Department of Neurology and Center of Clinical Neuroscience, Charles University in Prague, 1st Faculty of Medicine and General University Hospital, Prague, Czech Republic.
PLoS One. 2012;7(1):e29635. doi: 10.1371/journal.pone.0029635. Epub 2012 Jan 6.
Parkinson's disease (PD) patients are deficient in time estimation. This deficit improves after dopamine (DA) treatment and it has been associated with decreased internal timekeeper speed, disruption of executive function and memory retrieval dysfunction.
METHODOLOGY/FINDINGS: The aim of the present study was to explore the neurophysiologic correlates of this deficit. We performed functional magnetic resonance imaging on twelve PD patients while they were performing a time reproduction task (TRT). The TRT consisted of an encoding phase (during which visual stimuli of durations from 5 s to 16.6 s, varied at 8 levels were presented) and a reproduction phase (during which interval durations were reproduced by a button pressing). Patients were scanned twice, once while on their DA medication (ON condition) and once after medication withdrawal (OFF condition). Differences in Blood-Oxygenation-Level-Dependent (BOLD) signal in ON and OFF conditions were evaluated. The time course of activation in the brain areas with different BOLD signal was plotted. There were no significant differences in the behavioral results, but a trend toward overestimation of intervals ≤11.9 s and underestimation of intervals ≥14.1 s in the OFF condition (p<0.088). During the reproduction phase, higher activation in the precuneus was found in the ON condition (p<0.05 corrected). Time course was plotted separately for long (≥14.1 s) and short (≤11.9 s) intervals. Results showed that there was a significant difference only in long intervals, when activity gradually decreased in the OFF, but remained stable in the ON condition. This difference in precuneus activation was not found during random button presses in a control task.
CONCLUSIONS/SIGNIFICANCE: Our results show that differences in precuneus activation during retrieval of a remembered duration may underlie some aspects of time perception deficit in PD patients. We suggest that DA medication may allow compensatory activation in the precuneus, which results in a more accurate retrieval of remembered interval duration.
帕金森病（PD）患者在时间估计方面存在缺陷。这种缺陷在多巴胺（DA）治疗后得到改善，并且与内部定时器速度降低、执行功能障碍和记忆检索功能障碍有关。
方法/发现：本研究旨在探讨这种缺陷的神经生理相关性。我们对 12 名 PD 患者进行了功能磁共振成像，同时进行了时间复制任务（TRT）。TRT 包括一个编码阶段（在此期间，呈现了从 5 秒到 16.6 秒不等的 8 个水平的视觉刺激）和一个复制阶段（在此期间，通过按钮按压来复制间隔时间）。患者接受了两次扫描，一次在服用 DA 药物时（ON 条件），一次在停药后（OFF 条件）。评估了 ON 和 OFF 条件下血氧水平依赖性（BOLD）信号的差异。绘制了大脑区域中不同 BOLD 信号的激活时间过程。在行为结果方面没有显著差异，但在 OFF 条件下，11.9 秒以下的间隔被高估，14.1 秒以上的间隔被低估（p<0.088）。在复制阶段，ON 条件下发现楔前叶的激活更高（p<0.05 校正）。分别为长（≥14.1 s）和短（≤11.9 s）间隔绘制时间过程。结果表明，仅在长间隔时才存在显著差异，即 OFF 时活动逐渐降低，但 ON 时保持稳定。在控制任务中的随机按钮按下时，没有发现楔前叶激活的这种差异。
结论/意义：我们的结果表明，在检索记忆持续时间时，楔前叶激活的差异可能是 PD 患者时间感知缺陷的某些方面的基础。我们认为，DA 药物治疗可能允许在楔前叶中进行代偿性激活，从而更准确地检索记忆间隔持续时间。
