Real-time fMRI Neurofeedback in Patients With MCI

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Mild Cognitive Impairment

Intervention / Treatment
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* Other: real-time fMRI based neurofeedback from the hippocampus
* Other: real-time fMRI based neurofeedback from another brain area


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: healthy elderly participants receiving feedback from the hippocampus<br>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<br>* 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.<br>|
| Sham Comparator: healthy elderly participants receiving feedback from another area<br>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<br>* 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.<br>|
| Experimental: patients with MCI receiving feedback from the hippocampus<br>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<br>* 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.<br>|
| Sham Comparator: patients with MCI receiving feedback from another brain area<br>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<br>* 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.<br>|

What is the study measuring?
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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 |