Bernstein member involved: Nikolai Axmacher

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 fires 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.