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Neurons in cortical circuits are often coactivated as ensembles, yet it is unclear whether ensembles play a functional role in behavior. Some ensemble neurons have pattern completion properties, triggering the entire ensemble when activated. Using two-photon holographic optogenetics in mouse primary visual cortex, we tested whether recalling ensembles by activating pattern completion neurons alters behavioral performance in a visual task. Disruption of behaviorally relevant ensembles by activation of non-selective neurons decreased performance, whereas activation of only two pattern completion neurons from behaviorally relevant ensembles improved performance, by reliably recalling the whole ensemble. Also, inappropriate behavioral choices were evoked by the mistaken activation of behaviorally relevant ensembles. Finally, in absence of visual stimuli, optogenetic activation of two pattern completion neurons could trigger behaviorally relevant ensembles and correct behavioral responses. Our results demonstrate a causal role of neuronal ensembles in a visually guided behavior and suggest that ensembles implement internal representations of perceptual states.
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Comportamento Animal , Córtex Visual/fisiologia , Animais , Área Sob a Curva , Cálcio/metabolismo , Holografia , Processamento de Imagem Assistida por Computador , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Optogenética/métodos , Estimulação Luminosa , Fótons , Curva ROCRESUMO
BACKGROUND: The changes that occur in the gamma-aminobutyric acid (GABA) levels within specific brain regions throughout the day are less clear. PURPOSE: To evaluate the daily fluctuations of GABA levels within the parietal lobe (PL) and anterior cingulate gyrus (ACC) regions and explore their association with melatonin (MT) levels, heart rate (HR), and blood pressure. STUDY TYPE: Prospective. SUBJECTS: 26 healthy young adults (15 males and 11 females aged 22-27 years). FIELD STRENGTH/SEQUENCE: 3.0T, T1-weighted imaging, Mescher-Garwood point resolved spectroscopy (MEGA-PRESS) sequence. ASSESSMENT: The acquired GABA signal contained the overlapping signals of macromolecules and homocarnosine, hence expressed as GABA+. The creatine (Cr) signal was applied as an endogenous reference. The GABA+, GABA+/Cr were measured at six different time points (1:00, 5:00, 9:00, 13:00, 17:00, and 21:00 hours) using MEGA-PRESS. The blood pressure, HR and sputum MT levels, were also acquired. STATISTICAL TESTS: The one-way repeated-measures analysis of variance (ANOVA) was used to evaluate the GABA, blood pressure, HR, and MT levels throughout the day. A general linear model was used to find the correlation between GABA and blood pressure, HR, and MT. P < 0.05 was statistically significant. RESULTS: Significant variations in GABA+/Cr and GABA+ levels were observed throughout the day within the PL region. The lowest levels were recorded at 9:00 hour (GABA+/Cr: 0.100 ± 0.003ï¼GABA+:1.877 ± 0.051 i.u) and the highest levels were recorded at 21:00 hour (GABA+/Cr: 0.115 ± 0.003, GABA+:2.122 ± 0.052 i.u). The MT levels were positively correlated with GABA+/Cr (r = 0.301) and GABA+ (r = 0.312) within the ACC region. DATA CONCLUSION: GABA+/Cr and GABA+ in ACC are positively correlated with MT. GABA levels in the PL have diurnal differences. These findings may indicate that the body's GABA level change in response to the light-dark cycle. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.
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Prolonged medically induced coma (pMIC) is carried out routinely in intensive care medicine. pMIC leads to cognitive impairment, yet the underlying neuromorphological correlates are still unknown, as no direct studies of MIC exceeding â¼6 h on neural circuits exist. Here, we establish pMIC (up to 24 h) in adolescent and mature mice, and combine longitudinal two-photon imaging of cortical synapses with repeated behavioral object recognition assessments. We find that pMIC affects object recognition, and that it is associated with enhanced synaptic turnover, generated by enhanced synapse formation during pMIC, while the postanesthetic period is dominated by synaptic loss. Our results demonstrate major side effects of prolonged anesthesia on neural circuit structure.
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Anestesia Geral/efeitos adversos , Encéfalo/patologia , Coma/patologia , Animais , Encéfalo/fisiopatologia , Cognição , Coma/fisiopatologia , Feminino , Masculino , Camundongos , Plasticidade Neuronal , Sinapses/patologiaRESUMO
Neural processing of sensory information is strongly influenced by context. For instance, cortical responses are reduced to predictable stimuli, while responses are increased to novel stimuli that deviate from contextual regularities. Such bidirectional modulation based on preceding sensory context is likely a critical component or manifestation of attention, learning, and behavior, yet how it arises in cortical circuits remains unclear. Using volumetric two-photon calcium imaging and local field potentials in primary visual cortex (V1) from awake mice presented with visual "oddball" paradigms, we identify both reductions and augmentations of stimulus-evoked responses depending, on whether the stimulus was redundant or deviant, respectively. Interestingly, deviance-augmented responses were limited to a specific subset of neurons mostly in supragranular layers. These deviance-detecting cells were spatially intermixed with other visually responsive neurons and were functionally correlated, forming a neuronal ensemble. Optogenetic suppression of prefrontal inputs to V1 reduced the contextual selectivity of deviance-detecting ensembles, demonstrating a causal role for top-down inputs. The presence of specialized context-selective ensembles in primary sensory cortex, modulated by higher cortical areas, provides a circuit substrate for the brain's construction and selection of prediction errors, computations which are key for survival and deficient in many psychiatric disorders.
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Córtex Cerebral/fisiologia , Neurônios/fisiologia , Percepção Visual , Animais , Cálcio/metabolismo , Córtex Cerebral/citologia , Conectoma , Potenciais Evocados Visuais , Camundongos , Camundongos Endogâmicos C57BL , Microscopia de Fluorescência por Excitação Multifotônica , Neurônios/metabolismoRESUMO
Neuronal ensembles are groups of neurons with coordinated activity that could represent sensory, motor, or cognitive states. The study of how neuronal ensembles are built, recalled, and involved in the guiding of complex behaviors has been limited by the lack of experimental and analytical tools to reliably identify and manipulate neurons that have the ability to activate entire ensembles. Such pattern completion neurons have also been proposed as key elements of artificial and biological neural networks. Indeed, the relevance of pattern completion neurons is highlighted by growing evidence that targeting them can activate neuronal ensembles and trigger behavior. As a method to reliably detect pattern completion neurons, we use conditional random fields (CRFs), a type of probabilistic graphical model. We apply CRFs to identify pattern completion neurons in ensembles in experiments using in vivo two-photon calcium imaging from primary visual cortex of male mice and confirm the CRFs predictions with two-photon optogenetics. To test the broader applicability of CRFs we also analyze publicly available calcium imaging data (Allen Institute Brain Observatory dataset) and demonstrate that CRFs can reliably identify neurons that predict specific features of visual stimuli. Finally, to explore the scalability of CRFs we apply them to in silico network simulations and show that CRFs-identified pattern completion neurons have increased functional connectivity. These results demonstrate the potential of CRFs to characterize and selectively manipulate neural circuits.SIGNIFICANCE STATEMENT We describe a graph theory method to identify and optically manipulate neurons with pattern completion capability in mouse cortical circuits. Using calcium imaging and two-photon optogenetics in vivo we confirm that key neurons identified by this method can recall entire neuronal ensembles. This method could be broadly applied to manipulate neuronal ensemble activity to trigger behavior or for therapeutic applications in brain prostheses.
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Modelos Neurológicos , Neurônios/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Probabilidade , Córtex Visual/fisiologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microscopia de Fluorescência por Excitação Multifotônica/métodos , Neurônios/química , Optogenética/métodos , Estimulação Luminosa/métodos , Córtex Visual/química , Córtex Visual/citologiaRESUMO
Advanced, late-stage Epstein-Barr virus (EBV)-positive nasopharyngeal carcinoma (NPC) is incurable, and its treatment remains a clinical and therapeutic challenge. Results from a phase II clinical trial in advanced NPC patients employing a combined chemotherapy and EBV-specific T cell (EBVST) immunotherapy regimen showed a response rate of 71.4%. Longitudinal analysis of patient samples showed that an increase in EBV DNA plasma concentrations and the peripheral monocyte-to-lymphocyte ratio negatively correlated with overall survival. These parameters were combined into a multivariate analysis to stratify patients according to risk of death. Immunophenotyping at serial time points showed that low-risk individuals displayed significantly decreased amounts of monocytic myeloid-derived suppressor cells postchemotherapy, which subsequently influenced successful cytotoxic T-lymphocyte (CTL) immunotherapy. Examination of the low-risk group, 2 weeks post-EBVST infusion, showed that individuals with a greater overall survival possessed an increased frequency of CD8 central and effector memory T cells, together with higher levels of plasma interferon (IFN)-γ, and cytotoxic lymphocyte-associated transcripts. These results highlight the importance of the rational selection of chemotherapeutic agents and consideration of their impact on both systemic immune responses and downstream cellular immunotherapy outcomes.
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Imunoterapia Adotiva , Células Supressoras Mieloides/imunologia , Carcinoma Nasofaríngeo/imunologia , Carcinoma Nasofaríngeo/terapia , Linfócitos T/imunologia , Infecções por Vírus Epstein-Barr/imunologia , Herpesvirus Humano 4/imunologia , Humanos , Imunoterapia Adotiva/métodos , Células Supressoras Mieloides/metabolismo , Carcinoma Nasofaríngeo/patologia , Linfócitos T/metabolismo , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/metabolismo , Falha de Tratamento , Resultado do TratamentoRESUMO
Inactivation of horseradish peroxidase by hydrogen peroxide (H2O2) treatment is a convenient alternative to stripping for sequential chemiluminescent western blotting (WB). However, little evidence exists on whether H2O2 treatment affects epitope recognition. Here we show that H2O2 treatment had a negligible effect for most of the tested antibodies, whereas it could also eliminate or enhance antibody binding. Thus, H2O2 treatment has unpredictable effects on epitope recognition. Moreover, we demonstrate potential steric hindrance from previously bound antibodies. Hence, it would be advantageous to pre-test the suitability of antibodies for H2O2-treated WB, and to optimize conditions to mitigate steric interference with re-probing.
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Western Blotting , Epitopos/análise , Epitopos/efeitos dos fármacos , Peróxido de Hidrogênio/farmacologiaRESUMO
Neuronal necrosis induced by calcium overload causes devastating brain dysfunction in diseases such as stroke and brain trauma. It has been considered a stochastic event lacking genetic regulation, and pharmacological means to suppress neuronal necrosis are lacking. Using a Drosophila model of calcium overloading, we found JIL-1/mitogen- and stress-activated protein kinase 1/2 is a regulator of neuronal necrosis through phosphorylation of histone H3 serine 28 (H3S28ph). Further, we identified its downstream events including displacement of polycomb repressive complex 1 (PRC1) and activation of Trithorax (Trx). To test the role of JIL-1/PRC1/Trx cascade in mammals, we studied the necrosis induced by glutamate in rat cortical neuron cultures and rodent models of brain ischemia and found the cascade is activated in these conditions and inhibition of the cascade suppresses necrosis in vitro and in vivo. Together, our research demonstrates that neuronal necrosis is regulated by a chromatin-modifying cascade, and this discovery may provide potential therapeutic targets and biomarkers for neuronal necrosis.
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Cálcio/metabolismo , Cromatina/metabolismo , Neurônios/metabolismo , Animais , Biomarcadores/metabolismo , Cromatina/patologia , Proteínas Cromossômicas não Histona/genética , Proteínas Cromossômicas não Histona/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster , Feminino , Histonas/genética , Histonas/metabolismo , Sistema de Sinalização das MAP Quinases/genética , Masculino , Camundongos , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Necrose , Neurônios/patologia , Proteínas do Grupo Polycomb/genética , Proteínas do Grupo Polycomb/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
Animals adapt to a constantly changing world by predicting their environment and the consequences of their actions. The predictive coding hypothesis proposes that the brain generates predictions and continuously compares them with sensory inputs to guide behavior. However, how the brain reconciles conflicting top-down predictions and bottom-up sensory information remains unclear. To address this question, we simultaneously imaged neuronal populations in the mouse somatosensory barrel cortex and posterior parietal cortex during an auditory-cued texture discrimination task. In mice that had learned the task with fixed tone-texture matching, the presentation of mismatched pairing induced conflicts between tone-based texture predictions and actual texture inputs. When decisions were based on the predicted rather than the actual texture, top-down information flow was dominant and texture representations in both areas were modified, whereas dominant bottom-up information flow led to correct representations and behavioral choice. Our findings provide evidence for hierarchical predictive coding in the mouse neocortex.
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Percepção Auditiva , Neocórtex , Camundongos , Animais , Percepção Auditiva/fisiologia , Lobo Parietal/fisiologia , Córtex Somatossensorial/fisiologia , Discriminação Psicológica/fisiologiaRESUMO
The role of developmental cell death in the formation of brain circuits is not well understood. Cajal-Retzius cells constitute a major transient neuronal population in the mammalian neocortex, which largely disappears at the time of postnatal somatosensory maturation. In this study, we used mouse genetics, anatomical, functional, and behavioral approaches to explore the impact of the early postnatal death of Cajal-Retzius cells in the maturation of the cortical circuit. We find that before their death, Cajal-Retzius cells mainly receive inputs from layer 1 neurons, which can only develop their mature connectivity onto layer 2/3 pyramidal cells after Cajal-Retzius cells disappear. This developmental connectivity progression from layer 1 GABAergic to layer 2/3 pyramidal cells regulates sensory-driven inhibition within, and more so, across cortical columns. Here we show that Cajal-Retzius cell death prevention leads to layer 2/3 hyper-excitability, delayed learning and reduced performance in a multi-whisker-dependent texture discrimination task.
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Morte Celular , Células Piramidais , Córtex Somatossensorial , Animais , Córtex Somatossensorial/fisiologia , Córtex Somatossensorial/citologia , Camundongos , Células Piramidais/fisiologia , Células Piramidais/metabolismo , Neocórtex/citologia , Neocórtex/fisiologia , Neurônios GABAérgicos/fisiologia , Neurônios GABAérgicos/metabolismo , Masculino , Vibrissas/fisiologia , Feminino , Camundongos Endogâmicos C57BL , Inibição Neural/fisiologia , Neurônios/fisiologia , Neurônios/metabolismoRESUMO
The authors present the case of a 59-year-old lady diagnosed with lymphoepithelial carcinoma (LEC) of the left parotid gland. The primary tumour was identified using contrast-enhanced CT, and diagnosis was confirmed via fine needle aspiration cytology and immunohistochemistry. Staging using fluorine-18 fluorodeoxyglucose PET CT revealed regional nodal metastases, while no distant metastasis was evident. Following radical radiotherapy, a favourable locoregional response was observed on MRI, yet the patient's plasma Epstein-Barr virus load continued to rise. Given her primary tumour's somatostatin receptor type 2 (SSTR2) positivity, gallium-68 DOTA-[Tyr3] octreotate PET CT (68Ga-DOTATATE PET CT) was performed, revealing multiple distant metastases with DOTATATE avidity. Despite attempts at palliative chemotherapy and immunotherapy, disease progression led to the decision for the best supportive care. The unique presentation of metastatic LEC on 68Ga-DOTATATE PET CT suggests a potential role for SSTR2-targeted imaging in diagnosis and management.
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PURPOSE: The neural pathophysiology underlying primary dysmenorrhea (PDM), which leads to poor mode and changes in central pain modulatory systems, remains largely unknown. The objective of this study was to investigate the changes in glutamate/glutamine (Glx) and gamma-aminobutyric acid (GABA+) levels within anterior cingulate cortex (ACC), and their associations with clinical indicators in PDM women. METHODS: Using 3 T proton magnetic resonance spectroscopy (1H-MRS), we acquired and compared ACC-Glx and ACC-GABA+ levels in PDMs (N = 41) and age- and education-matched healthy controls (HCs) (N = 39) during both the menstrual and periovulatory phases, and between menstrual and periovulatory phases within each group. Total creatine (Cr referencing) level was used as an endogenous reference. The correlations of ACC-neurotransmitter levels with clinical characteristics and the correlations of ACC-Glx with ACC-GABA+ levels in the two groups were analyzed. RESULTS: Compared to HCs or the periovulatory phase, PDMs exhibited significantly increased ACC-Glx levels (p < 0.05) during the menstrual phase. Positive correlations between GABA+ and Glx levels (r = 0.385, p = 0.025) were found in PDMs during the menstrual phase. ACC-GABA+ levels were associated with self-rating distress scale (SDS) scores (GABA+/Cr: r = 0.369, p = 0.045) and pain catastrophizing scale (PCS) scores (GABA+/Cr: r = 0.373, p = 0.042) in PDM group in only the menstrual phase. CONCLUSION: Our study represents the first report of ACC-GABA+/Glx imbalances in PDMs during the menstrual phase, which may underlie the mechanisms mediating depression and painful catastrophic symptoms.
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Dismenorreia , Giro do Cíngulo , Humanos , Feminino , Giro do Cíngulo/diagnóstico por imagem , Dismenorreia/diagnóstico por imagem , Espectroscopia de Prótons por Ressonância Magnética , Creatina , Ácido gama-AminobutíricoRESUMO
ABSTRACT: We present a case of a 59-year-old woman with lymphoepithelial carcinoma of left parotid gland. She was treated with radical radiotherapy, but her plasma Epstein-Barr virus DNA load continued to increase despite good locoregional response. As her primary tumor was positive for somatostatin receptor type 2, we performed 68 Ga-DOTATATE PET/CT, which revealed multiple DOTATATE-avid distant metastases.
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Carcinoma de Células Escamosas , Infecções por Vírus Epstein-Barr , Compostos Organometálicos , Feminino , Humanos , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Glândula Parótida , Herpesvirus Humano 4RESUMO
Epstein-Barr virus (EBV), one of the most common human viruses, has been associated with both lymphoid and epithelial cancers. Undifferentiated nasopharyngeal carcinoma (NPC), EBV associated gastric cancer (EBVaGC) and lymphoepithelioma-like carcinoma (LELC) are amongst the few common epithelial cancers that EBV has been associated with. The pathogenesis of EBV-associated NPC has been well described, however, the same cannot be said for primary pulmonary LELC (PPLELC) owing to the rarity of the cancer. In this review, we outline the pathogenesis of EBV-associated NPC and EBVaGCs and their recent advances. By drawing on similarities between NPC and PPLELC, we then also postulated the pathogenesis of PPLELC. A deeper understanding about the pathogenesis of EBV enables us to postulate the pathogenesis of other EBV associated cancers such as PPLELC.
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PURPOSE: This study aimed to explore the changes in gamma-aminobutyric acid (GABA) and glutamate (Glu) levels, and their correlations with clinical indicators in patients with postherpetic neuralgia (PHN). METHODS: A totally of 22 PHN patients and 21 sex-, age-, and education-matched healthy controls (HCs) underwent proton magnetic resonance spectroscopy scanning. The spectral data of GABA in the precuneus was obtained by Mescher-Garwood point-resolved spectroscopy, whereas the spectral data of Glu, total N-acetyl-l-aspartic acid (tNAA) and total choline (tCho) were obtained by point-resolved spectroscopy. The pain intensity of PHN was assessed by numeric rating scales (NRS). The edited GABA signal was displayed as GABA+ due to overlapping macromolecules and homocarnosine signals. Total creatine (tCr) level in individual was used as an endogenous reference. The neurometabolites levels of PHN patients were compared with those of healthy individuals and the correlations with clinical variables (pain duration and intensity) were analyzed. RESULTS: PHN patients had higher GABA+/tCr levels in the precuneus than HCs (P = 0.009), with no significant differences in the levels of Glu/ tCr, tNAA/ tCr and tCho/ tCr (all P > 0.05). The GABA+/ tCr levels were positively correlated with the NRS scores of the PHN patients (r = 0.473, P = 0.030). CONCLUSION: Increased GABA+/tCr levels in the precuneus and their association with pain intensity of PHN patients suggested a key role of the abnormalities of regional GABAergic neurons in the pathophysiological mechanisms of pain in PHN.
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Neuralgia Pós-Herpética , Humanos , Espectroscopia de Prótons por Ressonância Magnética/métodos , Neuralgia Pós-Herpética/diagnóstico por imagem , Medição da Dor , Ácido gama-Aminobutírico , Ácido Glutâmico , Lobo Parietal , Creatina , Colina , Receptores de Antígenos de Linfócitos TRESUMO
OBJECTIVE: To investigate the value of pre-treatment spectral CT angiography (CTA) in predicting hemorrhagic transformation (HT) after intravenous thrombolysis (IVT) treatment in acute ischemic stroke (AIS) patients. MATERIALS AND METHODS: AIS patients who underwent IVT with recombinant tissue plasminogen activator and pre-treatment head and neck spectral CTA and head CT perfusion (CTP) from January 2018 to June 2020 were reviewed retrospectively. Finally, 20 patients were included in the HT group and 22 age-matched patients were included in the non-HT group. Spectral and CTP parameters of the region of interest on pre-treatment CTA axial raw images and CTP images, including the infarct core (IC) and ischemic penumbral (IP) regions, were recorded. The differences in clinical variables, CTP, collateral scores and spectral parameters between the two groups were analyzed. Three multivariate logistic regression models were then developed, where model 1 included clinical and spectral parameters, model 2 included clinical and CTP parameters and a combined model included clinical, CTP, and spectral parameters. Receiver operating characteristic analysis was used to evaluate the performance of the multivariate model. RESULTS: Patients with HT had higher Safe Implementation of Treatments in Stroke (SITS) score (p = 0.023), the volume of perfusion lesions (p = 0.005), the volume of IP (p = 0.003), the mean transit time (MIT) in the IC area (p = 0.012), as well as the TTP in IP area (p = 0.015) compared with patients without HT. The HT group showed significantly lower CBF in the IC area (p = 0.019), iodine concentration (p = 0.017) and the effective atomic number (p = 0.024) in the IP area than non-HT group. And the slope of the spectral curve of the HT group in the IP region was larger than that of the non-HT group (p = 0.023). Gender, age, SITS score, the volume of entire perfusion lesion, CBF and MIT in the IC area, TTP in the IP area, as well as iodine concentration in the IP area were included in the final multivariate model for predicting HT. And CBF in the IC area (OR = 0.779, 95 % CI:0.609-0.996, p = 0.046) as well as the iodine concentration of IP area (OR = 0.343, 95 % CI: 0.131-0.901, p = 0.030) were proved to be independent predictors for HT. The combined model including clinical, spectral, and CTP parameters, showed improved accuracy compared to the other two models, while the Delong test did not suggest a statistically significant difference (both p values > 0.05). CONCLUSIONS: The iodine concentration of IP area derived from pre-treatment spectral CTA was an independent predictor of HT after IVT treatment for AIS patients. Moreover, multivariate models combined with clinical, spectral, and CTP parameters may be able to predict HT.
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Isquemia Encefálica , Iodo , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Ativador de Plasminogênio Tecidual/uso terapêutico , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/tratamento farmacológico , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/tratamento farmacológico , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/patologia , Tomografia Computadorizada por Raios X/métodos , Terapia Trombolítica , Imagem de Perfusão/métodosRESUMO
Increasing neurophysiological studies had revealed that regional excitation-inhibition imbalance in the brain played a key role in the pathogenesis of migraine. This study aimed to explore the alterations in gamma-aminobutyric acid (GABA) and glutamate/glutamine complex (Glx) levels in the anterior cingulate gyrus (ACC) and medial prefrontal lobe (mPFC) of patients with migraine without aura (MWoA) and investigate the correlation between neurotransmitter levels and clinical indicators. A total of 28 patients with MWoA and 28 sex-, age-, and education level-matched healthy controls (HCs) underwent single-voxel proton magnetic resonance spectroscopy scanning at 3.0 Tesla. MEscher-Garwood Point RESolved Spectroscopy (MEGA-PRESS) sequence was performed to acquire the spectral data of GABA and Glx in the ACC and mPFC. The clinical indicators and anxiety-depression states of all participants were assessed. The acquired GABA signal contained the overlapping signals of macromolecules and homocarnosine, hence expressed as GABA+. The creatine (Cr) signal was applied as an endogenous reference. We observed that GABA+/Cr levels were significantly lower in ACC and mPFC of patients with MWoA than of HCs, with no significant difference in Glx levels. Negative correlations between GABA+/Cr levels and attack frequency were found in the ACC and mPFC regions of patients. These results suggested that there might be a close relationship between ACC and mPFC GABAergic neurons abnormalities and the pathophysiological mechanisms of MWoA. It might be beneficial to targeted treatment for patients with MWoA.
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Enxaqueca sem Aura , Creatina , Ácido Glutâmico , Glutamina , Giro do Cíngulo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética/métodos , Enxaqueca sem Aura/diagnóstico por imagem , Espectroscopia de Prótons por Ressonância Magnética , Ácido gama-AminobutíricoRESUMO
BACKGROUND: Cognitive impairment is one of the common symptoms in patients with neuromyelitis optica spectrum disorder (NMOSD). However, the underlying mechanism remains unclear. Resting-state functional magnetic resonance imaging (rs-fMRI) offers the opportunity to reveal the patterns of brain activity in patients with different cognitive states. Accordingly, this study investigated functional connectivity (FC) abnormalities within and between the main cognitive networks in cognitively impaired (CI) patients with NMOSD and their correlations with cognitive performance. METHODS: Thirty-four patients with NMOSD and 39 healthy controls (HC) were included. Neuropsychological evaluations and rs-fMRI scanning were performed. Patients were classified as CI (n = 16) or cognitively preserved (CP; n = 18) according to neuropsychological evaluations. Seven components representing six main cognitive networks were selected by group independent component analysis. The differences in inter- and intranetwork FC among CI, CP, and HC groups were assessed. The correlation between FC values and neuropsychological data in NMOSD was calculated. RESULTS: The CI group showed decreased intranetwork connectivity in the posterior default mode network (pDMN) compared with the HC group (P < 0.05, GRF corrected), and decreased internetwork connectivity between the salience network (SN) and pDMN, and between the SN and right frontoparietal network (rFPN) compared with CP and HC groups. The altered FC values were significantly correlated with cognitive performance in the whole NMOSD group. CONCLUSION: The disconnection within the pDMN and between the SN and pDMN or rFPN might suggest the neural substrates underlying cognitive impairment in NMOSD.
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Disfunção Cognitiva , Neuromielite Óptica , Humanos , Mapeamento Encefálico/métodos , Neuromielite Óptica/complicações , Neuromielite Óptica/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologiaRESUMO
BACKGROUND: Cognitive impairment is a symptom present in part of patients with neuromyelitis optica spectrum disorder (NMOSD) and its pathophysiology is unknown. Dysfunction of the GABAergic/glutamatergic pathways involving inhibitory and excitatory neurotransmitters have been implicated in several neurological disorders. This study aimed to investigate the changes in inhibitory gamma-aminobutyric acid (GABA) and excitatory glutamate and glutamine (Glx) neurotransmitter levels and their correlations with cognitive functions in patients with NMOSD. METHODS: A total of 29 patients with NMOSD and 28 sex-, age-, and education-matched healthy controls (HCs) were included in the study. All participants underwent clinical and cognitive assessments and proton magnetic resonance spectroscopy scanning. Meshcher-Garwood point-resolved spectroscopy was used to measure GABA and Glx levels in the medial prefrontal cortex (mPFC) and left thalamus. Total creatine (tCr) was applied as an internal reference. The GABA and Glx levels in the patient group were compared with those in HCs and correlated with cognitive scores and clinical variables. RESULTS: Patients with NMOSD showed lower GABA+/tCr levels in the mPFC compared with HCs (P = 0.028). The GABA+/tCr levels in the mPFC were significantly associated with verbal memory performance (r = 0.462, P = 0.027) and overall cognition (r = 0.440, P = 0.035) in the NMOSD group. The GABA+/tCr levels in the left thalamus or Glx/tCr levels in both regions were not significantly different between groups, nor were they related to any cognitive domain in patients with NMOSD (all P values > 0.05). CONCLUSION: The GABA+ levels in the mPFC decreased and correlated with cognitive dysfunction in patients with NMOSD, suggesting that the changes in regional GABA+ levels might be a potential metabolic feature of cognitive decline in patients with NMOSD.
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Disfunção Cognitiva , Neuromielite Óptica , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Ácido Glutâmico/metabolismo , Humanos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética/métodos , Neuromielite Óptica/complicações , Neuromielite Óptica/diagnóstico por imagem , Neuromielite Óptica/metabolismo , Córtex Pré-Frontal/diagnóstico por imagem , Ácido gama-Aminobutírico/análiseRESUMO
Postherpetic neuralgia (PHN) is a chronic neuropathic pain syndrome, similar to other chronic pains, the mechanisms of which are not fully understood. To further understand the neural mechanism of this chronic pain and its transition, we performed functional magnetic resonance imaging (fMRI) scans on PHN rat models. Twelve PHN rat models were established by intraperitoneal injection of resiniferatoxin, with an additional 12 rats serving as controls. Nociceptive behavioral tests were performed on these rats and fMRI scans were performed on days 7 and 14 after modeling. Functional connection (FC) analysis was used to investigate the brain FC alterations associated with chronic pain in PHN rats, with the anterior cingulate cortex (ACC) as a seed. Nociceptive behavioral tests showed that PHN rats presented symptoms similar to those of PHN patients. FC analysis showed that compared to the control group, the PHN group showed different FC patterns on days 7 and 14. As can be seen, the brain FC alterations in the rat model of PHN changed dynamically, shifting from brain regions processing sensory information to regions processing emotions and motives.