Department of Neurology, Hadassah Hebrew University Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel.
Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, General University Hospital, Charles University, Prague, Czech Republic.
Eur J Neurosci. 2021 Mar;53(6):1976-1987. doi: 10.1111/ejn.15053. Epub 2020 Dec 13.
Dopamine depletion in the axons of Parkinson's disease (PD) patients precedes depletion in cell bodies thus proposing that macroscopic connectivity can be used to understand disease mechanism. A novel multivariate functional connectivity analysis, based on high order coherence among four fMRI BOLD signals was applied on resting-state fMRI data of controls and PD patients (OFF and ON medication states) and unidirectional multiple-region pathways in the sensorimotor system were identified. Pathways were classified as "preserved" (unaffected by the disease), "damaged" (not observed in patients) and "corrected" (observed in controls and in PD-ON state). The majority of all pathways were feedforward, most of them with the pattern "S1→M1→SMA." Of these pathways, 67% were "damaged," 28% "preserved," and 5% "corrected." Prefrontal cortex (PFC) afferent and efferent pathways that corresponded to goal directed and habitual activities corresponded to recurrent circuits. Eighty-one percent of habitual afferent had internal cue (i.e., M1→S1→), of them 79% were "damaged" and the rest "preserved." All goal-directed afferent had external cue (i.e., S1→M1→) with third "damaged," third "preserved," and third "corrected." Corrected pathways were initiated in the dorsolateral PFC. Reduced connectivity of the SMA and PFC resulted from reduced sensorimotor afferent to these regions. Reduced sensorimotor internal cues to the PFC resulted with reduced habitual processes. Levodopa effects were for pathways that started in region reach with dopamine receptors. This methodology can enrich understudying of PD mechanisms in other (e.g., the default mode network) systems.
帕金森病（PD）患者的轴突多巴胺耗竭先于细胞体耗竭，因此提出宏观连通性可用于了解疾病机制。一种新的多变量功能连接分析方法，基于四个 fMRI BOLD 信号之间的高阶相干性，应用于对照和 PD 患者（药物治疗和停药状态）的静息状态 fMRI 数据，并确定了感觉运动系统中的单向多区域通路。通路被分类为“保留”（不受疾病影响）、“损伤”（在患者中未观察到）和“校正”（在对照和 PD-ON 状态中观察到）。所有通路中的大多数是前馈的，它们中的大多数具有“S1→M1→SMA”的模式。在这些通路中，67%是“损伤”，28%是“保留”，5%是“校正”。与目标导向和习惯性活动相对应的前额叶皮层（PFC）传入和传出通路对应于递归回路。习惯性传入的 81%有内部线索（即 M1→S1→），其中 79%是“损伤”，其余是“保留”。所有目标导向的传入都有外部线索（即 S1→M1→），其中三分之一是“损伤”，三分之一是“保留”，三分之一是“校正”。校正途径始于背外侧 PFC。SMA 和 PFC 的连接减少是由于这些区域的感觉运动传入减少所致。感觉运动内部线索到 PFC 的减少导致习惯性过程减少。左旋多巴的作用是针对那些在多巴胺受体到达的区域开始的通路。这种方法可以丰富其他系统（例如，默认模式网络）中对 PD 机制的研究。
