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Despite the known benefits of data-driven approaches, the lack of approaches for identifying functional neuroimaging patterns that capture both individual variations and inter-subject correspondence limits the clinical utility of rsfMRI and its application to single-subject analyses. Here, using rsfMRI data from over 100k individuals across private and public datasets, we identify replicable multi-spatial-scale canonical intrinsic connectivity network (ICN) templates via the use of multi-model-order independent component analysis (ICA). We also study the feasibility of estimating subject-specific ICNs via spatially constrained ICA. The results show that the subject-level ICN estimations vary as a function of the ICN itself, the data length, and the spatial resolution. In general, large-scale ICNs require less data to achieve specific levels of (within- and between-subject) spatial similarity with their templates. Importantly, increasing data length can reduce an ICN's subject-level specificity, suggesting longer scans may not always be desirable. We also find a positive linear relationship between data length and spatial smoothness (possibly due to averaging over intrinsic dynamics), suggesting studies examining optimized data length should consider spatial smoothness. Finally, consistency in spatial similarity between ICNs estimated using the full data and subsets across different data lengths suggests lower within-subject spatial similarity in shorter data is not wholly defined by lower reliability in ICN estimates, but may be an indication of meaningful brain dynamics which average out as data length increases.
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Mapeamento Encefálico , Imageamento por Ressonância Magnética , Humanos , Mapeamento Encefálico/métodos , Imageamento por Ressonância Magnética/métodos , Reprodutibilidade dos Testes , Rede Nervosa/diagnóstico por imagem , Encéfalo/diagnóstico por imagemRESUMO
Resting-state functional magnetic resonance imaging is currently the mainstay of functional neuroimaging and has allowed researchers to identify intrinsic connectivity networks (aka functional networks) at different spatial scales. However, little is known about the temporal profiles of these networks and whether it is best to model them as continuous phenomena in both space and time or, rather, as a set of temporally discrete events. Both categories have been supported by series of studies with promising findings. However, a critical question is whether focusing only on time points presumed to contain isolated neural events and disregarding the rest of the data is missing important information, potentially leading to misleading conclusions. In this work, we argue that brain networks identified within the spontaneous blood oxygenation level-dependent (BOLD) signal are not limited to temporally sparse burst moments and that these event present time points (EPTs) contain valuable but incomplete information about the underlying functional patterns. We focus on the default mode and show evidence that is consistent with its continuous presence in the BOLD signal, including during the event absent time points (EATs), i.e., time points that exhibit minimum activity and are the least likely to contain an event. Moreover, our findings suggest that EPTs may not contain all the available information about their corresponding networks. We observe distinct default mode connectivity patterns obtained from all time points (AllTPs), EPTs, and EATs. We show evidence of robust relationships with schizophrenia symptoms that are both common and unique to each of the sets of time points (AllTPs, EPTs, EATs), likely related to transient patterns of connectivity. Together, these findings indicate the importance of leveraging the full temporal data in functional studies, including those using event-detection approaches.
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Mapeamento Encefálico , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Neuroimagem Funcional , Humanos , Imageamento por Ressonância Magnética/métodos , Rede Nervosa/diagnóstico por imagemRESUMO
Macro- and microarchitectural, bone material property, dynamic histomorphometric, and bone turnover marker data were studied in normal bone mineral density (BMD) post-menopausal women with fragility fracture. Women with fracture had thinner iliac cortices and more homogeneous bone material properties in cortical bone than age/BMD-matched non-fracture women. Low cortical thickness and bone tissue heterogeneity in normal BMD women are associated with prevalent fragility fracture. INTRODUCTION: Bone mass (bone mineral density, (BMD)) of the spine and hip is today's best single measurement for evaluating future fragility fracture risk. However, the majority of fragility fractures occur in women with BMD T-score above the WHO osteoporotic BMD threshold of - 2.5, indicating that non-BMD endpoints may play a role in their fragility fractures. We hypothesize that in non-osteoporotic women, bone micoarchitecture, bone material properties, dynamic histomorphometric endpoints, and bone turnover markers are related to fragility fracture. METHODS: Two groups (N = 60 each) of post-menopausal women with total hip BMD T-score ranging from + 0.3 to -2.49 were recruited: fragility fracture and age/BMD-matched, non-fragility fracture women. Normal (T-score > - 0.99) and osteopenic (T-score ≤ - 1.0) BMD cohorts were designated within both the fracture and non-fracture groups. Transiliac biopsy specimens were obtained to evaluate dynamic histomorphometric and microarchitectural endpoints and bone material properties by static and dynamic nanoindentation testing. All variables for fracture and non-fracture women within each BMD cohort were compared by the Wilcoxon signed-rank test (P < 0.01). RESULTS: Compared to non-fracture/normal BMD women, fracture/normal BMD women display lower iliac cortical thickness (- 12%, P = 0.0041) and lower heterogeneity of hardness (- 27%, P = 0.0068), elastic modulus (- 35%, P = 0.0009), and storage modulus (- 23%, P = 0.0054) in the cortical bone tissue, and lower heterogeneity of hardness (- 13%, P = 0.0088) in the trabecular bone tissue. Osteopenic women had no abnormalities related to fracture status. CONCLUSION: Post-menopausal women with normal BMD and fragility fracture have low cortical thickness and heterogeneity of several bone material properties in cortical and trabecular mineralized bone tissue. These differences may explain a portion of the excess bone fragility in women with normal BMD and fragility fracture.
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Fraturas Ósseas , Fraturas por Osteoporose , Densidade Óssea , Remodelação Óssea , Osso Esponjoso/patologia , Feminino , Humanos , Ílio , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/patologia , Pós-MenopausaRESUMO
Objective: Identify determinants of emergency medical service (EMS) personnel's willingness to work during an influenza pandemic. Background: Little is known about the willingness of EMS personnel to work during a future influenza pandemic or the extent to which they are receiving pandemic training. Methods: EMS personnel were surveyed in July 2018 - Feb 2019 using a cross-sectional approach; the survey was available both electronically and on paper. Participants were provided a pandemic scenario and asked about their willingness to respond if requested or required; additional questions assessed their attitudes and beliefs and training received. Chi-square tests assessed differences in attitude/belief questions by willingness to work. Logistic regressions were used to identify significant predictors of response willingness when requested or required, controlling for gender and race. Results: 433 individuals completed the survey (response rate = 82.9%). A quarter (26.8%, n = 116) received no pandemic training; 14.3% (n = 62) participated in a pandemic exercise. Significantly more EMS personnel were willing to work when required versus when only requested (88.2% vs 76.9%, X2 = 164.1, p < .001). Predictors of willingness to work when requested included believing it is their responsibility to work, believing their coworkers were likely to work, receiving prophylaxis for themselves and their family members, and feeling safe working during a pandemic. Discussion: Many emergency medical services personnel report lacking training or disaster exercises related to influenza pandemics, and a fair percentage are unwilling to work during a future event. This may limit healthcare surge capacity and could contribute to increased morbidity and mortality. Findings from this study indicate that prehospital staff's attitudes and beliefs about pandemics influence their willingness to work. Pre-event training and planning should address these concerns.
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Atitude do Pessoal de Saúde , Serviços Médicos de Emergência , Pessoal de Saúde/educação , Influenza Humana , Pandemias , Adolescente , Adulto , Estudos Transversais , Feminino , Humanos , Influenza Humana/epidemiologia , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
We examine cross-modality commonalities in visual and auditory imageries during fMRI scanning in a sample of healthy young adults. In a visual task combining viewed and imagined stimuli, 28 participants were asked to imagine novel scenes related to the other images, and in a similar auditory task combining heard and imagined stimuli, to imagine novel sentences spoken by individuals they had heard speaking previously. We identified a common set of regions in medial and lateral Brodmann area 6, as well as inferior frontal gyrus (BA 44/45), partially supporting previous meta-analytic results. Comparing individuals with high or low reported imagery ability, we replicated a previous result showing individuals with lower visual imagery ability showed greater activation in the cerebellum, frontal and dorsolateral prefrontal cortex, while there was no relationship with auditory imagery ability in this sample. The emphasis on imagining novel stimuli, rather than familiar or previously experienced stimuli, confirms the role of the supramodal imagery network underlying creative imagery.
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Aptidão/fisiologia , Mapeamento Encefálico/métodos , Cerebelo/fisiologia , Imaginação/fisiologia , Córtex Motor/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Córtex Pré-Frontal/fisiologia , Percepção da Fala/fisiologia , Adulto , Cerebelo/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Córtex Motor/diagnóstico por imagem , Córtex Pré-Frontal/diagnóstico por imagem , Adulto JovemRESUMO
The human brain is a highly dynamic system with non-stationary neural activity and rapidly-changing neural interaction. Resting-state dynamic functional connectivity (dFC) has been widely studied during recent years, and the emerging aberrant dFC patterns have been identified as important features of many mental disorders such as schizophrenia (SZ). However, only focusing on the time-varying patterns in FC is not enough, since the local neural activity itself (in contrast to the inter-connectivity) is also found to be highly fluctuating from research using high-temporal-resolution imaging techniques. Exploring the time-varying patterns in brain activity and their relationships with time-varying brain connectivity is important for advancing our understanding of the co-evolutionary property of brain network and the underlying mechanism of brain dynamics. In this study, we introduced a framework for characterizing time-varying brain activity and exploring its associations with time-varying brain connectivity, and applied this framework to a resting-state fMRI dataset including 151 SZ patients and 163 age- and gender matched healthy controls (HCs). In this framework, 48 brain regions were first identified as intrinsic connectivity networks (ICNs) using group independent component analysis (GICA). A sliding window approach was then adopted for the estimation of dynamic amplitude of low-frequency fluctuation (dALFF) and dFC, which were used to measure time-varying brain activity and time-varying brain connectivity respectively. The dALFF was further clustered into six reoccurring states by the k-means clustering method and the group difference in occurrences of dALFF states was explored. Lastly, correlation coefficients between dALFF and dFC were calculated and the group difference in these dALFF-dFC correlations was explored. Our results suggested that 1) ALFF of brain regions was highly fluctuating during the resting-state and such dynamic patterns are altered in SZ, 2) dALFF and dFC were correlated in time and their correlations are altered in SZ. The overall results support and expand prior work on abnormalities of brain activity, static FC (sFC) and dFC in SZ, and provide new evidence on aberrant time-varying brain activity and its associations with brain connectivity in SZ, which might underscore the disrupted brain cognitive functions in this mental disorder.
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Mapeamento Encefálico/métodos , Encéfalo/fisiologia , Rede Nervosa/fisiologia , Esquizofrenia/fisiopatologia , Adulto , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Vias Neurais/fisiologia , Esquizofrenia/diagnóstico por imagemRESUMO
BACKGROUND: Schizophrenia (SZ) is a severe neuropsychiatric disorder associated with disrupted connectivity within the thalamic-cortico-cerebellar network. Resting-state functional connectivity studies have reported thalamic hypoconnectivity with the cerebellum and prefrontal cortex as well as thalamic hyperconnectivity with sensory cortical regions in SZ patients compared with healthy comparison participants (HCs). However, fundamental questions remain regarding the clinical significance of these connectivity abnormalities. METHOD: Resting state seed-based functional connectivity was used to investigate thalamus to whole brain connectivity using multi-site data including 183 SZ patients and 178 matched HCs. Statistical significance was based on a voxel-level FWE-corrected height threshold of p < 0.001. The relationships between positive and negative symptoms of SZ and regions of the brain demonstrating group differences in thalamic connectivity were examined. RESULTS: HC and SZ participants both demonstrated widespread positive connectivity between the thalamus and cortical regions. Compared with HCs, SZ patients had reduced thalamic connectivity with bilateral cerebellum and anterior cingulate cortex. In contrast, SZ patients had greater thalamic connectivity with multiple sensory-motor regions, including bilateral pre- and post-central gyrus, middle/inferior occipital gyrus, and middle/superior temporal gyrus. Thalamus to middle temporal gyrus connectivity was positively correlated with hallucinations and delusions, while thalamus to cerebellar connectivity was negatively correlated with delusions and bizarre behavior. CONCLUSIONS: Thalamic hyperconnectivity with sensory regions and hypoconnectivity with cerebellar regions in combination with their relationship to clinical features of SZ suggest that thalamic dysconnectivity may be a core neurobiological feature of SZ that underpins positive symptoms.
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Cerebelo/fisiopatologia , Córtex Cerebral/fisiopatologia , Conectoma/métodos , Rede Nervosa/fisiopatologia , Esquizofrenia/fisiopatologia , Tálamo/fisiopatologia , Adulto , Cerebelo/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Esquizofrenia/diagnóstico por imagem , Tálamo/diagnóstico por imagemRESUMO
Subcortical structures, which include the basal ganglia and parts of the limbic system, have key roles in learning, motor control and emotion, but also contribute to higher-order executive functions. Prior studies have reported volumetric alterations in subcortical regions in schizophrenia. Reported results have sometimes been heterogeneous, and few large-scale investigations have been conducted. Moreover, few large-scale studies have assessed asymmetries of subcortical volumes in schizophrenia. Here, as a work completely independent of a study performed by the ENIGMA consortium, we conducted a large-scale multisite study of subcortical volumetric differences between patients with schizophrenia and controls. We also explored the laterality of subcortical regions to identify characteristic similarities and differences between them. T1-weighted images from 1680 healthy individuals and 884 patients with schizophrenia, obtained with 15 imaging protocols at 11 sites, were processed with FreeSurfer. Group differences were calculated for each protocol and meta-analyzed. Compared with controls, patients with schizophrenia demonstrated smaller bilateral hippocampus, amygdala, thalamus and accumbens volumes as well as intracranial volume, but larger bilateral caudate, putamen, pallidum and lateral ventricle volumes. We replicated the rank order of effect sizes for subcortical volumetric changes in schizophrenia reported by the ENIGMA consortium. Further, we revealed leftward asymmetry for thalamus, lateral ventricle, caudate and putamen volumes, and rightward asymmetry for amygdala and hippocampal volumes in both controls and patients with schizophrenia. Also, we demonstrated a schizophrenia-specific leftward asymmetry for pallidum volume. These findings suggest the possibility of aberrant laterality in neural pathways and connectivity patterns related to the pallidum in schizophrenia.
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Encéfalo/fisiopatologia , Esquizofrenia/fisiopatologia , Adulto , Tonsila do Cerebelo , Gânglios da Base , Mapeamento Encefálico , Estudos de Coortes , Estudos Transversais , Feminino , Lateralidade Funcional/fisiologia , Hipocampo , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Putamen , TálamoRESUMO
Total mercury (THg) and selenium (Se) were analyzed by Inductively Coupled Plasma Mass Spectrometry in 11 internal and external tissues and stomach contents from 23 brown trout, Salmo trutta, of a 22.9-km reach of a high-gradient stream (upper Fountain Creek) in Colorado, USA, impacted by coal-fired power plants, shale deposits, and urbanization. Trout and water were sampled from four sites ranging from 2335 to 1818 m elevation. Lengths, weights, and ages of fish between pairs of the four sites were not significantly different. The dry weight (dw) to wet weight (ww) conversion factor for each tissue was calculated with egg-ovary highest at 0.379 and epaxial muscle fourth highest at 0.223. THg and Se in stomach contents indicated diet and not ambient water was the major source of Hg and Se bioaccumulated. Mean THg ww in kidney was 40.33 µg/kg, and epaxial muscle second highest at 36.76 µg/kg. None of the tissues exceeded the human critical threshold for Hg. However, all 23 trout had at least one tissue type that exceeded 0.02 mg/kg THg ww for birds, and four trout tissues exceeded 0.1 mg/kg THg ww for mammals, indicating that piscivorous mammals and birds should be monitored. Se concentrations in tissues varied depending on ww or dw listing. Mean Se dw in liver was higher than ovary at the uppermost site and the two lower sites. Liver tissue, in addition to egg-ovary, should be utilized as an indicator tissue for Se toxicity.
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Monitoramento Ambiental , Mercúrio/metabolismo , Selênio/metabolismo , Truta/metabolismo , Poluentes Químicos da Água/metabolismo , Animais , Colorado , Cadeia Alimentar , Mercúrio/análise , Rios , Selênio/análise , Urbanização/tendências , Poluentes Químicos da Água/análiseRESUMO
Background/Objective. Enlarged lateral ventricle (LV) volume and decreased volume in the corpus callosum (CC) are hallmarks of schizophrenia (SZ). We previously showed an inverse correlation between LV and CC volumes in SZ, with global functioning decreasing with increased LV volume. This study investigates the relationship between LV volume, CC abnormalities, and the microRNA MIR137 and its regulated genes in SZ, because of MIR137's essential role in neurodevelopment. Methods. Participants were 1224 SZ probands and 1466 unaffected controls from the GENUS Consortium. Brain MRI scans, genotype, and clinical data were harmonized across cohorts and employed in the analyses. Results. Increased LV volumes and decreased CC central, mid-anterior, and mid-posterior volumes were observed in SZ probands. The MIR137-regulated ephrin pathway was significantly associated with CC:LV ratio, explaining a significant proportion (3.42 %) of CC:LV variance, and more than for LV and CC separately. Other pathways explained variance in either CC or LV, but not both. CC:LV ratio was also positively correlated with Global Assessment of Functioning, supporting previous subsample findings. SNP-based heritability estimates were higher for CC central:LV ratio (0.79) compared to CC or LV separately. Discussion. Our results indicate that the CC:LV ratio is highly heritable, influenced in part by variation in the MIR137-regulated ephrin pathway. Findings suggest that the CC:LV ratio may be a risk indicator in SZ that correlates with global functioning.
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Data sharing efforts increasingly contribute to the acceleration of scientific discovery. Neuroimaging data is accumulating in distributed domain-specific databases and there is currently no integrated access mechanism nor an accepted format for the critically important meta-data that is necessary for making use of the combined, available neuroimaging data. In this manuscript, we present work from the Derived Data Working Group, an open-access group sponsored by the Biomedical Informatics Research Network (BIRN) and the International Neuroimaging Coordinating Facility (INCF) focused on practical tools for distributed access to neuroimaging data. The working group develops models and tools facilitating the structured interchange of neuroimaging meta-data and is making progress towards a unified set of tools for such data and meta-data exchange. We report on the key components required for integrated access to raw and derived neuroimaging data as well as associated meta-data and provenance across neuroimaging resources. The components include (1) a structured terminology that provides semantic context to data, (2) a formal data model for neuroimaging with robust tracking of data provenance, (3) a web service-based application programming interface (API) that provides a consistent mechanism to access and query the data model, and (4) a provenance library that can be used for the extraction of provenance data by image analysts and imaging software developers. We believe that the framework and set of tools outlined in this manuscript have great potential for solving many of the issues the neuroimaging community faces when sharing raw and derived neuroimaging data across the various existing database systems for the purpose of accelerating scientific discovery.
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Sistemas de Gerenciamento de Base de Dados/organização & administração , Sistemas de Gerenciamento de Base de Dados/normas , Informática/normas , Disseminação de Informação/métodos , Neuroimagem/métodos , Bases de Dados Factuais/normas , Humanos , Informática/métodos , Informática/tendências , Internet , Neuroimagem/normasRESUMO
Aquatic bryophytes, Hygrohypnum ochraceum, were deployed "in situ" at 14 sites in the Fountain Creek Watershed, spring and fall, 2007 to study selenium (Se) accumulation. Dissolved, total, and pore (sediment derived) water samples were collected and water quality parameters determined while plants were exposed to the water for 10 days. There was a trend showing plant tissue-Se uptake with distance downstream and we found a strong correlation between Se in the water with total hardness in both seasons. There was a modest association between Se-uptake in plants with hardness in the spring of 2007 but not the fall. Plants bioconcentrated Se from the water by a factor of 5.8 × 10(3) at Green Mountain Falls and 1.5 × 10(4) at Manitou Springs in the fall of 2007. Both are examples of the bioconcentration abilities of the plants, primarily in the upper reaches of the watershed where bioconcentration factors were highest. However, the mean minima and maxima of Se in the plants in each of the three watershed segments appeared similar during both seasons. We found direct relationships between the pore and dissolved Se in water in the spring (R (2) = 0.84) and fall (R (2) = 0.95) and dissolved Se and total hardness in the spring and fall (R (2) = 0.92). The data indicate that H. ochraceum was a suitable indicator of Se bioavailability and Se uptake in other trophic levels in the Fountain Creek Watershed based on a subsequent study of Se accumulation in fish tissues at all 14 sites.
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Briófitas/metabolismo , Selênio/metabolismo , Colorado , Modelos Estatísticos , Água/metabolismoRESUMO
We demonstrate the accurate nanoscale mapping of near-surface loss and storage moduli on a polystyrene-polypropylene blend with contact resonance force microscopy (CR-FM). These viscoelastic properties are extracted from spatially resolved maps of the contact resonance frequency and quality factor of the AFM cantilever. We consider two methods of data acquisition: (i) discrete stepping between mapping points and (ii) continuous scanning. For point mapping and low-speed scanning, the values of the relative loss and storage modulus are in good agreement with the time-temperature superposition of low-frequency dynamic mechanical analysis measurements to the high frequencies probed by CR-FM.
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Technological change has been a constant feature of livestock systems leading to the third agricultural 'green' revolution of the mid-20th century. Digital technologies are now leading us into the fourth agricultural revolution, where sustainable food production is supported by technologies that collect data useful for farm and supply chain performance improvement, along with task automation and compliance. However, the potential benefits of digital agricultural futures are uncertain and plagued by unrealized expectations of previous innovations. The aims of this paper are to articulate current trends in technology and livestock systems and anticipate future trajectories for Agriculture 4.0 in relation to meeting sustainability and animal welfare outcomes for livestock systems. We use a 'Futures Triangle' approach to review the role of technology in livestock systems. The main findings are that previous work envisioning technological livestock futures have favoured pull of the future factors (techno-optimists) or weight of the past (techno-pessimists), rather than a balance of pull, push and weighting factors. Responsible Agriculture 4.0 innovation requires public-private collaboration of innovation system stakeholders, including policy makers, farmers, consumers, as well as technology developers, to enable development of transition pathways from a systems perspective. The use of responsible innovation processes, including anticipation on alternative futures, should also be built into innovation processes to support critical reflection on technological trajectories and related innovation system consequences, both desirable and undesirable.
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Agricultura , Gado , Bem-Estar do Animal , Animais , Fazendeiros , Fazendas , HumanosRESUMO
We have discovered two genes, RSRC1 and ARHGAP18, associated with schizophrenia and in an independent study provided additional support for this association. We have both discovered and verified the association of two genes, RSRC1 and ARHGAP18, with schizophrenia. We combined a genome-wide screening strategy with neuroimaging measures as the quantitative phenotype and identified the single nucleotide polymorphisms (SNPs) related to these genes as consistently associated with the phenotypic variation. To control for the risk of false positives, the empirical P-value for association significance was calculated using permutation testing. The quantitative phenotype was Blood-Oxygen-Level Dependent (BOLD) Contrast activation in the left dorsal lateral prefrontal cortex measured during a working memory task. The differential distribution of SNPs associated with these two genes in cases and controls was then corroborated in a larger, independent sample of patients with schizophrenia (n=82) and healthy controls (n=91), thus suggesting a putative etiological function for both genes in schizophrenia. Up until now these genes have not been linked to any neuropsychiatric illness, although both genes have a function in prenatal brain development. We introduce the use of functional magnetic resonance imaging activation as a quantitative phenotype in conjunction with genome-wide association as a gene discovery tool.
Assuntos
Proteínas Ativadoras de GTPase/genética , Proteínas Nucleares/genética , Polimorfismo de Nucleotídeo Único/genética , Córtex Pré-Frontal/irrigação sanguínea , Esquizofrenia/genética , Proteínas Supressoras de Tumor/genética , Adolescente , Adulto , Idoso , Feminino , Frequência do Gene , Predisposição Genética para Doença , Testes Genéticos , Estudo de Associação Genômica Ampla/métodos , Genótipo , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Esquizofrenia/patologia , Adulto JovemRESUMO
Deficits in the connectivity between brain regions have been suggested to play a major role in the pathophysiology of schizophrenia. A functional magnetic resonance imaging (fMRI) analysis of schizophrenia was implemented using independent component analysis (ICA) to identify multiple temporally cohesive, spatially distributed regions of brain activity that represent functionally connected networks. We hypothesized that functional connectivity differences would be seen in auditory networks comprised of regions such as superior temporal gyrus as well as executive networks that consisted of frontal-parietal areas. Eight networks were found to be implicated in schizophrenia during the auditory oddball paradigm. These included a bilateral temporal network containing the superior and middle temporal gyrus; a default-mode network comprised of the posterior cingulate, precuneus, and middle frontal gyrus; and multiple dorsal lateral prefrontal cortex networks that constituted various levels of between-group differences. Highly task-related sensory networks were also found. These results indicate that patients with schizophrenia show functional connectivity differences in networks related to auditory processing, executive control, and baseline functional activity. Overall, these findings support the idea that the cognitive deficits associated with schizophrenia are widespread and that a functional connectivity approach can help elucidate the neural correlates of this disorder.
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Córtex Auditivo/fisiopatologia , Lobo Frontal/fisiopatologia , Imageamento por Ressonância Magnética , Lobo Parietal/fisiopatologia , Esquizofrenia/diagnóstico , Esquizofrenia/fisiopatologia , Lobo Temporal/fisiopatologia , Adolescente , Adulto , Idoso , Córtex Cerebral/fisiopatologia , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rede Nervosa/fisiopatologia , Testes Neuropsicológicos , Esquizofrenia/complicações , Tálamo/fisiopatologia , Adulto JovemRESUMO
INTRODUCTION: Auditory hallucinations are a hallmark symptom of schizophrenia. The neural basis of auditory hallucinations was examined using data from a working memory task. Data were acquired within a multisite consortium and this unique dataset provided the opportunity to analyze data from a large number of subjects who had been tested on the same procedures across sites. We hypothesized that regions involved in verbal working memory and language processing would show activity that was associated with levels of hallucinations during a condition where subjects were rehearsing the stimuli. METHODS: Data from the Sternberg Item Recognition Paradigm, a working memory task, were acquired during functional magnetic resonance imaging procedures. The data were collected and preprocessed by the functional imaging biomedical informatics research network consortium. Schizophrenic subjects were split into nonhallucinating and hallucinating subgroups and activity during the probe condition (in which subjects rehearsed stimuli) was examined. Levels of activation from contrast images for the probe phase (collapsed over levels of memory load) of the working memory task were also correlated with levels of auditory hallucinations from the Scale for the Assessment of Positive Symptoms scores. RESULTS: Patients with auditory hallucinations (relative to nonhallucinating subjects) showed decreased activity during the probe condition in verbal working memory/language processing regions, including the superior temporal and inferior parietal regions. These regions also showed associations between activity and levels of hallucinations in a correlation analysis. DISCUSSION: The association between activation and hallucinations scores in the left hemisphere language/working memory regions replicates the findings of previous studies and provides converging evidence for the association between superior temporal abnormalities and auditory hallucinations.
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Alucinações/diagnóstico , Alucinações/fisiopatologia , Imageamento por Ressonância Magnética , Memória de Curto Prazo , Lobo Parietal/fisiopatologia , Lobo Temporal/fisiopatologia , Adolescente , Adulto , Idoso , Feminino , Lateralidade Funcional/fisiologia , Alucinações/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Reconhecimento Psicológico , Esquizofrenia/complicações , Esquizofrenia/diagnóstico , Esquizofrenia/fisiopatologia , Índice de Gravidade de Doença , Comportamento Verbal , Adulto JovemRESUMO
BACKGROUND: The Functional Imaging Biomedical Informatics Network is a consortium developing methods for multisite functional imaging studies. Both prefrontal hyper- or hypoactivity in chronic schizophrenia have been found in previous studies of working memory. METHODS: In this functional magnetic resonance imaging (fMRI) study of working memory, 128 subjects with chronic schizophrenia and 128 age- and gender-matched controls were recruited from 10 universities around the United States. Subjects performed the Sternberg Item Recognition Paradigm1,2 with memory loads of 1, 3, or 5 items. A region of interest analysis examined the mean BOLD signal change in an atlas-based demarcation of the dorsolateral prefrontal cortex (DLPFC), in both groups, during both the encoding and retrieval phases of the experiment over the various memory loads. RESULTS: Subjects with schizophrenia performed slightly but significantly worse than the healthy volunteers and showed a greater decrease in accuracy and increase in reaction time with increasing memory load. The mean BOLD signal in the DLPFC was significantly greater in the schizophrenic group than the healthy group, particularly in the intermediate load condition. A secondary analysis matched subjects for mean accuracy and found the same BOLD signal hyperresponse in schizophrenics. CONCLUSIONS: The increase in BOLD signal change from minimal to moderate memory loads was greater in the schizophrenic subjects than in controls. This effect remained when age, gender, run, hemisphere, and performance were considered, consistent with inefficient DLPFC function during working memory. These findings from a large multisite sample support the concept not of hyper- or hypofrontality in schizophrenia, but rather DLPFC inefficiency that may be manifested in either direction depending on task demands. This redirects the focus of research from direction of difference to neural mechanisms of inefficiency.
Assuntos
Imageamento por Ressonância Magnética , Memória de Curto Prazo , Córtex Pré-Frontal/fisiopatologia , Esquizofrenia/diagnóstico , Esquizofrenia/fisiopatologia , Adolescente , Adulto , Idoso , Doença Crônica , Feminino , Lateralidade Funcional/fisiologia , Humanos , Masculino , Transtornos da Memória/diagnóstico , Transtornos da Memória/etiologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Esquizofrenia/complicações , Índice de Gravidade de Doença , Adulto JovemRESUMO
Women with similar areal Bone Mineral Densities (BMD) may show divergent fracture incidence due to differences in bone quality. The hypothesis tested in the present pilot study is that postmenopausal (PM) women who have sustained osteoporotic fractures have altered organic matrix quality compared to those who have not. We used Raman microspectroscopy to analyze transiliac biopsies collected from fracturing (nâ¯=â¯6, mean age 62.5⯱â¯7.4â¯yrs; Cases) and non-fracturing PM women (nâ¯=â¯6, age- and BMD-matched; mean age 62.2⯱â¯7.3â¯yrs; Controls). Previous results show differences in intrinsic material properties by nanoindentation that are more homogenously distributed and could facilitate microcrack propagation in Cases, along with lower mineral carbonate/phosphate ratio by Fourier transform infrared spectroscopic imaging, and no differences in bone tissue mineralization by digitized microradiography. No differences between groups were seen by conventional histomorphometry. Spectra were acquired 2⯵m away from previously performed nanoindents, in cortical and cancellous compartments. The determined parameters were: mineral to matrix ratio (MM), and nanoporosity (a surrogate for tissue water (TW)), glycosaminoglycan (GAG), pyridinoline (Pyd; trivalent enzymatic collagen cross-link), N(6)-carboxymethyllysine (CML; advanced glycation endproduct), and pentosidine (PEN; advanced glycation endproduct) content. ANCOVA indicated no differences in any of the spectroscopic outcomes between cancellous and cortical compartments. On the other hand, Cases had lower nanoporosity (TW) and GAG, and elevated Pyd, and CML content compared to Controls. In conclusion, the results of the present study indicate significant differences in organic matrix quality in PM women that sustain fragility fractures versus age- and BMD-matched controls, highlighting its importance as a potential independent determinant of fracture incidence.
Assuntos
Densidade Óssea , Matriz Óssea/patologia , Fraturas Ósseas/patologia , Fraturas Ósseas/fisiopatologia , Pós-Menopausa/fisiologia , Fatores Etários , Biópsia , Feminino , Humanos , Pessoa de Meia-Idade , Projetos Piloto , Análise Espectral RamanRESUMO
The Phenomenex EZ:faast amino acid analysis kit is available for gas (GC) or liquid (LC) chromatographic analysis of amino acids (AA) using mass spectrometry (MS) and other GC detectors. We used it for rapid GC determination of plasma tryptophan, its brain uptake competitors (Val, Leu, Ile, Phe and Tyr) and many other amino acids. Based on solid-phase extraction, this fast method enables one person to process two plasma samples in 8-10 min and six samples in approximately 15 min up to GC injection and a 7-min GC run per plasma sample. Using a Perkin-Elmer Clarus 500 GC, a Total Chrome software, a flame-ionisation detector (FID) and norvaline as internal standard, we used this method to analyse approximately 1,000 plasma samples from normal subjects undergoing acute tryptophan depletion and loading tests. The limit of detection for most amino acids is 1 nmol/ml (1 microM) and in many cases less. With manual injection, coefficients of variation for the above six amino acids were 1.5-6.2% (intra-assay) and 3.8-9.7% (inter-assay). This simple, rapid and elegant method will be valuable to the amino acid analyst and researcher, as it can save much manpower time and meet urgent emergency requests and the demands of a high-throughput laboratory.