About this trial
Insights into the mechanisms of expectation effects in the emotional domain can be invaluable for the development of potential therapeutic interventions for mood disorders. Recent findings demonstrate that positive expectations alone can induce a positivity bias on the behavioral and the neural level (Baker et al.,2022, Mostauli et al., 2025). This is intriguing given that antidepressant treatments, which have high placebo rates are reported to reduce a negativity bias commonly observed in depression.
Research on placebo analgesia has shown that both higher-order cognitive expectations and lower-level learning mechanisms, such as conditioning, play a key role in placebo effects. The role of such lower-level processes is particularly underexplored in affective placebo effects. Closing this gap is crucial, as the long-term modulation of the emotional system likely depends on cognitively less demanding, bottom-up processes shaped by learning and conditioning. This is particularly relevant in clinical populations, where cognitive resources may be limited, but there is an abundance of prior experiences (i.e., learning).
The present study therefore investigates how treatment expectations influence early psychophysiological processing of emotional stimuli. Beyond behavioral measures, we will directly assess early neural and attentional mechanisms using sensory event-related potentials (ERPs) and reflexive gaze shifts. By combining EEG and eye-tracking, we aim to identify early markers of expectation effects during emotional processing in healthy participants (N=44 plus 15% potential dropout, 50% women), who perform an emotion classification task. Emotional faces will be presented at varied levels of stimulus visibility (alpha transparency), allowing us to model perceptual sensitivity and response bias without inducing ceiling effects.
Treatment expectation will be induced by verbal instructions using an established protocol (e.g. Baker et al., 2022, Mostauli et al., 2025). We hypothesize that positive expectations enhance mood and decrease reaction times paralleled by better accuracy. Further, we hypothesize that positive treatment expectation enhances gaze shifts toward the mouth region which is the primary diagnostic feature for happy faces. On the neural level we expect that positive expectations modulate EEG signal patterns associated with early emotional valence processing. Additionally, whole-brain and time-frequency analyses, as well as representational similarity analyses, are planned to further explore into neural expectation effects and potential changes in the hierarchical representation of emotional processing.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Aged 18-35 years
Normal or corrected to normal vision
Signed declaration of consent
German speaking
Disqualifiers
No informed consent
Current intake of central nervous system active drugs
Under influence of alcohol
BDI score above 12
Trial design
Crossover
Treatments tested in this trial
Saline Nasal Spray
Other interventionA saline nasal spray will be introduced as oxytocin on the first day (induced positive expectations) and as saline on the second day (no induced expectations)
Saline Nasal Spray
Other interventionA saline nasal spray will be introduced as saline on the first day (no induced expectations) and as oxytocin on the second day (induced positive expectations)
Treatment groups
Trial outcomes
Primary outcomes
Effects of positive expectation on mood
Mood ratings via visual analogue scale (VAS), consisting of a scale from 0 to 200 points (0 meaning unhappy; 200 meaning happy, 200 incremental steps). VAS will be extracted as a raw score and then normalized to the baseline VAS (VASt0). Therefore, the VASt0 for each day will be subtracted from the VASt1-2 values. It will be analyzed to assess differences between interventions (placebo and control) and to evaluate changes over time throughout the experiment.
Effects of positive expectation on task performance data and eye movement
The proportion of fixation changes, as well as behavioral data (proportion of correct emotion classifications and response times), will be analyzed. Eye movements will be recorded at a sampling rate of 1000 Hz of the right eye using an EyeLink 1000 (SR Research) while participants are seated in a dimly lit room with their head stabilized at 50 cm distance from the computer screen.
Effects of positive expectation on evoked potentials
Electroencephalography will be used to extract and analyze stimulus-locked evoked potentials in response to the emotional conditions and interventions. Peak amplitudes and latencies will be analyzed. Additionally, time-frequency analysis, as well as representational similarity analyses are planned to capture treatment-related effects beyond ERP components and to characterize spatiotemporal and representational dynamics of emotional processing.
Sponsors and contacts
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