marshall.dalton@sydney.edu.au

The hippocampus is critical for a range of cognitive functions, particularly episodic memory, with well-documented functional differences along its anterior–posterior axis. These functional gradients are thought to arise from underlying patterns of anatomical connectivity between the hippocampus and the rest of the brain. However, much of what we know about these connectivity patterns comes from tract-tracing studies in rodents and non-human primates. Due to technical limitations, the anatomical connectivity of the in vivo human hippocampus has remained poorly characterized, with efforts to map these connections in sufficient detail only recently becoming feasible.
In this talk, I will present findings from two experiments that utilize our newly developed precision tractography pipeline to map the anatomical connectivity of the in vivo human hippocampus with unprecedented detail. I will describe two key studies. First, using high-quality diffusion MRI data from the Human Connectome Project, we systematically assessed and quantified anatomical connections between the hippocampus and the cortical mantle. Second, using a high-resolution diffusion MRI dataset acquired at 760 μm isotropic resolution, we mapped the anatomical connections more specifically between the entorhinal cortex (EC) and hippocampus with exceptional spatial precision, revealing the complexity of these connections.
For both studies, we performed meticulous manual segmentation of the hippocampus and EC to ensure anatomical accuracy and implemented a tailored DWI processing pipeline specifically designed to map hippocampal connectivity. This pipeline enabled us to track streamlines into the hippocampus and generate ‘endpoint density maps’ using Track Density Imaging. These maps allowed us to quantitatively assess, visualise, and map the spatial distribution and density of streamline endpoints within the hippocampus corresponding to each cortical area.
Our results revealed striking patterns of preferential connectivity along the anterior–posterior and medial–lateral axes of the hippocampus. Importantly, we observed distinct patterns of connections between different cortical areas and specific hippocampal subfields. These findings provide new insights into the neuroanatomical architecture underpinning hippocampal-dependent memory systems in the human brain and highlight the structural heterogeneity of hippocampal connectivity along its anterior-posterior axis.