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Motor and cognitive placebo-/nocebo-responses in hypokinetic-rigid Parkinson's disease patients with deep brain stimulation
Introduction: In Parkinson's disease (PD) placebo and nocebo responses have been observed repeatedly. Patients' expectation is considered a main mechanism mediating those responses. Subthalamic nucleus (STN) deep brain stimulation (DBS) improves proximal more than distal movements and can impair verbal fluency (VF) as a potential side-effect. In the present study, we investigated how expectation modulates the effect of STN-DBS on motor and non-motor functions particularly affected by STN-DBS.
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 hypokinetic-rigid PD patients. Patients participated with (MedON) and without (MedOFF) antiparkinsonian medication. Proximal alternating hand movements and distal finger tapping were determined by a 3D motion detection system. VF was quantified by lexical and semantic tests.
Results: In MedOFF, a significant effect of expectation was observed for proximal but not for distal movements resulting in better performance in the placebo than in the nocebo condition. A subgroup analysis revealed that patients who showed a placebo response in proximal movements (improvement of ≥25% compared to control) were also characterized by a trend for impaired lexical VF.
Conclusion: The results indicate that positive expectations exert placebo responses in motor function as well as nocebo responses in cognitive function by further enhancing the STN-DBS-effect on proximal movements and by impairing VF. The placebo response in motor symptoms resembles the clinically known STN-DBS-effect with stronger improvement in proximal than in distal movements. The cognitive nocebo response implies that nocebo responses cannot only be induced by nocebo interventions but may – putatively due to implicit learning between improvement of symptoms and side effects – also be triggered by placebo interventions.