Wiesman Alex I, Vinding Mikkel C, Tsitsi Panagiota, Svenningsson Per, Waldthaler Josefine, Lundqvist Daniel
Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, Canada.
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Mov Disord. 2025 Apr 18. doi: 10.1002/mds.30200.
Individual variability in clinical response to dopamine replacement therapy (DRT) is a key barrier to efficacious treatment for patients with Parkinson's disease (PD). A better understanding of the neurobiological sources of such interindividual differences is necessary to personalize DRT prescribing, inform future clinical interventions, and motivate translational research.
One potential source of this variability is an unintended secondary activation of extra-nigrostriatal dopamine systems by DRT, particularly in the neocortex. Our goal was to determine the clinical effects of cortical dopamine system activation by DRT in patients with PD.
We used pharmaco-magnetoencephalography data collected from patients with PD (N = 17, N = 20) before and after DRT to map their cortical neurophysiological responses to dopaminergic pharmacotherapy. By combining these DRT response maps with normative atlases of cortical dopamine system densities, we linked the variable enhancement of rhythmic cortical activity by DRT to dopamine-rich cortical regions and determined its clinical relevance.
We found beta-rhythmic responses to DRT in dopamine-rich regions of the cortex that are expressed variably across individuals. Importantly, patients who exhibited a larger dopaminergic beta cortical enhancement showed a smaller clinical improvement from DRT, indicating a potential source of individual variability in medication response for patients with PD.
We conclude that these findings inform our understanding of the dopaminergic basis of neurophysiological variability often seen in patients with PD, and indicate that our methodological approach may be useful for data-driven contextualization of medication effects on cortical neurophysiology in future research and clinical applications. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
帕金森病（PD）患者对多巴胺替代疗法（DRT）的临床反应存在个体差异，这是有效治疗的关键障碍。更好地理解这种个体差异的神经生物学来源对于个性化DRT处方、为未来临床干预提供信息以及推动转化研究至关重要。
这种变异性的一个潜在来源是DRT意外地继发激活了黑质纹状体以外的多巴胺系统，尤其是在新皮质中。我们的目标是确定DRT激活皮质多巴胺系统对PD患者的临床影响。
我们使用从PD患者（N = 17，N = 20）在DRT前后收集的药物磁脑电图数据，绘制他们对多巴胺能药物治疗的皮质神经生理反应。通过将这些DRT反应图谱与皮质多巴胺系统密度的标准图谱相结合，我们将DRT对节律性皮质活动的可变增强与富含多巴胺的皮质区域联系起来，并确定其临床相关性。
我们在皮质富含多巴胺的区域发现了对DRT的β节律反应，个体之间表现不同。重要的是，表现出较大多巴胺能β皮质增强的患者从DRT中获得的临床改善较小，这表明PD患者药物反应个体差异的一个潜在来源。
我们得出结论，这些发现有助于我们理解PD患者中常见的神经生理变异性的多巴胺能基础，并表明我们的方法学方法可能有助于在未来研究和临床应用中对药物对皮质神经生理的影响进行数据驱动的情境化。© 2025作者。《运动障碍》由Wiley Periodicals LLC代表国际帕金森和运动障碍协会出版。
