Paired associated magnetic stimulation promotes neural repair in the rat middle cerebral artery occlusion model of stroke

Paired associative stimulation has been used in stroke patients as an innovative recovery treatment. However, the mechanisms underlying the therapeutic effectiveness of paired associative stimulation on neurological function remain unclear. In this study, rats were randomly divided into middle cerebral occlusion model(MCAO) and paired associated magnetic stimulation(PAMS) groups. The MCAO rat model was produced by middle cerebral artery embolization. The PAMS group received PAMS on days 3 to 20 post MCAO. The MCAO group received sham stimulation, three times every week. Within 18 days after ischemia, rats were subjected to behavioral experiments—the foot-fault test, the balance beam walking test, and the ladder walking test. Balance ability was improved on days 15 and 17, and the footfault rate was less in their affected limb on day 15 in the PAMS group compared with the MCAO group. Western blot assay showed that the expression levels of brain derived neurotrophic factor, glutamate receptor 2/3, postsynaptic density protein 95 and synapsin-1 were significantly increased in the PAMS group compared with the MCAO group in the ipsilateral sensorimotor cortex on day 21. Resting-state functional magnetic resonance imaging revealed that regional brain activities in the sensorimotor cortex were increased in the ipsilateral hemisphere, but decreased in the contralateral hemisphere on day 20. By finite element simulation, the electric field distribution showed a higher intensity, of approximately 0.4 A/m~2, in the ischemic cortex compared with the contralateral cortex in the template. Together, our findings show that PAMS upregulates neuroplasticity-related proteins, increases regional brain activity, and promotes functional recovery in the affected sensorimotor cortex in the rat MCAO model. The experiments were approved by the Institutional Animal Care and Use Committee of Fudan University, China(approval No. 201802173 S) on March 3, 2018.     

Restoration of functional network state towards more physiological condition as the correlate of clinical effects of pallidal deep brain stimulation in dystonia

BackgroundDeep brain stimulation of the internal globus pallidus (GPi DBS) is an invasive therapeutic modality intended to retune abnormal central nervous system patterns and relieve the patient of dystonic or other motor symptoms.ObjectivesThe aim of the presented research was to determine the neuroanatomical signature of GPi DBS modulation and its association with the clinical outcome.MethodsThis open-label fixed-order study with cross-sectional validation against healthy controls analysed the resting-state functional MRI activity changes induced by GPi DBS in 18 dystonia patients of heterogeneous aetiology, focusing on both global (full brain) and local connectivity (local signal homogeneity).ResultsCompared to the switched-off state, the activation of GPi DBS led to the restoration of global subcortical connectivity patterns (in both putamina, diencephalon and brainstem) towards those of healthy controls, with positive direct correlation over large-scale cortico-basal ganglia-thalamo-cortical and cerebellar networks with the clinical improvement. Nonetheless, on average, GPi DBS also seemed to bring local connectivity both in the cortical and subcortical regions farther away from the state detected in healthy controls. Interestingly, its correlation with clinical outcome showed that in better DBS responders, local connectivity defied this effect and approached healthy controls.ConclusionsAll in all, the extent of restoration of both these main metrics of interest towards the levels found in healthy controls clearly correlated with the clinical improvement, indicating that the restoration of network state towards more physiological condition may be a precondition for successful GPi DBS outcome in dystonia.     

Cortical mechanisms underlying variability in intermittent theta-burst stimulation-induced plasticity: A TMS-EEG study

ObjectiveTo test the hypothesis that intermittent theta burst stimulation (iTBS) variability depends on the ability to engage specific neurons in the primary motor cortex (M1).MethodsIn a sham-controlled interventional study on 31 healthy volunteers, we used concomitant transcranial magnetic stimulation (TMS) and electroencephalography (EEG). We compared baseline motor evoked potentials (MEPs), M1 iTBS-evoked EEG oscillations, and resting-state EEG (rsEEG) between subjects who did and did not show MEP facilitation following iTBS. We also investigated whether baseline MEP and iTBS-evoked EEG oscillations could explain inter and intraindividual variability in iTBS aftereffects.ResultsThe facilitation group had smaller baseline MEPs than the no-facilitation group and showed more iTBS-evoked EEG oscillation synchronization in the alpha and beta frequency bands. Resting-state EEG power was similar between groups and iTBS had a similar non-significant effect on rsEEG in both groups. Baseline MEP amplitude and beta iTBS-evoked EEG oscillation power explained both inter and intraindividual variability in MEP modulation following iTBS.ConclusionsThe results show that variability in iTBS-associated plasticity depends on baseline corticospinal excitability and on the ability of iTBS to engage M1 beta oscillations.SignificanceThese observations can be used to optimize iTBS investigational and therapeutic applications.     

Gut microbiota interacts with intrinsic brain activity of patients with amnestic mild cognitive impairment

AimsTo explore the potential relationships among gut microbiota (GM), local brain spontaneous activity, and neuropsychological characteristics in amnestic mild cognitive impairment (aMCI) patients.MethodsTwenty aMCI and 22 healthy control (HC) subjects were recruited. The GM composition was determined by 16S ribosomal RNA gene sequencing. Resting‐state functional magnetic resonance imaging scans were performed, and fractional amplitude of low‐frequency fluctuations (fALFF) was calculated across different frequencies. The Spearman or Pearson correlation analysis was used to analyze the relationship between spontaneous brain activity and cognitive function, and GM composition.ResultsaMCI patients had altered GM state and local spontaneous brain activity as compared with HC subjects. Correlation analysis showed that aMCI and HC groups had different “GM‐intrinsic brain activity interaction” patterns. In aMCI group, at the typical band (0.01‐0.08 Hz), the relative abundance (RA) of Bacteroides from phylum to genus level was negatively correlated with fALFF value of cerebellar vermis IV‐V, and the Ruminococcaceae RA was negatively correlated with fALFF values of left lenticular nucleus and pallidum. The Clostridiaceae RA and Blautia RA were positively correlated with the left cerebellum lobules IV‐V at the slow‐4 band (0.027‐0.073 Hz). The Veillonellaceae RA was positively correlated with fALFF values of left precentral gyrus at the slow‐5 band (0.073‐0.08 Hz). Correlation analysis showed that Clostridium members (Lachnospiraceae and Blautia) were positively, while Veillonellaceae was negatively, correlated with cognition test. Bacteroides was positively correlated with attention and computation, and negatively correlated with the three‐stage command score.ConclusionsaMCI patients have a specific GM‐intrinsic brain activity‐cognitive function interaction pattern.     

首发精神分裂症患者静息态脑局部一致性功能性磁共振研究

目的:应用功能性磁共振(f MRI)技术,探讨首发精神分裂症患者静息状态下脑局部一致性(Re Ho)功能变化的特征。方法:对首发未用药精神分裂患者(急性期组)及性别、年龄、受教育年限匹配的经抗精神病药治疗后症状缓解的首发精神分裂症患者(缓解组)各17例,分别进行f MRI扫描,利用Re Ho的方法分析数据,比较两组间Re Ho变化。结果:与急性期组相比,缓解期组表现出右侧颞上回、舌回/梭状回、左侧和右侧额下回、左侧和右侧中央后回、小脑等脑区局部一致性异常,均有统计学意义(P均0.05)。结论:缓解期组较急性期组相比,多个脑区有相应的局部一致性异常,这种脑功能特征的变化,可能与抗精神病药改善症状有关,且可能反映精神分裂症生物内表型的变化。     

精神分裂症首次发病患者额顶网络功能连接与面孔情绪识别能力的关系

目的:探讨首发精神分裂症患者在静息状态下额顶网络的功能连接特点,及其与面孔情绪识别能力的相关性。方法:对37例首发未用药的精神分裂症患者(患者组)和30名年龄、性别、利手、受教育程度与患者相匹配的健康者(正常对照组)进行静息态功能磁共振(f MRI)扫描,收集两组的一般临床特征,并采用面孔情绪测试评价被试的面孔情绪认知功能;以双侧背外侧前额叶(DLPFC)为种子点比较两组间额顶网络功能连接的差异,并分析与面孔情绪认知功能的相关性。结果:与正常对照组相比,患者组DLPFC与左顶下小叶(t=-3.243,Alphasim校正P0.05)、左额下回(t=-3.151,Alphasim校正P0.05)、左额中回(t=-3.151,Alphasim校正P0.05)、双侧尾状核(t=-4.325,Alphasim校正P0.05)、左颞中回(t=-3.120,Alphasim校正P0.05)的功能连接减低;与双侧扣带回中部(t=2.731,Alphasim校正P0.05)、右中央前回(t=3.991,Alphasim校正P0.05)、右岛叶(t=3.991,Alphasim校正P0.05)功能连接增强。患者组额-顶通路的功能连接与面孔情绪认知障碍呈正相关(r=0.501,P0.05)。结论:首发精神分裂症患者额顶网络的功能连接存在异常,其中DLPFC-顶下小叶通路的功能连接降低可能影响患者面孔情绪识别能力。     

未经治疗的强迫障碍患者静息态磁共振脑功能局部一致性研究

目的:采用静息态功能磁共振成像(resting-state functional magnetic resonance imaging, RS-fMRI)技术,探讨未经治疗的强迫障碍(obsessive-compulsive disorder,OCD)患者脑局部一致性(regional homogeneity, ReHo)的变化以及与强迫症状严重程度的相关性?方法:对46例OCD患者和31例性别?年龄?受教育程度相匹配的健康对照进行静息态功能磁共振扫描,使用SPM8?DPARSF?REST等软件对影像学数据进行处理分析,比较两组间全脑ReHo的改变;采用耶鲁-布朗强迫量表(the Yale-Brown Obsessive Compulsive Scale,Y-BOCS)?17项汉密尔顿抑郁量表 (17-Item Hamilton Rating Scale for Depression,HAMD-17)?汉密尔顿焦虑量表(Hamilton Anxiety Rating Scale,HAMA)等评估临床症状,并分析OCD患者脑ReHo值与临床现象之间的关系?结果:和对照组相比,OCD患者左侧前额叶的ReHo值显著升高,左侧颞枕部和双侧梭状回的ReHo值显著降低,以上脑区的ReHo改变均未发现与Y-BOCs量表的相关性?结论:未经治疗的OCD患者在静息态下存在局部脑区的神经元活动一致性异常,这些异常改变可能与OCD的病理机制有关?     

精神分裂症患者及其一级亲属静息态脑功能网络的小世界属性研究

目的:探讨精神分裂症患者及其一级亲属静息态脑功能网络小世界属性特征的异同。方法:对符合DSM-IV诊断标准的33例精神分裂症患者、30例未患病一级亲属和34例健康对照进行静息态脑功能扫描,利用AAL模板将大脑划分为116个脑区并进行网络构建,比较三组被试的网络属性特征。结果:三组静息态脑功能网络均具有小世界属性,但患者组部分脑区节点属性(节点度和节点局部效率)显著异常(p<0.05, Bonferroni校正),主要位于右颞上回、左眶额皮质、左后扣带回和右小脑下叶;亲属组左后扣带回的节点度显著增加。结论:精神分裂症患者和一级亲属都存在左后扣带回节点属性异常,提示左后扣带回功能异常可能是精神分裂症的早期改变且受遗传易感性影响。