Somatosensory-evoked response induces extensive diffusivity and kurtosis changes associated with neural activity in rodents

Abstract

Neural tissue microstructure is dynamic during brain activity, presenting changes in cellular morphology and membrane permeability. The sensitivity of diffusion MRI (dMRI) to restrictions and hindrances in the form of cell membranes or subcellular structures enables the exploration of brain activity under a new paradigm, offering a more direct functional contrast than its BOLD counterpart. The current work aims at probing Mean Diffusivity (MD) and Mean Kurtosis (MK) changes and their time-dependence signature across various regions in the rat brain during somatosensory processing and integration, upon unilateral forepaw stimulation. We report a decrease in MD in the contralateral primary somatosensory cortex, forelimb region (S1FL), previously ascribed to cellular swelling and increased tortuosity in the extracellular space, paralleled by a positive BOLD response. For the first time, we also report a paired decrease in MK during stimulation in S1FL, suggesting increased membrane permeability. This observation was further supported by the reduction in exchange time estimated from the kurtosis time-dependence analyses. Conversely, the secondary somatosensory cortex and subcortical areas, formerly reported as responsive to sensory stimulation in rodents (thalamus, striatum, hippocampal subfields), displayed a marked MD and MK increase, paralleled by a weak-to-absent BOLD response. Overall, MD and MK uncovered functional-induced changes with higher sensitivity than BOLD. Although the exact origin of the MD and MK increase is yet to be unraveled, the potential of dMRI to provide complementary functional insights, even below the BOLD detection threshold, has been showcased.