Supplementary Material for: Structural connectivity of the basal ganglia from patient-individual tractography is key for understanding the effects of deep brain stimulation in Parkinson’s Disease

Background: In Parkinson's disease (PD) patients, modulation of the fibre tracts of the cortico-basal ganglia-thalamo-cortical loop is the presumed mechanism of action of deep brain stimulation (DBS) of the subthalamic nucleus (STN). Therefore, we explored patient-individual cortical structural connectivity of the volume of tissue activated (VTA), as well as DBS-induced modulation of fibre tracts connecting the STN with cortical and subcortical nodes, and their correlation with therapeutic effects.
Patients and Methods: A retrospective cohort of n = 69 PD patients treated with bilateral DBS of the STN was analysed. Clinical response was assessed from the DBS-induced change in the UPDRS-III motor scores (total and symptom-specific sub-scores) under regular medication after a median follow-up of 9.0 (range 2.6 – 20.2) months. Tractography based on patient-individual diffusion-weighted MRI was employed in two ways. Whole brain tractography was used to identify the cortical connections of fibres passing the VTAs, and reconstruction of specific white matter pathways of the motor loop connecting the STN with the basal ganglia and cortex were used to identify the proportion of fibres within these pathways which was modulated by STN-DBS. This proportion of pathway modulation was used in a correlative analysis with clinical outcomes.
Results: Fibres traversing the VTAs were primarily connected to the supplementary motor area (SMA) and to a lesser degree to the premotor cortex. Within the pathways connecting the STN with the cortical and subcortical nodes, on average 30-40% (range 10-80%) of the fibres were modulated by STN-DBS. This proportion correlated significantly with the percentage change in UPDRS motor score for fibres connecting the STN with the SMA (ρ=0.28), pre-SMA (ρ=0.26), ventral and dorsal pre-motor cortices (ρ=0.26 and ρ=0.29, respectively), and the globus pallidus externus (GPe, ρ=0.26) and internus (GPi, ρ=0.29). Also, good clinical responses for both tremor and rigidity were associated with a significantly (p < 0.05) higher proportion of modulated fibres for the same cortico- and sub-cortico-STN connections.
Conclusions: Patient-individual tractography reveals that, in PD, most of the cortical fibres traversing the VTA are connected to the SMA. In addition, clinical efficacy is related to the proportion of DBS-affected fibres connecting the STN with nodes of both the hyperdirect (cortex-STN) and the indirect pathways (STN-basal ganglia). As such, patient-specific tractography, in particular in the basal ganglia, could be used in a clinical context as a tool to guide therapy.

背景：在帕金森病（Parkinson's disease, PD）患者中，皮质-基底节-丘脑-皮质环路纤维束的调制被认为是丘脑底核（subthalamic nucleus, STN）深部脑刺激（deep brain stimulation, DBS）的作用机制。因此，我们探究了患者个体激活组织体积（volume of tissue activated, VTA）的皮质结构连接，以及DBS诱导的连接STN与皮质及皮质下节点纤维束的调制，及其与治疗效果的相关性。

患者与方法：
回顾性分析69例接受双侧STN-DBS治疗的PD患者队列。在中位随访9.0个月（范围2.6–20.2个月）后，评估规律用药下DBS诱导的统一帕金森病评定量表第三部分（UPDRS-III）运动评分（总分及症状特异性分项得分）变化，以反映临床应答。基于患者个体弥散加权磁共振成像的纤维束成像（tractography）用于两种分析：全脑纤维束成像用于识别穿过VTA的纤维的皮质连接；重建运动环路中连接STN与基底节及皮质的特定白质通路，以确定这些通路中受STN-DBS调制的纤维比例。通路调制比例与临床结局进行相关性分析。

结果：
穿过VTA的纤维主要连接至辅助运动区（supplementary motor area, SMA），其次为运动前区皮质。在连接STN与皮质及皮质下节点的通路中，平均30-40%（范围10-80%）的纤维受STN-DBS调制。该调制比例与以下纤维连接的UPDRS运动评分百分比变化显著相关：STN与SMA（ρ=0.28）、前SMA（pre-SMA，ρ=0.26）、腹侧及背侧运动前区皮质（分别为ρ=0.26和ρ=0.29）、外侧苍白球（globus pallidus externus, GPe，ρ=0.26）及内侧苍白球（globus pallidus internus, GPi，ρ=0.29）。此外，震颤和强直症状的良好临床应答与相同皮质-STN及皮质下-STN连接中更高比例的调制纤维显著相关（p < 0.05）。

结论：
患者个体纤维束成像显示，PD患者中穿过VTA的大部分皮质纤维连接至SMA。此外，临床疗效与连接STN与超直接通路（皮质-STN）及间接通路（STN-基底节）节点的DBS受影响纤维比例相关。因此，患者特异性纤维束成像（尤其在基底节区域）可在临床场景中用作指导治疗的工具。