最近对帕金森病(PD)患者的研究报告了动态功能连接的中断(dFC,即,功能连通性随时间自发波动的表征)。这里,我们评估了纹状体多巴胺末端的完整性是否直接调节两个独立PD队列中的dFC指标,大规模脑网络动力学中多巴胺相关变化的索引及其在临床特征中的意义。我们汇集了来自两个反映早期PD的疾病控制队列的数据。来自帕金森进展标志物倡议(PPMI)队列,对63例PD患者和16例年龄和性别匹配的健康对照者进行了静息态功能磁共振成像(rsfMRI)和多巴胺转运体(DaT)单光子发射计算机断层扫描(SPECT).从临床研究组219(KFO)队列中,对52例PD患者和17例年龄和性别匹配的健康对照者进行rsfMRI成像。41名PD患者和13名健康对照受试者的子集还接受了18F-DOPA-正电子发射断层扫描(PET)成像。提取18F-DOPAPET的纹状体合成能力和DaTSPECT图像的多巴胺终末量。经过rsfMRI预处理,对两个队列同时进行独立成分分析.基于派生的组件,对每个队列分别进行个体滑动窗口方法(44s窗口)和随后的k均值聚类,以得出dFC状态(重新出现的个体内和个体间连通性模式).从这些州,我们推导了时间指标,例如每个状态的平均停留时间,国家出席,和过渡次数,并在组和队列之间进行比较。Further,我们将这些与局部多巴胺能损害和临床严重程度的各自措施相关联。队列在年龄和性别方面没有差异。在队列之间,PD组在疾病持续时间方面有所不同,教育,认知评分和左旋多巴等效日剂量。在这两个队列中,DFC分析产生了三种不同的状态,连接模式和强度各不相同。在PPMI队列中,与对照组相比,PD患者对全球整合(GI)状态的状态出勤率较低,过渡次数较低。重要的是,更差的运动评分(统一帕金森病评定量表第III部分)和壳核和尾状核的多巴胺能损伤与GI状态下平均停留时间低和转变总数低相关.在KFO队列中未观察到这些结果:未观察到dFC测量值或dFC变量与多巴胺合成能力之间的关联的组差异。值得注意的是,在两个队列的PD组中,较差的运动表现与GI和较低连接(LC)状态之间的双向转换次数较少相关.因此,在早期的PD,运动性能的相对保留可能与相互联系的大脑状态的更动态参与有关。具体来说,这些大规模网络动力学似乎与纹状体多巴胺的可用性有关。值得注意的是,这些结果中的大多数只获得了一个队列,这表明dFC受到某些队列特征的影响,如教育水平,或疾病严重程度。由于我们无法用手头的数据来确定这些特征,我们怀疑另一个,在我们没有追踪的情况下,人口统计学特征驱动PD中的连通性动态。实践要点:在两个帕金森病(PD)队列中探索多巴胺在脑网络动力学中的作用,我们揭示了PD特定的动态功能连接变化。帕金森进展标记计划(PPMI)和KFO队列的结果表明,运动表现可能与相互关联的大脑状态的更动态参与和脱离有关。仅在PPMI队列中的结果表明,纹状体多巴胺的可用性会影响与运动控制相关的大规模网络动力学。
Recent studies in Parkinson\'s disease (PD) patients reported disruptions in dynamic functional connectivity (dFC, i.e., a characterization of spontaneous fluctuations in functional connectivity over time). Here, we assessed whether the integrity of striatal dopamine terminals directly modulates dFC metrics in two separate PD cohorts, indexing dopamine-related changes in large-scale brain
network dynamics and its implications in clinical features. We pooled data from two disease-control cohorts reflecting early PD. From the Parkinson\'s Progression Marker Initiative (PPMI) cohort, resting-state functional magnetic resonance imaging (rsfMRI) and dopamine transporter (DaT) single-photon emission computed tomography (SPECT) were available for 63 PD patients and 16 age- and sex-matched healthy controls. From the clinical research group 219 (KFO) cohort, rsfMRI imaging was available for 52 PD patients and 17 age- and sex-matched healthy controls. A subset of 41 PD patients and 13 healthy control subjects additionally underwent 18F-DOPA-positron emission tomography (PET) imaging. The striatal synthesis capacity of 18F-DOPA PET and dopamine terminal quantity of DaT SPECT images were extracted for the putamen and the caudate. After rsfMRI pre-processing, an independent component analysis was performed on both cohorts simultaneously. Based on the derived components, an individual sliding window approach (44 s window) and a subsequent k-means clustering were conducted separately for each cohort to derive dFC states (reemerging intra- and interindividual connectivity patterns). From these states, we derived temporal metrics, such as average dwell time per state, state attendance, and number of transitions and compared them between groups and cohorts. Further, we correlated these with the respective measures for local dopaminergic impairment and clinical severity. The cohorts did not differ regarding age and sex. Between cohorts, PD groups differed regarding disease duration, education, cognitive scores and L-dopa equivalent daily dose. In both cohorts, the dFC analysis resulted in three distinct states, varying in connectivity patterns and strength. In the PPMI cohort, PD patients showed a lower state attendance for the globally integrated (GI) state and a lower number of transitions than controls. Significantly, worse motor scores (Unified Parkinson\'s Disease Rating Scale Part III) and dopaminergic impairment in the putamen and the caudate were associated with low average dwell time in the GI state and a low total number of transitions. These results were not observed in the KFO cohort: No group differences in dFC measures or associations between dFC variables and dopamine synthesis capacity were observed. Notably, worse motor performance was associated with a low number of bidirectional transitions between the GI and the lesser connected (LC) state across the PD groups of both cohorts. Hence, in early PD, relative preservation of motor performance may be linked to a more dynamic engagement of an interconnected brain state. Specifically, those large-scale
network dynamics seem to relate to striatal dopamine availability. Notably, most of these results were obtained only for one cohort, suggesting that dFC is impacted by certain cohort features like educational level, or disease severity. As we could not pinpoint these features with the data at hand, we suspect that other, in our case untracked, demographical features drive connectivity dynamics in PD. PRACTITIONER POINTS: Exploring dopamine\'s role in brain
network dynamics in two Parkinson\'s disease (PD) cohorts, we unraveled PD-specific changes in dynamic functional connectivity. Results in the Parkinson\'s Progression Marker Initiative (PPMI) and the KFO cohort suggest motor performance may be linked to a more dynamic engagement and disengagement of an interconnected brain state. Results only in the PPMI cohort suggest striatal dopamine availability influences large-scale
network dynamics that are relevant in motor control.