B04
The hippocampus is critical for memory formation, but is also particularly susceptible to age-related degeneration and exhibits inter-personal variability in terms of its vascular supply. In our project, we want to find out how the vascularization pattern of the hippocampus affects age-related pathology, neural resources, and cognitive abilities.
Principal Investigators
Prof. Dr. Esther Kühn
Prof. Dr. Anne Maass
Prof. Dr. med. Stefanie Schreiber
Co-Workers
Dr. Nadine Diersch
Erelle Fuchs
Dr. Berta Garcia Garcia
Dr. Solveig Jandke
Christoph Knoll
Jonas Marquardt
Niklas Vockert
Why focus on the medial temporal lobe?
The medial temporal lobe (MTL) contains, among other brain regions, the hippocampus and the adjacent entorhinal cortex. These two areas form a neuronal circuit, which is significantly involved in the formation of episodic memory and spatial navigation. At the same time, the MTL is particularly affected by both normative and pathological age-related changes. Alzheimer’s disease-related tau protein accumulation in the MTL, independent of atrophy or beta-amyloid accumulation, explains approximately 20% of the variance concerning episodic memory performance in healthy elderly subjects (Maass et al., 2018). However, it is unclear which neural resources in the MTL can explain the larger amount of unexplained variance in episodic memory performance. The term neural resource generally refers to structures and/or processes in the brain (e.g. higher blood flow, volume, or myelin) that can affect cognition and vary between individuals.
One promising factor:
the hippocampal
vascularization pattern
The hippocampus can be supplied by both the anterior choroidal artery and the posterior cerebral artery (Erdem et al., 1993, Marinkovic et al., 1992). Some individuals have an augmented hippocampal supply (both arteries), whereas others only have a basic supply (only supplied by the posterior cerebral artery), which has been confirmed using high-resolution imaging in vivo (Perosa et al., 2020; Spallazzi et al., 2019). An augmented supply is associated with several benefits, including improved cognitive performance and increased hippocampal volume (Perosa et al., 2020, Vockert et al., 2021). Recent research suggests that the hippocampal vascularization pattern may play a key role in age-related MTL degeneration, cognitive decline, and training-induced plasticity; however, the underlying neural mechanisms remain yet to be identified
The aims of our project
The main goal of our project is to characterize the underlying neural resources that mediate the benefits of an augmented versus a basic vascular supply of the hippocampus on cognitive performance. For this purpose, we use multi-modal imaging techniques such as positron emission tomography, 3Tesla magnetic resonance imaging (MRI), and 7Tesla MRI. Among other aims, we will investigate how the difference in the vascular supply of the hippocampus affects the myelination of specific cortical layers in the MTL, regional blood flow and the volume of MTL areas. In addition, we will determine how augmented versus basic hippocampal vascularization affects individual learning behavior. Furthermore, we will investigate whether individuals with an augmented compared to a basic supply benefit more from cognitive training. To date, it is still unclear how the hippocampal vascularization pattern affects neural resources and cognitive performance in younger individuals, as previous research has only examined the influence of the hippocampal vascularization pattern in older individuals. Additionally, we highlight the concepts of resilience, resistance, and neural resources in our research.
Resilience, resistance, and neural resources.
The hippocampal vascularization pattern could have an influence on a wide variety of neural resources, including the volume of different MTL structures, layer-specific myelin, or blood flow in certain MTL areas. It is further important to distinguish between the two concepts of resilience and resistance. Resistance is defined as the ability to withstand pathology (e.g. to not accumulate abnormal tau protein), whereas resilience describes the preservation of cognitive performance in presence of pathology. Our project aims to determine whether the hippocampal vascularization pattern constitutes a factor for resistance or resilience.
Hippocampal vascularization patterns in younger & older individuals
Since only the influence of vascularization patterns on cognitive performance and neuronal resources in older individuals has been studied so far (Perosa et al., 2020; Vockert et al., 2021), our goal is to explore the effects of hippocampal vascularization patterns in younger adults as well. The influence on neuronal resources in the MTL with respect to the vascularization pattern in younger individuals will be examined using high-resolution imaging techniques. A focus will be on the blood supply to specific MTL areas, myelination of specific cortical layers, and functional connectivity analysis. In addition, the extent to which the hippocampal vascularization pattern affects memory and how this may be mediated by neuronal resources will also be explored. Comparable research questions will also be investigated in older individuals, but additional age-related Alzheimer’s disease pathology (amyloid-beta & tau protein) will be investigated. It will be examined whether the hippocampal vascularization pattern can lead to resistance (less pathology in the presence of augmented vascularization pattern) or resilience (unchanged cognition in the presence of pathology due to an augmented vascularization pattern). After two years, certain measurements will be repeated in some older individuals to examine the extent to which the hippocampal vascularization pattern affects age-related changes in cognition and changes in neural resources.
Hippocampal vascularization patterns and training-induced change
Brain areas that are fundamental for spatial navigation are also first affected by neurodegenerative diseases like dementia (Braak & Del Tredici, 2015, Coughlan et al., 2018). Therefore, we will conduct spatial navigation training over several weeks to assess the effect of the hippocampal vascularization pattern on navigational performance and MTL plasticity. Previously, exercise training over several months has been shown to have a positive effect on hippocampal blood flow and memory in older individuals (Maass et al., 2015). However, large differences between subjects were found, which might be explained by age-related pathology or hippocampal vascularization pattern. Therefore, we will explore how these factors affect training-induced plasticity of the MTL and cognitive performance in the elderly. We aim to determine whether an augmented compared to a basic hippocampal vascular supply leads to higher cognitive improvements from training. These findings could later be used to develop individually tailored training interventions.
