Summary: Have you ever felt disoriented under stress? It’s not just mental fog—stress hormones can interfere with the brain’s internal navigation system. New imaging research shows that cortisol directly blurs the activity of grid cells in the entorhinal cortex, the neurons responsible for mapping space and tracking position.
In an MRI-monitored virtual navigation task, participants who received cortisol performed worse: the precise, grid-like firing patterns normally seen in the entorhinal cortex became indistinct. As those internal maps degraded, the brain shifted to less efficient strategies, increasing activation in other regions such as the caudate nucleus.
Key Facts
- Grid cell disruption: Grid cells in the entorhinal cortex form a neural coordinate system for spatial orientation. Cortisol causes their firing patterns to become fuzzy, reducing the brain’s ability to maintain a stable internal map.
- Landmarks matter: The impairment was strongest in landmark-free environments, where navigation depends solely on internal path integration rather than external cues.
- Compensatory activation: When the entorhinal grid system failed, activity rose in the caudate nucleus, indicating the brain attempted to use alternative, less accurate navigation strategies.
- Relevance to Alzheimer’s disease: The entorhinal cortex is among the first regions affected in Alzheimer’s. Since chronic stress and elevated cortisol are risk factors for dementia, these findings point to a mechanism by which stress hormones may destabilize a vulnerable brain region.
Source: RUB
Research summary: Researchers at Ruhr University Bochum and collaborating institutions used functional MRI to test how cortisol affects spatial navigation and the neural grid code in humans. Forty healthy male participants completed a virtual homing task in the scanner on two separate days: once after taking 20 mg of cortisol and once after taking a placebo. The experiment compared performance and brain activity across landmark-rich and landmark-free virtual environments.
The study, published online in PLOS Biology on March 12, 2026, shows that cortisol impaired participants’ ability to find the direct route back to their starting point. Errors increased significantly after cortisol administration regardless of path complexity or the presence of some landmarks, but the effect was most pronounced when permanent reference cues were absent.
Virtual orientation test in the MRI scanner
During the task, participants moved through a wide virtual meadow and walked to successive trees that disappeared upon arrival. They then had to return directly to their original starting location without visible guidance. In one condition a permanent landmark such as a lighthouse was present; in the other, the scene contained only transient targets, forcing reliance on internal path integration.
Behavioral and neural effects of cortisol
Cortisol substantially worsened navigational accuracy compared with placebo. The fMRI results clarify why: grid-like representations in the right entorhinal cortex — normally visible in representational similarity analyses — were diminished after cortisol. In landmark-free conditions the grid signal was nearly absent, consistent with the largest behavioral deficits occurring when internal orientation alone was required.
Simultaneously, cortisol increased activity in the right caudate nucleus, particularly when landmarks were present. The authors interpret this as the brain recruiting a different, habit- or response-based system to compensate for the failing entorhinal map. That backup strategy is less precise and more error-prone than an intact grid-cell-based system.
Implications for stress, aging and dementia
Because the entorhinal cortex expresses glucocorticoid receptors and is among the first sites affected in Alzheimer’s disease, cortisol-induced disruption of grid cell activity could help explain how prolonged stress increases dementia risk. The current experiment used an acute cortisol dose and demonstrates reversible functional changes; however, chronic elevation of stress hormones may have longer-lasting consequences for the integrity of entorhinal circuitry.
Key Questions Answered:
A: Cortisol blurs the brain’s internal coordinate system. The hormone makes grid cell firing less distinct, so the brain cannot accurately determine its position relative to a starting point.
A: The brain attempts to compensate by activating other regions such as the caudate nucleus, but these alternative strategies are less efficient and more error-prone, especially without clear external landmarks.
A: This study examined the temporary effects of a single cortisol dose. While those effects were reversible, prolonged or chronic stress can keep cortisol levels elevated over time and may contribute to long-term weakening of entorhinal circuits implicated in dementia.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- The journal paper was reviewed in full by the editorial team.
- Additional context and clarification were added by staff for readability.
About this stress and neuroscience research news
Author: Julia Weiler
Source: RUB
Contact: Julia Weiler – RUB
Image credit: 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 produces a rise in cortisol that affects many cognitive functions. Path integration — the ability to track position by integrating self-motion cues — relies on grid cells in the entorhinal cortex. Because this region contains glucocorticoid receptors and is vulnerable in neurodegenerative disease, understanding how cortisol influences entorhinal function is important.
In this study of 39–40 healthy male participants tested across two sessions, each subject received 20 mg of cortisol on one day and a placebo on another day while performing a virtual homing task during fMRI. Cortisol substantially impaired path integration performance regardless of travel distance or the presence of spatial cues, and fMRI showed an increase in right caudate activation when landmarks were available.
Representational similarity analysis revealed grid-like representations in the right entorhinal cortex under placebo conditions on the first testing day; these representations were reduced after cortisol administration. The association between grid-like signals and path integration performance depended on cue availability and cortisol, suggesting cortisol disrupts the normal relationship between grid cell coding and navigational accuracy.
Overall, the findings indicate that cortisol-induced disruption of grid cell function in the entorhinal cortex may underlie acute stress-related impairments in human path integration and point to mechanisms that could contribute to long-term vulnerability of this region in stress-related cognitive decline.