Expectation modulates the effect of deep brain stimulation on motor and cognitive function in tremor-dominant Parkinson's disease
Introduction: Expectation is one of the main factors mediating placebo and nocebo responses. In Parkinson's disease (PD) there is evidence for expectation-induced modulations of bradykinesia. Yet, little is known about the impact of expectation on resting tremor. Subthalamic nucleus (STN) deep brain stimulation (DBS) improves cardinal motor symptoms including tremor whereas impairment in verbal fluency (VF) has been observed as a potential side-effect. In the present study we investigated how expectation modulates the effect of STN-DBS on resting tremor and its interaction with VF .
Methods: In a within-subject-design, expectation regarding the effect of STN-DBS on motor symptoms was manipulated by verbal suggestions (positive [placebo], negative [nocebo], neutral [control]) in 24 tremor-dominant PD patients. Patients participated with (MedON) and without (MedOFF) antiparkinsonian medication. Resting tremor was measured by accelerometry. Finger tapping and diadochokinesia were assessed using a 3D ultrasound motion detection system. VF was quantified by lexical and semantic tests.
Results: The effect of STN-DBS on resting tremor was modulated by expectation, i.e. tremor decreased (placebo response) or increased (nocebo response) by at least 10% as compared to control in a subgroup of patients whereas no significant effect was observed for the entire group. Nocebo responders in MedON were also characterized by significant impairment in semantic VF. Bradykinesia was not affected by expectation.
Conclusion: The results indicate that in a subgroup of PD patients positive expectation enhanced the effect of STN-DBS by further decreasing the magnitude of tremor while negative expectation counteracted the therapeutic effect and concomitantly exacerbated a side-effect often associated with STN-DBS. Thus, the findings underscore the potency of patients' expectation and its relevance for therapeutic outcomes, and should be considered in the context of patient-physician interaction.
 This study is under publication in PLOS ONE: Keitel, A., Ferrea, S., Südmeyer, M., Schnitzler, A., Wojtecki, L. Expectation modulates the Effect of Deep Brain Stimulation on Motor and Cognitive Function in Tremor-Dominant Parkinson's Disease.