The placebo effect in the motor domain: a neural and behavioral approach

The placebo effect is a fascinating psychobiological phenomenon that allows to investigate the mind-body interaction. It is typically induced by the application of an inert treatment along with verbal suggestion of beneficial outcomes. The placebo effect has been deeply investigated in the field of pain, although different lines of evidence suggest that it is also present in other domains, like the motor domain. Extending our knowledge of the placebo effect in the motor domain can have important future translational impacts in sports and pathology. The aim of my PhD project was to study the placebo effect in the motor domain at two different levels: the neural and the behavioral level. Regarding the neural level, knowledge on the brain regions related to placebo effect in the motor domain is limited. We aimed at filling in this knowledge gap by investigating the role of the dlPFC, a brain region also involved in placebo analgesia. The dlPFC elaborates expectation, a cognitive function at the basis of the placebo effect and shares some connections with other brain regions involved in motor control. Hence, there are many clues to hypothesize a role of the dlPFC in the motor placebo effect. To tackle this issue, three different experiments were conducted in which the dlPFC was stimulated by means of transcranial direct current stimulation (tDCS) together with a placebo procedure on force production. We found that the left dlPFC is involved in the expectation-induced enhancement of force, specifically in those subjects who respond to the placebo effect (placebo-responders). Regarding the behavioral level, it should be noticed that many behavioral studies have shown that the placebo effect can enhance different aspects of motor performance associated to sports, such as force, speed or endurance. It is still unknown, however, whether the placebo effect can also improve other motor functions, important for many daily life activities, like balance or motor sequence learning. Thus, another objective of my PhD was to investigate the potential influence of the placebo effect on two motor functions that are closer to daily life activities. To this aim, a first study was conducted to understand whether balance control, a motor function needed for many daily life activities and for preventing falls, could be enhanced in healthy participants by a placebo procedure consisting 9 of verbal suggestion. We found that different parameters of balance (in the three-dimensional space and in the medial-lateral direction) and the subjective perception of stability were improved by the placebo procedure. A second behavioural study was run to investigate whether the application of a placebo treatment consisting of verbal suggestion could help in improving motor sequence learning. In this case, we also aimed to tackle a differential role of two types of placebo treatments: one motor and one cognitive. The motor placebo procedure consisted of transcutaneous electrical nerve stimulation (TENS) applied the hand muscles involved in the task together with verbal information on the beneficial effects on muscle activity. The cognitive placebo procedure consisted of sham transcranial direct current stimulation (tDCS) applied over the frontal region together with verbal information on the beneficial effects on attention. Our findings did not show a clear improvement of performance following the placebo procedures, but a significant effect on the subjective perception of fatigue. More precisely, while the placebo procedure directed to the motor function (TENS) could reduce the perception of physical fatigue, the placebo procedure focused on cognitive functions (sham tDCS) could decrease the perception of both mental and physical fatigue. Altogether these investigations represent an attempt to deepen our understanding of the neural correlates of the motor placebo effect and to enlarge the potential behavioural influence of placebos on different motor functions.