title: Factors influencing the outcome of deep brain stimulation: Placebo, nocebo, lessebo, and lesion effects.
abstract: 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.
authors.affiliation: Parkinson's Disease and Movement Disorders Clinic, Division of Neurology, Department of Medicine, University of Ottawa, The Ottawa Hospital Research Institute, Ottawa, Canada.
authors.forename: Tiago A
authors.initials: TA
authors.lastname: Mestre
authors.affiliation: Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, University Health Network, Division of Neurology, Department of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Lang
authors.affiliation: Department of Neurology, Center for Movement Disorders and Neurorestoration, University of Florida Health, Gainesville, Florida, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Okun
mesh_terms: D000818:Animals; D046690:Deep Brain Stimulation; D006801:Humans; D009069:Movement Disorders / Q000503:physiopathology / Q000628:therapy*; D064786:Nocebo Effect; D010300:Parkinson Disease / Q000628:therapy*; D015990:Placebo Effect; D020531:Subthalamic Nucleus / Q000502:physiology / Q000503:physiopathology / Q000601:surgery*
keywords: Microlesion; Parkinson's disease; deep brain stimulation; essential tremor; lessebo; microelectrode recording; pallidotomy; placebo; subthalamotomy