Model-driven meta-analysis establishes a new consensus view: Inhibitory neurons dominate BOLD-fMRI responses.

Area of Science:

• Neuroscience
• Neuroimaging
• Computational Biology

Background:

• Functional magnetic resonance imaging (fMRI) traditionally assumes hemodynamic changes reflect excitatory neuron activity.
• Recent optogenetic studies suggest inhibitory interneurons significantly influence fMRI signals, creating complex and sometimes contradictory data.
• Quantifying cell-type contributions to fMRI is challenging due to regulatory interactions.

Purpose of the Study:

• To develop a model-driven meta-analysis for a unified, quantitative explanation of fMRI data.
• To resolve discrepancies in existing experimental findings regarding neuronal contributions to the BOLD signal.
• To establish a new paradigm for interpreting neuronal activity using fMRI.

Main Methods:

• A novel model-driven meta-analysis approach was employed.
• Quantitative analysis was used to determine the relative contributions of different neuronal cell types to the Blood-Oxygen-Level-Dependent (BOLD) signal.
• Mechanistic explanations for observed experimental variations were investigated.

Main Results:

• The BOLD signal is predominantly influenced by inhibitory interneurons (50-80% contribution), with excitatory cells contributing less than 20%.
• A biphasic vascular response (transient increase followed by decrease) was identified as a key factor explaining experiment-to-experiment variability.
• This biphasic response was shown to be intensity-dependent, appearing only during high-intensity stimulations.

Conclusions:

• fMRI signal interpretation requires a paradigm shift, acknowledging the dominant role of inhibitory interneurons.
• The developed model provides a unified explanation for complex fMRI data, reconciling conflicting experimental results.
• Understanding the biphasic vascular response mechanism enhances the accuracy of fMRI-based neuronal activity mapping.