Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota, United States.
Department of Neurology, University of Minnesota, Minneapolis, Minnesota, United States.
J Neurophysiol. 2024 Sep 1;132(3):953-967. doi: 10.1152/jn.00155.2024. Epub 2024 Aug 7.
Deep brain stimulation (DBS) of the internal segment of the globus pallidus (GPi) can markedly reduce muscle rigidity in people with Parkinson's disease (PD); however, the mechanisms mediating this effect are poorly understood. Computational modeling of DBS provides a method to estimate the relative contributions of neural pathway activations to changes in outcomes. In this study, we generated subject-specific biophysical models of GPi DBS (derived from individual 7-T MRI), including pallidal efferent, putamenal efferent, and internal capsule pathways, to investigate how activation of neural pathways contributed to changes in forearm rigidity in PD. Ten individuals (17 arms) were tested off medication under four conditions: off stimulation, on clinically optimized stimulation, and on stimulation specifically targeting the dorsal GPi or ventral GPi. Quantitative measures of forearm rigidity, with and without a contralateral activation maneuver, were obtained with a robotic manipulandum. Clinically optimized GPi DBS settings significantly reduced forearm rigidity ( < 0.001), which aligned with GPi efferent fiber activation. The model demonstrated that GPi efferent axons could be activated at any location along the GPi dorsal-ventral axis. These results provide evidence that rigidity reduction produced by GPi DBS is mediated by preferential activation of GPi efferents to the thalamus, likely leading to a reduction in excitability of the muscle stretch reflex via overdriving pallidofugal output. Subject-specific computational models of pallidal deep brain stimulation, in conjunction with quantitative measures of forearm rigidity, were used to examine the neural pathways mediating stimulation-induced changes in rigidity in people with Parkinson's disease. The model uniquely included internal, efferent and adjacent pathways of the basal ganglia. The results demonstrate that reductions in rigidity evoked by deep brain stimulation were principally mediated by the activation of globus pallidus internus efferent pathways.
深部脑刺激（DBS）内侧苍白球（GPi）可显著降低帕金森病（PD）患者的肌肉僵硬；然而，介导这种效应的机制尚未完全了解。DBS 的计算建模提供了一种估计神经通路激活对结果变化相对贡献的方法。在这项研究中，我们生成了个体 7-T MRI 衍生的 GPi DBS 的特定于个体的生物物理模型，包括苍白球传出、壳核传出和内囊通路，以研究神经通路的激活如何导致 PD 患者前臂僵硬的变化。在四种情况下，十名个体（17 只手臂）在未服药时接受测试：刺激关闭、临床优化刺激和针对背侧 GPi 或腹侧 GPi 的刺激。使用机器人操纵器获得有和没有对侧激活操作的前臂僵硬的定量测量。临床优化的 GPi DBS 设置可显著降低前臂僵硬（<0.001），与 GPi 传出纤维激活一致。该模型表明，GPi 传出轴突可以在 GPi 背腹轴上的任何位置被激活。这些结果提供了证据表明，GPi DBS 产生的僵硬减少是通过对丘脑的 GPi 传出纤维的优先激活介导的，这可能通过过度驱动苍白球传出输出导致肌肉拉伸反射兴奋性降低。结合前臂僵硬的定量测量，使用个体特定的苍白球深部脑刺激计算模型来检查介导帕金森病患者刺激诱导的僵硬变化的神经通路。该模型独特地包括基底神经节的内部、传出和相邻通路。结果表明，深部脑刺激引起的僵硬减少主要是通过激活内侧苍白球传出通路介导的。
