ABSTRACT Our long term goal is to establish the newly developed zero echo time MRI pulse sequence entitled Multi-Band SWeep Imaging with Fourier Transformation (MB-SWIFT) as the next-generation method of choice for artefact- free, quiet, high-resolution fMRI in humans, suitable for detecting neuronal activity via cellular mechanisms linked to electrical events that are intrinsically unattainable with standard readout sequences. MB-SWIFT has been already proven to offer remarkable advantages as compared to current fMRI techniques, since it is minimally impacted by susceptibility artefacts, has high tolerance for movement, and produces a nearly silent, continuous acoustic noise during acquisitions thanks to the use of slowly switching gradients. However, the origin of the functional contrast has remained elusive so far. Our general hypothesis is that MB-SWIFT functional signals closely reflect changes in local field potentials. We also advance the hypothesis that a non-negligible portion of the contrast may arise from T1 contrast mechanisms involving the pool of immobilized spins that are most likely sensitized to neuronal currents. Before undertaking a full-blown study that elucidates how relaxation mechanisms linked to membrane potentials and ions redistributions impact MB-SWIFT signals, we first need to validate that MB-SWIFT signals are sensitive proxies of neuronal activity, and determine whether they are substantially mediated by relaxation mechanisms not explained by blood flow or oxygenation changes. Ergo, the current proof- of-concept study in rodents will first establish to what extent MB-SWIFT signals reflect changes in neuronal activity under awake, physiological conditions by acquiring fMRI signals with MB-SWIFT and electrophysiological recording in somatosensory cortex during whisker stimulations of different duration and frequency. Then, we will evaluate to what extent MB-SWIFT signals are sensitive to changes in oxygenation levels and cerebral blood flow by conducting mechanistic studies during gas challenges, with different coil designs meant to isolate the inflow contribution, and with different magnetic fields, meant to verify the presence of T1-mechanisms of possible tissue origin. By achieving these aims we will gain pivotal insights into the substrates of the MB-SWIFT fMRI signals, and will reach initial milestones that will advance MB-SWIFT towards detection of neuronal currents, a goal that has been looked after for more than 20 years. In addition, the implications of the mechanistic studies will expand beyond MB-SWIFT, and they will be relevant to other MRI approaches with virtually zero echo time.