SORDINO functional connectivity mapping in awake behaving mice

Blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) has revolutionized our understanding of the brain activity landscape, bridging circuit neuroscience in animal models with noninvasive brain mapping in humans. This immensely utilized technique, however, faces challenges such as acoustic noise, electromagnetic interference, motion artifacts, magnetic-field inhomogeneity, and limitations in sensitivity and specificity. A solution addressing these issues would be transformative for mapping functional connectivity. Here, we introduce Steady-state On-the-Ramp Detection of INduction-decay with Oversampling (SORDINO), an fMRI technique that maintains a constant total gradient amplitude while acquiring data during continuously changing gradient direction. When benchmarked against conventional fMRI on a 9.4T system, SORDINO is silent, sensitive, specific, and resistant to artifacts. SORDINO offers superior compatibility with concurrent multimodal experiments such as electrophysiology, electrochemistry, and optical imaging at cellular resolution. It also carries novel T1 contrast mechanisms distinct from BOLD. SORDINO facilitates brain-wide activity and connectivity mapping in awake, behaving mice, overcoming stress- and motion-related confounds that are among the most challenging barriers in conventional fMRI studies.