New study links brain connectivity patterns to early cognitive decline in depression

Many people living with depression describe the same unsettling feeling: memory slips, words that won’t come, or a mind that feels slower than before. Doctors have long struggled to capture these complaints in a brain scan. In a new study in Translational Psychiatry (Nature portfolio), SciLifeLab Fellow Adil Mardinoglu and colleagues set out to see if that was possible.

The researchers used a method called dispersion entropy, basically a way of tracking how busy and variable the brain’s activity is. A bit like watching traffic flow through a city: some streets are crowded, some empty, patterns shifting every moment.

“We combined brain entropy mapping with functional connectivity analyses to reveal how alterations in the superior temporal gyrus and insula relate to subjective cognitive complaints in patients with depression,” says Adil Mardinoglu, SciLifeLab Fellow and associate professor at KTH.

They put 31 patients with depression and 28 healthy participants in an fMRI scanner for 12 minutes each. Then they used dispersion entropy to measure the brain’s “temporal complexity”, basically, how varied and active the signals were during that time.

The results stood out

Patients who reported memory problems had changes in parts of the brain that help make sense of the world and of ourselves. One area, the superior temporal gyrus, helps us understand language and sounds. Another, the insula, helps us notice how we feel inside and respond to it.

When these areas aren’t communicating normally, it can create conflicts with our everyday thinking skills: planning ahead, paying attention, or juggling multiple tasks.

So what does this mean?

Mardinoglu and his co-authors suggest these measures could one day serve as biomarkers, measurable brain signals that point to cognitive problems in depression. But at the same time, they emphasize that the study is small and needs to be followed up. 

“Our findings show that changes in brain entropy and connectivity in the superior temporal gyrus and insula may serve as early biomarkers of cognitive dysfunction in depression, paving the way for more precise diagnostic tools and targeted interventions. Future studies should track these changes over time and test whether therapies that normalize these brain patterns can improve cognitive outcomes”, Mardinoglu concludes.

The study opens the door to turning subjective complaints into something doctors can actually see, a first step toward more personalized assessment and management.

DOI: 10.1038/s41398-025-03518-w

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