FV 18 Reducing hippocampal hyperactivity with real-time fMRI neurofeedback in patients with amnestic mild cognitive impairment

Abstract

Question: Several fMRI studies found hyperactivity in the hippocampus during a memory task (i.e., pattern separation) in patients with amnestic Mild Cognitive Impairment (aMCI; a prodromal stage of dementia due to Alzheimer's disease). Hippocampal hyperactivity 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. In addition, an elderly population is likely to be on other medication so - apart from the possible side effects - drug interaction may be a problem. An alternative approach may be real-time fMRI neurofeedback, during which individuals learn to control region-specific brain activity voluntarily. In the current project we tested the potential of real-time fMRI neurofeedback to reduce hippocampal hyperactivity and thereby improve memory performance. Methods: In a single-blind, parallel-group study, we will randomize n = 84 individuals (n = 42 patients with aMCI, n = 42 healthy elderly volunteers) to one of two groups receiving feedback from either the hippocampus or a functionally independent region i.e., the intraparietal sulcus, IPS). The participants will try to downregulate activity in the respective region. Percent signal change of the hemodynamic response within that region will be displayed to the participant with a thermometer icon. We hypothesize that only feedback from the hippocampus will decrease hippocampal hyperactivity and thereby improve memory task performance. Results: So far, we included n= 36 participants in the study. All participants were able to regulate brain activity to a certain extent. Preliminary results indicate that the reduction of hippocampal activity in patients with aMCI led to improved memory task performance, while it worsened performance in healthy elderly volunteers. We found no change in memory task performance in those that received feedback from the control region (Fig. 1 left). We also found no change in performance in a non-memory task (Fig. 1 right). Conclusion: These results indicate that downregulating hippocampal activity only improves memory performance in patients with aMCI, while an upregulation in healthy elderly volunteers may be more promising. A bigger sample of participants will be presented at the conference. We will also present the most successful strategies for downregulation that have been reported by the participants. Legend Fig. 1. Performance in a memory task (left) or a non-memory task (right) in healthy elderly volunteers downregulating activity in the hippocampus (blue) or the intraparietal sulcus (orange) or patients with amnestic Mild Cognitive Impairment (MCI; green) downregulating hippocampal activity. Performance is shown before (pre), during (NF1 and NF2), and after neurofeedback (post).