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.

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.

For blinding of the participants, they will be told that they will be asked to regulate one of two brain regions, without mentioning the specific area.

This group will consist of healthy elderly volunteers, who will receive feedback from their hippocampal activity.

This group will consist of healthy elderly volunteers, who will receive feedback from another brain area.

This group will consist of patients with mild cognitive impairment, who will receive feedback from their hippocampal activity.

This group will consist of patients with mild cognitive impairment, who will receive feedback 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.

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.

Which strategies were particularly helpful in downregulation of hippocampal activity (number of times the strategies were mentioned)

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

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.