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Cerebral differences between dopamine-resistant and dopamine-responsive Parkinson's tremor
Michiel F Dirkx1,2, Heidemarie Zach1,2,3, Annelies van Nuland1
1Donders Institute for Brain, Cognition and Behaviour, Centre for Cognitive Neuroimaging, Radboud University Nijmegen, HB Nijmegen, The Netherlands.
Brain : a Journal of Neurology
|September 12, 2019
Summary
Parkinson's tremor varies in response to medication. Dopamine-resistant tremor may stem from increased cerebellar activity, while responsive tremor involves the thalamus and somatosensory cortex.
Area of Science:
- Neuroscience
- Neurology
- Movement Disorders
Background:
- Rest tremor in Parkinson's disease (PD) involves basal ganglia and cerebello-thalamo-cortical circuits.
- Significant inter-individual variability exists in therapeutic responses to dopaminergic medication for PD tremor.
- This heterogeneity suggests differing pathophysiological mechanisms underlying tremor in Parkinson's disease.
Purpose of the Study:
- To test the hypothesis that dopamine-resistant resting tremor is associated with increased contributions from non-dopaminergic regions, specifically the cerebellum.
- To investigate the neural underpinnings of dopamine-responsive versus dopamine-resistant tremor in Parkinson's disease patients.
Main Methods:
- Recruited 83 tremulous PD patients, performing levodopa challenge tests to select for dopamine-responsive (n=20) and dopamine-resistant (n=14) tremor groups.
- Utilized combined electromyography (EMG) and functional magnetic resonance imaging (fMRI) in a crossover, double-blind, placebo-controlled design.
- Quantified tremor-related brain activity during placebo and levodopa/benserazide administration sessions.
Main Results:
- Both groups exhibited tremor amplitude-related activity within the cerebello-thalamo-cortical circuit.
- Dopamine-resistant tremor patients showed heightened tremor-related activity in the cerebellum (non-dopaminergic area).
- Dopamine-responsive patients displayed increased tremor-related activity in the thalamus and secondary somatosensory cortex; levodopa more effectively inhibited thalamic responses in this group.
Conclusions:
- Dopamine-resistant Parkinson's disease tremor may be attributed to increased cerebellar influence and reduced somatosensory input to the cerebellar thalamus.
- This altered circuitry in dopamine-resistant tremor makes the cerebellar thalamus less responsive to the inhibitory effects of dopamine.
- Findings highlight distinct neurobiological pathways for different tremor phenotypes in Parkinson's disease, informing targeted therapeutic strategies.