Thesis defense Michiel Dirks (Donders series 451)

2 November 2020

Promotor: prof. dr. B. Bloem, prof. dr. I. Toni
Co-promotor: dr. R. Helmich

Neural mechanisms of Parkinson's tremor

Tremor in Parkinson’s disease can lead to serious disability in the everyday life of patients, but not much is clear about the underlying mechanisms of tremor. In this thesis, several new and promising insights in the neural mechanisms underlying Parkinson’s tremor are introduced. First, it is shown that tremor arises through an interaction between two cerebral circuits: the basal ganglia (which trigger a tremor episode) and a cerebello-thalamo-cortical motor circuit (which produces and modulates tremor amplitude). Furthermore evidence is provided that levodopa (which is the most important drug treatment of tremor) can decrease tremor by decreasing activity in the thalamus. More importantly, this mechanism fails in patients with a dopamine-resistant tremor due to increased activity of the cerebellum. Third, two different types of postural tremor in Parkinson's disease are identified: (1) re-emergent tremor which is an extension of rest tremor and has a dopaminergic basis; (2) pure postural tremor which has a higher frequency, smaller amplitude and does not respond to dopaminergic medication. Finally, it is shown that cognitive stress increases Parkinson’s tremor via increased activity in the thalamus. This is caused by increased influences of noradrenaline and strengthening of the connection between two cerebral networks: the tremor circuitry and a cognitive control network