Increased fMRI connectivity upon chemogenetic inhibition of the mouse prefrontal cortex

While shaped and constrained by axonal connections, fMRI-based functional connectivity reorganizes in response to varying interareal input or pathological perturbations. However, the causal contribution of regional brain activity to whole-brain fMRI network organization remains unclear. Here we combine neural manipulations, resting-state fMRI and in vivo electrophysiology to probe how inactivation of a cortical node causally affects brain-wide fMRI coupling in the mouse. We find that chronic inhibition of the medial prefrontal cortex (PFC) via overexpression of a potassium channel increases fMRI connectivity between the inhibited area and its direct thalamo-cortical targets. Acute chemogenetic inhibition of the PFC produces analogous patterns of fMRI overconnectivity. Using in vivo electrophysiology, we find that chemogenetic inhibition of the PFC enhances low frequency (0.1-4 Hz) oscillatory power via suppression of neural firing not phase-locked to slow rhythms, resulting in increased slow and delta band coherence between areas that exhibit fMRI overconnectivity. These results provide causal evidence that cortical inactivation can counterintuitively increase fMRI connectivity via enhanced, less-localized slow oscillatory processes. Pathological perturbation affects whole brain network activity. Here the authors show in mice that cortical inactivation unexpectedly results in increased fMRI connectivity between the manipulated regions and its direct axonal targets.

Automated summary

This study investigates how inactivation of a cortical node affects brain-wide fMRI connectivity in mice, providing causal evidence that cortical inactivation can unexpectedly increase fMRI connectivity.