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Dopaminergic modulation and dosage effects on brain state dynamics and working memory component processes in Parkinson’s disease

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Listed:
  • Byeongwook Lee

    (Stanford University School of Medicine)

  • Christina B. Young

    (Stanford University School of Medicine)

  • Weidong Cai

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • Rui Yuan

    (Stanford University School of Medicine)

  • Sephira Ryman

    (Stanford University School of Medicine)

  • Jeehyun Kim

    (Stanford University School of Medicine)

  • Laurice Yang

    (Stanford University School of Medicine)

  • Victor W. Henderson

    (Stanford University School of Medicine
    Stanford University School of Medicine
    Stanford University School of Medicine)

  • Kathleen L. Poston

    (Stanford University School of Medicine
    Stanford University School of Medicine
    Stanford University School of Medicine)

  • Vinod Menon

    (Stanford University School of Medicine
    Stanford University School of Medicine
    Stanford University School of Medicine)

Abstract

Parkinson’s disease (PD) is primarily diagnosed through its characteristic motor deficits, yet it also encompasses progressive cognitive impairments that profoundly affect quality of life. While dopaminergic medications are routinely prescribed to manage motor symptoms in PD, their influence extends to cognitive functions as well. Here we investigate how dopaminergic medication influences aberrant brain circuit dynamics associated with encoding, maintenance and retrieval working memory (WM) task-phases processes. PD participants, both on and off dopaminergic medication, and healthy controls, performed a Sternberg WM task during fMRI scanning. We employ a Bayesian state-space computational model to delineate brain state dynamics related to different task phases. Importantly, a within-subject design allows us to examine individual differences in the effects of dopaminergic medication on brain circuit dynamics and task performance. We find that dopaminergic medication alters connectivity within prefrontal-basal ganglia-thalamic circuits, with changes correlating with enhanced task performance. Dopaminergic medication also restores engagement of task-phase-specific brain states, enhancing task performance. Critically, we identify an “inverted-U-shaped” relationship between medication dosage, brain state dynamics, and task performance. Our study provides valuable insights into the dynamic neural mechanisms underlying individual differences in dopamine treatment response in PD, paving the way for more personalized therapeutic strategies.

Suggested Citation

  • Byeongwook Lee & Christina B. Young & Weidong Cai & Rui Yuan & Sephira Ryman & Jeehyun Kim & Laurice Yang & Victor W. Henderson & Kathleen L. Poston & Vinod Menon, 2025. "Dopaminergic modulation and dosage effects on brain state dynamics and working memory component processes in Parkinson’s disease," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56660-w
    DOI: 10.1038/s41467-025-56660-w
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    References listed on IDEAS

    as
    1. Andrew C. Murphy & Maxwell A. Bertolero & Lia Papadopoulos & David M. Lydon-Staley & Danielle S. Bassett, 2020. "Multimodal network dynamics underpinning working memory," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    2. Jalil Taghia & Weidong Cai & Srikanth Ryali & John Kochalka & Jonathan Nicholas & Tianwen Chen & Vinod Menon, 2018. "Uncovering hidden brain state dynamics that regulate performance and decision-making during cognition," Nature Communications, Nature, vol. 9(1), pages 1-19, December.
    3. Vinod Menon & Domenic Cerri & Byeongwook Lee & Rui Yuan & Sung-Ho Lee & Yen-Yu Ian Shih, 2023. "Optogenetic stimulation of anterior insular cortex neurons in male rats reveals causal mechanisms underlying suppression of the default mode network by the salience network," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
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