Investigating neuron-specific BOLD coupling via simultaneous two-photon microscopy imaging and rs-fMRI of the mouse brain at 16.4T

Motivation: Resting-state fMRI (rs-fMRI) based on BOLD contrast is powerful for mapping brain connectivity and function. However, the underlying neural vascular coupling is still elusive. Goal(s): To understand the neuron-specific contributions to the rs-fMRI BOLD signal. Approach: We simultaneously acquired rs-fMRI and calcium images using MRI-compatible two-photon microscopy imaging (TPMI) in mice brains at 16.4T; the signals from both imaging modalities were analyzed and correlated within the resting-state networks of interest. Results: Neurons show distinct correlations to the BOLD signal, with clustered spatial distributions across cortical layers, and the neuron co-activation patterns (NCAP) show time-dependent activity to drive BOLD events. Impact: We investigated neuron-specific BOLD coupling to be spatially distinct and time-dependent at resting state using simultaneous TPMI and rs-fMRI on mice at 16.4T. The findings provide new insights into how clustered neurons drive BOLD signal fluctuations in the resting brain.