Positive Expectation Effects on Early Emotional Processing

NCT07615530 | Not Yet Recruiting

• 1 other identifier: EyeFace
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Positive Expectations

Keywords

Treatment expectation; EEG; Eye Tracking; Emotional processing; Placebo; Positive expectation

Outcome Measures

Primary Outcomes (3)

• 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.

  On both day 2 and day 3, measurements will be taken before the intervention (VAS baseline, VASt0), 5 minutes after nasal spray application (VASt1), and after the measurement (~ 40 minutes after nasal spray application, VASt2).

• 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.

  Approximately 15 minutes after the nasal spray application, participants will perform an emotion classification task for 30 minutes while collecting behavioral and eye tracking data.

• 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.

  Approximately 15 minutes after the nasal spray application, participants will perform an emotion classification task for 30 minutes while collecting behavioral and eye tracking data.

Study Arms (2)

Experimental : Placebo - Control

EXPERIMENTAL

Participants in this group receive sham oxytocin on the first study day.

Other: Saline Nasal Spray

Control - Placebo

EXPERIMENTAL

Participants in this group receive sham oxytocin on the second study day

Other: Saline Nasal Spray

Interventions

Saline Nasal Spray OTHER

A 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)

Experimental : Placebo - Control

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Aged 18-35 years
• Normal or corrected to normal vision
• Signed declaration of consent
• German speaking

You may not qualify if:

• No informed consent
• Current intake of central nervous system active drugs
• Under influence of alcohol
• BDI score above 12
• Significant acute somatic or neurological diseases
• History of psychiatric or neurological disorders
• Acute nasal diseases or injuries
• EEG data with strong artefacts or excessive movement will be excluded from analysis
• If a participant does not believe in the treatment on the screening day, they will not be included for the main study days

Sponsors & Collaborators

• Universitätsklinikum Hamburg-Eppendorf: lead

Study Sites (1)

University Medical Center Hamburg-Eppendorf, Institute of Systems Neuroscience

Hamburg, Free and Hanseatic City of Hamburg, 20251, Germany

Location

Related Publications (3)

• Delorme A, Makeig S. EEGLAB: an open source toolbox for analysis of single-trial EEG dynamics including independent component analysis. J Neurosci Methods. 2004 Mar 15;134(1):9-21. doi: 10.1016/j.jneumeth.2003.10.009.

  PMID: 15102499 BACKGROUND

• Baker J, Gamer M, Rauh J, Brassen S. Placebo induced expectations of mood enhancement generate a positivity effect in emotional processing. Sci Rep. 2022 Mar 29;12(1):5345. doi: 10.1038/s41598-022-09342-2.

  PMID: 35351936 BACKGROUND

• Mostauli A, Rauh J, Gamer M, Buchel C, Rief W, Brassen S. Placebo treatment entails resource-dependent downregulation of negative inputs. Sci Rep. 2025 Mar 17;15(1):9088. doi: 10.1038/s41598-025-93589-y.

  PMID: 40097556 BACKGROUND

Study Officials

• Stefanie Brassen

  Department of Systems Neuroscience, University Hospital Hamburg-Eppendorf, Hamburg, Germany

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stefanie Brassen

CONTACT

+49 407410 54865; sbrassen@uke.de

Emma K.G. Specht

CONTACT

+49 407410 58203; e.specht@uke.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Participants will be blinded to the real substance (saline nasal spray).
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr.

Model Details: A crossover design will be employed by giving a saline nasal spray introduced either as oxytocin or as saline.

Study Record Dates

• First Submitted: May 22, 2026
• First Posted: May 29, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: June 2, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: with Publication

Locations

DE (1)