Expectation modulates the effect of deep brain stimulation on motor and cognitive function in tremor-dominant Parkinson's disease

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.

Placebo Intervention Enhances Reward Learning in Healthy Individuals

“…To date, only a handful of studies have investigated the placebo effect in the cognitive domain245354, and even fewer studies deal with healthy persons55565758. Only one study investigated the possible biological systems involved in the generation of cognitive placebo effects by examining PD patients24.…”

Do you believe in brain training? A questionnaire about expectations of computerised cognitive training

“…Brain training studies rarely account for participants' expectations, despite extensive evidence for their importance in other areas [16][17][18][19]. Our questionnaire can serve as a simple, easily incorporated tool to assess the face validity of brain training interventions.…”

“…Few studies, if any, have addressed the potential impact of participant expectations on brain training results (e.g., via the placebo effect), despite evidence for ubiquitous effects of expectations elsewhere [15]: In several psychiatric conditions, patients who begin with higher expectations of the effectiveness of their medications show greater improvement [16,17]. Patient expectations may even influence brain stimulation outcomes [18,19].…”

Nörodejeneratif Hastalıklarda Mezenkimal Kök Hücre Uygulamaları

“…Günümüzde en etkili tedavi Ldihidroksifenilalanin verilerek yapılan tedavidir 13 . Son zamanlarda beyinde stimulasyonla tedavi yöntemiyle umut veren sonuçlar elde edilmiştir 36 . Son zamanlarda Parkinson hastalığının tedavisinde gen ve hücre transplantasyonuna yönelik deneysel çalışmalar yapılmıştır.…”