Functional magnetic resonance imaging (fMRI) is one of the most powerful tools in neuroscience, but what does the measured signal really reflect? Traditionally, the fMRI signal has been assumed to mainly reflect excitatory neuron activity. However, recent findings by Nicholas Sundqvist and Henrik Podéus of the ISB Group suggest that inhibitory interneurons play a much more significant role.

Using a model-driven meta-analysis approach, we analysed data across several different studies, revealing that:

  • Less than 20% of the fMRI BOLD signal comes from excitatory neurons
  • A dominant 50–80% arises from inhibitory interneurons

Our model offers a unified mechanistic explanation for why fMRI responses sometimes appear contradictory across experiments. For example, the model provides a plausible mechanism that result in a biphasic vascular response that emerge only under high intensity stimulation.

Taken together, these results point towards a new consensus view: inhibitory interneurons, not excitatory neurons, are the primary drivers of fMRI signals.

We have recently published a manuscript about these findings in the journal Computers in Medicine and Biology – a leading publication in computational biology and medical informatics.