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Nat. Commun., Mar 11 2025, 16 (1) 2433 | https://doi.org/10.1038/s41467-025-56660-w
Dopaminergic modulation and dosage effects on brain state dynamics and working memory component processes in Parkinson's disease
Byeongwook Lee1,6, Christina B. Young2,6, Weidong Cai1,3, Rui Yuan1, Sephira Ryman2, Jeehyun Kim2, Laurice Yang2, Victor W. Henderson2,3,4, Kathleen L. Poston2,3,5 & Vinod Menon1,2,3
1Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
2Department of Neurology & Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
3Wu Tsai Neurosciences Institute, Stanford University School of Medicine, Stanford, CA, USA.
4Department of Epidemiology & Population Health, Stanford University School of Medicine, Stanford, CA, USA.
5Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.
6These authors contributed equally: Byeongwook Lee, Christina B. Young.
Corresponding authors
Correspondence to Byeongwook Lee or Vinod Menon.
1Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
2Department of Neurology & Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
3Wu Tsai Neurosciences Institute, Stanford University School of Medicine, Stanford, CA, USA.
4Department of Epidemiology & Population Health, Stanford University School of Medicine, Stanford, CA, USA.
5Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.
6These authors contributed equally: Byeongwook Lee, Christina B. Young.
Corresponding authors
Correspondence to Byeongwook Lee or Vinod Menon.
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.
논문정보
- Research article
- 2025년 03월 (BRIC 등록일 2025-03-27)
- 국외 연구진
- 생명과학 > 신경생물학
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