1: The BOLD signal is a complex representation of various hemodynamic processes. We used quantitative fMRI to measure all hemodynamic factors contributing to positive and negative BOLD signal changes.

2: We found inconsistent hemodynamic responses via blood flow (CBF) across the cortex and even within the same voxels, depending on task type and baseline oxygen extraction fraction (OEF).

3: Most voxels in the Default Mode Network (DMN) exhibited a paradoxical negative BOLD response to increased metabolism due to higher oxygen extraction instead of decreased blood flow.

4: In summary, we identified varying oxygen extraction as a novel hemodynamic response type to neuronal activity, leading to paradoxically inverse BOLD signal responses, particularly in the Default Mode Network.

5: BOLD-fMRI remains the most effective method for studying human brain activity. Yet, we might have to reconsider the regional interpretation of BOLD-signal changes in relation to neuronal activity.

6: Still, varying hemodynamic responses may offer new insights: -Does CBF regulation only kick in after the oxygen buffer is used? -Does OEF regulation indicate different signaling strategies or cell type metabolism? - Does oxygen availability indicate disease susceptibility?

7: Samira, @samomat.bsky.social, has collated all data and analysis code here: data: openneuro.org/datasets/ds0... code: github.com/Neuroenerget...