A Model-Driven Meta-Analysis Supports the Emerging Consensus View that Inhibitory Neurons Dominate BOLD-fMRI Responses.

Functional magnetic resonance imaging (fMRI) is a pivotal tool for mapping neuronal activity in the brain. Traditionally, the observed hemodynamic changes are assumed to reflect the activity of the most common neuronal type: excitatory neurons. In contrast, recent experiments, using optogenetic techniques, suggest that the fMRI-signal instead reflects the activity of inhibitory interneurons. However, these data paint a complex picture, with numerous regulatory interactions, and where the different experiments display many qualitative differences. It is therefore not trivial how to quantify the relative contributions of the different cell types and to combine all observations into a unified theory. To address this, we present a new model-driven meta-analysis, which provides a unified and quantitative explanation for all data. This model-driven analysis allows for quantification of the relative contribution of different cell types: the contribution to the BOLD-signal from the excitatory cells is <20 % and 50-80 % comes from the interneurons. Our analysis also provides a mechanistic explanation for the observed experiment-to-experiment differences, e.g. a biphasic vascular response dependent on different stimulation intensities and an emerging secondary post-stimulation peak during longer stimulations. In summary, our study provides a new, emerging consensus-view supporting the larger role of interneurons in fMRI.