A hierarchical coordinate system for sequence memory in human entorhinal cortex

Grid cells in rodent entorhinal cortex (EC) support a coordinate system for space, enabling robust memory and powerful flexibility in spatial behaviour. This coordinate system is abstract - with the same grid cells encoding position across different sensory environments; and hierarchical - with grid modules of increasing spatial scale occupying increasingly ventral locations in the EC. Recent theories suggest that a similar abstract coordinate system could offer the same benefits to general memories that are not sequences drawn from a 2D surface. Here we show that an abstract hierarchical coordinate system supports arbitrary sequences in the human medial temporal lobe (MTL). In single-unit recordings from MTL, we find abstract, coordinate-like coding of a simple sequential memory task. In an fMRI experiment with more complex hierarchical sequences, we discover an abstract hierarchical representation in EC: the coordinate representations at distinct levels in the hierarchy are arranged on an anatomical gradient along the EC’s anterior-posterior axis, homologous to the ventro-dorsal axis in rodents. These results therefore mirror the anatomical gradient of grid cells in the rodent EC but now for arbitrary non-spatial sequences. Together they suggest that memories are scaffolded on a hierarchical coordinate system using common neuronal coding principles, aligned to preserved anatomy, across domains and species.