Neuroscience Graduate Program, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA.
School of Psychology, University of Roehampton, London, SW15 4JD, UK; Department of Psychology, Goldsmiths, University of London, London, UK; Department of Psychology, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
Parkinsonism Relat Disord. 2023 Sep;114:105800. doi: 10.1016/j.parkreldis.2023.105800. Epub 2023 Aug 7.
Decreasing dopaminergic function is at the core of Parkinson's disease (PD) motor symptoms and changes in dopaminergic action are associated with many comorbid non-motor symptoms in PD. Notably, dopaminergic signaling in the striatum has been shown to play a critical role in the perception of time. We hypothesize that patients with PD perceive time differently and in accordance with their specific comorbid non-motor symptoms and clinical state. This means that individual differences in clinical symptoms may be reflected in individual differences in timing behavior. To test this hypothesis, we recruited patients with PD and compared individual differences in patients' clinical state with their ability to judge intervals of time ranging from 500 ms to 1100 ms while on and off their prescribed dopaminergic medications. We show that medication state (on vs. off medications) did not affect timing behavior, but individual differences in timing behavior are able to predict individual differences in comorbid non-motor symptoms, duration of PD diagnosis, and prescribed dopaminergic medications. We show that comorbid impulse control disorder is associated with temporal overestimation; depression is associated with decreased temporal accuracy; and increased PD 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. In future work, time perception tasks may augment clinical diagnosis strategies, or help disentangle the neural and cognitive mechanisms underlying PD motor and non-motor symptom etiology.
多巴胺能功能的降低是帕金森病 (PD) 运动症状的核心，多巴胺能作用的变化与 PD 中的许多并发非运动症状有关。值得注意的是，纹状体中的多巴胺能信号已被证明在时间感知中起着关键作用。我们假设 PD 患者对时间的感知不同，并且与他们特定的并发非运动症状和临床状态有关。这意味着临床症状的个体差异可能反映在计时行为的个体差异中。为了验证这一假设，我们招募了 PD 患者，并将患者临床状态的个体差异与他们在服用和不服用规定的多巴胺能药物时判断 500ms 至 1100ms 时间间隔的能力进行了比较。我们表明，药物状态（服用药物与不服用药物）不会影响计时行为，但计时行为的个体差异能够预测并发非运动症状、PD 诊断持续时间和规定的多巴胺能药物的个体差异。我们表明，并发冲动控制障碍与时间高估有关；抑郁与时间准确性降低有关；PD 持续时间增加和左旋多巴单一疗法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 运动和非运动症状的基础。在未来的工作中，时间感知任务可能会增强临床诊断策略，或有助于理清 PD 运动和非运动症状病因的神经和认知机制。
