Functional MRI signals can misrepresent true brain activity

Functional MRI signals can misrepresent true brain activity

Researchers at the Technical University of Munich (TUM) and the Friedrich-Alexander University Erlangen-Nuremberg (FAU) found that an increased fMRI signal is associated with reduced brain activity in around 40 percent of cases. At the same time, they observed reduced fMRI signals in regions with increased activity.

This contradicts the long-standing assumption that increased brain activity is always accompanied by increased blood flow to meet higher oxygen requirements. Since tens of thousands of fMRI studies worldwide are based on this assumption, our results could lead to opposite interpretations in many of them.”

Dr. Samira Epp, first author

Test items reveal deviations from the standard interpretation

PD Dr. Valentin Riedl, now a professor at FAU, and his colleague Epp examined more than 40 healthy participants during their time at TUM. Each was given several experimental tasks—such as mental arithmetic or retrieving autobiographical memories—that are known to elicit predictable fMRI signal changes in distributed brain regions. During these experiments, researchers simultaneously measured actual oxygen consumption using a novel quantitative MRI technique.

The physiological results varied depending on the task and brain region. Increased oxygen consumption – for example in the calculation areas – was not accompanied by the expected increase in blood flow. Rather, the quantitative analyzes showed that these regions met their additional energy needs by withdrawing more oxygen from the unchanged blood supply. This allowed them to use the oxygen present in the blood more efficiently without the need for increased blood flow.

Implications for the interpretation of brain disorders

According to Riedl, these findings also impact the interpretation of research results on brain diseases: "Many fMRI studies on psychiatric or neurological diseases - from depression to Alzheimer's - interpret changes in blood flow as a reliable signal of neuronal under- or over-activation. Given the limited significance of such measurements, this now needs to be re-evaluated. Particularly in patient groups with vascular changes - for example due to aging or vascular diseases - the measured values ​​can primarily reflect vascular differences and not neuronal deficits." Previous animal studies already point in this direction.

The researchers therefore propose complementing the traditional MRI approach with quantitative measurements. In the long term, this combination could form the basis for energy-based brain models: Instead of showing activation maps based on assumptions about blood flow, future analyzes could show values ​​that indicate how much oxygen - and therefore energy - is actually used to process information. This opens up new perspectives to examine – and understand more precisely – aging, psychiatric or neurodegenerative diseases with regard to absolute changes in energy metabolism.

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