Investigating the Effect of Normal Frequency-band and Infra-low Frequency Neurofeedback on Functional Brain Connectome

In this basic research project a novel form of neurofeedback is investigated, in which in addition to the use of 1) normal frequency bands (1-35 Hertz), 2) very slow signals (low frequency; < 0.1 Hertz) are used, which correspond more to the basic excitability of the brain. Because of the slow signal characteristics, this method is called infra-low frequency neurofeedback (ILF-NFB for short). Although this method has been successfully applied in clinical settings since the 1980s, the mechanisms underlying the effect are largely unexplored. For that purpose, a project consistiong of three studies will be conducted in order to investigate the neurophysiological effects of both signal elements on healthy participants:

• Study 1 examines the effects of normal frequency band training alone.
• Study 2 examines the effects of low frequency training.
• Study 3 examines the effects of the combination of normal frequency band and low frequency training

For each study, a total of 40 clean data sets are to be collected, resulting in a minimum amount of 120 participants for all three studies.

All three studies investigate the effects of the neurofeedback on brain connectivity patterns by means of functional magnetic resonance imaging (fMRI), accompanied by measurements of the autonomic nervous system (ANS) and behavior.

Study Overview

• Status: Completed
• Conditions: Neurofeedback
• Intervention / Treatment: Device: Real Neurofeedback; Device: Sham Neurofeedback

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Zurich, Switzerland, 8032
    • Psychiatric University Hospital Zurich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy
• Written informed consent after participants' information
• Fluent in German language (required for an adequate answering of the questionnaires)
• No previous experience with neurofeedback treatments

Exclusion Criteria:

• Alcohol, drug and analgesics consumption within the last 24 hours
• Pre-existing neurological and/or psychiatric conditions
• History of brain injuries
• Alcohol and drug abuse
• Chronic diseases that require permanent medication
• Exclusion criteria met based on the screening questionnaire
• General contraindications for MR-testings (e.g. claustrophobia, pace maker, cochlear implant, insulin pump)
• Hypersensitivity to loud noises
• Incapable of lying still during a longer period of time

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy Subjects: Study 1; This arm corresponds to study 1 (Real Neurofeedback uses only normal frequency band signals ranging from 1 to 35 Hz from the EEG-signal). All included participants participate at 2 experimental conditions (Real Neurofeedback, Sham Neurofeedback) at 2 different days in a randomized order. Both, the investigators and the participants are blinded in regard to the intervention they receive at the two experimental visits.	Device: Real Neurofeedback; Real Neurofeedback with visual and acoustic feedback presentation based on the EEG-signal from the participant (Signals used described in corresponding study arm). The NFB-signals are obtained from the T4 and P4 positions according to the 10-20 EEG placement consensus. NFB is done using the software package Cygnet (BEE Medic GmbH Technologies, Kirchberg, Switzerland) and for all participants the same neurofeedback-animation is used. NFB training duration is approx. 30min; Device: Sham Neurofeedback; The sham neurofeedback is performed in identical fashion using the same software, feedback, electrode placement, duration as in the real neurofeedback. Only difference is that a pre-recorded EEG-dataset will be used and the feedback signal is thus independent from the brain activity of the participant.
Experimental: Healthy Subjects: Study 2; This arm corresponds to study 2 (Real Neurofeedback uses only infra-low frequencies below 0.1Hz from the EEG-signal). All included participants participate at 2 experimental conditions (Real Neurofeedback, Sham Neurofeedback) at 2 different days in a randomized order. Both, the investigators and the participants are blinded in regard to the intervention they receive at the two experimental visits.	Device: Real Neurofeedback; Real Neurofeedback with visual and acoustic feedback presentation based on the EEG-signal from the participant (Signals used described in corresponding study arm). The NFB-signals are obtained from the T4 and P4 positions according to the 10-20 EEG placement consensus. NFB is done using the software package Cygnet (BEE Medic GmbH Technologies, Kirchberg, Switzerland) and for all participants the same neurofeedback-animation is used. NFB training duration is approx. 30min; Device: Sham Neurofeedback; The sham neurofeedback is performed in identical fashion using the same software, feedback, electrode placement, duration as in the real neurofeedback. Only difference is that a pre-recorded EEG-dataset will be used and the feedback signal is thus independent from the brain activity of the participant.
Experimental: Healthy Subjects: Study 3; This arm corresponds to study 3 (normal frequency band & infra-low frequencies are used in Real Neurofeedback). All included participants participate at 2 experimental conditions (Real Neurofeedback, Sham Neurofeedback) at 2 different days in a randomized order. Both, the investigators and the participants are blinded in regard to the intervention they receive at the two experimental visits.	Device: Real Neurofeedback; Real Neurofeedback with visual and acoustic feedback presentation based on the EEG-signal from the participant (Signals used described in corresponding study arm). The NFB-signals are obtained from the T4 and P4 positions according to the 10-20 EEG placement consensus. NFB is done using the software package Cygnet (BEE Medic GmbH Technologies, Kirchberg, Switzerland) and for all participants the same neurofeedback-animation is used. NFB training duration is approx. 30min; Device: Sham Neurofeedback; The sham neurofeedback is performed in identical fashion using the same software, feedback, electrode placement, duration as in the real neurofeedback. Only difference is that a pre-recorded EEG-dataset will be used and the feedback signal is thus independent from the brain activity of the participant.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional brain connectivity	Comparison of the Pre-Post intervention differences in resting state functional connectivity (assessed using fMRI)	90 Minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart rate Variability Pre/Post Interventions	Comparison of the Pre-Post intervention differences in heart rate variability (during fMRI measurements)	90 Minutes
Respiration frequency Pre/Post Interventions	Comparison of the Pre-Post intervention differences in respiration frequency (during fMRI measurements)	90 Minutes
Heart rate variability during interventions	Comparison of heart rate variability measured during both interventions (Neurofeedback and Sham Neurofeedback)	30 Minutes
Respiration frequency during interventions	Comparison of respirateion frequency measured during both interventions (Neurofeedback and Sham Neurofeedback)	30 Minutes
Electrodermal activity during interventions	Comparison of electrodermal activity (skin conductance) measured during both interventions (Neurofeedback and Sham Neurofeedback)	30 Minutes
Power spectrum density (PSD) of the delta, theta, alpha, beta and gamma bands in the EEG-signal recorded during interventions	Comparison of power spectral density (PSD) of the delta, theta, alpha, beta and gamma frequency bands recorded by the neurofeedback equipment during both interventions (Neurofeedback and Sham Neurofeedback)	30 Minutes
Power spectrum density (PSD) of low-frequency components (< 0.1Hz) in the EEG-signal recorded during interventions	Comparison of power spectral density (PSD) of low-frequency components (< 0.1Hz) recorded by the neurofeedback equipment during both interventions (Neurofeedback and Sham Neurofeedback)	30 Minutes

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mental state pre/post intervention	Participants complete a questionnaire immediately before and after intervention for assessment of participants' mental state pre and immediately after the interventions	40 Minutes
Sleep questionnaire	Questionnaires on sleep quality will be given to the participants at the beginning of each experimental visit and within 24 hours after participation in order to assess effects of the interventions on sleep quality.	24 Hours
Personality questionnaires	BFI-60 personality questionnaire will be completed by participants at the beginning of each experimental visit to assess interactions between personality attributes and other outcomes	10 Minutes

Collaborators and Investigators

• Sponsor: Philipp Stämpfli
• Investigators: Principal Investigator: Philipp Stämpfli, PD PhD, Psychiatric University Hospital, Zurich

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2023
• Primary Completion (Actual): December 18, 2024
• Study Completion (Actual): December 18, 2024

Study Registration Dates

• First Submitted: January 13, 2023
• First Submitted That Met QC Criteria: January 31, 2023
• First Posted (Actual): February 3, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 12, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Neurofeedback, fMRI, resting-state
• Other Study ID Numbers: ILF_NFB_Allstudies

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No