Effects of hippocampal vascularization patterns on the neural resources of MTL neurocognitive circuits

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

Dr. Esther Kühn

Dr. Anne Maass

Prof. Dr. med. Stefanie Schreiber

Dr. Esther Kühn

Esther Kühn is head of the Research Group “Cortical Microstructure in Health and Disease” at the Institute for Cognitive Neurology and Dementia Research at the Medical Faculty. She investigates adaptive and maladaptive changes in the cortical microstructure of the human sensorimotor system that she investigates using ultra-high field magnetic resonance imaging in combination with behavioral assessments. Her research aim is to understand and treat maladaptive brain states of the sensorimotor system, in particular those in advanced age, in mental illness, and in conditions of motor disorders. She contributes to the CRC by her expertise in the areas of mesoscale imaging using 7T-MRI, mesoscale data modelling, and the biological interpretation of MR-based tissue contrast.

Institut:Otto von Guericke University Magdeburg, Medical Faculty

Project Title:B04 Effects of hippocampal vascularization patterns on the neural resources of MTL neurocognitive circuits

:Z02 Human imaging at meso-scale

Dr. Anne Maass

Dr. Anne Maass is a group leader at the DZNE (since 2019) and her work focuses on the use of Multimodal neuroimaging techniques for understanding how brain function changes in aging and age-related disease, such as Alzheimer’s disease (AD). In her previous work, she used ultra-high resolution functional MRI to investigate memory pathways in the medial temporal lobe and its plasticity in the human brain in aging and disease. During her Post Doc at UC Berkeley, she combined functional MRI with molecular imaging (PET), which allows to assess AD pathology, to investigate how early tau and amyloid-beta pathology affects memory function, ultimately resulting in memory deficits. At the DZNE she now combines different neuroimaging techniques to better understand what drives the accumulation of age-related pathology (e.g. aberrant activation) and why some people do not develop pathology (are resistant) or why others remain cognitively normal in face of pathology (are resilient). Within the SFB1436 she leads the Z03 project together with Prof. Düzel and Prof. Kreissl as well as the project B04 together with Esther Kühn and Stefanie Schreiber (Co-PI: Nadine Diersch).

Institut:German Center for Neurodegenerative Diseases, Magdeburg

Project Title:B04 Effects of hippocampal vascularization patterns on the neural resources of MTL neurocognitive circuits

:Z03 Human molecular imaging ageing and SuperAgeing cohort

Prof. Dr. med. Stefanie Schreiber

As a clinician scientist my main research interest is the often devastating cerebral small vessel disease (CSVD) which, by causing a deterioration of the cerebral small vessels, leads to a cascade including impaired blood supply, blood-brain-barrier breakdown and reduced solute removal, facilitating cognitive impairment in later stages. Our experimental work is aimed at the identification of key neuropathologic mechanisms of earlier disease stages in animal models. Based on those insights we study a locally established cohort of CSVD patients to derive innovative markers of disease risk and progression using multimodal imaging, biofluids and cognitive testing that will enable new options for prevention, diagnostic and treatment of CSVD patients.

Institut:Otto von Guericke University Magdeburg, Medical Faculty

Project Title:B04 Effects of hippocampal vascularization patterns on the neural resources of MTL neurocognitive circuits

Co-Workers

Dr. Berta Garcia Garcia

Dr. Dayana Hayek

Dr. Solveig Jandke

Christoph Knoll

Lilli Marie Lümkemann

Jonas Maquardt

Niklas Vockert

Dr. Berta Garcia Garcia

Berta Garcia-Garcia is a nuclear medicine physician. During Medical School, she was recruited by the Anatomy, Histology, and Neuroscience Department at the Autonomous University of Madrid to initiate herself on the most used methodological procedures in medical research, leading to a five year-long cooperation agreement focused on ex vivo brain mapping. She graduated later as a medicine specialist at the Nuclear Medicine Department in Pamplona (Spain), whose latest cyclotron-related techniques let her get acquainted with radioactive-based in vivo brain assessment. Her current work takes place at the DZNE and the Universitätsklinikum Magdeburg. Among others, she collaborates actively in many research projects mainly with the Multimodal Neuroimaging and the Mixed Cerebral Pathology and Cognitive Ageing research groups while performing PET/MR studies with various radiotracers, acting as a radiation protection officer as well. Her research work is subspecialized in evaluating brain metabolism spectrum from normal ageing to risk stages of Alzheimer’s Disease towards Alzheimer’s Disease, and in the analysis of cerebral vascularization regarding cognitive status. Due to the potential implications of the latter, she is currently basing her doctoral dissertation on it for the attainment of the Dr. med. degree in Germany.

Dr. Dayana Hayek

coming soon

Institut:Otto von Guericke University Magdeburg, Medical Faculty

Dr. Solveig Jandke

Since my doctorate in neuroscience, I am working as a postdoc in the Department of Neurology at the OvGU Magdeburg in the field of human/experimental cerebral small vessel disease. We investigate the connection of blood-brain-barrier disruption/vascular wall damage/enlarged perivascular spaces with extracellular matrix changes, neurovascular unit damage and associated (perivascular) inflammation. Additionally, we want to uncover which microvascular reserve mechanisms play a role in the aging process and the accelerated aging process (in hypertension) and how they affect the development of other pathologies (e.g. Alzheimer’s) and cognitive deficits.

Christoph Knoll

“Ingenuity, excellence and continual learning” – these three words sum up my passion for the field of Cognitive Neuroscience and Sport Science. In my PhD, I aim to develop a research profile within the field of Cognitive Neuroscience and Microstructural Imaging that investigates in brain vasculature and connected ccognitive changes. I aspire to gain practical insights about the best spatial resolution system of 7 Tesla magnetic resonance imaging.

Lilli Marie Lümkemann

coming soon

Jonas Maquardt

Since May 2021 I am working as a PhD student at the German Center for Neurodegenerative Diseases in the collaborative research unit on project B04. I have a degree in psychology and I am particularly interested in cognitive science & neuroscience. Thematically, I am fascinated by neuroplasticity, spatial navigation, digital markers for cognitive health, and machine learning.

Niklas Vockert

I am a PhD student at the DZNE with a background in mathematical and computational modeling of biological processes. Nowadays, I generally investigate reserve (e.g. cognitive reserve, resistance, resilience) in the context of aging and disease with the use of multimodal neuroimaging techniques. For the most part my focus lies on the relationship between hippocampal vascularization and behavioral, structural as well as functional measures, which I will also analyze in the context of subproject B04 in this CRC.

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.

Publications of the project B04