Abstract
BackgroundSeveral fMRI studies found hyperactivity in the hippocampus during pattern separation tasks in patients with Mild Cognitive Impairment (MCI; a prodromal stage of Alzheimer’s disease). This was associated with memory deficits, subsequent cognitive decline, and faster clinical progression. A reduction of hippocampal hyperactivity with an antiepileptic drug improved memory performance. Pharmacological interventions, however, entail the risk of side effects. An alternative approach may be real-time fMRI neurofeedback, during which individuals learn to control region-specific brain activity. In the current project we aim to test the potential of neurofeedback to reduce hippocampal hyperactivity and thereby improve memory performance.MethodsIn a single-blind parallel-group study, we will randomize n = 84 individuals (n = 42 patients with MCI, n = 42 healthy elderly volunteers) to one of two groups receiving feedback from either the hippocampus or a functionally independent region. Percent signal change of the hemodynamic response within the respective target region will be displayed to the participant with a thermometer icon. We hypothesize that only feedback from the hippocampus will decrease hippocampal hyperactivity during pattern separation and thereby improve memory performance.DiscussionResults of this study will reveal whether real-time fMRI neurofeedback is able to reduce hippocampal hyperactivity and thereby improve memory performance. In addition, the results of this study may identify predictors of successful neurofeedback as well as the most successful regulation strategies.Trial registrationThe study has been registered with clinicaltrials.gov on the 16th of July 2019 (trial identifier: NCT04020744).
Highlights
Several functional magnetic resonance imaging (fMRI) studies found hyperactivity in the hippocampus during pattern separation tasks in patients with Mild Cognitive Impairment (MCI; a prodromal stage of Alzheimer’s disease)
Several fMRI studies in the prodromal stage of Alzheimer’s disease (AD) have found increased hippocampal activity during memory tasks that was associated with memory deficits, subsequent cognitive decline and faster clinical progression [4,5,6]
The current study aims to test whether real-time fMRI neurofeedback is capable of reducing hippocampal hyperactivity in patients with MCI and, in addition, whether the reduction of hyperactivity will be associated with an improvement in memory performance
Summary
Several fMRI studies found hyperactivity in the hippocampus during pattern separation tasks in patients with Mild Cognitive Impairment (MCI; a prodromal stage of Alzheimer’s disease). This was associated with memory deficits, subsequent cognitive decline, and faster clinical progression. Several fMRI studies in the prodromal stage of AD (i.e., in Mild Cognitive Impairment, MCI) have found increased hippocampal activity during memory tasks that was associated with memory deficits, subsequent cognitive decline and faster clinical progression [4,5,6]. Pharmacological treatment of hyperactivity in patients with MCI, or in mice with increased levels of Aβ, significantly reduced activity in the hippocampus and improved memory performance in pattern separation tasks [7]. The training is accomplished by continuously measuring brain activity in real-time, and providing feedback to the participant about the ongoing activity in the targeted brain area [11]
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