The good, the bad, and the ugly: A three-circuit model of Parkinson's tremor.

Abstract

Tremor is a common and disabling symptom of Parkinson's disease, which classically occurs at rest and often re-emerges during simple actions. The dimmer-switch hypothesis proposes that the basal ganglia trigger tremor, whereas the cerebello-thalamo-cortical circuit amplifies it. Recent findings suggest that this model may be expanded to include a potential anti-tremor network. This bilateral cortical network, comprising somatosensory, posterior parietal, insular, supplementary motor, and dorsal premotor regions, shows activity that is inversely related to tremor amplitude and clinical tremor severity. Its increased coupling with primary motor cortex during periods of low-amplitude tremor supports a potential role in tremor suppression, although so far causal evidence is lacking. We propose an updated pathophysiological model where Parkinson's tremor results from interactions between circuits that suppress (the good), initiate (the bad), and amplify (the ugly) tremor. Understanding these interactions may enable mechanism-based interventions targeting specific components of the tremor network, including non-invasive brain stimulation and behavioural approaches.