Multimodal methods to help interpret resting-state fMRI

Resting-state fMRI (rs-fMRI), mainly based on the blood‑oxygenation-level-dependent (BOLD) mechanism, has been widely used as a noninvasive, global functional connectivity mapping tool. This global mapping scheme presents a unique advantage in cross-scale brain functional studies. However, the low-frequency fluctuation of the rs-fMRI signal is indirectly coupled with neuronal oscillation; the underlying neuro-glio-vascular (NGV) signaling of which leads to varied sources contributing to the designated functional connectivity based on rs-fMRI. Based on the emerging neurotechniques for animal studies, there is an increasing trend to apply multimodal methodologies, e.g., electrophysiological recording (ephys), two-photon microscopy (2-PM), fiber photometry, with simultaneous fMRI to decipher the cellular and vascular origin of rs-fMRI. In this chapter, we introduce how advanced multimodal fMRI methods are developed and used to elucidate NGV signaling events, e.g., gamma frequency oscillation of EEG signal, vasomotion, astrocytic activity, contributing to rs-fMRI signal fluctuation. Also, we highlight non-BOLD rs-fMRI measurements, e.g., cerebral blood volume (CBV) and cerebral blood flow (CBF), and alternative methods, e.g., functional ultrasound (fUS) and functional optoacoustic (fOA), to better interpret the functional connectivity measured using rs-fMRI.