The effects of a noradrenergic drug in the brain of patients with Mild Cognitive Impairment: a 7T fmri study based on relevant events.
Resting state assessments of functional brain connectivity help us understand population differences in brain function, such as a decline in communication between brain areas with ageing or in dementia. Classical functional brain connectivity methods struggle however, to assess connectivity which is more variable over time, which is likely the case in older or clinical populations. Here we use methods robust to these differences in variability by focusing on activations exceeding an activation threshold. In doing so, we use 7T imaging in patients with amnestic mild cognitive impairment (aMCI) under placebo or a noradrenergic drug to investigate in particular functional connectivity within the noradrenergic system, which is known to be affect in the early stages of Alzheimers.
Image extracted from: Cifre et al. 2021
Role of the LC/NE system in flexible learning: An MRI investigation
Our project explores the connection between arousal systems and cognitive flexibility, focusing on the crucial role of the locus coeruleus-norepinephrine (LC/NE) system in flexible behavior. A recent computational model has suggested that latent state reset mechanisms can account for a broad range of adaptive learning behaviors as well as the context-dependence of arousal indicators and learning. The purpose of this research project is to test the key projections of this model by investigating the role of the LC/NE system in regulating such latent states and how they affect behavior. A behavioral task and simultaneous pupillometry-fMRI recording will be used to look into the relationship between arousal signals, neural latent states, and behavior. The findings hold potential for developing LC/NE-targeted interventions that may help relieve the behavioral symptoms of psychiatric illnesses characterized by inflexible as well as inconsistent behavior.
Neural dynamics of sleep-wake regulation in aging
Sleep disruption is common in old age and sleep disturbances are a feature of neurodegenerative conditions, including Alzheimer`s disease. This study aims at understanding the neurobiological mechanisms underlying sleep impairments in aging. To this end, we use simultaneous EEG-fMRI to characterize patterns of brain (dys)function across the sleep stages. Furthermore, we investigate the association between functional and structural alterations of sleep-wake maintenance systems, cognitive decline, and neuropathology.
Changes in noradrenergic brain function in early stages of Alzheimer's
Postmortem data suggest that for reasons that are not yet known, the noradrenergic locus coeruleus is one of the brain structures earliest affected by brain pathologies in Alzheimer's disease. In this study, we investigate to what extent a functional and structural decrease in the locus coeruleus can be detected using non-invasive methods in the early stages of Alzheimer's dementia. For this we use functional magnetic resonance imaging, volumetric magnetic resonance imaging and cognitive tasks sensitive to changes in noradrenergic modulation.
Relevance of the noradrenergic system for maintaining cognitive functions in old age
Noradrenaline not only supports cognitive functions such as memory and attention, but also physiological brain functions such as regulation of blood flow or inhibition of inflammatory processes. In this project, we investigate whether the nordrenergic system in older adults who are exceptionally good at maintaining cognitive function, differs from that of typically aging older adults. We are also investigating to what extent a drug increase in noradrenaline can improve cognitive functions in old age.
Picture reference: Sclocco et al. 2018
Stimulation of the noradrenergic system as a therapeutic intervention in old age
A decrease in noradrenergic modulation with age is related to a decrease in cognitive functions such as remembering things. In this project we try to find out whether an increase in noradrenergic modulation by non-invasive vagus nerve stimulation is possible in old age and whether this can be accompanied by an increase in cognitive functions. The vagus nerve projects indirectly to the noradrenergic locus coeruleus in the brain and can be reached by a stimulator placed in the ear. To better understand the mode of action of the stimulator, we are closely coordinating with a partner project investigating physiological correlates of noninvasive vagus nerve stimulation in mice.
Dopaminergic modulation of memory consolidation in old age
A decrease in dopaminergic modulation with age is associated with a decrease in the ability to consolidate memory. In this study, we investigate whether a single dose of a drug that increases dopamine levels can improve the consolidation of memories in old age. Here we also use functional and structural brain imaging to investigate whether inter-individual differences in brain health with age can explain inter-individual differences in the effects of increasing dopamine levels.
Picture reference: Sclocco et al. 2018
Dopamine release in memory encoding in old age
In this study, we investigate whether reduced dopamine release in old age is associated with poorer memory function. For this purpose, we simultaneously measure functional brain activity using magnetic resonance imaging and endogenous dopamine release using positron emission tomography while participants work on a memory task. Furthermore, we use high-resolution functional imaging to track the activation of dopaminergic and noradrenergic nuclei in memory encoding.