Spontaneous recovery frequently proves maladaptive or insufficient because the plasticity of the injured adult mammalian central nervous system is limited.This limited plasticity serves as a primary barrier to functio...Spontaneous recovery frequently proves maladaptive or insufficient because the plasticity of the injured adult mammalian central nervous system is limited.This limited plasticity serves as a primary barrier to functional recovery after brain injury.Neuromodulation technologies represent one of the fastest-growing fields in medicine.These techniques utilize electricity,magnetism,sound,and light to restore or optimize brain functions by promoting reorganization or long-term changes that support functional recovery in patients with brain injury.Therefore,this review aims to provide a comprehensive overview of the effects and underlying mechanisms of neuromodulation technologies in supporting motor function recovery after brain injury.Many of these technologies are widely used in clinical practice and show significant improvements in motor function across various types of brain injury.However,studies report negative findings,potentially due to variations in stimulation protocols,differences in observation periods,and the severity of functional impairments among participants across different clinical trials.Additionally,we observed that different neuromodulation techniques share remarkably similar mechanisms,including promoting neuroplasticity,enhancing neurotrophic factor release,improving cerebral blood flow,suppressing neuroinflammation,and providing neuroprotection.Finally,considering the advantages and disadvantages of various neuromodulation techniques,we propose that future development should focus on closed-loop neural circuit stimulation,personalized treatment,interdisciplinary collaboration,and precision stimulation.展开更多
Noninvasive brain stimulation techniques offer promising therapeutic and regenerative prospects in neurological diseases by modulating brain activity and improving cognitive and motor functions.Given the paucity of kn...Noninvasive brain stimulation techniques offer promising therapeutic and regenerative prospects in neurological diseases by modulating brain activity and improving cognitive and motor functions.Given the paucity of knowledge about the underlying modes of action and optimal treatment modalities,a thorough translational investigation of noninvasive brain stimulation in preclinical animal models is urgently needed.Thus,we reviewed the current literature on the mechanistic underpinnings of noninvasive brain stimulation in models of central nervous system impairment,with a particular emphasis on traumatic brain injury and stroke.Due to the lack of translational models in most noninvasive brain stimulation techniques proposed,we found this review to the most relevant techniques used in humans,i.e.,transcranial magnetic stimulation and transcranial direct current stimulation.We searched the literature in Pub Med,encompassing the MEDLINE and PMC databases,for studies published between January 1,2020 and September 30,2024.Thirty-five studies were eligible.Transcranial magnetic stimulation and transcranial direct current stimulation demonstrated distinct strengths in augmenting rehabilitation post-stroke and traumatic brain injury,with emerging mechanistic evidence.Overall,we identified neuronal,inflammatory,microvascular,and apoptotic pathways highlighted in the literature.This review also highlights a lack of translational surrogate parameters to bridge the gap between preclinical findings and their clinical translation.展开更多
Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in s...Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.展开更多
Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0...Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain injury.Behavioral experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain edema.Next,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 cells.Finally,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain edema.Furthermore,YL-0919 effectively combated oxidative stress both in vivo and in vitro.The protective effects of YL-0919 were partially inhibited by BD-1047.These results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist BD-1047.YL-0919 may have potential as a new treatment for traumatic brain injury.展开更多
Exogenous neural stem cell transplantation has become one of the most promising treatment methods for chronic stroke.Recent studies have shown that most ischemia-reperfusion model rats recover spontaneously after inju...Exogenous neural stem cell transplantation has become one of the most promising treatment methods for chronic stroke.Recent studies have shown that most ischemia-reperfusion model rats recover spontaneously after injury,which limits the ability to observe long-term behavioral recovery.Here,we used a severe stroke rat model with 150 minutes of ischemia,which produced severe behavioral deficiencies that persisted at 12 weeks,to study the therapeutic effect of neural stem cells on neural restoration in chronic stroke.Our study showed that stroke model rats treated with human neural stem cells had long-term sustained recovery of motor function,reduced infarction volume,long-term human neural stem cell survival,and improved local inflammatory environment and angiogenesis.We also demonstrated that transplanted human neural stem cells differentiated into mature neurons in vivo,formed stable functional synaptic connections with host neurons,and exhibited the electrophysiological properties of functional mature neurons,indicating that they replaced the damaged host neurons.The findings showed that human fetal-derived neural stem cells had long-term effects for neurological recovery in a model of severe stroke,which suggests that human neural stem cells-based therapy may be effective for repairing damaged neural circuits in stroke patients.展开更多
The organization of biological neuronal networks into functional modules has intrigued scientists and inspired engineers to develop artificial systems.These networks are characterized by two key properties.First,they ...The organization of biological neuronal networks into functional modules has intrigued scientists and inspired engineers to develop artificial systems.These networks are characterized by two key properties.First,they exhibit dense interconnectivity(Braitenburg and Schüz,1998;Campagnola et al.,2022).The strength and probability of connectivity depend on cell type,inter-neuronal distance,and species.Still,every cortical neuron receives input from thousands of other neurons while transmitting output to a similar number of neurons.Second,communication between neurons occurs primarily via chemical or electrical synapses.展开更多
BACKGROUND Successful aging(SA)refers to the ability to maintain high levels of physical,cognitive,psychological,and social engagement in old age,with high cognitive function being the key to achieving SA.AIM To explo...BACKGROUND Successful aging(SA)refers to the ability to maintain high levels of physical,cognitive,psychological,and social engagement in old age,with high cognitive function being the key to achieving SA.AIM To explore the potential characteristics of the brain network and functional connectivity(FC)of SA.METHODS Twenty-six SA individuals and 47 usual aging individuals were recruited from community-dwelling elderly,which were taken the magnetic resonance imaging scan and the global cognitive function assessment by Mini Mental State Examination(MMSE).The resting state-functional magnetic resonance imaging data were preprocessed by DPABISurf,and the brain functional network was conducted by DPABINet.The support vector machine model was constructed with altered functional connectivities to evaluate the identification value of SA.RESULTS The results found that the 6 inter-network FCs of 5 brain networks were significantly altered and related to MMSE performance.The FC of the right orbital part of the middle frontal gyrus and right angular gyrus was mostly increased and positively related to MMSE score,and the FC of the right supramarginal gyrus and right temporal pole:Middle temporal gyrus was the only one decreased and negatively related to MMSE score.All 17 significantly altered FCs of SA were taken into the support vector machine model,and the area under the curve was 0.895.CONCLUSION The identification of key brain networks and FC of SA could help us better understand the brain mechanism and further explore neuroimaging biomarkers of SA.展开更多
Distinct brain remodeling has been found after different nerve reconstruction strategies,including motor representation of the affected limb.However,differences among reconstruction strategies at the brain network lev...Distinct brain remodeling has been found after different nerve reconstruction strategies,including motor representation of the affected limb.However,differences among reconstruction strategies at the brain network level have not been elucidated.This study aimed to explore intranetwork changes related to altered peripheral neural pathways after different nerve reconstruction surgeries,including nerve repair,endto-end nerve transfer,and end-to-side nerve transfer.Sprague–Dawley rats underwent complete left brachial plexus transection and were divided into four equal groups of eight:no nerve repair,grafted nerve repair,phrenic nerve end-to-end transfer,and end-to-side transfer with a graft sutured to the anterior upper trunk.Resting-state brain functional magnetic resonance imaging was obtained 7 months after surgery.The independent component analysis algorithm was utilized to identify group-level network components of interest and extract resting-state functional connectivity values of each voxel within the component.Alterations in intra-network resting-state functional connectivity were compared among the groups.Target muscle reinnervation was assessed by behavioral observation(elbow flexion)and electromyography.The results showed that alterations in the sensorimotor and interoception networks were mostly related to changes in the peripheral neural pathway.Nerve repair was related to enhanced connectivity within the sensorimotor network,while end-to-side nerve transfer might be more beneficial for restoring control over the affected limb by the original motor representation.The thalamic-cortical pathway was enhanced within the interoception network after nerve repair and end-to-end nerve transfer.Brain areas related to cognition and emotion were enhanced after end-to-side nerve transfer.Our study revealed important brain networks related to different nerve reconstructions.These networks may be potential targets for enhancing motor recovery.展开更多
The rich club,as a community of highly interconnected nodes,serves as the topological center of the network.However,the similarities and differences in how the rich club supports functional integration and segregation...The rich club,as a community of highly interconnected nodes,serves as the topological center of the network.However,the similarities and differences in how the rich club supports functional integration and segregation in the brain across different species remain unknown.In this study,we first detected and validated the rich club in the structural networks of mouse,monkey,and human brains using neuronal tracing or diffusion magnetic resonance imaging data.Further,we assessed the role of rich clubs in functional integration,segregation,and balance using quantitative metrics.Our results indicate that the presence of a rich club facilitates whole-brain functional integration in all three species,with the functional networks of higher species exhibiting greater integration.These findings are expected to help to understand the relationship between brain structure and function from the perspective of brain evolution.展开更多
BACKGROUND Many patients with coronavirus disease 2019(COVID-19)may experience emotional issues and cognitive impairment.However,it remains unclear whether the brain mediates the impact of COVID-19 on the emergence of...BACKGROUND Many patients with coronavirus disease 2019(COVID-19)may experience emotional issues and cognitive impairment.However,it remains unclear whether the brain mediates the impact of COVID-19 on the emergence of psychopathological symptoms.It remains unclear whether anxiety and depression are caused by stressors or viral infection.AIM To use functional near-infrared spectroscopy(fNIRS)to detect cortical hemodynamic changes in patients with COVID-19 and their relationship with mental symptoms(mainly depression and anxiety),to investigate whether COVID-19 causes these changes by affecting brain function.METHODS A total of 58 subjects,comprising 29 patients with first acute COVID-19 infection and 29 healthy controls without COVID-19 infection and without anxiety or depression were recruited.Then cortical activation during the performance of the verbal fluency test(VFT)and brain connectivity during the resting state(rs)were evaluated by 53-channel fNIRS.For the COVID-19-infected group,Patient Health Questionnaire-9(PHQ-9)and General Anxiety Disorder-7(GAD-7)were used to assess the emotional state before fNIRS measures.RESULTS For the rs,compared to the uninfected group,the infected group exhibited lower rs functional connectivity(FC)in the dorsolateral prefrontal cortex(DLPFC),which was correlated with both the PHQ score and GAD score.During the VFT,the infected group exhibited significantly lower cortical activation than the uninfected group in both Broca-left and Broca-right.Besides,the integral value in the DLPFC-L showed a significant negative correlation with the PHQ-9 score during the VFT in the infected group.CONCLUSION There were significant differences in the bilateral Broca area and DLPFC between the COVID-19-infected and uninfected groups,which may be the reason why COVID-19 infection impairs cognitive function and language function and leads to psychiatric symptoms.In addition,the rsFC in patients with COVID-19 was positively correlated with the severity of depression and anxiety,which may be related to the fact that the mental symptoms of patients with COVID-19 are characterized by depression and anxiety,rather than depression or anxiety alone.Our study provides evidence that the psychological and emotional issues caused by COVID-19 are not only due to external social factors but also involve more direct brain neural mechanisms and abnormal neural circuits,which also provide insights into the future treatment and prognosis of individuals with COVID-19.展开更多
This editorial highlighted the central role of pancreatic β-cell dysfunction in the pathogenesis of diabetes mellitus and discussed the emerging significance of Ras homolog enriched in brain 1(Rheb1)as a key regulato...This editorial highlighted the central role of pancreatic β-cell dysfunction in the pathogenesis of diabetes mellitus and discussed the emerging significance of Ras homolog enriched in brain 1(Rheb1)as a key regulator of β-cell mass and insulinsecretory capacity.While molecular mechanisms governing β-cell homeostasis remain incompletely defined,Yang et al have recently demonstrated that Rheb1 could promote β-cell proliferation through dual activation of mechanistic target of rapamycin complex 1 and AMP-activated protein kinase signaling pathways,rather than relying solely on mechanistic target of rapamycin complex 1.Notably,Rheb1 expression is higher in pancreatic islets from younger individuals and upregulates hepatocyte nuclear factor 4 alpha,which is recognized as a transcription factor essential for β-cell identity and insulin production.These insights position Rheb1 as a pivotal regulator of β-cell growth and metabolic function,with potential therapeutic implications for diabetes.Targeting Rheb1 may shift treatment paradigms from conventional glucose-lowering strategies towardβ-cell restoration,providing a novel approach to preserve or enhance functionalβ-cell mass in diabetic patients.Further investigation into Rheb1’s upstream regulators and downstream effectors may provide innovative therapeutic directions.展开更多
Patients with mild traumatic brain injury have a diverse clinical presentation,and the underlying pathophysiology remains poorly understood.Magnetic resonance imaging is a non-invasive technique that has been widely u...Patients with mild traumatic brain injury have a diverse clinical presentation,and the underlying pathophysiology remains poorly understood.Magnetic resonance imaging is a non-invasive technique that has been widely utilized to investigate neuro biological markers after mild traumatic brain injury.This approach has emerged as a promising tool for investigating the pathogenesis of mild traumatic brain injury.G raph theory is a quantitative method of analyzing complex networks that has been widely used to study changes in brain structure and function.However,most previous mild traumatic brain injury studies using graph theory have focused on specific populations,with limited exploration of simultaneous abnormalities in structural and functional connectivity.Given that mild traumatic brain injury is the most common type of traumatic brain injury encounte red in clinical practice,further investigation of the patient characteristics and evolution of structural and functional connectivity is critical.In the present study,we explored whether abnormal structural and functional connectivity in the acute phase could serve as indicators of longitudinal changes in imaging data and cognitive function in patients with mild traumatic brain injury.In this longitudinal study,we enrolled 46 patients with mild traumatic brain injury who were assessed within 2 wee ks of injury,as well as 36 healthy controls.Resting-state functional magnetic resonance imaging and diffusion-weighted imaging data were acquired for graph theoretical network analysis.In the acute phase,patients with mild traumatic brain injury demonstrated reduced structural connectivity in the dorsal attention network.More than 3 months of followup data revealed signs of recovery in structural and functional connectivity,as well as cognitive function,in 22 out of the 46 patients.Furthermore,better cognitive function was associated with more efficient networks.Finally,our data indicated that small-worldness in the acute stage could serve as a predictor of longitudinal changes in connectivity in patients with mild traumatic brain injury.These findings highlight the importance of integrating structural and functional connectivity in unde rstanding the occurrence and evolution of mild traumatic brain injury.Additionally,exploratory analysis based on subnetworks could serve a predictive function in the prognosis of patients with mild traumatic brain injury.展开更多
BACKGROUND Mild cognitive impairment(MCI)has a high risk of progression to Alzheimer’s disease.The disease is often accompanied by sleep disorders,and whether sleep disorders have an effect on brain function in patie...BACKGROUND Mild cognitive impairment(MCI)has a high risk of progression to Alzheimer’s disease.The disease is often accompanied by sleep disorders,and whether sleep disorders have an effect on brain function in patients with MCI is unclear.AIM To explore the near-infrared brain function characteristics of MCI with sleep disorders.METHODS A total of 120 patients with MCI(MCI group)and 50 healthy subjects(control group)were selected.All subjects underwent the functional near-infrared spec-troscopy test.Collect baseline data,Mini-Mental State Examination,Montreal Cognitive Assessment scale,fatigue severity scale(FSS)score,sleep parameter,and oxyhemoglobin(Oxy-Hb)concentration and peak time of functional near-infrared spectroscopy test during the task period.The relationship between Oxy-RESULTS Compared with the control group,the FSS score of the MCI group was higher(t=11.310),and the scores of Pittsburgh sleep quality index,sleep time,sleep efficiency,nocturnal sleep disturbance,and daytime dysfunction were higher(Z=-10.518,-10.368,-9.035,-10.661,-10.088).Subjective sleep quality and total sleep time scores were lower(Z=-11.592,-9.924).The sleep efficiency of the MCI group was lower,and the awakening frequency,rem sleep latency period,total sleep time,and oxygen desaturation index were higher(t=5.969,5.829,2.887,3.003,5.937).The Oxy-Hb concentration at T0,T1,and T2 in the MCI group was lower(t=14.940,11.280,5.721),and the peak time was higher(t=18.800,13.350,9.827).In MCI patients,the concentration of Oxy-Hb during T0 was negatively correlated with the scores of Pittsburgh sleep quality index,sleep time,total sleep time,and sleep efficiency(r=-0.611,-0.388,-0.563,-0.356).It was positively correlated with sleep efficiency and total sleep time(r=0.754,0.650),and negatively correlated with oxygen desaturation index(r=-0.561)and FSS score(r=-0.526).All comparisons were P<0.05.CONCLUSION Patients with MCI and sleep disorders have lower near-infrared brain function than normal people,which is related to sleep quality.Clinically,a comprehensive assessment of the near-infrared brain function of patients should be carried out to guide targeted treatment and improve curative effect.展开更多
Objective Repetitive transcranial magnetic stimulation(rTMS)has demonstrated efficacy in enhancing neurocognitive performance in Alzheimer’s disease(AD),but the neurobiological mechanisms linking synaptic pathology,n...Objective Repetitive transcranial magnetic stimulation(rTMS)has demonstrated efficacy in enhancing neurocognitive performance in Alzheimer’s disease(AD),but the neurobiological mechanisms linking synaptic pathology,neural oscillatory dynamics,and brain network reorganization remain unclear.This investigation seeks to systematically evaluate the therapeutic potential of rTMS as a non-invasive neuromodulatory intervention through a multimodal framework integrating clinical assessments,molecular profiling,and neurophysiological monitoring.Methods In this prospective double-blind trial,12 AD patients underwent a 14-day protocol of 20 Hz rTMS,with comprehensive multimodal assessments performed pre-and postintervention.Cognitive functioning was quantified using the mini-mental state examination(MMSE)and Montreal cognitive assessment(MOCA),while daily living capacities and neuropsychiatric profiles were respectively evaluated through the activities of daily living(ADL)scale and combined neuropsychiatric inventory(NPI)-Hamilton depression rating scale(HAMD).Peripheral blood biomarkers,specifically Aβ1-40 and phosphorylated tau(p-tau181),were analyzed to investigate the effects of rTMS on molecular metabolism.Spectral power analysis was employed to investigate rTMS-induced modulations of neural rhythms in AD patients,while brain network analyses incorporating topological properties were conducted to examine stimulus-driven network reorganization.Furthermore,systematic assessment of correlations between cognitive scale scores,blood biomarkers,and network characteristics was performed to elucidate cross-modal therapeutic associations.Results Clinically,MMSE and MOCA scores improved significantly(P<0.05).Biomarker showed that Aβ1-40 level increased(P<0.05),contrasting with p-tau181 reduction.Moreover,the levels of Aβ1-40 were positively correlated with MMSE and MOCA scores.Post-intervention analyses revealed significant modulations in oscillatory power,characterized by pronounced reductions in delta(P<0.05)and theta bands(P<0.05),while concurrent enhancements were observed in alpha,beta,and gamma band activities(all P<0.05).Network analysis revealed frequency-specific reorganization:clustering coefficients were significantly decreased in delta,theta,and alpha bands(P<0.05),while global efficiency improvement was exclusively detected in the delta band(P<0.05).The alpha band demonstrated concurrent increases in average nodal degree(P<0.05)and characteristic path length reduction(P<0.05).Further research findings indicate that the changes in the clinical scale HAMD scores before and after rTMS stimulation are negatively correlated with the changes in the blood biomarkers Aβ1-40 and p-tau181.Additionally,the changes in the clinical scales MMSE and MoCA scores were negatively correlated with the changes in the node degree of the alpha frequency band and negatively correlated with the clustering coefficient of the delta frequency band.However,the changes in MMSE scores are positively correlated with the changes in global efficiency of both the delta and alpha frequency bands.Conclusion 20 Hz rTMS targeting dorsolateral prefrontal cortex(DLPFC)significantly improves cognitive function and enhances the metabolic clearance ofβ-amyloid and tau proteins in AD patients.This neurotherapeutic effect is mechanistically associated with rTMS-mediated frequency-selective neuromodulation,which enhances the connectivity of oscillatory networks through improved neuronal synchronization and optimized topological organization of functional brain networks.These findings not only support the efficacy of rTMS as an adjunctive therapy for AD but also underscore the importance of employing multiple assessment methods—including clinical scales,blood biomarkers,and EEG——in understanding and monitoring the progression of AD.This research provides a significant theoretical foundation and empirical evidence for further exploration of rTMS applications in AD treatment.展开更多
Mutations in the protocadherin-19(PCDH19)gene(Xq22.1)cause the X-linked syndrome known as developmental and epileptic encephalopathy 9(DEE9,OMIM#300088)(Dibbens et al.,2008).DEE9 is characterized by early-onset cluste...Mutations in the protocadherin-19(PCDH19)gene(Xq22.1)cause the X-linked syndrome known as developmental and epileptic encephalopathy 9(DEE9,OMIM#300088)(Dibbens et al.,2008).DEE9 is characterized by early-onset clustering epilepsy associated with intellectual disability ranging from mild to profound,autism spectrum disorder,and other neuropsychiatric features including schizophrenia,anxiety,attentiondeficit/hyperactivity,and obsessive or aggressive behaviors.While seizures may become less frequent in adolescence,psychiatric comorbidities persist and often worsen with age(Dibbens et al.,2008;Kolc et al.,2020).展开更多
Dementias such as Alzheimer disease(AD)and mild cognitive impairment(MCI)lead to problems with memory,language,and daily activities resulting from damage to neurons in the brain.Given the irreversibility of this neuro...Dementias such as Alzheimer disease(AD)and mild cognitive impairment(MCI)lead to problems with memory,language,and daily activities resulting from damage to neurons in the brain.Given the irreversibility of this neuronal damage,it is crucial to find a biomarker to distinguish individuals with these diseases from healthy people.In this study,we construct a brain function network based on electroencephalography data to study changes in AD and MCI patients.Using a graph-theoretical approach,we examine connectivity features and explore their contributions to dementia recognition at edge,node,and network levels.We find that connectivity is reduced in AD and MCI patients compared with healthy controls.We also find that the edge-level features give the best performance when machine learning models are used to recognize dementia.The results of feature selection identify the top 50 ranked edge-level features constituting an optimal subset,which is mainly connected with the frontal nodes.A threshold analysis reveals that the performance of edge-level features is more sensitive to the threshold for the connection strength than that of node-and network-level features.In addition,edge-level features with a threshold of 0 provide the most effective dementia recognition.The K-nearest neighbors(KNN)machine learning model achieves the highest accuracy of 0.978 with the optimal subset when the threshold is 0.Visualization of edge-level features suggests that there are more long connections linking the frontal region with the occipital and parietal regions in AD and MCI patients compared with healthy controls.Our codes are publicly available at https://github.com/Debbie-85/eeg-connectivity.展开更多
In the present study, 10 patients with ischemic stroke in the left hemisphere and six healthy controls were subjected to acupuncture at right Waiguan （TE5）. In ischemic stroke subjects, functional MRI showed enhance...In the present study, 10 patients with ischemic stroke in the left hemisphere and six healthy controls were subjected to acupuncture at right Waiguan （TE5）. In ischemic stroke subjects, functional MRI showed enhanced activation in Broadmann areas 5, 6, 7, 18, 19, 24, 32, the hypothalamic inferior lobe, the mamiilary body, and the ventral posterolateral nucleus of the left hemisphere, and Broadmann areas 4, 6, 7, 18, 19 and 32 of the right hemisphere, but attenuated activation of Broadmann area 13, the hypothalamic inferior lobe, the posterior lobe of the tonsil of cerebellum, and the culmen of the anterior lobe of hypophysis, in the left hemisphere and Broadmann area 13 in the right hemisphere. In ischemic stroke subjects, a number of deactivated brain areas were enhanced, including Broadmann areas 6, 11,20, 22, 37, and 47, the culmen of the anterior lobe of hypophysis, alae lingulae cerebella, and the posterior lobe of the tonsil of cerebellum of the left hemisphere, and Broadmann areas 8, 37, 45 and 47, the culmen of the anterior lobe of hypophysis, pars tuberalis adenohypophyseos, inferior border of lentiform nucleus, lateral globus pallidus, inferior temporal gyrus, and the parahippocampal gyrus of the right hemisphere. These subjects also exhibited attenuation of a number of deactivated brain areas, including Broadmann area 7. These data suggest that acupuncture at Waiguan specifically alters brain function in regions associated with sensation, vision, and motion in ischemic stroke patients. By contrast, in normal individuals, acupuncture at Waiguan generally activates brain areas associated with insomnia and other functions.展开更多
Fifty-one patients with mild （n -- 14）, moderate （n = 10） and severe traumatic brain injury （n = 27） received early rehabilitation. Level of consciousness was evaluated using the Glasgow Coma Score Functional le...Fifty-one patients with mild （n -- 14）, moderate （n = 10） and severe traumatic brain injury （n = 27） received early rehabilitation. Level of consciousness was evaluated using the Glasgow Coma Score Functional level was determined using the Glasgow Outcome Score, whilst mobility was evaluated using the Mobility Scale for Acute Stroke. Activities of daily living were assessed using the Barthel Index. Following Bobath neurodevelopmental therapy, the level of consciousness was significantly improved in patients with moderate and severe traumatic brain injury, but was not greatly influenced in patients with mild traumatic brain injury. Mobility and functional level were significantly improved in patients with mild, moderate and severe traumatic brain injury. Gait recovery was more obvious in patients with mild traumatic brain injury than in patients with moderate and severe traumatic brain injury. Activities of daily living showed an improvement but this was insignificant except for patients with severe traumatic brain injury. Nevertheless, complete recovery was not acquired at discharge. Multiple regression analysis showed that gait and Glasgow Coma Scale scores can be considered predictors of functional outcomes following traumatic brain injury.展开更多
BACKGROUND:Post-cardiac arrest syndrome(PCAS) significantly contributes to mortality after initially successful cardiopulmonary resuscitation(CPR) in cardiac arrest(CA) patients.Effective cardiocerebral protection is ...BACKGROUND:Post-cardiac arrest syndrome(PCAS) significantly contributes to mortality after initially successful cardiopulmonary resuscitation(CPR) in cardiac arrest(CA) patients.Effective cardiocerebral protection is essential for improving post-resuscitation survival.This study investigated the mechanisms and common targets of myocardial dysfunction and brain injury after resuscitation.METHODS:The male Sprague-Dawley rats(10–12 weeks old,400–500 g) were divided into two groups:the control group(n=6),which received sham surgery,and the CA/CPR group(n=10),which received ventricular fibrillation(VF) followed by CPR.After 24 h,brain and heart tissues were collected for analysis.The sequencing was used to identify differentially expressed genes(DEGs) between control and CA/CPR rats.RESULTS:At 24 h after resuscitation,CA/CPR rats presented 217 DEGs in the hippocampus and 80 DEGs in the left ventricle(LV) compared to the control group.In the hippocampus,the most notable biological process was the positive regulation of tumor necrosis factor production,with key pathways related to inflammation and the immune response.In the LV,the Gene Ontology(GO)enrichment analysis revealed that gene alterations were primarily associated with amyloid-beta clearance,a pathway that was also relevant in the brain.Eleven common targets were identified in the DEGs of both heart and brain tissues.The reverse transcription-polymerase chain reaction(RTPCR) validation revealed significant differences in the mRNA expression of Timp1,Apln,Ccl7,and Lgals3 in both LV and hippocampus.CONCLUSION:This study identified possible key genes and underlying mechanisms involved in PCAS.The differential genes Timp1,Apln,Ccl7,and Lgals3 might serve as common biomarkers for myocardial and neurological injury following resuscitation.展开更多
It has since long been known, from everyday experience as well as from animal and human studies, that psychological processes-both affective and cognitive- exert an influence on gastrointestinal sensorimotor function....It has since long been known, from everyday experience as well as from animal and human studies, that psychological processes-both affective and cognitive- exert an influence on gastrointestinal sensorimotor function. More specifically, a link between psychological factors and visceral hypersensitivity has been suggested, mainly based on research in functional gastrointestinal disorder patients. However, until recently, the exact nature of this putative relationship remained unclear, mainly due to a lack of non-invasive methods to study the （neurobiological） mechanisms underlying this relationship in non-sleeping humans. As functional brain imaging, introduced in visceral sensory neuroscience some 10 years ago, does provide a method for in vivo study of brain-gut interactions, insight into the neurobiological mechanisms underlying visceral sensation in general and the influence of psychological factors more particularly, has rapidly grown. In this article, an overview of brain imaging evidence on gastrointestinal sensation will be given, with special emphasis on the brain mechanisms underlying the interaction between affective ＆ cognitive processes and visceral sensation. First, the reciprocal neural pathways between the brain and the gut （brain- gut axis） will be briefly outlined, including brain imaging evidence in healthy volunteers. Second, functional brain imaging studies assessing the influence of psychological factors on brain processing of visceral sensation in healthy humans will be discussed in more detail. Finally, brain imaging work investigating differences in brain responses to visceral distension between healthy volunteers and functional gastrointestinal disorder patients will be highlighted.展开更多
基金supported by the National Natural Science Foundation of China,No.82371399(to YY)the Natural Science Foundation of Jiangsu Province,No.BK20221206(to YY)+1 种基金the Young Elite Scientists Sponsorship Program of Jiangsu Province,No.TJ-2022-028(to YY)the Scientific Research Program of Wuxi Health Commission,No.Z202302(to LY)。
文摘Spontaneous recovery frequently proves maladaptive or insufficient because the plasticity of the injured adult mammalian central nervous system is limited.This limited plasticity serves as a primary barrier to functional recovery after brain injury.Neuromodulation technologies represent one of the fastest-growing fields in medicine.These techniques utilize electricity,magnetism,sound,and light to restore or optimize brain functions by promoting reorganization or long-term changes that support functional recovery in patients with brain injury.Therefore,this review aims to provide a comprehensive overview of the effects and underlying mechanisms of neuromodulation technologies in supporting motor function recovery after brain injury.Many of these technologies are widely used in clinical practice and show significant improvements in motor function across various types of brain injury.However,studies report negative findings,potentially due to variations in stimulation protocols,differences in observation periods,and the severity of functional impairments among participants across different clinical trials.Additionally,we observed that different neuromodulation techniques share remarkably similar mechanisms,including promoting neuroplasticity,enhancing neurotrophic factor release,improving cerebral blood flow,suppressing neuroinflammation,and providing neuroprotection.Finally,considering the advantages and disadvantages of various neuromodulation techniques,we propose that future development should focus on closed-loop neural circuit stimulation,personalized treatment,interdisciplinary collaboration,and precision stimulation.
基金funded by the Deutsche Forschungsgemeinschaft(DFG,German Research Foundation):project ID 431549029-SFB 1451the Marga-und-Walter-Boll-Stiftung(#210-10-15)(to MAR)a stipend from the'Gerok Program'(Faculty of Medicine,University of Cologne,Germany)。
文摘Noninvasive brain stimulation techniques offer promising therapeutic and regenerative prospects in neurological diseases by modulating brain activity and improving cognitive and motor functions.Given the paucity of knowledge about the underlying modes of action and optimal treatment modalities,a thorough translational investigation of noninvasive brain stimulation in preclinical animal models is urgently needed.Thus,we reviewed the current literature on the mechanistic underpinnings of noninvasive brain stimulation in models of central nervous system impairment,with a particular emphasis on traumatic brain injury and stroke.Due to the lack of translational models in most noninvasive brain stimulation techniques proposed,we found this review to the most relevant techniques used in humans,i.e.,transcranial magnetic stimulation and transcranial direct current stimulation.We searched the literature in Pub Med,encompassing the MEDLINE and PMC databases,for studies published between January 1,2020 and September 30,2024.Thirty-five studies were eligible.Transcranial magnetic stimulation and transcranial direct current stimulation demonstrated distinct strengths in augmenting rehabilitation post-stroke and traumatic brain injury,with emerging mechanistic evidence.Overall,we identified neuronal,inflammatory,microvascular,and apoptotic pathways highlighted in the literature.This review also highlights a lack of translational surrogate parameters to bridge the gap between preclinical findings and their clinical translation.
基金supported by the National Natural Science Foundation of China,Nos.82072165 and 82272256(both to XM)the Key Project of Xiangyang Central Hospital,No.2023YZ03(to RM)。
文摘Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.
基金supported by the National Natural Science Foundation of China,Nos.82204360(to HM)and 82270411(to GW)National Science and Technology Innovation 2030 Major Program,No.2021ZD0200900(to YL)。
文摘Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain injury.Behavioral experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain edema.Next,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 cells.Finally,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain edema.Furthermore,YL-0919 effectively combated oxidative stress both in vivo and in vitro.The protective effects of YL-0919 were partially inhibited by BD-1047.These results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist BD-1047.YL-0919 may have potential as a new treatment for traumatic brain injury.
文摘Exogenous neural stem cell transplantation has become one of the most promising treatment methods for chronic stroke.Recent studies have shown that most ischemia-reperfusion model rats recover spontaneously after injury,which limits the ability to observe long-term behavioral recovery.Here,we used a severe stroke rat model with 150 minutes of ischemia,which produced severe behavioral deficiencies that persisted at 12 weeks,to study the therapeutic effect of neural stem cells on neural restoration in chronic stroke.Our study showed that stroke model rats treated with human neural stem cells had long-term sustained recovery of motor function,reduced infarction volume,long-term human neural stem cell survival,and improved local inflammatory environment and angiogenesis.We also demonstrated that transplanted human neural stem cells differentiated into mature neurons in vivo,formed stable functional synaptic connections with host neurons,and exhibited the electrophysiological properties of functional mature neurons,indicating that they replaced the damaged host neurons.The findings showed that human fetal-derived neural stem cells had long-term effects for neurological recovery in a model of severe stroke,which suggests that human neural stem cells-based therapy may be effective for repairing damaged neural circuits in stroke patients.
基金supported in part by the Rosetrees Trust(#CF-2023-I-2_113)by the Israel Ministry of Innovation,Science,and Technology(#7393)(to ES).
文摘The organization of biological neuronal networks into functional modules has intrigued scientists and inspired engineers to develop artificial systems.These networks are characterized by two key properties.First,they exhibit dense interconnectivity(Braitenburg and Schüz,1998;Campagnola et al.,2022).The strength and probability of connectivity depend on cell type,inter-neuronal distance,and species.Still,every cortical neuron receives input from thousands of other neurons while transmitting output to a similar number of neurons.Second,communication between neurons occurs primarily via chemical or electrical synapses.
基金Supported by the Wuxi Municipal Health Commission Major Project,No.Z202107。
文摘BACKGROUND Successful aging(SA)refers to the ability to maintain high levels of physical,cognitive,psychological,and social engagement in old age,with high cognitive function being the key to achieving SA.AIM To explore the potential characteristics of the brain network and functional connectivity(FC)of SA.METHODS Twenty-six SA individuals and 47 usual aging individuals were recruited from community-dwelling elderly,which were taken the magnetic resonance imaging scan and the global cognitive function assessment by Mini Mental State Examination(MMSE).The resting state-functional magnetic resonance imaging data were preprocessed by DPABISurf,and the brain functional network was conducted by DPABINet.The support vector machine model was constructed with altered functional connectivities to evaluate the identification value of SA.RESULTS The results found that the 6 inter-network FCs of 5 brain networks were significantly altered and related to MMSE performance.The FC of the right orbital part of the middle frontal gyrus and right angular gyrus was mostly increased and positively related to MMSE score,and the FC of the right supramarginal gyrus and right temporal pole:Middle temporal gyrus was the only one decreased and negatively related to MMSE score.All 17 significantly altered FCs of SA were taken into the support vector machine model,and the area under the curve was 0.895.CONCLUSION The identification of key brain networks and FC of SA could help us better understand the brain mechanism and further explore neuroimaging biomarkers of SA.
基金supported by the National Natural Science Foundation of China,Nos.81871836(to MZ),82172554(to XH),and 81802249(to XH),81902301(to JW)the National Key R&D Program of China,Nos.2018YFC2001600(to JX)and 2018YFC2001604(to JX)+3 种基金Shanghai Rising Star Program,No.19QA1409000(to MZ)Shanghai Municipal Commission of Health and Family Planning,No.2018YQ02(to MZ)Shanghai Youth Top Talent Development PlanShanghai“Rising Stars of Medical Talent”Youth Development Program,No.RY411.19.01.10(to XH)。
文摘Distinct brain remodeling has been found after different nerve reconstruction strategies,including motor representation of the affected limb.However,differences among reconstruction strategies at the brain network level have not been elucidated.This study aimed to explore intranetwork changes related to altered peripheral neural pathways after different nerve reconstruction surgeries,including nerve repair,endto-end nerve transfer,and end-to-side nerve transfer.Sprague–Dawley rats underwent complete left brachial plexus transection and were divided into four equal groups of eight:no nerve repair,grafted nerve repair,phrenic nerve end-to-end transfer,and end-to-side transfer with a graft sutured to the anterior upper trunk.Resting-state brain functional magnetic resonance imaging was obtained 7 months after surgery.The independent component analysis algorithm was utilized to identify group-level network components of interest and extract resting-state functional connectivity values of each voxel within the component.Alterations in intra-network resting-state functional connectivity were compared among the groups.Target muscle reinnervation was assessed by behavioral observation(elbow flexion)and electromyography.The results showed that alterations in the sensorimotor and interoception networks were mostly related to changes in the peripheral neural pathway.Nerve repair was related to enhanced connectivity within the sensorimotor network,while end-to-side nerve transfer might be more beneficial for restoring control over the affected limb by the original motor representation.The thalamic-cortical pathway was enhanced within the interoception network after nerve repair and end-to-end nerve transfer.Brain areas related to cognition and emotion were enhanced after end-to-side nerve transfer.Our study revealed important brain networks related to different nerve reconstructions.These networks may be potential targets for enhancing motor recovery.
基金supported by STI2030-Major Projects(2021ZD0200200)the National Natural Science Foundation of China(62327805 and 82151307)+1 种基金the Equipment Development Project of the Chinese Academy of Sciences(YJKYYQ20190040)the Science and Technology Innovation Program of Hunan Province(2024RC4028).
文摘The rich club,as a community of highly interconnected nodes,serves as the topological center of the network.However,the similarities and differences in how the rich club supports functional integration and segregation in the brain across different species remain unknown.In this study,we first detected and validated the rich club in the structural networks of mouse,monkey,and human brains using neuronal tracing or diffusion magnetic resonance imaging data.Further,we assessed the role of rich clubs in functional integration,segregation,and balance using quantitative metrics.Our results indicate that the presence of a rich club facilitates whole-brain functional integration in all three species,with the functional networks of higher species exhibiting greater integration.These findings are expected to help to understand the relationship between brain structure and function from the perspective of brain evolution.
基金Supported by Hunan Provincial Scientific Research Plan Project of Traditional Chinese MedicineNational Natural Science Foundation of China,No.82371521Special Tasks for the Construction of Hunan Innovative Province,No.2023SK4002.
文摘BACKGROUND Many patients with coronavirus disease 2019(COVID-19)may experience emotional issues and cognitive impairment.However,it remains unclear whether the brain mediates the impact of COVID-19 on the emergence of psychopathological symptoms.It remains unclear whether anxiety and depression are caused by stressors or viral infection.AIM To use functional near-infrared spectroscopy(fNIRS)to detect cortical hemodynamic changes in patients with COVID-19 and their relationship with mental symptoms(mainly depression and anxiety),to investigate whether COVID-19 causes these changes by affecting brain function.METHODS A total of 58 subjects,comprising 29 patients with first acute COVID-19 infection and 29 healthy controls without COVID-19 infection and without anxiety or depression were recruited.Then cortical activation during the performance of the verbal fluency test(VFT)and brain connectivity during the resting state(rs)were evaluated by 53-channel fNIRS.For the COVID-19-infected group,Patient Health Questionnaire-9(PHQ-9)and General Anxiety Disorder-7(GAD-7)were used to assess the emotional state before fNIRS measures.RESULTS For the rs,compared to the uninfected group,the infected group exhibited lower rs functional connectivity(FC)in the dorsolateral prefrontal cortex(DLPFC),which was correlated with both the PHQ score and GAD score.During the VFT,the infected group exhibited significantly lower cortical activation than the uninfected group in both Broca-left and Broca-right.Besides,the integral value in the DLPFC-L showed a significant negative correlation with the PHQ-9 score during the VFT in the infected group.CONCLUSION There were significant differences in the bilateral Broca area and DLPFC between the COVID-19-infected and uninfected groups,which may be the reason why COVID-19 infection impairs cognitive function and language function and leads to psychiatric symptoms.In addition,the rsFC in patients with COVID-19 was positively correlated with the severity of depression and anxiety,which may be related to the fact that the mental symptoms of patients with COVID-19 are characterized by depression and anxiety,rather than depression or anxiety alone.Our study provides evidence that the psychological and emotional issues caused by COVID-19 are not only due to external social factors but also involve more direct brain neural mechanisms and abnormal neural circuits,which also provide insights into the future treatment and prognosis of individuals with COVID-19.
基金Supported by Hubei Provincial Natural Science Foundation,No.2025AFB845Graduate Innovation and Entrepreneurship Fund of Wuhan University of Science and Technology,No.JCX2024044.
文摘This editorial highlighted the central role of pancreatic β-cell dysfunction in the pathogenesis of diabetes mellitus and discussed the emerging significance of Ras homolog enriched in brain 1(Rheb1)as a key regulator of β-cell mass and insulinsecretory capacity.While molecular mechanisms governing β-cell homeostasis remain incompletely defined,Yang et al have recently demonstrated that Rheb1 could promote β-cell proliferation through dual activation of mechanistic target of rapamycin complex 1 and AMP-activated protein kinase signaling pathways,rather than relying solely on mechanistic target of rapamycin complex 1.Notably,Rheb1 expression is higher in pancreatic islets from younger individuals and upregulates hepatocyte nuclear factor 4 alpha,which is recognized as a transcription factor essential for β-cell identity and insulin production.These insights position Rheb1 as a pivotal regulator of β-cell growth and metabolic function,with potential therapeutic implications for diabetes.Targeting Rheb1 may shift treatment paradigms from conventional glucose-lowering strategies towardβ-cell restoration,providing a novel approach to preserve or enhance functionalβ-cell mass in diabetic patients.Further investigation into Rheb1’s upstream regulators and downstream effectors may provide innovative therapeutic directions.
基金supported by the National Natural Science Foundation of China,Nos.81671671(to JL),61971451(to JL),U22A2034(to XK),62177047(to XK)the National Defense Science and Technology Collaborative Innovation Major Project of Central South University,No.2021gfcx05(to JL)+6 种基金Clinical Research Cen terfor Medical Imaging of Hunan Province,No.2020SK4001(to JL)Key Emergency Project of Pneumonia Epidemic of Novel Coronavirus Infection of Hu nan Province,No.2020SK3006(to JL)Innovative Special Construction Foundation of Hunan Province,No.2019SK2131(to JL)the Science and Technology lnnovation Program of Hunan Province,Nos.2021RC4016(to JL),2021SK53503(to ML)Scientific Research Program of Hunan Commission of Health,No.202209044797(to JL)Central South University Research Program of Advanced Interdisciplinary Studies,No.2023Q YJC020(to XK)the Natural Science Foundation of Hunan Province,No.2022JJ30814(to ML)。
文摘Patients with mild traumatic brain injury have a diverse clinical presentation,and the underlying pathophysiology remains poorly understood.Magnetic resonance imaging is a non-invasive technique that has been widely utilized to investigate neuro biological markers after mild traumatic brain injury.This approach has emerged as a promising tool for investigating the pathogenesis of mild traumatic brain injury.G raph theory is a quantitative method of analyzing complex networks that has been widely used to study changes in brain structure and function.However,most previous mild traumatic brain injury studies using graph theory have focused on specific populations,with limited exploration of simultaneous abnormalities in structural and functional connectivity.Given that mild traumatic brain injury is the most common type of traumatic brain injury encounte red in clinical practice,further investigation of the patient characteristics and evolution of structural and functional connectivity is critical.In the present study,we explored whether abnormal structural and functional connectivity in the acute phase could serve as indicators of longitudinal changes in imaging data and cognitive function in patients with mild traumatic brain injury.In this longitudinal study,we enrolled 46 patients with mild traumatic brain injury who were assessed within 2 wee ks of injury,as well as 36 healthy controls.Resting-state functional magnetic resonance imaging and diffusion-weighted imaging data were acquired for graph theoretical network analysis.In the acute phase,patients with mild traumatic brain injury demonstrated reduced structural connectivity in the dorsal attention network.More than 3 months of followup data revealed signs of recovery in structural and functional connectivity,as well as cognitive function,in 22 out of the 46 patients.Furthermore,better cognitive function was associated with more efficient networks.Finally,our data indicated that small-worldness in the acute stage could serve as a predictor of longitudinal changes in connectivity in patients with mild traumatic brain injury.These findings highlight the importance of integrating structural and functional connectivity in unde rstanding the occurrence and evolution of mild traumatic brain injury.Additionally,exploratory analysis based on subnetworks could serve a predictive function in the prognosis of patients with mild traumatic brain injury.
文摘BACKGROUND Mild cognitive impairment(MCI)has a high risk of progression to Alzheimer’s disease.The disease is often accompanied by sleep disorders,and whether sleep disorders have an effect on brain function in patients with MCI is unclear.AIM To explore the near-infrared brain function characteristics of MCI with sleep disorders.METHODS A total of 120 patients with MCI(MCI group)and 50 healthy subjects(control group)were selected.All subjects underwent the functional near-infrared spec-troscopy test.Collect baseline data,Mini-Mental State Examination,Montreal Cognitive Assessment scale,fatigue severity scale(FSS)score,sleep parameter,and oxyhemoglobin(Oxy-Hb)concentration and peak time of functional near-infrared spectroscopy test during the task period.The relationship between Oxy-RESULTS Compared with the control group,the FSS score of the MCI group was higher(t=11.310),and the scores of Pittsburgh sleep quality index,sleep time,sleep efficiency,nocturnal sleep disturbance,and daytime dysfunction were higher(Z=-10.518,-10.368,-9.035,-10.661,-10.088).Subjective sleep quality and total sleep time scores were lower(Z=-11.592,-9.924).The sleep efficiency of the MCI group was lower,and the awakening frequency,rem sleep latency period,total sleep time,and oxygen desaturation index were higher(t=5.969,5.829,2.887,3.003,5.937).The Oxy-Hb concentration at T0,T1,and T2 in the MCI group was lower(t=14.940,11.280,5.721),and the peak time was higher(t=18.800,13.350,9.827).In MCI patients,the concentration of Oxy-Hb during T0 was negatively correlated with the scores of Pittsburgh sleep quality index,sleep time,total sleep time,and sleep efficiency(r=-0.611,-0.388,-0.563,-0.356).It was positively correlated with sleep efficiency and total sleep time(r=0.754,0.650),and negatively correlated with oxygen desaturation index(r=-0.561)and FSS score(r=-0.526).All comparisons were P<0.05.CONCLUSION Patients with MCI and sleep disorders have lower near-infrared brain function than normal people,which is related to sleep quality.Clinically,a comprehensive assessment of the near-infrared brain function of patients should be carried out to guide targeted treatment and improve curative effect.
文摘Objective Repetitive transcranial magnetic stimulation(rTMS)has demonstrated efficacy in enhancing neurocognitive performance in Alzheimer’s disease(AD),but the neurobiological mechanisms linking synaptic pathology,neural oscillatory dynamics,and brain network reorganization remain unclear.This investigation seeks to systematically evaluate the therapeutic potential of rTMS as a non-invasive neuromodulatory intervention through a multimodal framework integrating clinical assessments,molecular profiling,and neurophysiological monitoring.Methods In this prospective double-blind trial,12 AD patients underwent a 14-day protocol of 20 Hz rTMS,with comprehensive multimodal assessments performed pre-and postintervention.Cognitive functioning was quantified using the mini-mental state examination(MMSE)and Montreal cognitive assessment(MOCA),while daily living capacities and neuropsychiatric profiles were respectively evaluated through the activities of daily living(ADL)scale and combined neuropsychiatric inventory(NPI)-Hamilton depression rating scale(HAMD).Peripheral blood biomarkers,specifically Aβ1-40 and phosphorylated tau(p-tau181),were analyzed to investigate the effects of rTMS on molecular metabolism.Spectral power analysis was employed to investigate rTMS-induced modulations of neural rhythms in AD patients,while brain network analyses incorporating topological properties were conducted to examine stimulus-driven network reorganization.Furthermore,systematic assessment of correlations between cognitive scale scores,blood biomarkers,and network characteristics was performed to elucidate cross-modal therapeutic associations.Results Clinically,MMSE and MOCA scores improved significantly(P<0.05).Biomarker showed that Aβ1-40 level increased(P<0.05),contrasting with p-tau181 reduction.Moreover,the levels of Aβ1-40 were positively correlated with MMSE and MOCA scores.Post-intervention analyses revealed significant modulations in oscillatory power,characterized by pronounced reductions in delta(P<0.05)and theta bands(P<0.05),while concurrent enhancements were observed in alpha,beta,and gamma band activities(all P<0.05).Network analysis revealed frequency-specific reorganization:clustering coefficients were significantly decreased in delta,theta,and alpha bands(P<0.05),while global efficiency improvement was exclusively detected in the delta band(P<0.05).The alpha band demonstrated concurrent increases in average nodal degree(P<0.05)and characteristic path length reduction(P<0.05).Further research findings indicate that the changes in the clinical scale HAMD scores before and after rTMS stimulation are negatively correlated with the changes in the blood biomarkers Aβ1-40 and p-tau181.Additionally,the changes in the clinical scales MMSE and MoCA scores were negatively correlated with the changes in the node degree of the alpha frequency band and negatively correlated with the clustering coefficient of the delta frequency band.However,the changes in MMSE scores are positively correlated with the changes in global efficiency of both the delta and alpha frequency bands.Conclusion 20 Hz rTMS targeting dorsolateral prefrontal cortex(DLPFC)significantly improves cognitive function and enhances the metabolic clearance ofβ-amyloid and tau proteins in AD patients.This neurotherapeutic effect is mechanistically associated with rTMS-mediated frequency-selective neuromodulation,which enhances the connectivity of oscillatory networks through improved neuronal synchronization and optimized topological organization of functional brain networks.These findings not only support the efficacy of rTMS as an adjunctive therapy for AD but also underscore the importance of employing multiple assessment methods—including clinical scales,blood biomarkers,and EEG——in understanding and monitoring the progression of AD.This research provides a significant theoretical foundation and empirical evidence for further exploration of rTMS applications in AD treatment.
基金supported by a grant from Telethon Foundation(grant No.GGP20056 to SB)The generation of Pcdh19 floxed mouse model was funded by Cariplo Foundation(grant No.2014-0972 to SB)。
文摘Mutations in the protocadherin-19(PCDH19)gene(Xq22.1)cause the X-linked syndrome known as developmental and epileptic encephalopathy 9(DEE9,OMIM#300088)(Dibbens et al.,2008).DEE9 is characterized by early-onset clustering epilepsy associated with intellectual disability ranging from mild to profound,autism spectrum disorder,and other neuropsychiatric features including schizophrenia,anxiety,attentiondeficit/hyperactivity,and obsessive or aggressive behaviors.While seizures may become less frequent in adolescence,psychiatric comorbidities persist and often worsen with age(Dibbens et al.,2008;Kolc et al.,2020).
基金supported by the National Natural Science Foundation of China(Grant Nos.62071451,62331025,and U21A20447)the National Key Research and Development Project(Grant No.2021YFC3002204)the CAMS Innovation Fund for Medical Sciences(Grant No.2019-I2M-5-019).
文摘Dementias such as Alzheimer disease(AD)and mild cognitive impairment(MCI)lead to problems with memory,language,and daily activities resulting from damage to neurons in the brain.Given the irreversibility of this neuronal damage,it is crucial to find a biomarker to distinguish individuals with these diseases from healthy people.In this study,we construct a brain function network based on electroencephalography data to study changes in AD and MCI patients.Using a graph-theoretical approach,we examine connectivity features and explore their contributions to dementia recognition at edge,node,and network levels.We find that connectivity is reduced in AD and MCI patients compared with healthy controls.We also find that the edge-level features give the best performance when machine learning models are used to recognize dementia.The results of feature selection identify the top 50 ranked edge-level features constituting an optimal subset,which is mainly connected with the frontal nodes.A threshold analysis reveals that the performance of edge-level features is more sensitive to the threshold for the connection strength than that of node-and network-level features.In addition,edge-level features with a threshold of 0 provide the most effective dementia recognition.The K-nearest neighbors(KNN)machine learning model achieves the highest accuracy of 0.978 with the optimal subset when the threshold is 0.Visualization of edge-level features suggests that there are more long connections linking the frontal region with the occipital and parietal regions in AD and MCI patients compared with healthy controls.Our codes are publicly available at https://github.com/Debbie-85/eeg-connectivity.
基金supported by the National Basic Research Program of China(973 Program),No.2006CB504505,2012CB518504the Third Key Construction Program of "211 Project" of Guangdong Province
文摘In the present study, 10 patients with ischemic stroke in the left hemisphere and six healthy controls were subjected to acupuncture at right Waiguan （TE5）. In ischemic stroke subjects, functional MRI showed enhanced activation in Broadmann areas 5, 6, 7, 18, 19, 24, 32, the hypothalamic inferior lobe, the mamiilary body, and the ventral posterolateral nucleus of the left hemisphere, and Broadmann areas 4, 6, 7, 18, 19 and 32 of the right hemisphere, but attenuated activation of Broadmann area 13, the hypothalamic inferior lobe, the posterior lobe of the tonsil of cerebellum, and the culmen of the anterior lobe of hypophysis, in the left hemisphere and Broadmann area 13 in the right hemisphere. In ischemic stroke subjects, a number of deactivated brain areas were enhanced, including Broadmann areas 6, 11,20, 22, 37, and 47, the culmen of the anterior lobe of hypophysis, alae lingulae cerebella, and the posterior lobe of the tonsil of cerebellum of the left hemisphere, and Broadmann areas 8, 37, 45 and 47, the culmen of the anterior lobe of hypophysis, pars tuberalis adenohypophyseos, inferior border of lentiform nucleus, lateral globus pallidus, inferior temporal gyrus, and the parahippocampal gyrus of the right hemisphere. These subjects also exhibited attenuation of a number of deactivated brain areas, including Broadmann area 7. These data suggest that acupuncture at Waiguan specifically alters brain function in regions associated with sensation, vision, and motion in ischemic stroke patients. By contrast, in normal individuals, acupuncture at Waiguan generally activates brain areas associated with insomnia and other functions.
文摘Fifty-one patients with mild （n -- 14）, moderate （n = 10） and severe traumatic brain injury （n = 27） received early rehabilitation. Level of consciousness was evaluated using the Glasgow Coma Score Functional level was determined using the Glasgow Outcome Score, whilst mobility was evaluated using the Mobility Scale for Acute Stroke. Activities of daily living were assessed using the Barthel Index. Following Bobath neurodevelopmental therapy, the level of consciousness was significantly improved in patients with moderate and severe traumatic brain injury, but was not greatly influenced in patients with mild traumatic brain injury. Mobility and functional level were significantly improved in patients with mild, moderate and severe traumatic brain injury. Gait recovery was more obvious in patients with mild traumatic brain injury than in patients with moderate and severe traumatic brain injury. Activities of daily living showed an improvement but this was insignificant except for patients with severe traumatic brain injury. Nevertheless, complete recovery was not acquired at discharge. Multiple regression analysis showed that gait and Glasgow Coma Scale scores can be considered predictors of functional outcomes following traumatic brain injury.
基金supported by the National High Level Hospital Clinical Research Funding (2022-NHLHCRF-YS-03)the National Natural Science Foundation of China (82272196)。
文摘BACKGROUND:Post-cardiac arrest syndrome(PCAS) significantly contributes to mortality after initially successful cardiopulmonary resuscitation(CPR) in cardiac arrest(CA) patients.Effective cardiocerebral protection is essential for improving post-resuscitation survival.This study investigated the mechanisms and common targets of myocardial dysfunction and brain injury after resuscitation.METHODS:The male Sprague-Dawley rats(10–12 weeks old,400–500 g) were divided into two groups:the control group(n=6),which received sham surgery,and the CA/CPR group(n=10),which received ventricular fibrillation(VF) followed by CPR.After 24 h,brain and heart tissues were collected for analysis.The sequencing was used to identify differentially expressed genes(DEGs) between control and CA/CPR rats.RESULTS:At 24 h after resuscitation,CA/CPR rats presented 217 DEGs in the hippocampus and 80 DEGs in the left ventricle(LV) compared to the control group.In the hippocampus,the most notable biological process was the positive regulation of tumor necrosis factor production,with key pathways related to inflammation and the immune response.In the LV,the Gene Ontology(GO)enrichment analysis revealed that gene alterations were primarily associated with amyloid-beta clearance,a pathway that was also relevant in the brain.Eleven common targets were identified in the DEGs of both heart and brain tissues.The reverse transcription-polymerase chain reaction(RTPCR) validation revealed significant differences in the mRNA expression of Timp1,Apln,Ccl7,and Lgals3 in both LV and hippocampus.CONCLUSION:This study identified possible key genes and underlying mechanisms involved in PCAS.The differential genes Timp1,Apln,Ccl7,and Lgals3 might serve as common biomarkers for myocardial and neurological injury following resuscitation.
文摘It has since long been known, from everyday experience as well as from animal and human studies, that psychological processes-both affective and cognitive- exert an influence on gastrointestinal sensorimotor function. More specifically, a link between psychological factors and visceral hypersensitivity has been suggested, mainly based on research in functional gastrointestinal disorder patients. However, until recently, the exact nature of this putative relationship remained unclear, mainly due to a lack of non-invasive methods to study the （neurobiological） mechanisms underlying this relationship in non-sleeping humans. As functional brain imaging, introduced in visceral sensory neuroscience some 10 years ago, does provide a method for in vivo study of brain-gut interactions, insight into the neurobiological mechanisms underlying visceral sensation in general and the influence of psychological factors more particularly, has rapidly grown. In this article, an overview of brain imaging evidence on gastrointestinal sensation will be given, with special emphasis on the brain mechanisms underlying the interaction between affective ＆ cognitive processes and visceral sensation. First, the reciprocal neural pathways between the brain and the gut （brain- gut axis） will be briefly outlined, including brain imaging evidence in healthy volunteers. Second, functional brain imaging studies assessing the influence of psychological factors on brain processing of visceral sensation in healthy humans will be discussed in more detail. Finally, brain imaging work investigating differences in brain responses to visceral distension between healthy volunteers and functional gastrointestinal disorder patients will be highlighted.
