Fatigue is a common and disabling nonmotor manifestation in patients with Parkinson’s disease (PD), and the supplementary motor area (SMA) has been implicated in its pathophysiology. SMA is usually divided in its rostro-caudal axis, with the rostral (pre-) SMA playing a major role in motor planning, and the caudal (proper) SMA related to movement execution. To investigate brain functional connectivity of SMA subregions in de novo, drug-naïve PD patients affected by fatigue, 17 patients with fatigue, 18 without fatigue, and 16 matched healthy controls were recruited. All the participants were not depressed and did not suffer from daytime sleepiness. Parkinson Fatigue Scale (PFS) was used for fatigue screening (cut-off > 3.3 points) and severity rating. Seed-based resting-state functional MRI was used to compare the functional connectivity from bilateral SMA subregions to the whole brain. Voxel-based morphometry analysis was employed to test whether functional connectivity results were related to brain structural differences. PD-related fatigue was associated with an increased connectivity between the left pre-SMA and the left postcentral gyrus as well as a decreased connectivity between the left SMA proper and the left middle frontal gyrus (p_s < 0.01). These patterns of functional connectivity were tightly correlated with PFS scores (Pearson’s r_s < 0.01). No structural brain changes were observed. In early PD, altered functional connectivity of both SMA subregions might play a crucial role in fatigue pathophysiology. These results offer new insights into the mechanisms responsible for fatigue in PD, suggesting possible targets for neuromodulation strategies oriented to modulate the SMA activity.

疲劳是帕金森病 (PD) 患者常见且致残的非运动表现，其病理生理学涉及辅助运动区 (SMA)。SMA 通常在其 rostro-caudal 轴上划分，头端（前）SMA 在运动规划中起主要作用，尾端（适当）SMA 与运动执行相关。为了从头研究 SMA 亚区的脑功能连接，招募了受疲劳影响的未使用药物的 PD 患者、17 名疲劳患者、18 名无疲劳患者和 16 名匹配的健康对照。所有参与者都没有抑郁，也没有白天嗜睡。帕金森疲劳量表 (PFS) 用于疲劳筛查（临界值 > 3.3 分）和严重程度评级。基于种子的静息状态功能 MRI 用于比较从双侧 SMA 亚区到整个大脑的功能连接。采用基于体素的形态测量分析来测试功能连接结果是否与大脑结构差异有关。PD 相关疲劳与左侧前 SMA 和左侧中央后回之间的连通性增加以及左侧 SMA 本体和左侧额中回之间的连通性降低有关。p_小号 <0.01）。这些功能连接模式与 PFS 评分密切相关（Pearson's r _s  < 0.01）。没有观察到结构性大脑变化。在早期 PD 中，两个 SMA 亚区的功能连接改变可能在疲劳病理生理学中起关键作用。这些结果为 PD 疲劳的机制提供了新的见解，提出了以调节 SMA 活动为导向的神经调节策略的可能目标。