Jaebum Park1, Mechelle M Lewis2, Xuemei Huang3, Mark L Latash4. 1. Department of Kinesiology, The Pennsylvania State University, Rec. Hall-268N, University Park, PA 16802, USA. 2. Department of Neurology, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, PA 17033, USA; Department of Pharmacology, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, PA 17033, USA. 3. Department of Kinesiology, The Pennsylvania State University, Rec. Hall-268N, University Park, PA 16802, USA; Department of Neurology, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, PA 17033, USA; Department of Pharmacology, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, PA 17033, USA; Department of Radiology, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, PA 17033, USA; Department of Neurosurgery, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, PA 17033, USA. 4. Department of Kinesiology, The Pennsylvania State University, Rec. Hall-268N, University Park, PA 16802, USA. Electronic address: mll11@psu.edu.
Abstract
BACKGROUND: We applied the idea of synergies and the framework of the uncontrolled manifold hypothesis to explore the effects of dopamine replacement therapy on finger interaction and coordination in patients with early-stage Parkinson's disease (PD). METHODS: Eight patients performed single-finger and multi-finger force production tasks with both the dominant and non-dominant hand before (off-drug) and after (on-drug) taking their dopaminergic medications. Synergy indices were defined as co-varied adjustments of commands to fingers that stabilized the total force produced by the hand. RESULTS: PD patients showed significantly lower maximal finger forces off-drug compared to the on-drug condition, while indices of finger individuation (enslaving) were unchanged. The synergy indices were weaker during steady-state force production off-drug compared to on-drug. Anticipatory adjustments of synergies prior to the quick force pulse initiation were delayed and reduced off-drug as compared to the on-drug condition. These drug effects were observed in both the symptomatic and asymptomatic hands of the patients whose symptoms were limited to one side of the body. CONCLUSIONS: The study demonstrates dopaminergic modulation of motor coordination in PD and supports that the analysis of different components of multi-finger synergies offers a set of indices sensitive to the effects of dopamine replacement therapy in early-stage PD. The results suggest an important role of the basal ganglia in synergy formation and in feed-forward synergy adjustments. Future studies using these methods may yield more objective, quantitative biomarker(s) of motor coordination impairments in PD, and better understanding of subcortical involvement in the neural control of natural actions.
BACKGROUND: We applied the idea of synergies and the framework of the uncontrolled manifold hypothesis to explore the effects of dopamine replacement therapy on finger interaction and coordination in patients with early-stage Parkinson's disease (PD). METHODS: Eight patients performed single-finger and multi-finger force production tasks with both the dominant and non-dominant hand before (off-drug) and after (on-drug) taking their dopaminergic medications. Synergy indices were defined as co-varied adjustments of commands to fingers that stabilized the total force produced by the hand. RESULTS:PDpatients showed significantly lower maximal finger forces off-drug compared to the on-drug condition, while indices of finger individuation (enslaving) were unchanged. The synergy indices were weaker during steady-state force production off-drug compared to on-drug. Anticipatory adjustments of synergies prior to the quick force pulse initiation were delayed and reduced off-drug as compared to the on-drug condition. These drug effects were observed in both the symptomatic and asymptomatic hands of the patients whose symptoms were limited to one side of the body. CONCLUSIONS: The study demonstrates dopaminergic modulation of motor coordination in PD and supports that the analysis of different components of multi-finger synergies offers a set of indices sensitive to the effects of dopamine replacement therapy in early-stage PD. The results suggest an important role of the basal ganglia in synergy formation and in feed-forward synergy adjustments. Future studies using these methods may yield more objective, quantitative biomarker(s) of motor coordination impairments in PD, and better understanding of subcortical involvement in the neural control of natural actions.
Authors: Sandra M S F Freitas; Paulo B de Freitas; Ali Falaki; Tyler Corson; Mechelle M Lewis; Xuemei Huang; Mark L Latash Journal: Exp Brain Res Date: 2020-10-17 Impact factor: 1.972
Authors: Ali Falaki; Hang Jin Jo; Mechelle M Lewis; Barbara O'Connell; Sol De Jesus; James McInerney; Xuemei Huang; Mark L Latash Journal: Clin Neurophysiol Date: 2018-03-09 Impact factor: 3.708
Authors: Mechelle M Lewis; Eun-Young Lee; Hang Jin Jo; Guangwei Du; Jaebum Park; Michael R Flynn; Lan Kong; Mark L Latash; Xuemei Huang Journal: Neurotoxicology Date: 2016-06-30 Impact factor: 4.294