implanted with a DBS lead containing directionally segmented electrodes (dDBS). Multi-compartment neuron models of the thalamocortical, cerebellothalamic and medial lemniscal pathways were first simulated in the context of patient-specific anatomies, lead placements and programming parameters from three ET patients who had been implanted with Medtronic 3389 DBS leads. The models showed that in these patients, complete suppression of tremor was associated most closely with activating an average of 62% of the cerebellothalamic afferent input into Vim (n = 10), while persistent paresthesias were associated with activating 35% of the medial lemniscal tract input into Vc thalamus (n = 12). The dDBS lead design demonstrated superior targeting of the cerebello-thalamo-cortical pathway, especially in cases of misaligned DBS leads. Given the close proximity of Vim to Vc thalamus, the models suggest that dDBS will enable clinicians to more effectively sculpt current through and around thalamus in order to achieve a more consistent therapeutic effect without inducing side-effects.
丘脑腹中间核（Vim）的深部脑刺激（DBS）已知对特发性震颤（ET）患者的姿势性和运动性震颤具有治疗作用。然而，对于植入 Vim 尾部边界附近的 DBS 导联，刺激丘脑腹侧尾核（Vc）感觉通路内的神经元，更有可能引起感觉异常的副作用。这项计算研究的目的是：（1）研究 3 例 ET 患者的治疗、亚治疗和感觉异常诱导 DBS 设置调制的神经元通路；（2）确定如果这些患者植入含有定向分段电极的 DBS 导联（dDBS），结果可能会更好。首先，根据来自 3 名接受 Medtronic 3389 DBS 导联植入的 ET 患者的特定患者解剖结构、导联位置和编程参数，在患者特异性解剖结构中模拟了丘脑皮质、小脑丘脑和内侧丘系通路的多室神经元模型。模型表明，在这些患者中，完全抑制震颤最密切地与激活 Vim 中平均 62%的小脑丘脑传入输入有关（n=10），而持续的感觉异常与激活 Vc 丘脑内 35%的内侧丘系传入输入有关（n=12）。dDBS 导联设计展示了对小脑丘脑皮质通路的优越靶向性，尤其是在 DBS 导联不对准的情况下。鉴于 Vim 与 Vc 丘脑的接近，这些模型表明，dDBS 将使临床医生能够更有效地塑造通过和围绕丘脑的电流，以实现更一致的治疗效果而不引起副作用。
