Spatial and Spectral Components of the BOLD Global Signal in Rat Resting-State Functional MRI.

Purpose: In resting-state fMRI (rs-fMRI), the global signal average captures widespread fluctuations related to unwanted sources of variance such as motion and respiration, as well as widespread neural activity; however, relative contributions of neural and non-neural sources to the global signal remain poorly understood. This study sought to tackle this problem through the comparison of the BOLD global signal to an adjacent non-brain tissue signal, where neural activity was absent, from the same rs-fMRI scan obtained from anesthetized rats. In this dataset, motion was minimal and ventilation was phase-locked to image acquisition to minimize respiratory fluctuations. Data were acquired using three different anesthetics: isoflurane, dexmedetomidine, and a combination of dexmedetomidine and light isoflurane.

Methods: A power spectral density estimate, a voxel-wise spatial correlation via Pearson's correlation, and a co-activation pattern analysis were performed using the global signal and the non-brain tissue signal. Functional connectivity was calculated using Pearson's linear correlation on default mode network (DMN) regions.

Results: We report differences in the spectral composition of the two signals and show spatial selectivity within DMN structures that show an increased correlation to the global signal and decreased intra-network connectivity after global signal regression. All of the observed differences between the global signal and the non-brain tissue signal were maintained across anesthetics.

Conclusion: These results show that the global signal is distinct from the noise contained in the tissue signal, as support for a neural contribution. This study provides a unique perspective to the contents of the global signal and their origins.