Resting-state Functional Connectivity Based On The Spontaneous Neural Signals And The Hemodynamic Signals

Spontaneous, low-frequency hemodynamic signals could represent the resting-state functional connectivity (RSFC) of the brain, and the RSFC based on the hemodynamic signals (hRSFC) is widely used to study some diseases. However, the neural mechanisms underlying the spontaneous hemodynamic signals are not very clear. Moreover, the effects of consciousness on the RSFC need further study. In addition, the hRSFC reflects the neural RSFC (nRSFC) based on the mechanisms of neurovascular coupling, and under the condition of neurovascular uncoupling, whether the hRSFC could still reflect the nRSFC needs to be tested.Cortical spreading depression (CSD) is an important disease model, which is involved in lots of pathological processes, such as migraine and stroke. The previous studies focused on the unilateral cortex where CSD spreads, and whether CSD could influence the RSFC between the bilateral cortexes is not clear. Moreover, CSD could produce neurovascular uncoupling, and the comparison between the hRSFC and the nRSFC after CSD would help to understand the feasibility of reflecting the nRSFC by the hRSFC in the case of neurovascular uncoupling.To address these issues, we measured the hRSFC and the nRSFC in mice based on the optical imaging methods. The hRSFC was visualized using optical intrinsic signal (OIS) imaging, and the nRSFC was visualized using voltage-sensitive dye (VSD) imaging.The main findings were as below:(1) Studying the neural mechanisms underlying the spontaneous hemodynamic signals by the comparison between the hRSFC and the nRSFC. The results showed that the spatial topology of the nRSFC calculated by0.1-4Hz VSD signals was most similar to that of the hRSFC, while nRSFC calculated by VSD signals in the higher frequency bands (5-40Hz) just covered the area around the seed regions, suggesting that the slow cortical potentials (0.1～4Hz) are closely correlated with the spontaneous hemodynamic signals and neural signals in the higher frequency bands have little contribution to the hRSFC. The correlation strength and the bilateral symmetry of the nRSFC based on the slow cortical potentials were significantly lower than those of the hRSFC, indicating that there are differences between the nRSFC and the hRSFC.(2)Studying the effects of consciousness on the nRSFC based on the slow cortical potentials and the hRSFC based on the spontaneous hemodynamic signals by increasing anesthetic levels. These results showed that as the anesthetic levels were increased, both the nRSFC and the hRSFC were reduced, suggesting that consciousness could affect the RSFC. As the anesthetic level was increased to1.5%isoflurane, the nRSFC persisted, but hRSFC became discrete, suggesting that coherent slow cortical potentials reveal a superior localization of RSFC networks.(3) Comparing the nRSFC based on the slow cortical potentials and the hRSFC based on the spontaneous hemodynamic signals under the condition of neurovascular uncoupling. The neurovascular uncoupling was induced by CSD in the unilateral cortex of mice. Either evaluated by OIS imaging or by VSD imaging, the correlations between the bilateral somatosensory cortexes and between the bilateral visual cortexes were reduced within one hour after CSD, but the reduced correlations between the bilateral somatosensory cortexes were more significant for OIS imaging than for VSD imaging. The correlations between the somatosensory cortex and the visual cortex in the ipsilateral cortex and between those in the contralateral cortex were significantly increased, but the increased correlations in the contralateral cortex were more significant for OIS imaging than for VSD imaging. These results suggested that the nRSFC was altered to a less extent than the hRSFC during the periods of neurovascular uncoupling after CSD. Moreover, the spatial correlations evaluated by OIS imaging were significantly smaller than those evaluated by VSD imaging, suggesting that the nRSFC recovered much faster than the hRSFC. All of these findings suggest that the hRSFC and the nRSFC were altered by CSD, and under the condition of neurovascular uncoupling produced by CSD, the hRSFC displayed similar trends as the nRSFC, but the nRSFC was altered to a lesser extent and recovered much faster.