Department of Electrical Engineering, Sharif University of Technology, Tehran, Iran.
Sci Rep. 2023 Nov 18;13(1):20195. doi: 10.1038/s41598-023-47410-3.
The motor symptoms of Parkinson's disease (PD) have been shown to significantly improve by Levodopa. However, despite the widespread adoption of Levodopa as a standard pharmaceutical drug for the treatment of PD, cognitive impairments linked to PD do not show visible improvement with Levodopa treatment. Furthermore, the neuronal and network mechanisms behind the PD-induced cognitive impairments are not clearly understood. In this work, we aim to explain these cognitive impairments, as well as the ones exacerbated by Levodopa, through examining the differential dynamic patterns of the phase-amplitude coupling (PAC) during cognitive functions. EEG data recorded in an auditory oddball task performed by a cohort consisting of controls and a group of PD patients during both on and off periods of Levodopa treatment were analyzed to derive the temporal dynamics of the PAC across the brain. We observed distinguishing patterns in the PAC dynamics, as an indicator of information binding, which can explain the slower cognitive processing associated with PD in the form of a latency in the PAC peak time. Thus, considering the high-level connections between the hippocampus, the posterior and prefrontal cortices established through the dorsal and ventral striatum acting as a modulatory system, we posit that the primary issue with cognitive impairments of PD, as well as Levodopa's cognitive deficit side effects, can be attributed to the changes in temporal dynamics of dopamine release influencing the modulatory function of the striatum.
左旋多巴已被证明可显著改善帕金森病（PD）的运动症状。然而，尽管左旋多巴已被广泛采用为治疗 PD 的标准药物，但与 PD 相关的认知障碍在接受左旋多巴治疗时并未显示出明显改善。此外，PD 引起的认知障碍背后的神经元和网络机制尚不清楚。在这项工作中，我们旨在通过检查认知功能期间相位-振幅耦合（PAC）的差异动态模式来解释这些认知障碍，以及左旋多巴加剧的认知障碍。我们分析了由对照组和一组 PD 患者在接受左旋多巴治疗的开和关期间执行的听觉Oddball 任务中记录的 EEG 数据，以得出大脑中 PAC 的时间动态。我们观察到 PAC 动力学的区分模式，作为信息结合的指标，这可以解释与 PD 相关的较慢认知处理，其形式为 PAC 峰值时间的延迟。因此，考虑到通过充当调节系统的背侧和腹侧纹状体在海马体、后皮质和前额皮质之间建立的高级连接，我们假设 PD 的认知障碍以及左旋多巴的认知缺陷副作用的主要问题可以归因于多巴胺释放的时间动态变化影响纹状体的调节功能。
