EEG-based Neurofeedback to Improve Emotion Regulation in Major Depressive Disorder: A Randomized Clinical Trial

Summary

The goal of this clinical trial is to evaluate whether EEG-based neurofeedback targeting the emotion regulation network through swLORETA can improve emotional regulation and reduce symptoms in adults with Major Depressive Disorder (MDD) who have not responded sufficiently to first-line treatments. The main questions it aims to answer are:

* Does EEG-neurofeedback improve emotional self-regulation and reduce clinical symptoms in patients with MDD with or without anxiety symptoms?
* Are changes in EEG resting-state activity and stress biomarkers (e.g., cortisol) associated with clinical improvement?

Researchers will compare an active neurofeedback group, a sham (placebo) neurofeedback group, and a treatment-as-usual control group to see if real-time EEG-neurofeedback leads to greater improvement in mood, emotional regulation, and neurophysiological indicators than placebo or no additional intervention.

Participants will:

* Receive 10 sessions of either real or sham EEG-neurofeedback (or no sessions in the control group) over 5 weeks.
* Complete clinical, psychological, and neurophysiological assessments before (week 0) and after the intervention (week 6).
* Provide repeated saliva samples to assess stress-related biomarkers at week 0 and week 6.
* Continue their standard pharmacological treatment throughout the study.

Conditions

• Major Depression With Comorbid Anxiety Symptoms
• Major Depressive Disorder (MDD)

Interventions

DEVICE

Active swLORETA Z-score Neurofeedback

Participants receive 10 sessions (25 minutes each, twice per week for 5 weeks) of EEG-based neurofeedback using the NeuroGuide® software and a 24-channel EEG recording system (eego™, ANT Neuro). The neurofeedback protocol is based on real-time swLORETA Z-score training targeting brain regions involved in emotion regulation. Feedback is provided via gamified visual displays when EEG activity moves toward normative patterns. This is an operant conditioning-based protocol designed to enhance emotional self-regulation.

DEVICE

Yoked-sham swLORETA Z-score Neurofeedback

Participants receive 10 sessions identical in appearance and duration to the active neurofeedback condition. However, the feedback provided is not based on their own EEG activity. Instead, it is pre-recorded data from a matched participant in the active group ("yoked" design), ensuring no real-time neurophysiological modulation occurs. The same EEG equipment and visual feedback interface are used to maintain blinding.

Sponsors & Collaborators

• Horizon 2020 - European Commission

  collaborator OTHER

• Corporacion Parc Tauli

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-05-19

Primary Completion

2026-03-31

Completion

2026-09-30

FDA Device

Yes

Countries

• Spain

Study Locations