A rapid-onset diffusion functional MRI signal reflects neuromorphological coupling dynamics

Functional Magnetic Resonance Imaging (fMRI) has transformed our understanding of brain function in-vivo. However, the neurovascular coupling mechanisms underlying fMRI are somewhat "distant" from neural activity. Interestingly, evidence from Intrinsic Optical Signals (IOSs) indicates that neural activity is also coupled to (sub)cellular morphological modulations. Diffusion-weighted functional MRI (dfMRI) experiments have been previously proposed to probe such neuromorphological couplings, but the underlying mechanisms have remained highly contested. Here, we provide the first direct link between in vivo ultrafast dfMRI signals upon rat forepaw stimulation and IOSs in acute slices stimulated optogenetically. We reveal a hitherto unreported rapid onset (<100 ms) dfMRI signal component which (i) agrees with fast-rising IOSs dynamics; (ii) evidences a punctate quantitative correspondence to the stimulation period; and (iii) is rather insensitive to a vascular challenge. Our findings suggest that neuromorphological coupling can be detected via dfMRI signals, auguring well for future mapping of neural activity more directly compared with blood-oxygenation-level-dependent mechanisms.