DiMarco Emily, Sadibolova Renata, Jiang Angela, Liebenow Brittany, Jones Rachel E, Ul Haq Ihtsham, Siddiqui Mustafa S, Terhune Devin B, Kishida Kenneth T
bioRxiv. 2023 Mar 2:2023.03.02.530411. doi: 10.1101/2023.03.02.530411.
Dopaminergic signaling in the striatum has been shown to play a critical role in the perception of time. Decreasing striatal dopamine efficacy is at the core of Parkinson's disease (PD) motor symptoms and changes in dopaminergic action have been associated with many comorbid non-motor symptoms in PD. We hypothesize that patients with PD perceive time differently and in accordance with their specific comorbid non-motor symptoms and clinical state. We recruited patients with PD and compared individual differences in patients' clinical features with their ability to judge millisecond to second intervals of time (500ms-1100ms) while on or off their prescribed dopaminergic medications. We show that individual differences in comorbid non-motor symptoms, PD duration, and prescribed dopaminergic pharmacotherapeutics account for individual differences in time perception performance. We report that comorbid impulse control disorder is associated with temporal overestimation; depression is associated with decreased temporal accuracy; and PD disease duration and prescribed levodopa monotherapy are associated with reduced temporal precision and accuracy. Observed differences in time perception are consistent with hypothesized dopaminergic mechanisms thought to underlie the respective motor and non-motor symptoms in PD, but also raise questions about specific dopaminergic mechanisms. In future work, time perception tasks like the one used here, may provide translational or reverse translational utility in investigations aimed at disentangling neural and cognitive systems underlying PD symptom etiology.
Quantitative characterization of time perception behavior reflects individual differences in Parkinson's disease motor and non-motor symptom clinical presentation that are consistent with hypothesized neural and cognitive mechanisms.
纹状体中的多巴胺能信号已被证明在时间感知中起关键作用。纹状体多巴胺效能降低是帕金森病(PD)运动症状的核心,多巴胺能作用的改变与PD的许多共病非运动症状有关。我们假设PD患者对时间的感知不同,且与他们特定的共病非运动症状和临床状态一致。我们招募了PD患者,并比较了患者临床特征的个体差异与他们在服用或停用规定的多巴胺能药物时判断毫秒到秒时间间隔(500毫秒 - 1100毫秒)的能力。我们发现,共病非运动症状、PD病程和规定的多巴胺能药物治疗的个体差异导致了时间感知表现的个体差异。我们报告,共病冲动控制障碍与时间高估有关;抑郁症与时间低估有关;PD病程和规定的左旋多巴单药治疗与时间精度和准确性降低有关。观察到的时间感知差异与假设的多巴胺能机制一致,这些机制被认为是PD中各自运动和非运动症状的基础,但也引发了关于特定多巴胺能机制的问题。在未来的研究中,像这里使用的时间感知任务,可能在旨在理清PD症状病因背后的神经和认知系统时提供转化或反向转化的效用。
时间感知行为的定量表征反映了帕金森病运动和非运动症状临床表现中的个体差异,这些差异与假设的神经和认知机制一致。