Gourisankar Amritha, Eisenstein Sarah A, Trapp Nicholas T, Koller Jonathan M, Campbell Meghan C, Ushe Mwiza, Perlmutter Joel S, Hershey Tamara, Black Kevin J
Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63130, USA.
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA.
R Soc Open Sci. 2018 Jul 18;5(7):171177. doi: 10.1098/rsos.171177. eCollection 2018 Jul.
The anatomical connections of the subthalamic nucleus (STN) have driven hypotheses about its functional anatomy, including the hypothesis that the precise anatomical location of STN deep brain stimulation (DBS) contributes to the variability of motor and non-motor responses across patients with Parkinson's disease (PD). We previously tested the hypothesis using a three-dimensional (3D) statistical method to interpret the acute effects of unilateral DBS at each patient's clinically optimized DBS settings and active contact. Here, we report a similar analysis from a new study in which DBS parameters were standardized and DBS locations were chosen blind to clinical response. In 74 individuals with PD and STN DBS, STN contacts were selected near the dorsal and ventral borders of the STN contralateral to the more affected side of the body. Participants were tested off PD medications in each of three unilateral DBS conditions (ventral STN DBS, dorsal STN DBS and DBS off) for acute effects on mood, apathy, working memory, response inhibition and motor function. Voltage, frequency and pulse width were standardized, and participants and raters were blind to condition. In a categorical analysis, both dorsal and ventral STN DBS improved mean motor function without affecting cognitive measures. Ventral STN DBS induced greater improvement in rigidity and anxiety than dorsal STN DBS. In the 3D analysis, contact location was significant for body hypokinesia, rigidity and resting tremor, with the greatest improvement occurring with DBS in dorsal STN and zona incerta. The 3D results provide new, direct functional evidence for the anatomically derived model of STN, in which motor function is best represented in dorsal STN. However, our data suggest that functional segregation between motor and non-motor areas of the STN is limited, because locations that induced improvements in motor function and mood overlapped substantially.
底丘脑核（STN）的解剖学连接引发了关于其功能解剖学的各种假说，其中包括这样一种假说：STN深部脑刺激（DBS）的确切解剖位置导致帕金森病（PD）患者在运动和非运动反应方面存在个体差异。我们之前使用三维（3D）统计方法对这一假说进行了验证，该方法用于解释在每位患者临床优化的DBS设置和有效触点处进行单侧DBS的急性效应。在此，我们报告一项新研究的类似分析，该研究中DBS参数实现了标准化，且DBS位置的选择对临床反应不知情。在74例接受STN DBS治疗的PD患者中，在身体受累更严重一侧对侧的STN背侧和腹侧边界附近选择STN触点。参与者在三种单侧DBS状态（腹侧STN DBS、背侧STN DBS和关闭DBS）下停用PD药物，以测试对情绪、冷漠、工作记忆、反应抑制和运动功能的急性效应。电压、频率和脉冲宽度均实现了标准化，参与者和评估者对状态不知情。在分类分析中，背侧和腹侧STN DBS均改善了平均运动功能，但未影响认知指标。腹侧STN DBS比背侧STN DBS在改善僵硬和焦虑方面效果更显著。在3D分析中，触点位置对身体运动迟缓、僵硬和静止性震颤具有显著影响，背侧STN和未定带的DBS改善效果最为明显。3D分析结果为基于解剖学得出的STN模型提供了新的直接功能证据，该模型认为运动功能在背侧STN中表现最佳。然而，我们的数据表明，STN运动和非运动区域之间的功能分离是有限的，因为导致运动功能和情绪改善的位置有很大重叠。
