Mechanisms of Repetitive Transcranial Magnetic Stimulation on Post-stroke Depression: A Resting-State Functional Magnetic Resonance Imaging Study.

We aimed to identify neural mechanisms underlying clinical response to repetitive transcranial magnetic stimulation (rTMS) in post-stroke depression (PSD) by the Resting-state functional magnetic resonance imaging (rs-fMRI). Thirty-two depressed patients after ischemic stroke were randomized in a 1:1 ratio to receive 20 min of 5 Hz rTMS or sham over left dorsolateral prefrontal cortex (DLPFC) in addition to routine supportive treatments. The clinical outcome was measured by the 17-item Hamilton Depression Rating Scale (HDRS-17), while the imaging results were acquired from rs-fMRI, including regional homogeneity (ReHo), fractional amplitude of low-frequency fluctuation (fALFF) and seed-based dynamic functional connection (dFC). HRSD-17 scores were improved in the two groups after treatment (P < 0.01), while greater mood improvement was observed in the rTMS group (P < 0.05). Compared with the sham group, the rTMS group demonstrated regions with higher ReHo and fALFF values locating mainly in the left hemisphere and highly consistent with the default mode network (DMN) (p < 0.05). Using the medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC) as seeds, significant difference between the two groups in dFC within the DMN was found after treatment, including 10 connections with increased connectivity strength and 2 connections with reduced connectivity strength. The ReHo, fALFF and dFC values within DMN in the rTMS group were negatively correlated with the HDRS scores after treatment (P < 0.05). Our results indicated reductions in depressive symptoms following rTMS in PSD are associated with functional alterations of different depression-related areas within the DMN.

[Correlations Between Gut Microbiota Changes and Cognitive Function in Patients with Post-Stroke Cognitive Impairment in the Early Stage].

Objective: To observe the changes in the composition of gut microbiota in stroke patients showing cognitive impairment within one month after the stroke, and to explore the correlation between bacteria presenting dissimilarity and cognitive functions and other clinical indicators. Methods: A cross-sectional study was conducted, involving 12 patients with post-stroke cognitive impairment (PSCI group), 12 stroke patients without cognitive impairment (Non-PSCI group), and 12 healthy volunteers in a normal control group (NC group). The demographic and clinical data were gathered. The abundance, diversity and dissimilarity of gut bacterial communities were determined by 16S rRNA gene sequencing. Then, we studied the correlation between gut microbiota and clinical characteristics and the effectiveness of using microbiome markers to identify cognitive decline. Results: The Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores of the PSCI group were significantly lower than those the Non-PSCI group ( P<0.001). There was no significant intergroup difference in the demographic data, the clinical data, and the Alpha diversity of gut microbiota among the three groups ( P>0.05). Microbial composition analysis of the three groups revealed proportion alternations at the phylum, genus and species levels. At the phylum level, linear discriminant analysis (LDA) effect size (LEfSe) analysis suggested that the Actinomycetes had significantly increased relative abundance in the PSCI group (LDA score>2). At the genus and species levels, Firmicutes had the highest diversity among the top 10 bacteria in the three groups, while the relative abundance of Verrucomicrophyla presented an increasing trend in the Non-PSCI group and that of Actinobacteria showed an increasing trend in the PSCI group. Further LEfSe analysis revealed that there were different microbiome markers in each group, among which the Bifidobacterium, Alloscardovia, and Alloscardovia omnicolens of the phylum Actinomycetes and Lactobacillus gasseri and Anaerostipes hadrus of the phylum Firmicutes in the PSCI group increased significantly (LDA score>2). Correlation analysis indicated that Anaerostipes hadrus was negatively correlated with the MoCA scores, while Bifidobacterium was positively correlated with blood uric acid (UA). Bifidobacterium, Lactobacillus gasseri and Anaerostipes hadrus could be used to distinguish PSCI patients from Non-PSCI patients, presenting an area under the curve of 0.785, 0.792 and 0.750, respectively ( P<0.05). Conclusion: Stroke patients with cognitive impairment in the early stage showed composition changes in their gut microbiota, and the bacteria exhibiting dissimilarity were correlated, to some degree, with cognitive function and related risk factors, which could provide new clues for the early management of PSCI.

[Dysbiosis of Gut Microbiota in Patients with Post-Stroke Cognitive Impairment].

OBJECTIVE: To identify the differences in the composition of gut microbiota of patients with post-stroke cognitive impairment (PSCI) in comparison with the normal cognition healthy controls (HC), and to study the potential association between gut microbiota and cognition function. METHODS: A total of 24 patients were recruited for the PSCI group, which was matched with 23 healthy subjects with no history of cardiovascular disease recruited over the same period for the control group. Fecal samples were collected for both groups, and Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to evaluate cognitive functions. The abundance, diversity and group difference of gut bacterial communities were determined with 16S rRNA gene sequencing, and the correlations between differences in bacterial species of the gut microbiota and cognitive function scores were examined with redundancy analysis (RDA)/canonical correspondence analysis (CCA). RESULTS: There was no significant difference in the general data or the alpha diversity of gut microbiota between the two groups ( P>0.05). Inter-group comparison of microbial species composition revealed differences at the phylum and species levels, mainly represented as reduction in the relative abundance of Firmicutes and Bacteroidetes, and the relative enrichment of Proteobacteria. The relative abundance of Intestinibacter bartlettii, uncultured bacterium Tyzzerella_3, Lactobacillus gasseri, and Fusicatenibacter saccharivorans of phylum Firmicutes in the PSCI patients were significantly reduced in comparison to that of the HC (LDA score>2), and these bacteria were positively correlated with MMSE and MoCA scores. In addition, the Ruminococcus gnavus and Faecalimonas umbilicata of phylum Firmicutes and uncultured bacterium Prevotellaceae_NK3 B31 group of phylum Bacteroidetes were significantly enriched in comparison with those of the HC (LDA score>2), and these bacteria were negatively correlated with MMSE and MoCA scores. There were also correlations among these bacteria. CONCLUSION: In this study, we observed compositional differences between the gut microbiota of PSCI patients and those of HC, and revealed that the differences were correlated, to some degree, to the cognitive functions, which will provide new perspectives for the clinical diagnosis and treatment of PSCI.

Effect of Repetitive Transcranial Magnetic Stimulation on Post-Stroke Comorbid Cognitive Impairment and Depression: A Randomized Controlled Trial.

Background: There are currently no uniform treatments for post-stroke comorbid cognitive impairment and depression (PSCCID). Objective: To verify whether repetitive transcranial magnetic stimulation (rTMS) can improve PSCCID symptoms and explore the underlying roles of resting-state functional magnetic resonance imaging (rs-fMRI). Methods: Thirty PSCCID patients were randomized in a 1 : 1 ratio to receive 4 weeks of rTMS (intervention group) or sham rTMS (control group) over the left dorsolateral prefrontal cortex (DLPFC). rs-fMRI was acquired to analyze the functional plasticity of brain regions at baseline and immediately after the last intervention. Results: Cognition, depression status, and neural electrophysiology were improved in both intervention and control groups after treatment (p = 0.015-0.042), and the intervention group had more significant improvement than the control group. Analysis of functional connectivities (FCs) within the default mood network (DMN) showed that the connection strength of the left temporal pole/left parahippocampal cortex and right lateral temporal cortex/right retrosplenial cortex in the intervention group were enhanced compared with its pre-intervention and that in the control group after treatment (p < 0.05), and the both FC values were positively correlated with MMSE scores (p < 0.001). The intervention group had stronger FCs within the DMN compared with the control group after treatment, and some of the enhanced FCs were correlated with the P300 latency and amplitude. Conclusions: rTMS over the left DLPFC is an effective treatment for improving both cognitive impairment and depression among patients with PSCCID. The enhanced FCs within the DMN may serve as a compensatory functional recombination to promote clinical recovery.