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

Diffusion MRI (dMRI) facilitates the exploration of microstructural features within the brain owing to its sensitivity to restrictions and hindrances in the form of cell membranes or subcellular structures. As such, alterations in cell morphology and water transport mechanisms linked to neuronal activity are inherently embedded in the dMRI signal. In this context, the goal of our study was to investigate changes in Mean Diffusivity (MD) and Mean Kurtosis (MK) across the rat brain upon unilateral forepaw electrical stimulation and compare them to BOLD-fMRI mapping of brain activity. The positive BOLD response in the contralateral primary somatosensory cortex, forelimb region (S1FL) was accompanied by a significant decrease in MD in the same region, described in the literature as the result of cellular swelling and increased tortuosity in the extracellular space. For the first time, we also report a paired decrease in MK during stimulation in S1FL, most likely indicative of increased membrane permeability, as suggested by the slight decrease in exchange time estimated from kurtosis time-dependence analyses. The primary motor (M1) and the secondary somatosensory (S2) cortices, part of the cortical somatosensory processing and integration pathways, also displayed a positive BOLD response during stimulation, albeit with a lower amplitude, while MD and MK had differentiated dynamics in these two areas. In M1, the trends of MD and MK mirrored those observed in S1FL, whereas in S2, the opposite pattern was identified, that is MD and MK increased. Subcortical regions implicated in somatosensory information processing and integration, such as the thalamus and hippocampus, also exhibited an increase in MD and MK as in S2, remarkably in the absence of a discernible BOLD response. In the striatum a marginal negative BOLD response coincided with an increase in MD and MK. These findings highlight the capacity of dMRI to offer complementary functional insights into excitatory and inhibitory neural activity, potentially below the BOLD detection threshold. ### Competing Interest Statement The authors have declared no competing interest.