Title Brain resting-state functional MRI connectivity: Morphological foundation and plasticity

Despite the immense ongoing efforts to map brain functional connections and organizations with resting-state functional MRI (rsfMRI), the mechanisms governing the temporally coherent rsfMRI signals remain elusive. In particular, there is a lack of direct evidence regarding the morphological foundation and plasticity of these rsfMRI derived connections. In this study, we investigated the role of axonal projections in rsfMRI connectivity and its plasticity. Well-controlled rodent models of complete and posterior corpus callosotomy were longitudinally examined with rsfMRI at 7 Tesla in conjunction with intracortical EEG recording and functional MRI tracing of interhemispheric neuronal pathways by manganese (Mn2+). At post-callosotomy day 7, significantly decreased interhemispheric rsfMRI connectivity was observed in both groups in the specific cortical areas whose callosal connections were severed. At day 28, the disrupted connectivity was restored in the partial callosotomy group but not in the complete callosotomy group, likely due to the compensation that occurred through the remaining interhemispheric axonal pathways. This restoration-along with the increased intrahemispheric functional connectivity observed in both groups at day 28-highlight the remarkable adaptation and plasticity in brain rsfMRI connections. These rsfMRI findings were paralleled by the intracortical EEG recording and Mn2+ tracing results. Taken together, our experimental results directly demonstrate that axonal connections are the indispensable foundation for rsfMRI connectivity and that such functional connectivity can be plastic and dynamically reorganized atop the morphological connections. Abstract Despite the immense ongoing efforts to map brain functional connections and organizations with resting-state functional MRI (rsfMRI), the mechanisms governing the temporally coherent rsfMRI signals remain unclear. In particular, there is a lack of direct evidence regarding the morphological foundation and plasticity of these rsfMRI derived connections. In this study, we investigated the role of axonal projections in rsfMRI connectivity and its plasticity. Well-controlled rodent models of complete and posterior corpus callosotomy were longitudinally examined with rsfMRI at 7 Tesla in conjunction with intracortical EEG recording and functional MRI tracing of interhemispheric neuronal pathways by manganese (Mn 2+). At post-callosotomy day 7, significantly decreased interhemispheric rsfMRI connectivity was observed in both groups in the specific cortical areas whose callosal connections were severed. At day 28, the disrupted connectivity was restored in the partial callosotomy group but not in the complete callosotomy group, likely due to the compensation that occurred through the remaining interhemispheric axonal pathways. This restoration – along with the increased intrahemispheric functional connectivity observed in both groups at day 28 – highlight the …