Real-time fMRI Neurofeedback in Patients With MCI

Targeting Hippocampal Hyperactivity With Real-time Functional MRI Based Neurofeedback in Elderly Individuals With and Without Memory Problems

Increased activity in the hippocampus (i.e., hyperactivity) during a fMRI memory task was found in patients with Mild Cognitive Impairment due to Alzheimer's disease (MCI). Those with increased hippocampal activity exhibited elevated clinical progression. Reducing hippocampal hyperactivity with pharmacological treatment reduced hyperactivity and improved memory performance. The investigators of this study will test whether real-time fMRI neurofeedback will also downregulate hippocampal activity and thereby improve memory performance.

Study Overview

• Status: Active, not recruiting
• Conditions: Mild Cognitive Impairment
• Intervention / Treatment: Other: real-time fMRI based neurofeedback from the hippocampus; Other: real-time fMRI based neurofeedback from another brain area

Detailed Description

Alzheimer's disease (AD) is an insidious and progressive neurodegenerative disorder accompanied by extracellular deposits of beta-amyloid ( aβ) and the increase of cognitive dysfunctions. Several functional magnet resonance imaging (fMRI) studies in the prodromal stage of AD (i.e., in MCI) have found increased hippocampal activity during a memory task to be predictive of memory worsening and disease progression. In this study the investigators are aiming to reduce hippocampal hyperactivity with real-time fMRI neurofeedback and test whether this will improve memory performance.

This study will use a randomized, single-blind, parallel group design. Patients with MCI and healthy participants will be assigned to receive feedback from either the hippocampus (experimental group, N=42) or from another brain area (alternate ROI feedback group, N=42). All participants will be instructed to downregulate activity.

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jessica Peter; Phone Number: +41 31 932 89 03; Email: jessica.peter@upd.unibe.ch
• Study Contact Backup: Name: Jessica Peter, PD Dr.; Phone Number: +41 31 932 89 03; Email: jessica.peter@upd.unibe.ch

Study Locations

• Switzerland
  • Bern, Switzerland, 3010
    • SITEM (Swiss Institute for Translational and Entrepreneurial Medicine)
  • Zurich, Switzerland, 8092
    • University of Zurich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Intact activities of daily living
• Fluent in German
• Normal/corrected-to-normal vision
• Written informed consent

Exclusion Criteria:

• Dementia
• Current/lifetime severe psychiatric or neurological disorder
• History of seizures
• Psychotropic medication
• Currently/lifetime drug or alcohol abuse
• Brain damage
• Magnetisable implants

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: healthy elderly participants receiving feedback from the hippocampus; This group will consist of healthy elderly volunteers, who will receive feedback from their hippocampal activity.	Other: real-time fMRI based neurofeedback from the hippocampus; During real-time fMRI neurofeedback, participants are trained to 'control' hippocampal activity. The training is accomplished by continuously measuring brain activity, analysing it in real-time, and then providing feedback about the current (and the targeted) brain activity to the participant.
Sham Comparator: healthy elderly participants receiving feedback from another area; This group will consist of healthy elderly volunteers, who will receive feedback from another brain area.	Other: real-time fMRI based neurofeedback from another brain area; During real-time fMRI neurofeedback, participants are trained to 'control' hippocampal activity. The training is accomplished by continuously measuring brain activity, analysing it in real-time, and then providing feedback about the current (and the targeted) brain activity to the participant.
Experimental: patients with MCI receiving feedback from the hippocampus; This group will consist of patients with mild cognitive impairment, who will receive feedback from their hippocampal activity.	Other: real-time fMRI based neurofeedback from the hippocampus; During real-time fMRI neurofeedback, participants are trained to 'control' hippocampal activity. The training is accomplished by continuously measuring brain activity, analysing it in real-time, and then providing feedback about the current (and the targeted) brain activity to the participant.
Sham Comparator: patients with MCI receiving feedback from another brain area; This group will consist of patients with mild cognitive impairment, who will receive feedback from another brain area.	Other: real-time fMRI based neurofeedback from another brain area; During real-time fMRI neurofeedback, participants are trained to 'control' hippocampal activity. The training is accomplished by continuously measuring brain activity, analysing it in real-time, and then providing feedback about the current (and the targeted) brain activity to the participant.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of change in hippocampal activity during a memory task	Measured by fMRI (rate of change in activity from baseline to after the intervention)	Directly after the intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of change in memory performance	Measured by fMRI (memory performance change from baseline to after the intervention)	Directly after the intervention
Rate of change from in memory performance (behavioural)	Measured behaviourally (memory performance change from baseline to after the intervention)	Directly after the intervention

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Strategies for Regulation of hippocampal activity	Which strategies were particularly helpful in downregulation of hippocampal activity (number of times the strategies were mentioned)	Intervention
Predictors of neurofeedback success	Variables extracted from questionnaires that may predict who will respond to neurofeedback	Post-Intervention

Collaborators and Investigators

• Sponsor: University of Bern
• Collaborators: University of Zurich
• Investigators: Principal Investigator: Jessica Peter, PD Dr., University of Bern; Study Chair: Frank Scharnowski, Prof. Dr., University of Vienna; Study Chair: Roland Wiest, Prof. Dr., University of Bern; Study Chair: Katharina Klink, University of Bern; Principal Investigator: Stefan Klöppel, Prof. Dr., University of Bern

Publications and helpful links

General Publications

• Klink K, Jaun U, Federspiel A, Wunderlin M, Teunissen CE, Kiefer C, Wiest R, Scharnowski F, Sladky R, Haugg A, Hellrung L, Peter J. Targeting hippocampal hyperactivity with real-time fMRI neurofeedback: protocol of a single-blind randomized controlled trial in mild cognitive impairment. BMC Psychiatry. 2021 Feb 9;21(1):87. doi: 10.1186/s12888-021-03091-8.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2020
• Primary Completion (Actual): October 31, 2023
• Study Completion (Estimated): January 31, 2024

Study Registration Dates

• First Submitted: July 4, 2019
• First Submitted That Met QC Criteria: July 15, 2019
• First Posted (Actual): July 16, 2019

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: November 6, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction
• Other Study ID Numbers: 1163

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No