Quantitative modeling of the emergence of macroscopic grid-like representations

Grid cells are neurons in the entorhinal cortex that play a key role in spatial navigation. When subjects navigate through spatial environments, grid cells exhibit firing fields that are arranged in a triangular grid pattern. As direct recordings of grid cells from the human brain are only rarely possible, functional magnetic resonance imaging (fMRI) studies proposed and described an indirect measure of entorhinal grid-cell activity, which is quantified as a hexadirectional modulation of fMRI activity as a function of the subject’s movement direction. However, it still remains unclear how the activity of single grid cells is related to the sum activity of a population of grid cells, which may exhibit hexadirectional modulation and thus provide the basis for the hexadirectional modulation of entorhinal cortex activity measured with fMRI. Here, we thus performed numerical simulations and analytical calculations to better understand how the aggregated activity of many grid cells may be hexadirectionally modulated. Our simulations implemented three different hypotheses proposing that the hexadirectional modulation occurs because grid cells show head-direction tuning aligned with the grid axes; are subjected to repetition suppression; or exhibit a bias towards a particular grid phase offset. Our simulations demonstrate that all three hypotheses can, in principle, lead to a hexadirectional modulation of sum grid-cell activity. However, the magnitude of the hexadirectional modulation appears to depend considerably on the subject’s navigation pattern and the exact biological properties of grid cells. Our results thus indicate that future fMRI studies could be designed to test which of the three hypotheses most likely accounts for the fMRI measure of grid cells. These findings also underline the importance of quantifying the biological properties of single grid cells in humans to further elucidate how hexadirectional modulations of fMRI activity may emerge.