Dopamine replacement therapy does not restore the ability of Parkinsonian patients to make rapid adjustments in motor strategies according to changing sensorimotor contexts

Tunik, Eugene; Feldman, Anatol G.; Poizner, Howard

doi:10.1016/j.parkreldis.2007.02.003

Cited by 34 publications

(32 citation statements)

References 44 publications

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“…The impairment in voluntary movement in PD is characterized by a number of specific sensorimotor processing deficits, including a generalized slowness of movement; 3 a difficulty in carrying out sequential movements; 4 a reliance on sensory input, particularly visual input, to guide and correct movement; 5,6 and difficulties in timing, synchronizing, and coordinating movements. [7][8][9] Since Parkinson's disease is a degenerative disease, an effective tool is needed to track changes in its severity and the effectiveness of remedial treatments. Clinical evaluations can be costly and difficult to execute consistently over the long duration of the disease.…”

Section: Introductionmentioning

confidence: 99%

Finger tapping movements of Parkinson’s disease patients automatically rated using nonlinear delay differential equations

Lainscsek

Rowat

Schettino

et al. 2012

Chaos: An Interdisciplinary Journal of Nonlinear Science

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Parkinson's disease is a degenerative condition whose severity is assessed by clinical observations of motor behaviors. These are performed by a neurological specialist through subjective ratings of a variety of movements including 10-s bouts of repetitive finger-tapping movements. We present here an algorithmic rating of these movements which may be beneficial for uniformly assessing the progression of the disease. Finger-tapping movements were digitally recorded from Parkinson's patients and controls, obtaining one time series for every 10 s bout. A nonlinear delay differential equation, whose structure was selected using a genetic algorithm, was fitted to each time series and its coefficients were used as a six-dimensional numerical descriptor. The algorithm was applied to time-series from two different groups of Parkinson's patients and controls. The algorithmic scores compared favorably with the unified Parkinson's disease rating scale scores, at least when the latter adequately matched with ratings from the Hoehn and Yahr scale. Moreover, when the two sets of mean scores for all patients are compared, there is a strong (r ¼ 0.785) and significant (p < 0:0015) correlation between them. Parkinson's disease (PD) is a common disease affecting tens of millions of people worldwide. Its cardinal signs are resting tremor, bradykinesia (slowness clumsiness of movement), rigidity, and loss of postural reflexes. The disease evolves slowly and, to adjust medications to the severity of the disease, there is a need for automatic and objective evaluation of movements. Such objective movement assessments would supplement subjective clinical ratings, which are ordinal rather than metric and often show large inter-rater variability. Rather than using a spectral based technique, we rated dynamical features of each individuals' finger-tapping-one of the items from the unified Parkinson's disease rating scale (UPDRS) used for rating the severity of the disease-by using data models based on nonlinear delay differential equations (DDEs). The coefficients of the DDEs are then used to assess the severity of the disease.

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Section: Introductionmentioning

confidence: 99%

Finger tapping movements of Parkinson’s disease patients automatically rated using nonlinear delay differential equations

Lainscsek

Rowat

Schettino

et al. 2012

Chaos: An Interdisciplinary Journal of Nonlinear Science

Self Cite

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“…If the BG have a critical contribution in processing sensory information for on-line movement guidance, then dysfunction in neural networks involving the BG such as in Huntington's disease (HD) and Parkinson's diseases (PD) should lead to impairments in producing effective adjustments during movement execution. However, previous studies investigating on-line movement control in BG-damaged patients have found conflicting results (Smith et al 2000;Desmurget et al 2004;Tunik et al 2007).…”

Section: Introductionmentioning

confidence: 95%

“…If the patterns of final errors are primarily determined by planning processes before the initiation of the movement, the initial kinematics of reaching movements should show similar trends and predict the pattern of final errors. Medicated and non-medicated PD patients showed a greater mean level of final 3D errors than healthy controls when proprioception was the sole source of information guiding the movement, but this difference reached significance only for medicated PD While there is considerable behavioural and neurophysiological evidence that the basal ganglia (BG) contribute to action selection and planning mechanisms, far fewer studies have examined whether these subcortical structures are involved in real-time movement guidance (Smith et al 2000;Desmurget et al 2004;Tunik et al 2007Tunik et al , 2009Roy et al 2008;Grafton and Tunik 2011). BG are part of a network that processes and integrates multisensory information to produce accurate motor action (Graziano and Gross 1993;Houk and Wise 1995;Contreras-Vidal 1999;Nagy et al 2006).…”

Section: Introductionmentioning

confidence: 99%

Impact of Parkinson’s disease on proprioceptively based on-line movement control

et al. 2015

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Evidence suggests that Parkinson's disease (PD) patients produce large spatial errors when reaching to proprioceptively defined targets. Here, we examined whether these movement inaccuracies result mainly from impaired use of proprioceptive inputs for movement planning mechanisms or from on-line movement guidance. Medicated and non-medicated PD patients and healthy controls performed three-dimensional reaching movements in four sensorimotor conditions that increase proprioceptive processing requirements. We assessed the influence of these sensorimotor conditions on the final accuracy and initial kinematics of the movements. If the patterns of final errors are primarily determined by planning processes before the initiation of the movement, the initial kinematics of reaching movements should show similar trends and predict the pattern of final errors. Medicated and non-medicated PD patients showed a greater mean level of final 3D errors than healthy controls when proprioception was the sole source of information guiding the movement, but this difference reached significance only for medicated PD patients. However, the pattern of initial kinematics and final spatial errors were markedly different both between sensorimotor conditions and between groups. Furthermore, medicated and non-medicated PD patients were less efficient than healthy controls in compensating for their initial spatial errors (hand distance from target location at peak velocity) when aiming at proprioceptively defined compared to visually defined targets. Considered together, the results are consistent with a selective deficit in proprioceptively based movement guidance in PD. Furthermore, dopaminergic medication did not improve proprioceptively guided movements in PD patients, indicating that dopaminergic dysfunction within the basal ganglia is not solely responsible for these deficits.

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“…The insufficiency of phasic release restoration also likely underlies the inability of Parkinson's patients on L-Dopa replacement therapy to rapidly adjust to ongoing motoric demands [108]. To accomplish a relative surge in dopamine release at a critical behavioral juncture such that the presence of dopamine provides sufficient ongoing support during more emergency situations, such as the need to escape from entrapment or predation, or falling into a body of water and needing to swim, phasic firing of nigrostriatal neurons occurs.…”

Section: Adaptation Of Endogenous Host Tissue To Neural Transplantationmentioning

confidence: 99%

“…Animal models benefit from rudimentary delivery mechanisms that also largely appear to maintain dopamine presence with little to no dynamic shifting according to "need," as might be expected of the phasic attributes of an intact dopamine system. Clearly the previously-mentioned movement tests that reveal the insufficient temporal precision of behavioral control with classic treatment has heightened awareness of the concern [108]. Nevertheless it is readily apparent that dopamine cell transplantation for the Parkinson's patient remains largely conceptualized as a more sophisticated delivery system for dopamine that may become increasingly necessary as the ongoing deterioration of dopaminergic neurons diminishes the patient's capacity to convert Levodopa into dopamine.…”

Section: Adaptation Of Transplanted Neural Cells To the Endogenous Homentioning

confidence: 99%

Plastic Adaptation: A Neuronal Imperative Capable of Confounding the Goals of Stem Cell Replacement Therapy for either Huntington’s or Parkinson’s Disease

Sandstrom¹,

Anderson²,

Jayaprakash³

et al. 2018

Neuroplasticity - Insights of Neural Reorganization

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Although stem cell transplant therapy offers considerable promise for deteriorative diseases, the efficacy of its application may be mitigated by endogenous compensatory mechanisms in the host brain. Plastic compensation follows neurodegeneration, beginning at its very onset and minimizing early symptom expression. As researchers attempt to correlate symptom remission with the ability of transplanted cells to adopt specific cell phenotypes, they need to be vigilant of the possibility that competing, local compensatory effects may be altering the outcome. Clearly plastic compensatory mechanisms could confound desired transplant-derived improvements by supplanting the beneficial contributions of the transplants. As circuit-level adaptations occur, more explicit explorations of their relevance to neuronal transplantation success are needed. Conceptual models of undirected transplanted cells adopting preconceived appropriate roles require revision. The notion that newly transplanted neuronal precursors will incorporate themselves into host circuitry with mutual cooperation across both parties (i.e., transplant and host) without some symbiosis-promoting mechanism is naïve. Undirected local circuits could react to newly transplanted additions as intruders. We advocate that appropriate signaling from transplanted cells to the host environment is required to optimize the therapeutic relevance of transplantation. This review surveys critical signaling mechanisms that might promote symbiotic interdependence between the host and new transplants.

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Dopamine replacement therapy does not restore the ability of Parkinsonian patients to make rapid adjustments in motor strategies according to changing sensorimotor contexts

Cited by 34 publications

References 44 publications

Finger tapping movements of Parkinson’s disease patients automatically rated using nonlinear delay differential equations

Finger tapping movements of Parkinson’s disease patients automatically rated using nonlinear delay differential equations

Impact of Parkinson’s disease on proprioceptively based on-line movement control

Plastic Adaptation: A Neuronal Imperative Capable of Confounding the Goals of Stem Cell Replacement Therapy for either Huntington’s or Parkinson’s Disease

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