The relationship between cortisol, grid-like representations and path integration

Acute stress triggers the release of cortisol, which broadly affects cognitive processes. Path integration, a specific navigational process, relies heavily on grid cells in the entorhinal cortex (EC). The EC contains glucocorticoid receptors and is therefore likely to be influenced by cortisol, though little is known about this relationship. Given the role of the EC in neurological diseases such as Alzheimer’s Disease, investigating the effects of cortisol on this brain region may offer insights into how stress affects these diseases. In this study, we examined the effects of cortisol on human path integration in thirty-nine healthy participants across two sessions. On each day, they received either 20mg cortisol or a placebo and performed a virtual homing task during functional magnetic resonance imaging (fMRI). Cortisol markedly impaired path integration performance, independent of path distance or the presence of spatial cues. Additionally, cortisol altered navigational strategies, leading participants to navigate further away from landmarks, which was associated with worse performance. FMRI results showed that cortisol increased the activation of right caudate nucleus in the presence of landmarks. Using a representational similarity analysis, we observed grid-like representations in the right posterior-medial EC specifically on day one under placebo, but these were diminished by cortisol. Grid-like representations facilitated performance over short distances but hindered it over longer ones, suggesting that grid cells support PI specifically in case of short trajectories. Overall, the study indicates that cortisol-induced disruption in grid cell function in the EC may underly stress effects on path integration.