Abstract
Expectation contributes to placebo and nocebo responses in Parkinson's disease (PD). While there is evidence for expectation-induced modulations of bradykinesia, little is known about the impact of expectation on resting tremor. Subthalamic nucleus (STN) deep brain stimulation (DBS) improves cardinal PD motor symptoms including tremor whereas impairment of verbal fluency (VF) has been observed as a potential side-effect. Here we investigated how expectation modulates the effect of STN-DBS on resting tremor and its interaction with VF. In a within-subject-design, expectation of 24 tremor-dominant PD patients regarding the impact of STN-DBS on motor symptoms was manipulated by verbal suggestions (positive [placebo], negative [nocebo], neutral [control]). Patients participated with (MedON) and without (MedOFF) antiparkinsonian medication. Resting tremor was recorded by accelerometry and bradykinesia of finger tapping and diadochokinesia were assessed by a 3D ultrasound motion detection system. VF was quantified by lexical and semantic tests. In a subgroup of patients, the effect of STN-DBS on tremor was modulated by expectation, i.e. tremor decreased (placebo response) or increased (nocebo response) by at least 10% as compared to the control condition while no significant effect was observed for the overall group. Interestingly, nocebo responders in MedON were additionally characterized by significant impairment in semantic verbal fluency. In contrast, bradykinesia was not affected by expectation. These results indicate that the therapeutic effect of STN-DBS on tremor can be modulated by expectation in a subgroup of patients and suggests that tremor is also among the parkinsonian symptoms responsive to placebo and nocebo interventions. While positive expectations enhanced the effect of STN-DBS by further decreasing the magnitude of tremor, negative expectations counteracted the therapeutic effect and at the same time exacerbated a side-effect often associated with STN-DBS. The present findings underscore the potency of patients' expectation and its relevance for therapeutic outcomes.
Highlights
In Parkinson’s disease (PD), dopamine replacement therapy and deep brain stimulation (DBS) of the subthalamic nucleus (STN) are well established and effective treatments for the cardinal symptoms resting tremor, bradykinesia and rigidity [1,2,3]
A modulation of verbal fluency has been described in relation to expectation-induced placebo responses in bradykinesia in PD patients treated with STN-DBS [21]
A placebo/ nocebo response was defined as an improvement or worsening in resting tremor of at least 10% compared to the control condition
Summary
In Parkinson’s disease (PD), dopamine replacement therapy and deep brain stimulation (DBS) of the subthalamic nucleus (STN) are well established and effective treatments for the cardinal symptoms resting tremor, bradykinesia and rigidity [1,2,3]. Both treatments generally lead to improvement in motor symptoms, tremor is usually more effectively supressed by STN-DBS as compared to dopamine replacement therapy (for a review see [4]). A modulation of verbal fluency has been described in relation to expectation-induced placebo responses in bradykinesia in PD patients treated with STN-DBS [21]
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