Parkinson’s disease as a system-level disorder

Caligiore, Daniele; Helmich, Rick C.; Hallett, Mark; Moustafa, Ahmed A.; Timmermann, Lars; Toni, Ivan; Baldassarre, Gianluca

doi:10.1038/npjparkd.2016.25

Cited by 118 publications

(132 citation statements)

References 139 publications

(207 reference statements)

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“…Translating to the clinic, movement disorders that were previously ascribed to basal ganglia are now recognized as system-level or network disorders [205][206][207]. I will first discuss Parkinson's disease (PD), a neurodegenerative disorder characterized by motor dysfunctions including, among others, tremor, bradykinesia, rigidity as well as non-motor functions.…”

Section: Laura Avanzinomentioning

confidence: 99%

Consensus paper: Decoding the Contributions of the Cerebellum as a Time Machine. From Neurons to Clinical Applications

et al. 2018

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Time perception is an essential element of conscious and subconscious experience, coordinating our perception and interaction with the surrounding environment. In recent years, major technological advances in the field of neuroscience have helped foster new insights into the processing of temporal information, including extending our knowledge of the role of the cerebellum as one of the key nodes in the brain for this function. This consensus paper provides a state-of-the-art picture from the experts in the field of the cerebellar research on a variety of crucial issues related to temporal processing, drawing on recent anatomical, neurophysiological, behavioral, and clinical research.The cerebellar granular layer appears especially well-suited for timing operations required to confer millisecond precision for cerebellar computations. This may be most evident in the manner the cerebellum controls the duration of the timing of agonist-antagonist EMG bursts associated with fast goal-directed voluntary movements. In concert with adaptive processes, interactions within the cerebellar cortex are sufficient to support sub-second timing. However, supra-second timing seems to require cortical and basal ganglia networks, perhaps operating in concert with Cerebellum.Additionally, sensory information such as an unexpected stimulus can be forwarded to the cerebellum via the climbing fiber system, providing a temporally constrained mechanism to adjust on-going behavior and modify future processing. Patients with cerebellar disorders exhibit impairments on a range of tasks that require precise timing, and recent evidence suggest that timing problems observed in other neurological conditions such as Parkinson's disease, essential tremor, and dystonia, may reflect disrupted interactions between the basal ganglia and cerebellum.The complex concepts emerging from this consensus paper should provide a foundation for further discussion, helping identify basic research questions required to understand how the brain represents and utilizes time, as well as delineating ways in which this knowledge can help improve the lives of those with neurological conditions that disrupt this most elemental sense. The panel of experts agrees that timing control in the brain is a complex concept in whom cerebellar circuitry is deeply involved. The concept of a timing machine has now expanded to clinical disorders. The Cerebellum Represents Isolated Temporal Intervals Across Task Domains Assaf Breska and Richard B. IvryIt is widely accepted that the cerebellum contributes, in some manner, to temporal processing, but the functional domain and computational mechanisms remain the subject of considerable debate. An early hypothesis was that the cerebellum served as a centralized, dedicated timing system [6,7].

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Section: Laura Avanzinomentioning

confidence: 99%

Consensus paper: Decoding the Contributions of the Cerebellum as a Time Machine. From Neurons to Clinical Applications

et al. 2018

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“…D) than a single brain region in isolation . Future approaches may use these models based on neuroimaging and clinical data to predict the response to treatment and ultimately form the basis for rational treatment choices …”

Section: Translational Implicationsmentioning

confidence: 99%

The cerebral basis of Parkinsonian tremor: A network perspective

Helmich¹

2017

Movement Disorders

115

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Tremor in Parkinson's disease is a poorly understood sign. Although it is one of the clinical hallmarks of the disease, its pathophysiology remains unclear. It is clear that tremor involves different neural mechanisms than bradykinesia and rigidity, the other core motor signs of Parkinson's disease. In particular, the role of dopamine in tremor has been heavily debated given clinical observations that tremor has a variable response to dopaminergic medication. From a neuroscience perspective, tremor is also a special sign; unlike other motor signs, it has a clear electrophysiological signature (frequency, phase, and power). These unique features of tremor, and newly available neuroimaging methods, have sparked investigations into the pathophysiology of tremor. In this review, evidence will be discussed for the idea that parkinsonian tremor results from increased interactions between the basal ganglia and the cerebello-thalamo-cortical circuit, driven by altered dopaminergic projections to nodes within both circuits, and modulated by context-dependent factors, such as psychological stress. Models that incorporate all of these features may help our understanding of the pathophysiology of tremor and interindividual differences between patients. One example that will be discussed in this article is the "dimmer-switch" model. According to this model, cerebral activity related to parkinsonian tremor first arises in the basal ganglia and is then propagated to the cerebello-thalamo-cortical circuit, where the tremor rhythm is maintained and amplified. In the future, detailed knowledge about the architecture of the tremor circuitry in individual patients ("tremor fingerprints") may provide new, mechanism-based treatments for this debilitating motor sign. © 2017 International Parkinson and Movement Disorder Society.

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“…Parkinson's has classically been associated with the degeneration of the dopaminergic pathways of the basal ganglia, leading to both motor and affective symptoms. Recent studies propose however that the disease mechanism(s) may be better understood as a dysfunction of a basal ganglia-cortical-cerebellar network [59], and evidence for a role of the cerebellum has been building [60]. Indeed there are Parkinsonian symptoms (particularly resting tremor) in populations with spinocerebellar ataxia type 3 [61], which support a cerebellar link in such symptoms.…”

Section: Parkinson's Disease and Essential Tremormentioning

confidence: 99%

Non-invasive Stimulation of the Cerebellum in Health and Disease

Darch¹,

Cerminara²,

Gilchrist³

et al. 2018

Transcranial Magnetic Stimulation in Neuropsychiatry

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The cerebellum is linked to motor, cognitive and affective functions. Anatomically, the cerebellum is part of an interconnected network including a wide range of other brain structures. This chapter reviews ways in which non-invasive stimulation has been used to activate or inhibit these circuits and how this has contributed to our understanding of cerebellar function in both motor and non-motor domains. The utility of non-invasive stimulation of the cerebellum in the treatment of neurological and psychiatric diseases (Parkinson's disease, cerebellar ataxia, stroke, depression and schizophrenia) is discussed. The chapter concludes with consideration of the challenges that must be overcome if noninvasive cerebellar stimulation is to be adopted in a wider clinical setting.

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Parkinson’s disease as a system-level disorder

Cited by 118 publications

References 139 publications

Consensus paper: Decoding the Contributions of the Cerebellum as a Time Machine. From Neurons to Clinical Applications

Consensus paper: Decoding the Contributions of the Cerebellum as a Time Machine. From Neurons to Clinical Applications

The cerebral basis of Parkinsonian tremor: A network perspective

Non-invasive Stimulation of the Cerebellum in Health and Disease

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