title: Cerebral causes and consequences of parkinsonian resting tremor: a tale of two circuits?
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.
authors.affiliation: Donders Institute for Brain, Cognition and Behaviour, Centre for Cognitive Neuroimaging, Radboud University Nijmegen, 6500 HB Nijmegen, The Netherlands, The Netherlands. r.helmich@neuro.umcn.nl
authors.forename: Rick C
authors.initials: RC
authors.lastname: Helmich
authors.forename: Mark
authors.initials: M
authors.lastname: Hallett
authors.forename: Günther
authors.initials: G
authors.lastname: Deuschl
authors.forename: Ivan
authors.initials: I
authors.lastname: Toni
authors.forename: Bastiaan R
authors.initials: BR
authors.lastname: Bloem
mesh_terms: D001479:Basal Ganglia / Q000503:physiopathology; D002531:Cerebellum / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000503:physiopathology*; D018450:Disease Progression; D059290:Dopaminergic Neurons / Q000000981:diagnostic imaging / Q000502:physiology; D059907:Functional Neuroimaging / Q000379:methods / Q000706:statistics & numerical data; D006801:Humans; D008959:Models, Neurological; D009434:Neural Pathways / Q000503:physiopathology; D010300:Parkinson Disease / Q000150:complications / Q000175:diagnosis / Q000473:pathology / Q000503:physiopathology*; D011877:Radionuclide Imaging; D059326:Serotonergic Neurons / Q000000981:diagnostic imaging / Q000502:physiology; D013788:Thalamus / Q000503:physiopathology*; D014202:Tremor / Q000150:complications / Q000473:pathology / Q000503:physiopathology*