Discussion
cognitive functioning, fatigue, OLP
Here, we investigated the performance-enhancing effects of OLPs using an extensive battery of subjective and objective cognitive performance measures and well-being. Our analyses suggest that this treatment had no significant impact on any of the outcomes, compared to a no-treatment control condition. As expected, participants’ performance generally improved from Baseline to Test in most tasks, most likely reflecting training effects in tasks assessing attention and concentration, working memory, and instrumental learningThe lack of objective improvements in cognitive performance is not unusual. Previous studies using deceptive placebos also yielded mixed results for objective parameters in healthy participantsThe absence of any improvement in subjective outcome including perceived performance and satisfaction therewith as well as no improvements of general well-being, however, is surprising given that many studies in clinical, but also non-clinical samples report subjective improvement under OLP treatment. Importantly, this also applies to trials with no changes in objective measures, which indicates that the perception of the patient or healthy participant can deviate from measurable outcome. In contrast to objective outcome parameters which are judged against an external criterion, subjective outcomes require the individual to compare any perceived changes in the relevant metric (e.g., processing speed in a cognitive task) to an internal standard to decide whether the change is meaningful, i.e., significantly different from noise. This threshold is likely to be influenced by the individual’s motivation to categorize changes as meaningful—particularly when they are subtle in nature. A strong motivation will lower the threshold whereas a weak motivation will lead to a higher threshold. Furthermore, the change must be attributed to the treatment (as opposed to coincidence). Several of our subjective outcome measures seem to indicate a rather critical assessment of their treatment in the OLP group which could reflect a high threshold to detect change. Participants in this group were significantly less satisfied with their group allocation than the control group, would have preferred to be in the control group, would not recommend OLPs to others and provided low ratings on their willingness to continue the treatment. Moreover, 5% of participants were excluded because they indicated that they had taken the OLP less than 70% of the time and 12% did not attend the second session.Psychological theories consider motivation or attitude towards an entity as the product of two components—expectancy and valueExpectancy as the second determinant has been a focus of several investigations into factors determining placebo outcome in the past. For deceptive placebo treatments, beneficial effects are thought to depend on an individual’s positive treatment expectationExplicit verbal information about the nature and potential benefits of placebos are a key component of many OLP studiesOur findings have to be interpreted in light of some limitations. First, our sample size was smaller than anticipated. To explore the robustness of our findings, we therefore decided to also apply Bayesian statistics. These analyses provided direct relative evidence for the null vs. the alternative hypothesis. Moreover, to ensure that the results we report are also of clinical significance, we were mainly interested in medium to large effects which can also be detected in a smaller sample such as ours. Second, not all tasks were administered in a randomized order. Especially for the learning task, which was always administered last, we therefore cannot rule out that the results are confounded by an increasing level of fatigue. However, as our findings compare two groups, such an effect (and also training effects) should occur in both groups. Third, we chose established cognitive tasks that had been successfully implemented in previous work and which are sensitive to performance improvement through OLPs while avoiding ceiling effects (e.g., 2-back vs. 3-back). It remains to be investigated whether more cognitively demanding tasks (e.g., 3- or 4-back) would be even more sensitive to the effect of OLPs. Fourth, previous work has shown that a 3-week treatment with OLPs is sufficient to induce effectsTogether, our findings do not support the assumption that OLPs can enhance cognitive functioning in healthy adults, and thereby showcase potential limitations of OLP treatments. Instead, we highlight important considerations for future studies aiming to include OLP treatments. Our proposed framework that follows expectancy-value considerations of motivation suggests several trajectories for future research to gain a more comprehensive understanding of the mechanisms and effects of OLP treatments and predictors for an individual’s response. First, the role of expectancy, value and costs, their respective determinants and interactions need to be investigated in more detail. A better understanding could not only help patient stratification but also aid the systematic investigation of differences in OLP responses between clinical and non-clinical groups and between objective and subjective outcome measures. Second, information about individual expectation, value and cost estimations could inform computational models which promise to reveal (neural) mechanisms underlying observable behaviour. Lastly, a deeper understanding could guide efforts to improve OLP outcome. For instance, expectations might be easier to modulate than costs, which are often outside the control of the practitioner. Information provided before OLP treatment could therefore focus on raising expectations while managing costs or may be tailored to fit the needs or preferences of the individual patient.