The relationship between cholinergic system brain structure and function in healthy adults and patients with mild cognitive impairment.

We assessed the structure-function relationship of the human cholinergic system and hypothesized that structural measures are associated with short-latency sensory afferent inhibition (SAI), an electrophysiological measure of central cholinergic signal transmission. Healthy volunteers (n = 36) and patients with mild cognitive impairment (MCI, n = 20) underwent median nerve SAI and 3T structural MRI to determine the volume of the basal forebrain and the thalamus. Patients with MCI had smaller basal forebrain (p < 0.001) or thalamus volumes (p < 0.001) than healthy volunteers. Healthy SAI responders (> 10% SAI) had more basal forebrain volume than non-responders (p = 0.004) or patients with MCI (p < 0.001). More basal forebrain volume was associated with stronger SAI in healthy volunteers (r = 0.33, p < 0.05) but not patients with MCI. There was no significant relationship between thalamus volumes and SAI. Basal forebrain volume is associated with cholinergic function (SAI) in healthy volunteers but not in MCI patients. The in-vivo investigation of the structure-function relationship could further our understanding of the human cholinergic system in patients with suspected or known cholinergic system degeneration.

Targeting hippocampal hyperactivity with real-time fMRI neurofeedback: protocol of a single-blind randomized controlled trial in mild cognitive impairment.

BACKGROUND: 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. 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. METHODS: In 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. DISCUSSION: Results 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 REGISTRATION: The study has been registered with clinicaltrials.gov on the 16th of July 2019 (trial identifier: NCT04020744 ).