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AIMS: Reward processing and regulation of emotions are thought to impact the development of addictive behaviors. In this study, we aimed to determine whether neural responses during reward anticipation, threat appraisal, emotion reactivity, and cognitive reappraisal predicted the transition from low-level to hazardous alcohol use over a 12-month period. METHODS: Seventy-eight individuals aged 18-22 with low-level alcohol use [i.e. Alcohol Use Disorder Identification Test (AUDIT) score <7] at baseline were enrolled. They completed reward-based and emotion regulation tasks during magnetic resonance imaging to examine reward anticipation, emotional reactivity, cognitive reappraisal, and threat anticipation (in the nucleus accumbens, amygdala, superior frontal gyrus, and insula, respectively). Participants completed self-report measures at 3-, 6-, 9-, and 12-month follow-up time points to determine if they transitioned to hazardous use (as defined by AUDIT scores ≥8). RESULTS: Of the 57 participants who completed follow-up, 14 (24.6%) transitioned to hazardous alcohol use. Higher baseline AUDIT scores were associated with greater odds of transitioning to hazardous use (odds ratio = 1.73, 95% confidence interval 1.13-2.66, P = .005). Brain activation to reward, threat, and emotion regulation was not associated with alcohol use. Of the neural variables, the amygdala response to negative imagery was numerically larger in young adults who transitioned to hazardous use (g = 0.31), but this effect was not significant. CONCLUSIONS: Baseline drinking levels were significantly associated with the transition to hazardous alcohol use. Studies with larger samples and longer follow-up should test whether the amygdala response to negative emotional imagery can be used to indicate a future transition to hazardous alcohol use.
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Regulação Emocional , Imageamento por Ressonância Magnética , Recompensa , Humanos , Masculino , Feminino , Adulto Jovem , Regulação Emocional/fisiologia , Adolescente , Alcoolismo/psicologia , Alcoolismo/fisiopatologia , Alcoolismo/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Consumo de Bebidas Alcoólicas/psicologia , Consumo de Bebidas Alcoólicas/fisiopatologia , Tonsila do Cerebelo/diagnóstico por imagem , Tonsila do Cerebelo/fisiopatologia , Emoções/fisiologia , AdultoRESUMO
BACKGROUND AND OBJECTIVE: Insomnia is one of the common problems encountered in the hemodialysis (HD) population, but the mechanisms remain unclear. we aimed to (1) detect the spontaneous brain activity pattern in HD patients with insomnia (HDWI) by using fractional fractional amplitude of low frequency fluctuation (fALFF) method and (2) further identify brain regions showing altered fALFF as neural markers to discriminate HDWI patients from those on hemodialysis but without insomnia (HDWoI) and healthy controls (HCs). METHOD: We compared fALFF differences among HDWI subjects (28), HDWoI subjects (28) and HCs (28), and extracted altered fALFF features for the subsequent discriminative analysis. Then, we constructed a support vector machine (SVM) classifier to identify distinct neuroimaging markers for HDWI. RESULTS: Compared with HCs, both HDWI and HDWoI patients exhibited significantly decreased fALFF in the bilateral calcarine (CAL), right middle occipital gyrus (MOG), left precentral gyrus (PreCG), bilateral postcentral gyrus (PoCG) and bilateral temporal middle gyrus (TMG), whereas increased fALFF in the bilateral cerebellum and right insula. Conversely, increased fALFF in the bilateral CAL/right MOG and decreased fALFF in the right cerebellum was observed in HDWI patients when compared with HDWoI patients. Moreover, the SVM classification achieved a good performance [accuracy = 82.14%, area under the curve (AUC) = 0.8202], and the consensus brain regions with the highest contributions to classification were located in the right MOG and right cerebellum. CONCLUSION: Our result highlights that HDWI patients had abnormal neural activities in the right MOG and right cerebellum, which might be potential neural markers for distinguishing HDWI patients from non-insomniacs, providing further support for the pathological mechanism of HDWI.
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Imageamento por Ressonância Magnética , Distúrbios do Início e da Manutenção do Sono , Humanos , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Distúrbios do Início e da Manutenção do Sono/diagnóstico por imagem , Mapeamento Encefálico/métodos , NeuroimagemRESUMO
Human dental pulp stem cells (hDPSCs) are some of the most promising stem cell types for regenerative therapies given their ability to grow in the absence of serum and their realistic possibility to be used in autologous grafts. In this review, we describe the particular advantages of hDPSCs for neuroregenerative cell therapies. We thoroughly discuss the knowledge about their embryonic origin and characteristics of their postnatal niche, as well as the current status of cell culture protocols to maximize their multilineage differentiation potential, highlighting some common issues when assessing neuronal differentiation fates of hDPSCs. We also review the recent progress on neuroprotective and immunomodulatory capacity of hDPSCs and their secreted extracellular vesicles, as well as their combination with scaffold materials to improve their functional integration on the injured central nervous system (CNS) and peripheral nervous system (PNS). Finally, we offer some perspectives on the current and possible future applications of hDPSCs in neuroregenerative cell therapies.
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Terapia Baseada em Transplante de Células e Tecidos/métodos , Polpa Dentária/citologia , Regeneração Nervosa/fisiologia , Células-Tronco/citologia , Diferenciação Celular , Vesículas Extracelulares/fisiologia , Humanos , Neuroglia/citologia , Transplante de Células-Tronco , Células-Tronco/fisiologia , Engenharia Tecidual/métodos , Alicerces TeciduaisRESUMO
The physiological roles of corticotropin-releasing factor (CRF) have recently been extended to cytoprotection. Here, to determine whether CRF is neuroprotective in fish, the effects of CRF against high environmental ammonia (HEA)-mediated neurogenic impairment and cell death were investigated in zebrafish. In vivo, exposure of 1â day post-fertilization (dpf) embryos to HEA only reduced the expression of the determined neuron marker neurod1 In contrast, in 5â dpf larvae, HEA increased the expression of nes and sox2, neural progenitor cell markers, and reduced the expression of neurog1, gfap and mbpa, proneuronal cell, radial glia and oligodendrocyte markers, respectively, and neurod1 The N-methyl-d-aspartate (NMDA) receptor inhibitor MK801 rescued the HEA-induced reduction in neurod1 in 5â dpf larvae but did not affect the HEA-induced transcriptional changes in other neural cell types, suggesting that hyperactivation of NMDA receptors specifically contributes to the deleterious effects of HEA in determined neurons. As observed in vivo, HEA exposure elicited marked changes in the expression of cell type-specific markers in isolated 5â dpf larval brains. The addition of CRF reversed the in vitro effects of HEA on neurod1 expression and prevented an HEA-induced increase in cell death. Finally, the protective effects of CRF against HEA-mediated neurogenic impairment and cell death were prevented by the CRF type 1 receptor selective antagonist antalarmin. Together, these results provide novel evidence that HEA has developmental time- and cell type-specific neurotoxic effects, that NMDA receptor hyperactivation contributes to HEA-mediated impairment of determined neurons, and that CRF has neuroprotective properties in the larval zebrafish brain.
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Amônia/toxicidade , Hormônio Liberador da Corticotropina/farmacologia , Peixe-Zebra/embriologia , Animais , Encéfalo/metabolismo , Morte Celular/efeitos dos fármacos , Maleato de Dizocilpina/farmacologia , Regulação da Expressão Gênica no Desenvolvimento , Larva/efeitos dos fármacos , Larva/metabolismo , Pirimidinas/farmacologia , Pirróis/farmacologia , Receptores de Hormônio Liberador da Corticotropina/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/efeitos dos fármacos , Peixe-Zebra/genética , Peixe-Zebra/metabolismoRESUMO
OBJECTIVE: We examine the relationship between individual differences in temperament (cognitive control, fear, and shyness) and the error-related negativity (i.e., the ERN) in a large sample of young children. Furthermore, we explore to what extent variation in temperament may underlie the associations between the ERN and anxiety disorders versus externalizing disorders. METHOD: Using the Children's Behavior Questionnaire (CBQ), we focus on scales related to cognitive control (attentional focusing, attentional shifting, and inhibitory control) and a fearful/anxious temperament (fearfulness and shyness). We use diagnostic interviews to assess anxiety (specific phobia, separation anxiety disorder, social phobia, generalized anxiety disorder, obsessive-compulsive disorder, and agoraphobia) and externalizing disorders (attention deficit hyperactivity disorder; ADHD, and oppositional defiant disorder; ODD). A go/no-go task was used to measure the ERN. RESULTS: Results suggest that while shyness was related to an increased ERN, fearfulness was associated with a decreased ERN. Moreover, increased cognitive control was related to an increased ERN, and an exploratory model suggested that while shyness displayed an independent relationship with the ERN, the relationship between fear and the ERN was accounted for by deficits in cognitive control. Additionally, we found that the ERN was increased in children with anxiety disorders, and that this association was explained by shyness, but not fear or cognitive control. In contrast, the ERN was blunted in children with externalizing disorders (ADHD or ODD), and this association was accounted for by lower levels of both shyness and cognitive control. CONCLUSIONS: Overall, these results are novel insofar as they suggest that the temperamental factors of shyness and cognitive control may underlie the associations between the ERN and internalizing versus externalizing disorders.
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Transtornos de Ansiedade/psicologia , Medo , Inibição Psicológica , Timidez , Análise e Desempenho de Tarefas , Transtornos de Ansiedade/fisiopatologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/psicologia , Encéfalo/fisiopatologia , Criança , Pré-Escolar , Cognição , Feminino , Humanos , Estudos Longitudinais , Masculino , Fobia Social/psicologia , Inquéritos e Questionários , TemperamentoRESUMO
Extremely low-frequency electromagnetic field (ELFEMF) can stimulate neural differentiation in human bone marrow-derived mesenchymal cells (hBM-MSCs), and this provides an opportunity for research on neurodegenerative diseases such as Alzheimer's disease (AD). Metallothionein-3 (MT3), an isoform of the metal-binding proteins, metallothioneins, involved in maintaining intracellular zinc (Zn) homeostasis and the deregulation of zinc homeostasis, has separately been implicated in AD. Here, we investigated the effect of ELFEMF-induced neural differentiation of hBM-MSCs on Zn-MT3 homeostatic interaction. Exposure to ELFEMF induced neural differentiation of hBM-MSCs, which was characterized by decreased proliferation and enhanced neural-like morphology. We observed expression of neuronal markers such as ß-tubulin3, pleiotrophin, and neurofilament-M at the mRNA level and MAP2 at the protein level. ELFEMF-induced neural differentiation correlated with decreased expression of metal-response element-transcription factor 1 and MT3, as well as decreased intracellular Zn concentration. In addition, upregulation of dihydropyrimidinase-related protein 2 was observed, but there was no change in γ-enolase expression. These data indicate a possible regulatory mechanism for MT3 during neural differentiation. Our findings provide considerable insight into molecular mechanisms involved in neural differentiation, which is useful for developing new treatments for neurodegenerative diseases. Bioelectromagnetics. 38:364-373, 2017. © 2017 Wiley Periodicals, Inc.
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Diferenciação Celular/efeitos da radiação , Campos Eletromagnéticos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos da radiação , Metalotioneína/metabolismo , Neurônios/citologia , Neurônios/efeitos da radiação , Regulação para Baixo/efeitos da radiação , Homeostase/efeitos da radiação , Células-Tronco Mesenquimais/metabolismo , Metalotioneína/genéticaRESUMO
The majority of functional neuroimaging investigations aim to characterize an average human brain. However, another important goal of cognitive neuroscience is to understand the ways in which individuals differ from one another and the significance of these differences. This latter goal is given special weight by the recent reconceptualization of neurological disorders where sharp boundaries are no longer drawn either between health and neuropsychiatric and neurodevelopmental disorders, or among different disorders (e.g., Insel et al., 2010). Consequently, even the variability in the healthy population can inform our understanding of brain disorders. However, because the use of functional neural markers is still in its infancy, no consensus presently exists about which measures (e.g., effect size?, extent of activation?, degree of lateralization?) are the best ones to use. We here attempt to address this question with respect to one large-scale neural system: the set of brain regions in the frontal and temporal cortices that jointly support high-level linguistic processing (e.g., Binder et al., 1997; Fedorenko, Hsieh, Nieto-Castanon, Whitfield-Gabrieli, & Kanwisher, 2010). In particular, using data from 150 individuals all of whom had performed a language "localizer" task contrasting sentences and nonword sequences (Fedorenko et al., 2010), we: a) characterize the distributions of the values for four key neural measures of language activity (region effect sizes, region volumes, lateralization based on effect sizes, and lateralization based on volumes); b) test the reliability of these measures in a subset of 32 individuals who were scanned across two sessions; c) evaluate the relationship among the different regions of the language system; and d) evaluate the relationship among the different neural measures. Based on our results, we provide some recommendations for future studies of brain-behavior and brain-genes relationships. Although some of our conclusions are specific to the language system, others (e.g., the fact that effect-size-based measures tend to be more reliable than volume-based measures) are likely to generalize to the rest of the brain.
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Mapeamento Encefálico/métodos , Encéfalo/anatomia & histologia , Encéfalo/fisiologia , Lateralidade Funcional/fisiologia , Interpretação de Imagem Assistida por Computador/métodos , Idioma , Rede Nervosa/fisiologia , Adolescente , Adulto , Biomarcadores , Cognição/fisiologia , Compreensão/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Rede Nervosa/anatomia & histologia , Tamanho do Órgão/fisiologia , Valores de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto JovemRESUMO
OBJECTIVES: Given the potential use of neural markers for the development of novel treatments in spinal cord pain, we aimed to characterize the most effective neural markers of neuropathic pain following spinal cord injury (SCI). METHODS: A systematic PubMed review was conducted, compiling studies that were published prior to April, 2014 that examined neural markers associated with neuropathic pain after SCI using electrophysiological and neuroimaging techniques. RESULTS: We identified 6 studies: Four using electroencephalogram (EEG); 1 using magnetic resonance imaging (MRI) and FDG-PET (positron emission tomography); and 1 using MR spectroscopy. The EEG recordings suggested a reduction in alpha EEG peak frequency activity in the frontal regions of SCI patients with neuropathic pain. The MRI scans showed volume loss, primarily in the gray matter of the left dorsolateral prefrontal cortex, and by FDG-PET, hypometabolism in the medial prefrontal cortex was observed in SCI patients with neuropathic pain compared with healthy subjects. In the MR spectroscopy findings, the presence of pain was associated with changes in the prefrontal cortex and anterior cingulate cortex. CONCLUSIONS: When analyzed together, the results of these studies seem to point out to a common marker of pain in SCI characterized by decreased cortical activity in frontal areas and possibly increased subcortical activity. These results may contribute to planning further mechanistic studies as to better understand the mechanisms by which neuropathic pain is modulated in patients with SCI as well as clinical studies investigating best responders of treatment.
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Neuralgia/diagnóstico , Neuralgia/epidemiologia , Plasticidade Neuronal , Traumatismos da Medula Espinal/diagnóstico , Traumatismos da Medula Espinal/epidemiologia , Biomarcadores , Humanos , Imageamento por Ressonância Magnética/métodos , Neuralgia/terapia , Medição da Dor/métodos , Traumatismos da Medula Espinal/terapiaRESUMO
It was with the promise of rendering an experimental approach to consciousness that psychology started its trajectory as an independent science more than 150 years ago. Here, we will posit that the neurosciences were instrumental in leading psychology to resume the study of consciousness by projecting an empirical agenda for the future. First, we will start by showing how scientists were able to venture into the consciousness of supposedly unconscious patients, opening the door for the identification of important neural correlates of distinct consciousness states. Then, we will describe how different technological advances and elegant experimental paradigms helped in establishing important neuronal correlates of global consciousness (i.e., being conscious at all), perceptual consciousness (i.e., being conscious of something), and self-consciousness (i.e., being conscious of itself). Finally, we will illustrate how the study of complex consciousness experiences may contribute to the clarification of the mechanisms associated with global consciousness, the relationship between perceptual and self-consciousness, and the interface among distinct self-consciousness domains. In closing, we will elaborate on the road ahead of us for re-establishing psychology as a science of consciousness.
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BACKGROUND: Previous studies suggested that children with reading difficulty have impaired statistical learning ability in extracting distributional orthographic regularities. However, the neural mechanisms underlying have not been fully investigated. AIMS: The current study aimed to identify the electrophysiological markers and to examine the neural underpinnings of statistical learning of orthographic regularities in children with reading difficulties. METHODS AND PROCEDURES: Using the event-related potentials (ERPs) and the orthographic learning task, 157 children were exposed to a sequence of artificial pseudocharacters with varying levels of positional and semantic consistency (low at 60 %, moderate at 80 %, and high at 100 %). OUTCOMES AND RESULTS: Poor readers elicited an increased N170 response in the low consistency and a lack of left-lateralized P300 effect when learning positional regularities of radicals. Similarly, larger N170 effects were observed in poor readers, while similar N400 effects were found in both poor and average readers when learning semantic regularities of radicals. CONCLUSIONS AND IMPLICATIONS: Our findings indicate that poor readers may have trouble using statistical information for early-stage orthographic pattern extraction, yet they can identify semantic inconsistencies after sufficient exposure. These results deepen our understanding of the neural mechanisms involved in statistical learning for poor readers and aid in improving criteria for differentiating between typically developing children and those with reading challenges.
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Dislexia , Eletroencefalografia , Potenciais Evocados , Leitura , Semântica , Humanos , Criança , Feminino , Masculino , Potenciais Evocados/fisiologia , Dislexia/fisiopatologia , Aprendizagem/fisiologia , Reconhecimento Visual de Modelos/fisiologiaRESUMO
INTRODUCTION: No studies systematically examined sex differences in neural mechanisms underlying depression and mania/hypomania risk. METHOD: 80 females and 35 males, n = 115(age21.6±1.90) were scanned using 3TfMRI during an implicit emotional-faces task. We examined neural activation to all emotional faces versus baseline, using an anatomical region-of-interest mask comprising regions supporting emotion and salience processing. Sex was a covariate. Extracted parameter estimates(FWE < 0.05,k > 15), age, IQ and their sex interactions were independent variables(IV) in two penalized regression models: dependent variable either MOODS-SR-lifetime, depressive or manic domain score as measures of mania and depression risk. Subsequent Poisson regression models included the non-zero variables identified in the penalized regression models. We tested each model in 2 independent samples. Test sample-I,n = 108(21.6 ± 2.09 years,males/females = 33/75); Test sample-II,n = 93(23.7 ± 2.9 years,males/females = 31/62). RESULTS: Poisson regression models yielded significant relationships with depression and mania risk: Positive correlations were found between right fusiform activity and depression(beta = 0.610) and mania(beta = 0.690) risk. There was a significant interaction between sex and right fusiform activity(beta = -0.609) related to depression risk, where females had a positive relationship than; and a significant interaction(beta = 0.743) between sex and left precuneus activity related to mania risk, with a more negative relationship in females than males. All findings were replicated in the test samples(qs < 0.05,FDR). LIMITATIONS: No longitudinal follow-up. CONCLUSION: Greater visual attention to emotional faces might underlie greater depression and mania risk, and confer greater vulnerability to depression in females, because of heightened visual attention to emotional faces. Females have a more negative relationship between mania risk and left precuneus activity, suggesting heightened empathy might be associated with reduced mania/hypomania risk in females more than males.
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Emoções , Expressão Facial , Imageamento por Ressonância Magnética , Mania , Humanos , Feminino , Masculino , Adulto Jovem , Adulto , Emoções/fisiologia , Mania/fisiopatologia , Transtorno Bipolar/fisiopatologia , Transtorno Bipolar/psicologia , Transtorno Bipolar/diagnóstico por imagem , Depressão/fisiopatologia , Depressão/psicologia , Reconhecimento Facial/fisiologia , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagem , Fatores SexuaisRESUMO
BACKGROUND: Depressive symptoms are highly prevalent, present in heterogeneous symptom patterns, and share diverse neurobiological underpinnings. Understanding the links between psychopathological symptoms and biological factors is critical in elucidating its etiology and persistence. We aimed to evaluate the utility of using symptom-brain network models to parse the heterogeneity of depressive complaints in a large adolescent sample. METHODS: We used data from the third wave of the IMAGEN study, a multi-center panel cohort study involving 1317 adolescents (52.49 % female, mean ± SD age = 18.5 ± 0.7). Two network models were estimated: one including an overall depressive symptom severity sum score based on the Adolescent Depression Rating Scale (ADRS), and one incorporating individual ADRS item scores. Both networks included measures of cortical thickness in several regions (insula, cingulate, mOFC, fusiform gyrus) and hippocampal volume derived from neuroimaging. RESULTS: The network based on individual item scores revealed associations between cortical thickness measures and specific depressive complaints, obscured when using an aggregate depression severity score. Notably, the insula's cortical thickness showed negative associations with cognitive dysfunction (partial cor. = -0.15); the cingulate's cortical thickness showed negative associations with feelings of worthlessness (partial cor. = -0.10), and mOFC was negatively associated with anhedonia (partial cor. = -0.05). LIMITATIONS: This cross-sectional study relied on the self-reported assessment of depression complaints and used a non-clinical sample with predominantly healthy participants (19 % with depression or sub-threshold depression). CONCLUSIONS: This study showcases the utility of network models in parsing heterogeneity in depressive complaints, linking individual complaints to specific neural substrates. We outline the next steps to integrate neurobiological and cognitive markers to unravel MDD's phenotypic heterogeneity.
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Depressão , Imageamento por Ressonância Magnética , Humanos , Feminino , Masculino , Adolescente , Depressão/fisiopatologia , Depressão/psicologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Estudos de Coortes , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Hipocampo/fisiopatologia , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/fisiopatologia , Córtex Cerebral/patologia , Escalas de Graduação Psiquiátrica , Adulto Jovem , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/fisiopatologiaRESUMO
MSCs (Mesenchymal Stem Cells) can differentiate into various lineages, including neurons and glial cells. In the past few decades, MSCs have been well explored in the context of neuronal differentiation and have been reported to have the immense potential to form distinct kinds of neurons. The distinguishing features of MSCs make them among the most desired cell sources for stem cell therapy. This study involved the trans-differentiation of Adipose-derived human Mesenchymal Stem Cells (ADMSCs) into neurons. The protocol employs a cocktail of chemical inducers in different combinations, including Brain-derived neurotrophic factor (BDNF), epidermal growth factor (EGF), and Nerve growth factor (NGF) Fibroblastic growth factor (FGF), in induction media. Both types have been successfully differentiated into neurons, confirmed by morphological aspects and the presence of neural-specific markers through RT-PCR (Reverse transcription polymerase chain reaction) studies and immunocytochemistry assay. They have shown excellent morphology with long neurites, synaptic connections, and essential neural markers to validate their identity. The results may significantly contribute to cell replacement therapy for neurological disorders.
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Fator Neurotrófico Derivado do Encéfalo , Células-Tronco Mesenquimais , Humanos , Fator Neurotrófico Derivado do Encéfalo/genética , Fator de Crescimento Epidérmico/farmacologia , Fator de Crescimento Epidérmico/metabolismo , Fator de Crescimento Neural/farmacologia , Fator de Crescimento Neural/metabolismo , Diferenciação Celular/fisiologia , Células CultivadasRESUMO
Background: Depressive symptoms are highly prevalent, present in heterogeneous symptom patterns, and share diverse neurobiological underpinnings. Understanding the links between psychopathological symptoms and biological factors is critical in elucidating its etiology and persistence. We aimed to evaluate the utility of using symptom-brain networks to parse the heterogeneity of depressive symptomatology in a large adolescent sample. Methods: We used data from the third wave of the IMAGEN study, a multi-center panel cohort study involving 1,317 adolescents (52.49% female, mean±SD age=18.5±0.72). Two network models were estimated: one including an overall depressive symptom severity sum score based on the Adolescent Depression Rating Scale (ADRS), and one incorporating individual ADRS symptom/item scores. Both networks included measures of cortical thickness in several regions (insula, cingulate, mOFC, fusiform gyrus) and hippocampal volume derived from neuroimaging. Results: The network based on individual symptom scores revealed associations between cortical thickness measures and specific symptoms, obscured when using an aggregate depression severity score. Notably, the insula's cortical thickness showed negative associations with cognitive dysfunction (partial cor.=-0.15); the cingulate's cortical thickness showed negative associations with feelings of worthlessness (partial cor. = -0.10), and mOFC was negatively associated with anhedonia (partial cor. = -0.05). Limitations: This cross-sectional study included participants who were relatively healthy and relied on the self-reported assessment of depression symptoms. Conclusions: This study showcases the utility of network models in parsing heterogeneity in depressive symptoms, linking individual symptoms to specific neural substrates. We outline the next steps to integrate neurobiological and cognitive markers to unravel MDD's phenotypic heterogeneity.
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BACKGROUND: Identifying neural predictors of worsening subthreshold hypomania severity can help identify risk of progression to BD. While diffusion Magnetic Resonance Imaging (dMRI) studies reported white matter microstructural abnormalities in tracts supporting emotional regulation in individuals with BD, it remains unknown whether similar patterns of white matter microstructure predict worsening of subthreshold hypomania severity in non-BD individuals. METHODS: dMRI data were collected in: 81 non-BD individuals recruited across a range of subthreshold depression and hypomania, and followed for six months; and independent samples of 75 BD and 58 healthy individuals. All individuals were assessed using standardized diagnostic assessments, mood and anxiety symptom rating scales. Global probabilistic tractography and a tract-profile approach examined fractional anisotropy (FA), a measure of fiber collinearity, in tracts supporting emotional regulation shown to have abnormalities in BD: forceps minor (FMIN), anterior thalamic radiation (ATR), cingulum bundle (CB), and uncinate fasciculus (UF). RESULTS: Lower FA in left CB (middle, ß = -0.22, P = 0.022; posterior, ß = -0.32, P < 0.001), right CB (anterior, ß = -0.30, P = 0.003; posterior, ß = -0.27, P = 0.005), and right UF (frontal, ß = -0.29, P = 0.002; temporal, ß = -0.40, P < 0.001) predicted worsening of subthreshold hypomania severity in non-BD individuals. BD versus healthy individuals showed lower FA in several of these segments: middle left CB (F = 8.7, P = 0.004), anterior right CB (F = 9.8, P = 0.002), and frontal right UF (F = 7.0, P = 0.009). Non-BD individuals with worsening 6-month hypomania had lower FA in these three segments versus HC and non-BD individuals without worsening hypomania, but similar FA to BD individuals. LIMITATIONS: Relatively short follow-up. CONCLUSIONS: White matter predictors of worsening subthreshold hypomania in non-BD individuals parallel abnormalities in BD individuals, and can guide early risk identification and interventions.
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Transtorno Bipolar , Substância Branca , Anisotropia , Transtorno Bipolar/psicologia , Imagem de Tensor de Difusão/métodos , Humanos , Mania , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Adulto JovemRESUMO
Depression and alcohol misuse, frequently comorbid, are associated with altered reward processing. However, no study has examined whether and how the neural markers of reward processing are shared between depression and alcohol misuse. We studied 43 otherwise-healthy drinking adults in a monetary incentive delay task (MIDT) during fMRI. All participants were evaluated with the Alcohol Use Disorders Identification Test (AUDIT) and Beck's Depression Inventory (BDI-II) to assess the severity of drinking and depression. We performed whole brain regressions against each AUDIT and BDI-II score to investigate the neural correlates and evaluated the findings at a corrected threshold. We performed mediation analyses to examine the inter-relationships between win/loss responses, alcohol misuse, and depression. AUDIT and BDI-II scores were positively correlated across subjects. Alcohol misuse and depression shared win-related activations in frontoparietal regions and parahippocampal gyri (PHG), and right superior temporal gyri (STG), as well as loss-related activations in the right PHG and STG, and midline cerebellum. These regional activities (ß's) completely mediated the correlations between BDI-II and AUDIT scores. The findings suggest shared neural correlates interlinking depression and problem drinking both during win and loss processing and provide evidence for co-morbid etiological processes of depressive and alcohol use disorders.
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Objective: Mechanical thrombectomy (MT) has been an effective first-line therapeutic strategy for ischemic stroke. With impairment characteristics separating it from anterior circulation stroke, we aimed to explore prognostic structural neural markers for basilar artery occlusion (BAO) after MT. Methods: Fifty-four BAO patients with multi-modal magnetic resonance imaging at admission from the multicenter real-world designed BASILAR research were enrolled in this study. Features including volumes for cortical structures and subcortical regions, locations and volumes of infarctions, and white matter hyperintensity (WMH) volumes were recorded from all individuals. The impact features were identified using ANCOVA and logistic analysis. Another cohort (n = 21) was further recruited to verify the prognostic roles of screened prognostic structures. Results: For the primary clinical outcome, decreased brainstem volume and total infarction volumes from mesencephalon and midbrain were significantly related to reduced 90-day modified Rankin score (mRS) after MT treatment. WMH volume, WMH grade, average cortex thickness, white matter volume, and gray matter volume did not exhibit a remarkable relationship with the prognosis of BAO. The increased left caudate volume was obviously associated with early symptomatic recovery after MT. The prognostic role of the ratio of pons and midbrain infarct volume in brainstem was further confirmed in another cohort with area under the curve (AUC) = 0.77. Conclusions: This study was the first to provide comprehensive structural markers for the prognostic evaluation of BAO. The fully automatic and semiautomatic segmentation approaches in our study supported that the proportion of mesencephalon and midbrain infarct volume in brainstem was a crucial prognostic structural neural marker for BAO.
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Mind-wandering (MW) is a common phenomenon, defined as task-unrelated thoughts. This study is based on event-related potentials (ERPs), using modified sustained attention to response task (modified SART, mSART) to discuss the neural patterns of different types of MW. In the current study, we defined the MW realized by participants as self-caught MW, and the MW measurement acquired by probes as probe-caught MW. The behavioral results showed that the reaction times (RTs) during self-caught MW were greater than those during non-self-caught MW. The ERP results showed that during self-caught MW, the mean amplitudes of N1 decreased significantly, indicating that the participants' attention had deviated from the current task. The increase in the mean amplitudes of P2 during self-caught MW indicated lower vigilance. We also found that the mean amplitudes of N300 reduced during self-caught MW, which indicated that cognitive control or monitoring might be affected by self-caught MW. The average amplitudes of P300 were significantly lower during probe-caught MW than during on-task, indicating the impact on high-level cognitive processing. In addition, the amplitudes of N1, P2, and N300 in anterior regions were greater than those in posterior regions. P300 amplitudes during probe-caught MW in the right hemisphere were greater than those of the left hemisphere. In summary, our research results demonstrated that alertness and cognitive processing decreased during both self-caught MW and probe-caught MW. ERPs were statistically different under the conditions of self-caught MW and probe-caught MW. The current study provided new insights into the relationship between MW and neural markers. It was the first study exploring the ERP correlates between self-caught MW and probe-caught MW based on mSART.
RESUMO
More than 15% of adults suffer from pathological procrastination, which leads to substantial harm to their mental and psychiatric health. Our previous work demonstrated the role of three neuroanatomical networks as neural substrates of procrastination, but their potential interaction remains unknown. Three large-scale independent samples (total n = 901) were recruited. In sample A, tract-based spatial statistics (TBSS) and connectome-based graph-theoretical analysis was conducted to probe association between topological properties of white matter (WM) network and procrastination. In sample B, the above analysis was reproduced to demonstrate replicability. In sample C, machine learning models were built to predict individual procrastination. TBSS results showed a negative association between procrastination and WM integrity of limbic-prefrontal connection, and a positive relationship between intra-connection within the limbic system and procrastination. Also, both the efficiency and integrity of limbic WM network were found to be linked to procrastination. The above findings were all confirmed to replicate in an independent sample; prediction models demonstrated that these WM features can predict procrastination accurately in sample C. In conclusion, this study moves forward our understanding of procrastination by clarifying the role of interplay of self-control and emotional regulation with it.
Assuntos
Regulação Emocional , Procrastinação , Autocontrole , Substância Branca/diagnóstico por imagem , Adolescente , Adulto , Conectoma , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Aprendizado de Máquina , Masculino , Vias Neurais/diagnóstico por imagem , Adulto JovemRESUMO
BACKGROUND: Adipose-derived stem cells (ASCs) have been increasingly explored for cell-based medicine because of their numerous advantages in terms of easy availability, high proliferation rate, multipotent differentiation ability and low immunogenicity. In this respect, they have been widely investigated in the last two decades to develop therapeutic strategies for a variety of human pathologies including eye disease. In ocular diseases involving the retina, various cell types may be affected, such as Müller cells, astrocytes, photoreceptors and retinal pigment epithelium (RPE), which plays a fundamental role in the homeostasis of retinal tissue, by secreting a variety of growth factors that support retinal cells. AIM: To test ASC neural differentiation using conditioned medium (CM) from an RPE cell line (ARPE-19). METHODS: ASCs were isolated from adipose tissue, harvested from the subcutaneous region of healthy donors undergoing liposuction procedures. Four ASC culture conditions were investigated: ASCs cultured in basal Dulbecco's Modified Eagle Medium (DMEM); ASCs cultured in serum-free DMEM; ASCs cultured in serum-free DMEM/F12; and ASCs cultured in a CM from ARPE-19, a spontaneously arising cell line with a normal karyotype derived from a human RPE. Cell proliferation rate and viability were assessed by crystal violet and MTT assays at 1, 4 and 8 d of culture. At the same time points, ASC neural differentiation was evaluated by immunocytochemistry and western blot analysis for typical neuronal and glial markers: Nestin, neuronal specific enolase (NSE), protein gene product (PGP) 9.5, and glial fibrillary acidic protein (GFAP). RESULTS: Depending on the culture medium, ASC proliferation rate and viability showed some significant differences. Overall, less dense populations were observed in serum-free cultures, except for ASCs cultured in ARPE-19 serum-free CM. Moreover, a different cell morphology was seen in these cultures after 8 d of treatment, with more elongated cells, often showing cytoplasmic ramifications. Immunofluorescence results and western blot analysis were indicative of ASC neural differentiation. In fact, basal levels of neural markers detected under control conditions significantly increased when cells were cultured in ARPE-19 CM. Specifically, neural marker overexpression was more marked at 8 d. The most evident increase was observed for NSE and GFAP, a modest increase was observed for nestin, and less relevant changes were observed for PGP9.5. CONCLUSION: The presence of growth factors produced by ARPE-19 cells in tissue culture induces ASCs to express neural differentiation markers typical of the neuronal and glial cells of the retina.