Objective: To identify cerebral mechanisms explaining the effects of dopamine on rest tremor in Parkinson’s disease.

Background: Resting tremor in Parkinson’s disease is related to altered activity in the basal ganglia and in the cerebello-thalamo-cortical circuit. Dopaminergic medication reduces resting tremor in some patients, but many patients have a dopamine-resistant tremor. The cerebral mechanisms underlying the effect of dopamine on resting tremor, and the large inter-individual differences in this effect, are unexplained.

Methods: Here we investigated the influence of dopaminergic medication on tremor-related activity and effective connectivity, using combined EMG-fMRI recordings in 15 tremor-dominant Parkinson patients that were measured both on and off dopamine. Building on a recently developed model of Parkinson’s tremor, we distinguished between BOLD signals associated with tremor initiation (in the basal ganglia) and tremor amplification (in the cerebello-thalamo-cortical circuit).

Results: We found that dopaminergic medication reduced tremor initiation-related activity in the globus pallidus, and tremor amplification-related activity in the thalamic ventral intermediate nucleus (VIM). Network analyses with dynamic causal modeling showed that dopamine specifically increased thalamic self-inhibition, but only in patients with a clinically dopamine-responsive tremor.

Conclusions: Our findings suggest that dopamine reduces resting tremor by potentiating inhibitory mechanisms in the thalamic VIM nucleus. The failure of dopamine to target thalamic inhibition may explain why some patients have a dopamine-resistant tremor.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/dopamine-reduces-parkinsons-tremor-through-increased-thalamic-inhibition/