Cerebral causes and consequences of parkinsonian resting tremor: a tale of two circuits?
Open accessAbstract
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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Abnormal cerebellum and basal ganglia related to tremor and akinetic-rigid symptoms lead to longer RT or MT in PD patients.
“The abnormal cerebellum and basal ganglia that related to tremor [14, 22, 43, 44] and akinetic-rigid symptoms [6–9, 42] also lead to the longer RT or MT in PD patients.”
From Evaluation of tremor interference with control of voluntary reaching movements in patients with Parkinson's disease (2019) · cites this paper as [22]
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“Evidence for this view comes from work showing that peripheral deafferentation (Pollock and Davis, 1930), peripheral anaesthesia of tremulous muscles (Walshe, 1924) and mechanical perturbations (Lee and Stein, 1981; Homberg et al., 1987) have little effect on Parkinson’s disease tremor although peripheral reflexes (mu…”
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“The Functional Neurosurgery unit, UCL Institute of Neurology, is supported by the Parkinson’s Appeal and the Sainsbury Monument Trust.”
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Neurodegenerative Disorders of Speech and Language: Non-language-dominant Diseases
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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
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-03-01
- Volume
- 135
- Issue
- 11
- Pages
- 3206-3226
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- PMC
- PMC3501966
- 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
- bronze
- doi.org
- 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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