Abstract
SummaryAimsResting tremor in Parkinson′s disease (PD) increases markedly during cognitive stress. Dopamine depletion in the basal ganglia is involved in the pathophysiology of resting tremor, but it is unclear whether this contribution is altered under cognitive stress. We test the hypothesis that cognitive stress modulates the levodopa effect on resting tremor.MethodsTremulous PD patients (n = 69) were measured in two treatment conditions (OFF vs. ON levodopa) and in two behavioral contexts (rest vs. cognitive co‐activation). Using accelerometry, we tested the effect of both interventions on tremor intensity and tremor variability.ResultsLevodopa significantly reduced tremor intensity (across behavioral contexts), while cognitive co‐activation increased it (across treatment conditions). Crucially, the levodopa effect was significantly smaller during cognitive co‐activation than during rest. Resting tremor variability increased after levodopa and decreased during cognitive co‐activation.ConclusionCognitive stress reduces the levodopa effect on Parkinson's tremor. This effect may be explained by a stress‐related depletion of dopamine in the basal ganglia motor circuit, by stress‐related involvement of nondopaminergic mechanisms in tremor (e.g., noradrenaline), or both. Targeting these mechanisms may open new windows for treatment. Clinical tremor assessments under evoked cognitive stress (e.g., counting tasks) may avoid overestimation of treatment effects in real life.
Highlights
Tremor in Parkinson’s disease (PD) is a highly heterogeneous and, for many patients, an agonizing symptom
We address this issue by testing whether the effect of levodopa on resting tremor is modulated by the presence of acute cognitive stress
We found that levodopa increased the spontaneous variability of resting tremor amplitude, while cognitive stress decreased it
Summary
Tremor in Parkinson’s disease (PD) is a highly heterogeneous and, for many patients, an agonizing symptom. Many patients complain about worsened tremor under stressful circumstances in daily life [2]. This may create a feeling of stigmatization and embarrassment, often leading to a vicious circle [3]. The neural mechanisms that contribute to tremor amplification during stress, and to the spontaneous variations in tremor, are unclear. Having such insights would be helpful for the development of improved treatment strategies for tremor.
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