A strategy that helps identify the types of cells contributing to signals recorded in functional magnetic resonance imaging (fMRI) is reported this week in Nature Methods.

MRI machines detect the functional activation of the brain by measuring changes in the blood flow. Blood oxygen level-dependent (BOLD) fMRI based on contrast has become a widespread tool to noninvasively investigate brain function in healthy and disease-affected animal models and humans. However, the extent to which a change in BOLD signal reflects local cellular activation remains unknown, raising uncertainties in the interpretation of fMRI studies. One can follow the activity of individual cells in the brain of animal models by microscopy using fluorescent sensors, but to date this has not been directly combined with fMRI.

Fritjof Helmchen and colleagues recorded fluorescence-based activity signals of individual cells simultaneously with fMRI in rats. By monitoring the activity of neurons and glial cells in the brain and their relationship to the BOLD signals, the authors discover that the activation of glial cells also contributes to this signal under certain circumstances.

This study highlights the complexity of fMRI BOLD signals and provides new leads that can help with the interpretation of fMRI studies.