Objective The changes in resting-state functional networks and their correlations with clinical traits remain to be clarified in migraine. Here we aim to investigate the brain spatio-temporal dynamics of resting-state networks and their possible correlations with the clinical traits in migraine. Methods Twenty Four migraine patients without aura and 26 healthy controls (HC) were enrolled. Each included subject underwent a resting-state EEG and echo planar imaging examination. The disability of migraine patients was evaluated by Migraine Disability Assessment (MIDAS). After data acquisition, EEG microstates (Ms) combining functional connectivity (FC) analysis based on Schafer 400-seven network atlas were performed. Then, the correlation between obtained parameters and clinical traits was investigated. Results Compared with HC group, the brain temporal dynamics depicted by microstates showed significantly increased activity in functional networks involving MsB and decreased activity in functional networks involving MsD; The spatial dynamics were featured by decreased intra-network FC within the executive control network( ECN) and inter-network FC between dorsal attention network (DAN) and ECN (P < 0.05); Moreover, correlation analysis showed that the MIDAS score was positively correlated with the coverage and duration of MsC, and negatively correlated with the occurrence of MsA; The FC within default mode network (DMN), and the inter-FC of ECN- visual network (VN), ECN- limbic network, VN-limbic network was negatively correlated with MIDAS. However, the FC of DMN-ECN was positively correlated with MIDAS; Furthermore, significant interactions between the temporal and spatial dynamics were also obtained. Conclusions Our study confirmed the notion that altered spatio-temporal dynamics exist in migraine patients during resting-state. And the temporal dynamics, the spatial changes and the clinical traits such as migraine disability interact with each other. The spatio-temporal dynamics obtained from EEG microstate and fMRI FC analyses may be potential biomarkers for migraine and with a huge potential to change future clinical practice in migraine.

IntroductionAlthough vascular dementia (VaD) is the second most prevalent form of dementia, there is currently a lack of effective treatments. Tilianin, isolated from the traditional drug Dracocephalum moldavica L., may protect against ischemic injury by inhibiting oxidative stress and inflammation via the CaMKII-related pathways but with weak affinity with the CaMKII molecule. microRNAs (miRNAs), functioning in post-transcriptional regulation of gene expression, may play a role in the pathological process of VaD via cognitive impairment, neuroinflammatory response, and neuronal dysfunction. This study aimed to investigate the role of tilianin in VaD therapy and the underlying mechanism through which tilianin regulates CaMKII signaling pathways based on miRNA-associated transcriptional action.MethodsRats with 2-vessel occlusion (2VO), a standard model of VaD, were treated with tilianin, vehicle control, and target overexpression or downregulation. High-throughput sequencing, qRT-PCR, and western blot analyses were utilized to identify the downstream target genes and signaling pathways of tilianin involved in VaD.ResultsOur results showed that tilianin ameliorated cognitive deficits, neurodegeneration, and microglial and astrocytic activation in rats with 2VO. Subsequent high-throughput sequencing and qRT-PCR analyses revealed that tilianin increased the downregulated miR-193b-3p and miR-152-3p levels in the cortex and hippocampus of 2VO rats. Mechanistically, miR-193b-3p targeting CaM and miR-152-3p targeting CaMKIIα were identified to play a role in VaD-associated pathology, inhibiting the p38 MAPK/NF--κB p65 pathway and decreasing TNF-α and IL-6 levels. Further gain- and loss-of-function experiments for these key genes showed that tilianin-exerted cognitive improvement by activating the p38 MAPK/NF--κB p65 and Bcl-2/Bax/caspase-3/PARP pathways in the brain of 2VO rats was abolished by miR-193b-3p and miR-152-3p inhibition. Moreover, CaM and CaMKIIα overexpression eliminated the elevated effects of miR-193b-3p and miR-152-3p on tilianin’s protection against ischemic injury through increased inflammatory reactions and apoptotic signaling.DiscussionTogether, these findings indicate that tilianin improves cognition by regulating the miR-193b-3p/CaM- and miR-152-3p/CaMKIIα-mediated inflammatory and apoptotic pathways, suggesting a potential small-molecule regulator of miRNA associated with inflammatory signaling for VaD treatment.

SummaryElectroencephalogram‐microstate analysis was conducted using low‐resolution electromagnetic tomography (LORETA)‐KEY to evaluate dynamic brain network changes in patients with acute large artery atherosclerotic cerebral infarction (LAACI) during the rest and sleep stages. This study included 35 age‐ and sex‐matched healthy controls and 34 patients with acute LAACI. Each participant performed a 3‐h, 19‐channel video electroencephalogram test. Subsequently, 20 epochs of 2‐s sleep spindles during stage N2 sleep and five epochs of 10‐s electroencephalogram data in the resting state for each participant were obtained. In both the resting state and sleep spindles, patients with LAACI displayed altered neural oscillations. The parameters of microstate A (coverage, occurrence, and duration) increased during the resting state in the patients with LAACI compared with healthy controls. The coverage and occurrence of microstate B and D were reduced in the LAACI group compared with the healthy controls (p < 0.05). Moreover, during sleep spindles, the duration of microstate A and the transition probability from microstate A and B to C decreased, but the coverage of microstate B and the transition rate from microstate B to D increased (p < 0.05) in the LAACI group compared with the healthy controls. These results enable better understanding of how neural oscillations are modified in patients with LAACI during the resting state and sleep spindles. Following LAACI, the dynamic brain network undergoes changes during sleep spindles and the resting state. Continued long‐term investigations are required to determine how well these changes in brain dynamics reflect the clinical characteristics of patients with LAACI.