Evidence for grid cells in a human memory network

Abstract

The discovery by Edvard Moser and colleagues that rats and mice possess an orientation map of their surroundings, produced and updated by a network of cerebral cortex neurons known as 'grid cells' was one of the most exciting neuroscientific findings in recent years. These cells provide a strikingly periodic representation of self-location. The question naturally arises, does a similar mechanism operate in humans? The answer is provided in a paper by Christian Doeller, Caswell Barry and Neil Burgess in which single-unit recordings of grid cells in freely moving rats were combined with whole-brain functional magnetic resonance imaging (fMRI) in humans navigating within virtual environments. Doeller et al. were able to detect a macroscopic fMRI signal representing a subject's position in a virtual reality environment that met the criteria for defining grid-cell encoding. Thus, humans appear to represent position and support spatial cognition in a manner very like that used by rodents. Rodents have an orientation map of their surroundings, produced and updated by a network of neurons in the entorhinal cortex known as 'grid cells'. However, it is currently unknown whether humans encode their location in a similar manner. Using functional magnetic resonance imaging in humans, a macroscopic signal representing a subject's position in a virtual reality environment is now detected that meets the criteria for defining grid-cell encoding. Grid cells in the entorhinal cortex of freely moving rats provide a strikingly periodic representation of self-location1 which is indicative of very specific computational mechanisms2,3,4. However, the existence of grid cells in humans and their distribution throughout the brain are unknown. Here we show that the preferred firing directions of directionally modulated grid cells in rat entorhinal cortex are aligned with the grids, and that the spatial organization of grid-cell firing is more strongly apparent at faster than slower running speeds. Because the grids are also aligned with each other1,5, we predicted a macroscopic signal visible to functional magnetic resonance imaging (fMRI) in humans. We then looked for this signal as participants explored a virtual reality environment, mimicking the rats’ foraging task: fMRI activation and adaptation showing a speed-modulated six-fold rotational symmetry in running direction. The signal was found in a network of entorhinal/subicular, posterior and medial parietal, lateral temporal and medial prefrontal areas. The effect was strongest in right entorhinal cortex, and the coherence of the directional signal across entorhinal cortex correlated with spatial memory performance. Our study illustrates the potential power of combining single-unit electrophysiology with fMRI in systems neuroscience. Our results provide evidence for grid-cell-like representations in humans, and implicate a specific type of neural representation in a network of regions which supports spatial cognition and also autobiographical memory.