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<p> Background: Parkinson’s disease (PD), the second most common neurodegenerative disorder, affects over 10&#xa0;million people and leads to progressive motor and non-motor decline. Levodopa (L-DOPA) remains the primary treatment, yet long-term use causes motor fluctuations and dyskinesias, and tools to optimize therapy remain limited. Objectives: This review systematically evaluates studies assessing how L-DOPA affects functional connectivity within the motor network, to inform more precise and personalized treatment strategies. Methods: A systematic search of PubMed and Web of Science was performed using terms related to PD, L-DOPA, and resting-state connectivity. Included studies examined L-DOPA–induced changes in resting-state functional connectivity within motor network–related regions in humans. Results: L-DOPA broadly modulates connectivity within motor and cognitive resting-state networks. In 28/32 comparisons, L-DOPA increased striatal connectivity with cortical motor regions, basal ganglia nuclei, the cerebellum, and the brainstem. In 21/26 comparisons, connectivity increased between motor cortical areas, the basal ganglia, thalamus, and cerebellum. In 9/16 comparisons, intracerebral connectivity decreased. In all 9 comparisons, L-DOPA increased cerebellar connectivity with the globus pallidus, midbrain, and brainstem. In all 6 comparisons, connectivity increased within the midbrain and between the midbrain, thalamus, and brainstem. Conclusion: This review consolidates ON/OFF L-DOPA findings to characterize how L-DOPA modulates motor network connectivity. These insights may advance precision therapies, guide individualized dose titration, and support the development of treatments with improved side-effect profiles.</p>

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Resting-state motor network connectivity as a biomarker of Levodopa response in Parkinson’s disease

  • 期刊论文

  • 发表日期：

    2026年2月12日

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  • Emma E. Russo,
  • Leif E. R. Simmatis,
  • Kevin Kadak,
  • Zoyeb Ehsan,
  • Selma Sieber,
  • Hannah Seo,
  • Christina Xie,
  • Aditya Pancholi,
  • Emma Abray,
  • Irene E. Harmsen,
  • Nardin Samuel

摘要

Background: Parkinson’s disease (PD), the second most common neurodegenerative disorder, affects over 10 million people and leads to progressive motor and non-motor decline. Levodopa (L-DOPA) remains the primary treatment, yet long-term use causes motor fluctuations and dyskinesias, and tools to optimize therapy remain limited. Objectives: This review systematically evaluates studies assessing how L-DOPA affects functional connectivity within the motor network, to inform more precise and personalized treatment strategies. Methods: A systematic search of PubMed and Web of Science was performed using terms related to PD, L-DOPA, and resting-state connectivity. Included studies examined L-DOPA–induced changes in resting-state functional connectivity within motor network–related regions in humans. Results: L-DOPA broadly modulates connectivity within motor and cognitive resting-state networks. In 28/32 comparisons, L-DOPA increased striatal connectivity with cortical motor regions, basal ganglia nuclei, the cerebellum, and the brainstem. In 21/26 comparisons, connectivity increased between motor cortical areas, the basal ganglia, thalamus, and cerebellum. In 9/16 comparisons, intracerebral connectivity decreased. In all 9 comparisons, L-DOPA increased cerebellar connectivity with the globus pallidus, midbrain, and brainstem. In all 6 comparisons, connectivity increased within the midbrain and between the midbrain, thalamus, and brainstem. Conclusion: This review consolidates ON/OFF L-DOPA findings to characterize how L-DOPA modulates motor network connectivity. These insights may advance precision therapies, guide individualized dose titration, and support the development of treatments with improved side-effect profiles.