On the Origin of Tremor in Parkinson’s Disease

Dovzhenok, Andrey; Rubchinsky, Leonid L.

doi:10.1371/journal.pone.0041598

Cited by 62 publications

(57 citation statements)

References 72 publications

(103 reference statements)

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“…The resting tremor in PD patients typically has a frequency between 4 and 6 Hz and is enhanced by motor or cognitive activity [7, 8]. However, extrapyramidal signs, including bradykinesia or rigidity, were not seen in this case.…”

Section: Discussionmentioning

confidence: 96%

Neuronal Intranuclear Inclusion Disease Presenting with Resting Tremor

Kitagawa¹,

Sone

Sobue

et al. 2014

Case Rep Neurol

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Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disease with various neurological symptoms. A 73-year-old woman presented with slowly progressive tremor in both hands. The resting tremor was enhanced by cognitive activity and walking. However, there were no other signs of parkinsonism. Levodopa and trihexyphenidyl were ineffective against the tremor. A diagnosis of NIID was made based on skin biopsy findings. The tremor in this case was very similar to that seen in Parkinson's disease (PD). Previous reports and the present case indicate that NIID patients can develop tremor that is similar in character to that seen in PD. NIID should be considered in the differential diagnosis of resting tremor similar to PD.

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Section: Discussionmentioning

confidence: 96%

Neuronal Intranuclear Inclusion Disease Presenting with Resting Tremor

Kitagawa¹,

Sone

Sobue

et al. 2014

Case Rep Neurol

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“…The feedback from the basal ganglia through the thalamus back to cortex is probably physiologically important. Even in relatively basic models of cortico-subcortical interactions it was shown to have a significant effect (e.g., Dovzhenok and Rubchinsky, 2012; Pavlides et al, 2015). This limits the interpretation of our modeling results because basal ganglia-thalamo-cortical feedback is not explicitly represented in our model.…”

Section: Discussionmentioning

confidence: 99%

Synchronized Beta-Band Oscillations in a Model of the Globus Pallidus-Subthalamic Nucleus Network under External Input

Ahn

Zauber

Worth

et al. 2016

Front. Comput. Neurosci.

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Hypokinetic symptoms of Parkinson's disease are usually associated with excessively strong oscillations and synchrony in the beta frequency band. The origin of this synchronized oscillatory dynamics is being debated. Cortical circuits may be a critical source of excessive beta in Parkinson's disease. However, subthalamo-pallidal circuits were also suggested to be a substantial component in generation and/or maintenance of Parkinsonian beta activity. Here we study how the subthalamo-pallidal circuits interact with input signals in the beta frequency band, representing cortical input. We use conductance-based models of the subthalamo-pallidal network and two types of input signals: artificially-generated inputs and input signals obtained from recordings in Parkinsonian patients. The resulting model network dynamics is compared with the dynamics of the experimental recordings from patient's basal ganglia. Our results indicate that the subthalamo-pallidal model network exhibits multiple resonances in response to inputs in the beta band. For a relatively broad range of network parameters, there is always a certain input strength, which will induce patterns of synchrony similar to the experimentally observed ones. This ability of the subthalamo-pallidal network to exhibit realistic patterns of synchronous oscillatory activity under broad conditions may indicate that these basal ganglia circuits are directly involved in the expression of Parkinsonian synchronized beta oscillations. Thus, Parkinsonian synchronized beta oscillations may be promoted by the simultaneous action of both cortical (or some other) and subthalamo-pallidal network mechanisms. Hence, these mechanisms are not necessarily mutually exclusive.

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“…In this work, each module is represented by a single Hopfield-type model neuron. Similar simplification is also used in previous computational studies [24, 42]. In Fig 2, we show the phase diagram with changing dopamine input derived by the analysis of the deterministic equations for neural network dynamics.…”

Section: Resultsmentioning

confidence: 95%

“…As we have discussed in the Introduction section, we consider the whole basal ganglia-thalamo-cortical circuit rather than the inhibitory-excitatory loop architecture of the STN-GPe network for exploring the dynamics in PD [22–24]. A computational model of the modulatory network has been constructed, which includes most of the main modulation modules in the circuit as shown in Fig 1 [8–11, 39–41].…”

Section: Methods and Modelsmentioning

confidence: 99%

“…In order to uncover the origin of abnormal neuronal oscillations in the basal ganglia circuit that may contribute to parkinsonian symptoms, some computational studies used the inhibitory-excitatory loop architecture of the STN-GPe network for the generation of oscillatory behavior in PD [22–24]. However, there are evidences showing that an isolated subthalamic-globus pallidus circuit in vitro is not sufficient to generate pathological oscillations [25].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Quantification of motor network dynamics in Parkinson’s disease by means of landscape and flux theory

Yan

Wang

2017

PLoS ONE

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The basal ganglia neural circuit plays an important role in motor control. Despite the significant efforts, the understanding of the principles and underlying mechanisms of this modulatory circuit and the emergence of abnormal synchronized oscillations in movement disorders is still challenging. Dopamine loss has been proved to be responsible for Parkinson’s disease. We quantitatively described the dynamics of the basal ganglia-thalamo-cortical circuit in Parkinson’s disease in terms of the emergence of both abnormal firing rates and firing patterns in the circuit. We developed a potential landscape and flux framework for exploring the modulatory circuit. The driving force of the circuit can be decomposed into a gradient of the potential, which is associated with the steady-state probability distributions, and the curl probability flux term. We uncovered the underlying potential landscape as a Mexican hat-shape closed ring valley where abnormal oscillations emerge due to dopamine depletion. We quantified the global stability of the network through the topography of the landscape in terms of the barrier height, which is defined as the potential difference between the maximum potential inside the ring and the minimum potential along the ring. Both a higher barrier and a larger flux originated from detailed balance breaking result in more stable oscillations. Meanwhile, more energy is consumed to support the increasing flux. Global sensitivity analysis on the landscape topography and flux indicates how changes in underlying neural network regulatory wirings and external inputs influence the dynamics of the system. We validated two of the main hypotheses(direct inhibition hypothesis and output activation hypothesis) on the therapeutic mechanism of deep brain stimulation (DBS). We found GPe appears to be another effective stimulated target for DBS besides GPi and STN. Our approach provides a general way to quantitatively explore neural networks and may help for uncovering more efficacious therapies for movement disorders.

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On the Origin of Tremor in Parkinson’s Disease

Cited by 62 publications

References 72 publications

Neuronal Intranuclear Inclusion Disease Presenting with Resting Tremor

Neuronal Intranuclear Inclusion Disease Presenting with Resting Tremor

Synchronized Beta-Band Oscillations in a Model of the Globus Pallidus-Subthalamic Nucleus Network under External Input

Quantification of motor network dynamics in Parkinson’s disease by means of landscape and flux theory

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