Terao Yasuo, Honma Motoyasu, Asahara Yuki, Tokushige Shin-Ichi, Furubayashi Toshiaki, Miyazaki Tai, Inomata-Terada Satomi, Uchibori Ayumi, Miyagawa Shinji, Ichikawa Yaeko, Chiba Atsuro, Ugawa Yoshikazu, Suzuki Masahiko
Department of Medical Physiology, School of Medicine, Kyorin University, Tokyo, Japan.
Department of Physiology, School of Medicine, Showa University, Tokyo, Japan.
Front Neurosci. 2021 Mar 19;15:648814. doi: 10.3389/fnins.2021.648814. eCollection 2021.
Although animal studies and studies on Parkinson's disease (PD) suggest that dopamine deficiency slows the pace of the internal clock, which is corrected by dopaminergic medication, timing deficits in parkinsonism remain to be characterized with diverse findings. Here we studied patients with PD and progressive supranuclear palsy (PSP), 3-4 h after drug intake, and normal age-matched subjects. We contrasted perceptual (temporal bisection, duration comparison) and motor timing tasks (time production/reproduction) in supra- and sub-second time domains, and automatic versus cognitive/short-term memory-related tasks. Subjects were allowed to count during supra-second production and reproduction tasks. In the time production task, linearly correlating the produced time with the instructed time showed that the "subjective sense" of 1 s is slightly longer in PD and shorter in PSP than in normals. This was superposed on a prominent trend of underestimation of longer (supra-second) durations, common to all groups, suggesting that the pace of the internal clock changed from fast to slow as time went by. In the time reproduction task, PD and, more prominently, PSP patients over-reproduced shorter durations and under-reproduced longer durations at extremes of the time range studied, with intermediate durations reproduced veridically, with a shallower slope of linear correlation between the presented and produced time. In the duration comparison task, PD patients overestimated the second presented duration relative to the first with shorter but not longer standard durations. In the bisection task, PD and PSP patients estimated the bisection point (BP50) between the two supra-second but not sub-second standards to be longer than normal subjects. Thus, perceptual timing tasks showed changes in opposite directions to motor timing tasks: underestimating shorter durations and overestimating longer durations. In PD, correlation of the mini-mental state examination score with supra-second BP50 and the slope of linear correlation in the reproduction task suggested involvement of short-term memory in these tasks. Dopamine deficiency didn't correlate significantly with timing performances, suggesting that the slowed clock hypothesis cannot explain the entire results. Timing performance in PD may be determined by complex interactions among time scales on the motor and sensory sides, and by their distortion in memory.
尽管动物研究以及帕金森病(PD)研究表明,多巴胺缺乏会减缓生物钟的节奏,而多巴胺能药物可纠正这种情况,但帕金森综合征的时间缺陷仍有待通过各种不同的研究结果来加以描述。在此,我们研究了PD患者、进行性核上性麻痹(PSP)患者(在服药后3 - 4小时)以及年龄匹配的正常受试者。我们对比了在超秒和亚秒时间域中的知觉(时间二等分、时长比较)和运动计时任务(时间生成/再现),以及自动任务与认知/短期记忆相关任务。在超秒生成和再现任务期间允许受试者计数。在时间生成任务中,将生成的时间与指示时间进行线性相关分析表明,与正常受试者相比,PD患者的1秒“主观感觉”略长,而PSP患者的1秒“主观感觉”略短。这叠加在所有组都存在的对较长(超秒)时长低估的显著趋势之上,表明随着时间推移,生物钟的节奏从快变慢。在时间再现任务中,在研究的时间范围的极端情况下,PD患者以及更显著的PSP患者对较短时长过度再现,对较长时长再现不足,中间时长则如实再现,呈现时间与生成时间之间的线性相关斜率较浅。在时长比较任务中,相对于第一个呈现时长,当标准时长较短而非较长时,PD患者高估了第二个呈现时长。在二等分任务中,PD和PSP患者估计两个超秒而非亚秒标准之间的二等分点(BP50)比正常受试者更长。因此,知觉计时任务显示出与运动计时任务相反的变化方向:低估较短时长,高估较长时长。在PD中,简易精神状态检查评分与超秒BP50以及再现任务中的线性相关斜率之间的相关性表明,短期记忆参与了这些任务。多巴胺缺乏与计时表现无显著相关性,这表明生物钟减慢假说无法解释所有结果。PD患者的计时表现可能由运动和感觉方面的时间尺度之间的复杂相互作用及其在记忆中的扭曲所决定。