Summary: Have you ever felt completely lost when you’re stressed? It isn’t just a lack of focus—it’s a biological “jamming” of your internal GPS. Researchers have discovered that the stress hormone cortisol directly disrupts grid cells in the entorhinal cortex.
These cells are responsible for spatial orientation and mapping. In an MRI-monitored virtual navigation task, participants who received cortisol performed significantly worse, as their brain’s precise “grid” activity became blurred and indistinct, forcing the brain to rely on less efficient backup systems.
Key Facts
- The “Grid Cell” Failure: Grid cells in the entorhinal cortex act as a coordinate system for the brain. Cortisol causes these cells to fire in a “fuzzy” or indistinct pattern, effectively erasing the internal map.
- Landmark vs. Luck: The navigation failure was most severe in environments devoid of landmarks, where the brain has to rely entirely on its internal sense of direction (path integration).
- The “Backup” System: When the primary GPS (entorhinal cortex) failed, the brain showed increased activity in the caudate nucleus, suggesting a desperate attempt to use alternative, less effective strategies to find the way back.
- Alzheimer’s Link: The entorhinal cortex is one of the first regions damaged by Alzheimer’s. Since chronic stress is a risk factor for dementia, this study identifies a mechanism for how stress hormones destabilize this vulnerable region.
Source: RUB
The stress hormone cortisol disrupts the brain’s navigational system. It impairs the function of the grid cells that play a crucial role in orientation. This has been verified by researchers from Ruhr University Bochum, Germany, in an imaging study with 40 individuals.
The participants completed a virtual navigation experiment while their brain activity was recorded in an MRI scanner. If the subjects had received cortisol prior to the experiment, they performed more poorly and the exact activity pattern of the grid cells became indistinct.
The results were published online in the journal PLOS Biology on March 12, 2026.
It is well known that stress influences human behavior and thinking, but it was mostly unclear how cortisol disrupts the circuits in the brain responsible for navigation. A team working with Dr. Osman Akan from the Ruhr University Bochum, Department of Cognitive Psychology, and colleagues from the Department of Neuropsychology, as well as researchers from University Hospital Hamburg-Eppendorf, set out to investigate this very question.
Virtual orientation test in the MRI scanner
40 healthy men took part in the experiment, each on two different days. On one day, the subjects received 20 milligrams of cortisol; on the second day, they were given a placebo. On each day, they took an orientation test while their brain activity was recorded in the MRI scanner.
For the test, the subjects were placed in a vast, virtual meadow landscape, where they had to move toward various trees in succession that disappeared upon arrival. They then had to find the direct path back to the starting point without any indication of where the path could be. In one part of the test, the environment was entirely devoid of permanent landmarks, featuring only the trees as temporary targets. In another part, a lighthouse served as a permanent reference point.
Orientation worsened under the influence of cortisol
Cortisol significantly worsened the participants’ orientation. Compared with the results after taking the placebo, they made far greater errors in finding their destinations regardless of any spatial landmarks or the complexity of the path.
Neuronal coordinate system fails under stress
The influence of cortisol was also evident in the functional MRI recordings. Without any influence from cortisol, a subset of nerve cells in the entorhinal cortex fire in a grid pattern during spatial orientation tasks, hence their name “grid cells.” They make up humans’ internal GPS system, so to speak.
The grid cells’ activity pattern became less distinct under the influence of cortisol. In particular, when navigating environments without any landmarks, the cells had virtually no function. “Under stress, the brain loses the ability to effectively utilize its internal navigation maps,” explains Akan.
The researchers noticed that cortisol also led to increased activation in another area of the brain, the caudate nucleus. “This indicates that the brain is trying to compensate for the loss of the main navigation system in the entorhinal cortex through alternative strategies,” says Akan.
Significance for understanding Alzheimer’s disease
The entorhinal cortex is one of the first regions of the brain that Alzheimer’s disease affects. “Because chronic stress is a risk factor for dementia, our study reveals a critical mechanism for how stress hormones destabilize this sensitive region,” explains Akan.
Key Questions Answered:
A: Because your brain’s “coordinate system” has been blurred. Cortisol—the hormone your body releases during stress—acts like static on a radio. It makes the firing pattern of your grid cells “smudgy,” so your brain can no longer pinpoint exactly where you are in relation to where you started.
A: The study found that the brain tries to compensate by using the caudate nucleus. However, this is like trying to navigate a city using a list of turn-by-turn directions instead of a map; it’s much harder and more prone to error, especially if you don’t have a lighthouse or a landmark to look at.
A: In this study, the effect was temporary (based on a single dose of cortisol). However, the researchers warn that chronic stress keeps these levels high, which can lead to long-term destabilization of the entorhinal cortex—the very area that is first attacked by Alzheimer’s disease. Managing stress isn’t just about “feeling better”; it’s about protecting your brain’s hardware.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this stress and neuroscience research news
Author: Julia Weiler
Source: RUB
Contact: Julia Weiler – RUB
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Cortisol Treatment Impairs Path Integration and Alters Grid-like Representations in the Male Human Entorhinal Cortex” by Osman Akan, Varnan Chandreswaran, Henry D. Soldan, Anne Bierbrauer, Nikolai Axmacher, Oliver T. Wolf, and Christian J. Merz. PLOS Biology
DOI:10.1371/journal.pbio.3003661
Abstract
Cortisol Treatment Impairs Path Integration and Alters Grid-like Representations in the Male Human Entorhinal Cortex
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.
The entorhinal cortex contains glucocorticoid receptors and is therefore likely to be influenced by cortisol, though little is known about this relationship. Given the role of the entorhinal cortex 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 39 healthy men across two sessions.
On each day, they received either 20 mg cortisol or a placebo and performed a virtual homing task during functional magnetic resonance imaging (fMRI).
Cortisol markedly impaired path integration performance, independent of incoming distance or the presence of spatial cues, but did not affect navigational pattern as measured by proximity to the landmark. 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 entorhinal cortex specifically on day one under placebo, but these were diminished by cortisol.
Grid-like representations were associated with PI performance dependent on the availability of spatial cues and cortisol administration, suggesting that cortisol may interfere with the typical relationship of grid cells and PI.
Overall, the study indicates that cortisol-induced disruption in grid cell function in the entorhinal cortex may underly stress effects on path integration.
