For over three years, I’ve been investigating the complex web of illnesses we now classify under long COVID, ME/CFS, and fibromyalgia. These conditions are often misunderstood and frequently dismissed. What ties them together? That’s the question that has driven my recent focus.
A new study out of Spain has brought clarity. Researchers examined individuals with post-COVID condition using MRI and neurocognitive tests, and the results are both fascinating and concerning.
Those with long COVID performed significantly worse on tests of working memory, verbal fluency, and executive function. But the most striking finding came from their brain scans.
They showed increased cortical thickness in regions of the brain that are typically thinner in neurodegenerative diseases.
Why does that matter? Cortical thickness reflects the grey matter of the brain, where the neurons live. More thickness may sound good, but in this context, it's likely the result of inflammation, not enhancement. Thicker cortex, worse function.
They also found changes in the white matter, the brain’s communication wiring, using diffusion tensor imaging. Think of it as damaged insulation on electrical cables. Signals don't travel properly.
Pacheco-Jaime, Laura, et al. "Structural brain changes in post-COVID condition and its relationship with cognitive impairment." Brain Communications 7.1 (2025): fcaf070.
These changes were most prominent in areas with high blood flow, suggesting a link to microvascular damage. We know COVID-19 can damage the endothelial lining of blood vessels. This could explain the inflammation observed in the brain.
One mechanism stands out. Ongoing activation of macrophages. These immune cells seem stuck in high gear, unable to switch off. And when that inflammatory state takes hold in the brain, it disrupts key circuits involved in memory, regulation, and awareness.
One population of neurons may be especially vulnerable, the von Economo neurons. These large, fast-acting cells connect distant parts of the brain. If they’re damaged, it could explain much of the brain fog and disconnection patients report.
None of this is meant to alarm. It’s meant to clarify. Understanding the mechanism brings us closer to treatment.
The road is long, but the path is clearer.
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