Cited by 581Neurological disorders and treatmentsParkinson's Disease Mechanisms and TreatmentsMotor Control and Adaptation

Cerebral causes and consequences of parkinsonian resting tremor: a tale of two circuits?

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Helmich, R. C., Hallett, M., Deuschl, G., Toni, I., Bloem, B. R.·2012·Brain

Abstract

Tremor in Parkinson's disease has several mysterious features. Clinically, tremor is seen in only three out of four patients with Parkinson's disease, and tremor-dominant patients generally follow a more benign disease course than non-tremor patients. Pathophysiologically, tremor is linked to altered activity in not one, but two distinct circuits: the basal ganglia, which are primarily affected by dopamine depletion in Parkinson's disease, and the cerebello-thalamo-cortical circuit, which is also involved in many other tremors. The purpose of this review is to integrate these clinical and pathophysiological features of tremor in Parkinson's disease. We first describe clinical and pathological differences between tremor-dominant and non-tremor Parkinson's disease subtypes, and then summarize recent studies on the pathophysiology of tremor. We also discuss a newly proposed 'dimmer-switch model' that explains tremor as resulting from the combined actions of two circuits: the basal ganglia that trigger tremor episodes and the cerebello-thalamo-cortical circuit that produces the tremor. Finally, we address several important open questions: why resting tremor stops during voluntary movements, why it has a variable response to dopaminergic treatment, why it indicates a benign Parkinson's disease subtype and why its expression decreases with disease progression.

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Authors
Helmich, R. C., Hallett, M., Deuschl, G., Toni, I., & Bloem, B. R.
Affiliations
  • Radboud University Nijmegen (NL)
  • National Institutes of Health (US)
  • Christian-Albrechts-Universität zu Kiel (DE)
  • Radboud University Medical Center (NL)
Corresponding author
Helmich, R. C.
Venue
Brain
Published
2012-03-01
Volume
135
Issue
11
Pages
3206-3226
ISSN
  • 0006-8950 (ISSN-L)
  • 1460-2156
OpenAlex
W2105515675
Cited by
581
References
187
Citations by year
2026: 50 · 2025: 48 · 2024: 47 · 2023: 43 · 2022: 37 · 2021: 47 · 2020: 65 · 2019: 33 · 2018: 26 · 2017: 40 · 2016: 42 · 2015: 31 · 2014: 31 · 2013: 36 · 2012: 5
FWCI
4.61
Type
journal article
Language
en
Open access
Locations
  • Brain (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Radboud Repository (Radboud University) (submittedVersion)
Funders
  • Nederlandse Organisatie voor Wetenschappelijk Onderzoek (016.076.352)
  • National Institutes of Health
Topics
  • Health Sciences › Medicine › Neurology › Neurological disorders and treatments
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Motor Control and Adaptation
Keywords
Parkinson's disease, resting tremor, tremor-dominant Parkinson's disease, basal ganglia, cerebello-thalamo-cortical circuit, dopamine depletion, tremor pathophysiology, disease progression
MeSH terms
Basal Ganglia, Cerebellum, Cerebral Cortex, Humans, Models, Neurological, Neural Pathways, Parkinson Disease, Radionuclide Imaging, Thalamus, Tremor, Disease Progression, Dopaminergic Neurons, Serotonergic Neurons, Functional Neuroimaging

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