The hippocampus (HIP) and adjacent entorhinal cortex (EC) form a neural circuit within the medial temporal lobe (MTL) that is crucial for memory formation. Integrity of this circuit is massively affected by age-related degeneration, often accompanied by MTL pathology. One major question is which neural resources contribute to the preservation and/or vulnerability of this circuit for age-related degeneration and associated behavioural decline. The hippocampal vascularization patterns vary among individuals. In fact, there are individuals with a single supply, and there are individuals with a double vascular supply. We recently found that a double hippocampal supply benefits verbal memory and global cognition in older adults with age-related small vessel pathology. This indicates a positive influence of the double hippocampal supply on hippocampal functioning in older adults with age-related brain pathology. However, many questions remain: ‘How does a double supply contribute to neural resources in the MTL?’, ‘How does a double versus a single hippocampal supply affect cognition in younger adults, older adults, and SuperAgers?’, and ‘Does a double hippocampal supply aid training-related neuronal plasticity and cognitive transfer?’. We will use hippocampal vascularization patterns in these studies as a model system to understand how vascularization influences neural resources, resilience, resistance, and transfer in younger and older adults (cf. Fig. 1 for definitions). We will combine ultra-high resolution functional and structural magnetic resonance imaging at 7 Tesla with advanced modelling techniques to investigate how the fine-grained hippocampal vascular supply affects age-related pathology (e.g. tau, cerebral small vessel disease) or neural resources in MTL and how this mediates MTL-dependent cognitive performance, such as spatial memory. We will also test for global effects of hippocampal vascular supply patterns on pathology (e.g. amyloid, whole brain tau, cerebral small vessel disease) and neural resources, and transfer to other cognitive domains. Finally, we will test how the effect of cognitive interventions on MTL neural resources is modified by the hippocampal vascularisation patterns.

Hippocampal vascularization patterns  Contribution of one (PCA) or two arteries (PCA, AchA) to hippocampal vascular supply

Resilience
Preserved cognitive performance or neural resources  in the face of pathology

Pathology
Tau, cerebral small vessel disease, amyloid
Resistance
Avoidance of pathology

Neural resources
Volume, layer- and region-dependent myeloarchitecture, perfusion/blood flow

Transfer
Benefit of vascularisation pattern and cognitive training for non-spatial tasks

Conceptual framework of the project:

B04 aims at taking the influence of hippocampal vascularization patterns on human cognition as a model system to understand the underlying neural resources. PCA = posterior cerebral artery, AchA = anterior choroidal artery. Double supply is existent when both the PCA and the AchA contribute to the hippocampal