Data from: Mapping movement, mood, motivation, and mentation in the subthalamic nucleus

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 Parkinson disease (PD) patients. We previously tested that 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 border of the STN contralateral to the more affected side of the body. Participants were tested off PD medications in each of 3 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, since locations that induced improvements in motor function and mood overlapped substantially.

丘脑底核（subthalamic nucleus, STN）的解剖连接催生了诸多针对其功能解剖学的假说，其中一项假说认为，丘脑底核脑深部电刺激术（deep brain stimulation, DBS）的精准解剖位置，是导致帕金森病（Parkinson disease, PD）患者运动与非运动反应存在个体差异的重要因素。我们此前曾采用三维（three-dimensional, 3D）统计方法，基于每位患者临床优化后的DBS参数与有效刺激触点，验证单侧DBS的急性效应以检验该假说。

本文报道了一项全新研究的类似分析结果：该研究中DBS参数已被标准化，且刺激位置的选取采用盲法，不参照临床反应。本研究纳入74名罹患帕金森病且接受STN-DBS的受试者，其STN刺激触点被安置于对侧（相对于症状更严重的肢体侧）丘脑底核的背侧与腹侧边界附近。受试者在停服抗PD药物的状态下，分别接受3种单侧DBS干预条件的测试：背侧STN-DBS、腹侧STN-DBS以及DBS关闭状态，以评估其对情绪、淡漠、工作记忆、反应抑制与运动功能的急性影响。本次研究统一了电压、频率与脉宽参数，且受试者与评估者均对干预条件不知情。

分类分析结果显示，背侧与腹侧STN-DBS均能改善受试者的平均运动功能，但未对认知指标产生影响。腹侧STN-DBS相较于背侧STN-DBS，对肌强直与焦虑症状的改善效果更为显著。三维分析结果则表明，刺激触点位置对肢体运动迟缓、肌强直以及静止性震颤存在显著影响，其中以背侧STN与未定带（zona incerta）内的DBS干预效果最佳。

本次三维研究结果为基于解剖学推导的STN功能模型提供了全新的直接功能证据——该模型认为运动功能在背侧STN中具有最优表征。然而，我们的数据也提示STN的运动与非运动功能区之间的功能分隔较为有限，因为能够改善运动功能与情绪的刺激位置存在大量重叠。