Resting fMRI functional connectivity reflects fluctuations in inhibitory interneuron activity.

Primate brain function relies on distributed cortical networks. These networks are commonly identified through fMRI functional connectivity, defined as the spatial correlation of hemodynamic fluctuations measured at rest. To assess the contribution of distinct neuronal populations to fMRI functional connectivity, we obtained concurrent fMRI and dense single-unit recordings at rest in the macaque. Then, using standard waveform-based classification of action potential shape, we compared the activity of different neural subtypes to the local and brain-wide patterns of fMRI activity. Putative excitatory neurons were functionally intermixed, with approximately half having positive and half negative correlation with the local fMRI signal. By contrast, all putative inhibitory interneurons were positively correlated, with one subclass exhibiting brain-wide correlation that closely matched conventional seed-based functional connectivity. These findings indicate that, although excitatory projection neurons may underpin long-range network communication interneuron activity most closely matches the fMRI fluctuations at the heart of resting functional connectivity.