Abstract
Inactive interventions can have significant effects on cognitive performance. Understanding the generation of these cognitive placebo/nocebo effects is crucial for evaluating the cognitive impacts of interventional methods, such as non-invasive brain stimulation (NIBS). We report both cognitive placebo and nocebo effects on reward-based learning performance induced using an active sham NIBS protocol, verbal suggestions and conditioning in 80 healthy participants. Whereas our placebo manipulation increased both expected and perceived cognitive performance, nocebo had a detrimental effect on both. Model-based analysis suggests manipulation-specific strategic adjustments in learning-rates: Participants in the placebo group showed stronger learning from losses and reduced behavioral noise, participants in the nocebo group showed stronger learning from gains and increased behavioral noise. We conclude that experimentally induced expectancy can impact cognitive functions of healthy adult participants. This has important implications for the use of double-blind study designs that can effectively maintain blinding in NIBS studies.
Highlights
Placebos and nocebos are physiologically inert substances or simulated interventions, which produce complex psychobiological responses despite the fact that they do not have any direct therapeutic effects[1,2,3]
To study cognitive placebo/nocebo effects, we propose an experimental framework in which we focus on instrumental learning in conjunction with the administration of sham protocols of non-invasive brain stimulation (NIBS) interventions[18]
We investigate the effect of placebo and nocebo interventions on instrumental learning[35], which is a well-suited behavioral paradigm for studying cognitive placebo and nocebo effects because of two reasons
Summary
Placebos and nocebos are physiologically inert substances or simulated interventions, which produce complex psychobiological responses despite the fact that they do not have any direct therapeutic effects[1,2,3]. To study cognitive placebo/nocebo effects, we propose an experimental framework in which we focus on instrumental learning in conjunction with the administration of sham protocols of non-invasive brain stimulation (NIBS) interventions[18]. Most of the commercially available and certified tDCS devices are equipped with double-blind operation mode, a large number of studies still use a single-blind study design, inadequate blinding or no blinding at all[31] In these studies, the impact of intentional and unconscious preferences, bias mechanisms and expectations from the side of the participants as well as the researchers can eventually lead to an overestimation of its effectiveness[32,33,34]. Understanding how these biasing mechanisms are generated and maintained is essential to further understand how the effects of NIBS interventions are induced and to judge the magnitude of the bias inherent in a large body of research
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