Why blood flow is not a reliable sign of the energy requirements of the brain

For almost three decades, functional magnetic resonance imaging (fMRI) has been one of the main instruments of brain research. However, a new study published in the renowned journal Nature Neuroscience is now questioning the conventional interpretation of data surrounding neuronal activity. In conjunction with their colleagues, Dr. Samira Epp and Dr. Valentin Riedl, both researchers at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), have now been able to demonstrate in their study that there is no generally applicable link between the oxygen levels measured in MRI scans and neuronal activity.

In their study, the researchers at Alexander-Universität Erlangen-Nürnberg (FAU) and Technische Universität München (TUM) discovered that in around 40 percent of cases an elevated fMRI signal is associated with lower brain activity. At the same time, they found low fMRI signals in regions with increased activity. Lead author Dr. Samira Epp emphasizes: “This contradicts the previously accepted assumption that increased brain activity is always associated with increased blood flow to meet the increased demand in oxygen. Since tens of thousands of fMRI studies worldwide are based on this assumption, our results could lead to contrasting interpretations.”

Tests show deviations from standard interpretations

Dr. Samira Epp and Dr. Valentin Riedl, Professor of Neuroimaging of Immunological and Metabolic Processes at the Institute of Neuroradiology at Uniklinikum Erlangen, performed their research with more than 40 healthy participants. They gave them various tasks to complete such as mental arithmetic or autobiographical memory tasks that lead to expected changes in signal in various regions of the brain in fMRI. During the scan, the researchers measured the actual oxygen consumption using a new quantitative MRI procedure.

Various physiological results were shown, depending on the task and region of the brain. An increase in oxygen consumption, for example in regions involved in arithmetic, did not correspond to the expected increase in blood flow. On the other hand, the quantitative evaluations showed that these areas of the brain met their additional energy requirements by increasing the amount of oxygen they extracted from the unchanged blood flow. They use the oxygen in the blood more efficiently, without requiring an increase in blood flow. Riedl put forward this theory several years ago and was awarded a Starting Grant for high-risk research from the European Research Council (ERC) for his work.

Effects on interpretation of brain diseases

According to Riedl, the findings will also have an effect on the results of research on brain diseases: “Many fMRI studies on psychiatric or neurological conditions from depression to Alzheimer’s interpret changes in blood flow as a reliable sign of neuronal under or over activation. This must now be re-evaluated due to the limited informative value of these results. Particularly in patient groups with vascular changes such as age-related or vascular diseases, the measurements could primarily be based on changes in the blood vessels themselves rather than on neuronal deficits.” This is what earlier results from animal experimentation suggest.

The researchers are therefore proposing that the conventional MRI method is supplemented by quantitative measurements. In the long term, this combination could form the basis for energy-based brain models. Instead of activation maps with assumptions about blood flow, the values would map how much oxygen and thus energy is actually being used for processing information. This opens up new ways of observing and improving our understanding of aging processes and psychiatric or neurodegenerative diseases from the standpoint of a completely altered energy metabolism.

DOI: https://www.nature.com/articles/s41593-025-02132-9

Download Bild: