Motor and cognitive placebo-/nocebo-responses in Parkinson's disease patients with deep brain stimulation

Keitel, Ariane; Wojtecki, Lars; Hirschmann, Jan V.; Hartmann, Christian; Ferrea, Stefano; Südmeyer, Martin; Schnitzler, Alfons

doi:10.1016/j.bbr.2013.04.051

Cited by 47 publications

(45 citation statements)

References 27 publications

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“…This result differs from the findings of previous studies where a modulation of bradykinesia by expectation was reported [18][19][20][21]; yet in those studies either exclusively hypokinetic-rigid or a mixture of hypokinetic-rigid and tremor-dominant PD patients were analyzed suggesting that placebo and nocebo responses mainly manifest on symptoms of predominant relevance to the patients, that is, tremor in the patients of the present study. Moreover, although expectations regarding the effect of STN-DBS were not exclusively induced with respect to tremor but also regarding motor symptoms in general, patients may have specifically focused their expectation on tremor rather than on other symptoms such as bradykinesia.…”

Section: Effect Of Expectation On Bradykinesiacontrasting

confidence: 99%

“…In contrast to patients in the subgroup who showed a nocebo response in tremor, no significant effect of expectation on verbal fluency was observed on group level. In a previous study using the same paradigm as employed in the present study [21], hypokinetic-rigid PD patients who showed a placebo response in bradykinesia were also characterized by a tendency for impairment in lexical verbal fluency. Thus, in contrast to the present study, expectation of beneficial STN-DBS modulated motor and cognitive functions in opposite directions.…”

Section: Effect Of Expectation On Verbal Fluencymentioning

confidence: 83%

“…Furthermore, the therapeutic effect of STN-DBS on bradykinesia can be modulated by verbally induced opposite expectations regarding the effect of STN-DBS with improvement following positive expectation and impairment in consequence of negative expectation [18][19][20][21]. Interestingly, 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].…”

Section: Introductionmentioning

confidence: 98%

“…For example, the administration of placebo drugs which PD patients expect to be a potent antiparkinsonian medication induces a substantial dopamine release in the striatum and alterations in the firing rate of single neurons in the STN associated with improvement in rigidity [15][16][17]. Furthermore, the therapeutic effect of STN-DBS on bradykinesia can be modulated by verbally induced opposite expectations regarding the effect of STN-DBS with improvement following positive expectation and impairment in consequence of negative expectation [18][19][20][21]. Interestingly, 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].…”

Section: Introductionmentioning

confidence: 99%

“…While it has been repeatedly shown that bradykinesia and rigidity are responsive to verbally induced expectation [15,[18][19][20][21], research regarding its effect on resting tremor in PD patients treated with STN-DBS is scarce. Given evidence of a worsening of resting tremor in PD patients performing cognitive tasks or during mental stress [22], it is of clinical relevance to investigate whether the therapeutic effect of STN-DBS on tremor can also be modulated by patients' expectations.…”

Section: Introductionmentioning

confidence: 99%

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

Keitel¹,

Ferrea²,

Südmeyer³

et al. 2014

Klin Neurophysiol

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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.

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Section: Effect Of Expectation On Bradykinesiacontrasting

confidence: 99%

Section: Effect Of Expectation On Verbal Fluencymentioning

confidence: 83%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Keitel¹,

Ferrea²,

Südmeyer³

et al. 2014

Klin Neurophysiol

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Probabilistic Mapping of Deep Brain Stimulation: Insights from 15 Years of Therapy

Elias

Boutet

Joel³

et al. 2020

Annals of Neurology

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Deep brain stimulation (DBS) depends on precise delivery of electrical current to target tissues. However, the specific brain structures responsible for best outcome are still debated. We applied probabilistic stimulation mapping to a retrospective, multidisorder DBS dataset assembled over 15 years at our institution (ntotal = 482 patients; nParkinson disease = 303; ndystonia = 64; ntremor = 39; ntreatment‐resistant depression/anorexia nervosa = 76) to identify the neuroanatomical substrates of optimal clinical response. Using high‐resolution structural magnetic resonance imaging and activation volume modeling, probabilistic stimulation maps (PSMs) that delineated areas of above‐mean and below‐mean response for each patient cohort were generated and defined in terms of their relationships with surrounding anatomical structures. Our results show that overlap between PSMs and individual patients' activation volumes can serve as a guide to predict clinical outcomes, but that this is not the sole determinant of response. In the future, individualized models that incorporate advancements in mapping techniques with patient‐specific clinical variables will likely contribute to the optimization of DBS target selection and improved outcomes for patients. ANN NEUROL 2021;89:426–443

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Factors influencing the outcome of deep brain stimulation: Placebo, nocebo, lessebo, and lesion effects

2016

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Deep brain stimulation (DBS) is a well-established treatment option for movement disorders, especially for Parkinson's disease (PD). There is a need to determine the role of expectation of benefit and the use of placebo to better understand the effects of electrode placement including the (micro)lesion effect. These factors must be understood to better interpret and attribute the therapeutic value of DBS. In this review, we critically present currently available data on the placebo, nocebo, lessebo, and lesion effects in the context of DBS. We provide a discussion of strategies that have the potential for controlling these effects in the setting of future DBS trials. We conclude that there is a need to standardize definitions for nocebo and (micro)lesion effects and that there are intrinsic limitations in defining the effect of expectation of benefit in DBS. These issues will be challenging to overcome especially with current technology and available study designs. New stimulation paradigms, better study designs, and the use of adaptive closed-loop DBS devices may facilitate a more accurate assessment of the placebo, nocebo, and lessebo effects in future DBS trials.

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Motor and cognitive placebo-/nocebo-responses in Parkinson's disease patients with deep brain stimulation

Cited by 47 publications

References 27 publications

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

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

Probabilistic Mapping of Deep Brain Stimulation: Insights from 15 Years of Therapy

Factors influencing the outcome of deep brain stimulation: Placebo, nocebo, lessebo, and lesion effects

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