Brain connectivityPub Date : 2023-09-01Epub Date: 2023-06-14DOI: 10.1089/brain.2022.0082
Nicholas Theis, Jonathan Rubin, Joshua Cape, Satish Iyengar, Konasale M Prasad
{"title":"Threshold Selection for Brain Connectomes.","authors":"Nicholas Theis, Jonathan Rubin, Joshua Cape, Satish Iyengar, Konasale M Prasad","doi":"10.1089/brain.2022.0082","DOIUrl":"10.1089/brain.2022.0082","url":null,"abstract":"<p><p><b><i>Introduction:</i></b> Structural and functional brain connectomes represent macroscale data collected through techniques such as magnetic resonance imaging (MRI). Connectomes may contain noise that contributes to false-positive edges, thereby obscuring structure-function relationships and data interpretation. Thresholding procedures can be applied to reduce network density by removing low-signal edges, but there is limited consensus on appropriate selection of thresholds. This article compares existing thresholding methods and introduces a novel alternative \"objective function\" thresholding method. <b><i>Methods:</i></b> The performance of thresholding approaches, based on percolation and objective functions, is assessed by (1) computing the normalized mutual information (NMI) of community structure between a known network and a simulated, perturbed networks to which various forms of thresholding have been applied, and by (2) comparing the density and the clustering coefficient (CC) between the baseline and thresholded networks. An application to empirical data is provided. <b><i>Results:</i></b> Our proposed objective function-based threshold exhibits the best performance in terms of resulting in high similarity between the underlying networks and their perturbed, thresholded counterparts, as quantified by NMI and CC analysis on the simulated functional networks. <b><i>Discussion:</i></b> Existing network thresholding methods yield widely different results when graph metrics are subsequently computed. Thresholding based on the objective function maintains a set of edges such that the resulting network shares the community structure and clustering features present in the original network. This outcome provides a proof of principle that objective function thresholding could offer a useful approach to reducing the network density of functional connectivity data.</p>","PeriodicalId":9155,"journal":{"name":"Brain connectivity","volume":"13 7","pages":"383-393"},"PeriodicalIF":2.4,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10517318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10227277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brain connectivityPub Date : 2023-09-01Epub Date: 2023-07-26DOI: 10.1089/brain.2022.0073
Yingying Wang, Yi Wang, Guowei Hua, Min Yu, Lu Lin, Lichi Zhang, Hongxin Li
{"title":"Changes of Functional Brain Network in Neonates with Different Degrees of Hypoxic-Ischemic Encephalopathy.","authors":"Yingying Wang, Yi Wang, Guowei Hua, Min Yu, Lu Lin, Lichi Zhang, Hongxin Li","doi":"10.1089/brain.2022.0073","DOIUrl":"10.1089/brain.2022.0073","url":null,"abstract":"<p><p><b><i>Background:</i></b> Neonatal hypoxic-ischemic encephalopathy (HIE) is the main cause of neonatal death and disability worldwide. At present, there are few researches on the application of resting-state functional magnetic resonance imaging (rs-fMRI) to explore the brain development of HIE children. This study aimed to explore the changes of brain function in neonates with different degrees of HIE using rs-fMRI. <b><i>Methods:</i></b> From February 2018 to May 2020, 44 patients with HIE were recruited, including 21 mild patients and 23 moderate and severe patients. The recruited patients were scanned by conventional and functional magnetic resonance image, and the method of amplitude of low-frequency fluctuation and connecting edge analysis of brain network was used. <b><i>Results:</i></b> Compared with the mild group, the connections between the right supplementary motor area and the right precentral gyrus, the right lingual gyrus and the right hippocampus, the left calcarine cortex and the right amygdala, and the right pallidus and the right posterior cingulate cortex in the moderate and severe groups were reduced (<i>t</i> values were 4.04, 4.04, 4.04, 4.07, all <i>p</i> < 0.001, uncorrected). <b><i>Conclusion:</i></b> By analyzing the functional connection changes of brain network in infants with different degrees of HIE, the findings of the current study suggested that neonates with moderate to severe HIE lag behind those with mild HIE in emotional processing, sensory movement, cognitive function, and learning and memory. <b><i>Chinese Clinical Trial Registry registration number:</i></b> ChiCTR1800016409.</p>","PeriodicalId":9155,"journal":{"name":"Brain connectivity","volume":"13 7","pages":"427-435"},"PeriodicalIF":3.4,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10290933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brain connectivityPub Date : 2023-09-01Epub Date: 2023-05-29DOI: 10.1089/brain.2022.0076
Giulia Carli, Marco Cavicchioli, Anna Lisa Martini, Matteo Bruscoli, Antonella Mafredi, Luca Presotto, Christian Mazzeo, Stelvio Sestini, Daniela Perani
{"title":"Neurobiological Dysfunctional Substrates for the Self-Medication Hypothesis in Adult Individuals with Attention-Deficit Hyperactivity Disorder and Cocaine Use Disorder: A Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography Study.","authors":"Giulia Carli, Marco Cavicchioli, Anna Lisa Martini, Matteo Bruscoli, Antonella Mafredi, Luca Presotto, Christian Mazzeo, Stelvio Sestini, Daniela Perani","doi":"10.1089/brain.2022.0076","DOIUrl":"10.1089/brain.2022.0076","url":null,"abstract":"<p><p><b><i>Objectives:</i></b> Attention-deficit hyperactivity disorder (ADHD) in adulthood shows high co-occurrence rates with cocaine use disorder (CoUD). The self-medication hypothesis (SMH) provides a theoretical explanation for this comorbidity. This study investigates the neurobiological mechanisms that could support SMH in adult patients with attention-deficit hyperactivity disorder with cocaine use disorder (ADHD-CoUD). <b><i>Materials and Methods:</i></b> We included 19 ADHD<i>-</i>CoUD patients (84.2% male; age: 32.11 years [7.18]) and 16 CoUD patients (68.7% male; age: 36.63 years [8.12]). All subjects underwent a fluorine-18-fluorodeoxyglucose positron emission tomography (<sup>18</sup>F-FDG PET) brain scan. We tested brain metabolism differences between ADHD-CoUD and CoUD patients using voxel-based and regions of interest (ROIs)-based analyses. The correlation between dependence/abstinence duration and regional brain metabolism was also assessed in the two groups. Lastly, we investigated the integrity of brain metabolic connectivity of mesocorticolimbic and nigrostriatal dopaminergic systems, and large-scale brain networks involved in ADHD and addictions. <b><i>Results:</i></b> The voxel-wise and ROIs-based approaches showed that ADHD-CoUD patients had a lower metabolism in the thalamus and increased metabolism in the amygdala and parahippocampus, bilaterally, than CoUD subjects and healthy controls (HCs). Metabolism in the thalamus negatively correlated with years of dependence in ADHD-CoUD patients. Moreover, connectivity analyses revealed that ADHD-CoUD patients had a more preserved metabolic connectivity than CoUD patients in the dopaminergic networks and large-scale networks involved in self-regulation mechanisms of attention and behaviors (i.e., anterior default mode network [ADMN], executive network [ECN], and anterior salience network [aSAN]). <b><i>Conclusions:</i></b> We demonstrated distinct neuropathological substrates underlying substance-use behaviors in ADHD-CoUD and CoUD patients. Furthermore, we provided neurobiological evidence in support of SMH, demonstrating that ADHD-CoUD patients might experience short-term advantages of cocaine assumption (i.e., compensation of dopaminergic deficiency and related cognitive-behavioral deficits).</p>","PeriodicalId":9155,"journal":{"name":"Brain connectivity","volume":"13 7","pages":"370-382"},"PeriodicalIF":3.4,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10601718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brain connectivityPub Date : 2023-09-01Epub Date: 2023-07-24DOI: 10.1089/brain.2022.0077
M Fiona Molloy, Emily J Yu, Whitney I Mattson, Kristen R Hoskinson, H Gerry Taylor, David E Osher, Eric E Nelson, Zeynep M Saygin
{"title":"Effect of Extremely Preterm Birth on Adolescent Brain Network Organization.","authors":"M Fiona Molloy, Emily J Yu, Whitney I Mattson, Kristen R Hoskinson, H Gerry Taylor, David E Osher, Eric E Nelson, Zeynep M Saygin","doi":"10.1089/brain.2022.0077","DOIUrl":"10.1089/brain.2022.0077","url":null,"abstract":"<p><p><b><i>Introduction:</i></b> Extremely preterm (EPT) birth, defined as birth at a gestational age (GA) <28 weeks, can have a lasting impact on cognition throughout the life span. Previous investigations reveal differences in brain structure and connectivity between infants born preterm and full-term (FT), but how does preterm birth impact the adolescent connectome? <b><i>Methods:</i></b> In this study, we investigate how EPT birth can alter broadscale network organization later in life by comparing resting-state functional magnetic resonance imaging connectome-based parcellations of the entire cortex in adolescents born EPT (<i>N</i> = 22) to age-matched adolescents born FT (GA ≥37 weeks, <i>N</i> = 28). We compare these parcellations to adult parcellations from previous studies and explore the relationship between an individual's network organization and behavior. <b><i>Results:</i></b> Primary (occipital and sensorimotor) and frontoparietal networks were observed in both groups. However, there existed notable differences in the limbic and insular networks. Surprisingly, the connectivity profile of the limbic network of EPT adolescents was more adultlike than the same network in FT adolescents. Finally, we found a relationship between adolescents' overall cognition score and their limbic network maturity. <b><i>Discussion:</i></b> Overall, preterm birth may contribute to the atypical development of broadscale network organization in adolescence and may partially explain the observed cognitive deficits.</p>","PeriodicalId":9155,"journal":{"name":"Brain connectivity","volume":"13 7","pages":"394-409"},"PeriodicalIF":3.4,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10585050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brain connectivityPub Date : 2023-09-01DOI: 10.1089/brain.2023.29053.editorial
Paul Edison
{"title":"<i>Brain Connectivity:A Journal of Clinical Neurology, Neuroscience, & Neuroimaging</i> Advancing the Field of Neurology.","authors":"Paul Edison","doi":"10.1089/brain.2023.29053.editorial","DOIUrl":"10.1089/brain.2023.29053.editorial","url":null,"abstract":"","PeriodicalId":9155,"journal":{"name":"Brain connectivity","volume":"13 7","pages":"367-369"},"PeriodicalIF":3.4,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10589618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brain connectivityPub Date : 2023-08-01DOI: 10.1089/brain.2023.29052.editorial
Paul Edison
{"title":"Brain Connectivity: <i>A Journal of Clinical Neurology, Neuroscience, & Neuroimaging Advancing the Field of Neurology</i> Advances in Alzheimer's Disease.","authors":"Paul Edison","doi":"10.1089/brain.2023.29052.editorial","DOIUrl":"https://doi.org/10.1089/brain.2023.29052.editorial","url":null,"abstract":"","PeriodicalId":9155,"journal":{"name":"Brain connectivity","volume":"13 6","pages":"316-318"},"PeriodicalIF":3.4,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9986278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brain connectivityPub Date : 2023-08-01Epub Date: 2021-09-07DOI: 10.1089/brain.2020.0847
Mohammad S E Sendi, Elaheh Zendehrouh, Zening Fu, Jingyu Liu, Yuhui Du, Elizabeth Mormino, David H Salat, Vince D Calhoun, Robyn L Miller
{"title":"Disrupted Dynamic Functional Network Connectivity Among Cognitive Control Networks in the Progression of Alzheimer's Disease.","authors":"Mohammad S E Sendi, Elaheh Zendehrouh, Zening Fu, Jingyu Liu, Yuhui Du, Elizabeth Mormino, David H Salat, Vince D Calhoun, Robyn L Miller","doi":"10.1089/brain.2020.0847","DOIUrl":"10.1089/brain.2020.0847","url":null,"abstract":"<p><p><b><i>Background:</i></b> Alzheimer's disease (AD) is the most common age-related dementia that promotes a decline in memory, thinking, and social skills. The initial stages of dementia can be associated with mild symptoms, and symptom progression to a more severe state is heterogeneous across patients. Recent work has demonstrated the potential for functional network mapping to assist in the prediction of symptomatic progression. However, this work has primarily used static functional connectivity (sFC) from resting-state functional magnetic resonance imaging. Recently, dynamic functional connectivity (dFC) has been recognized as a powerful advance in functional connectivity methodology to differentiate brain network dynamics between healthy and diseased populations. <b><i>Methods:</i></b> Group independent component analysis was applied to extract 17 components within the cognitive control network (CCN) from 1385 individuals across varying stages of AD symptomology. We estimated dFC among 17 components within the CCN, followed by clustering the dFCs into 3 recurring brain states, and then estimated a hidden Markov model and the occupancy rate for each subject. Then, we investigated the link between CCN dFC features and AD progression. Also, we investigated the link between sFC and AD progression and compared its results with dFC results. <b><i>Results:</i></b> Progression of AD symptoms was associated with increases in connectivity within the middle frontal gyrus. Also, the very mild AD (vmAD) showed less connectivity within the inferior parietal lobule (in both sFC and dFC) and between this region and the rest of CCN (in dFC analysis). Also, we found that within-middle frontal gyrus connectivity increases with AD progression in both sFC and dFC results. Finally, comparing with vmAD, we found that the normal brain spends significantly more time in a state with lower within-middle frontal gyrus connectivity and higher connectivity between the hippocampus and the rest of CCN, highlighting the importance of assessing the dynamics of brain connectivity in this disease. <b><i>Conclusion:</i></b> Our results suggest that AD progress not only alters the CCN connectivity strength but also changes the temporal properties in this brain network. This suggests the temporal and spatial pattern of CCN as a biomarker that differentiates different stages of AD.</p>","PeriodicalId":9155,"journal":{"name":"Brain connectivity","volume":"13 6","pages":"334-343"},"PeriodicalIF":2.4,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10442683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10043596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brain connectivityPub Date : 2023-08-01DOI: 10.1089/brain.2023.29051.rfs2022
Tara Chand
{"title":"Rosalind Franklin Society Proudly Announces the 2022 Award Recipient for <i>Brain Connectivity</i>.","authors":"Tara Chand","doi":"10.1089/brain.2023.29051.rfs2022","DOIUrl":"https://doi.org/10.1089/brain.2023.29051.rfs2022","url":null,"abstract":"","PeriodicalId":9155,"journal":{"name":"Brain connectivity","volume":"13 6","pages":"315"},"PeriodicalIF":3.4,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9961577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mass Spectrometry Imaging in Alzheimer's Disease.","authors":"Masaya Ikegawa, Nobuto Kakuda, Tomohiro Miyasaka, Yumiko Toyama, Takashi Nirasawa, Karolina Minta, Jörg Hanrieder","doi":"10.1089/brain.2022.0057","DOIUrl":"10.1089/brain.2022.0057","url":null,"abstract":"<p><p><b><i>Introduction:</i></b> Amyloid-beta (Aβ) pathology is the precipitating histopathological characteristic of Alzheimer's disease (AD). Although the formation of amyloid plaques in human brains is suggested to be a key factor in initiating AD pathogenesis, it is still not fully understood the upstream events that lead to Aβ plaque formation and its metabolism inside the brains. <b><i>Methods:</i></b> Matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) has been successfully introduced to study AD pathology in brain tissue both in AD mouse models and human samples. By using MALDI-MSI, a highly selective deposition of Aβ peptides in AD brains with a variety of cerebral amyloid angiopathy (CAA) involvement was observed. <b><i>Results:</i></b> MALDI-MSI visualized depositions of shorter peptides in AD brains; Aβ1-36 to Aβ1-39 were quite similarly distributed with Aβ1-40 as a vascular pattern, and deposition of Aβ1-42 and Aβ1-43 was visualized with a distinct senile plaque pattern distributed in parenchyma. Moreover, how MALDI-MSI covered <i>in situ</i> lipidomics of plaque pathology has been reviewed, which is of interest as aberrations in neuronal lipid biochemistry have been implicated in AD pathogenesis. <b><i>Discussion:</i></b> In this study, we introduce the methodological concepts and challenges of MALDI-MSI for the studies of AD pathogenesis. Diverse Aβ isoforms including various C- and N-terminal truncations in AD and CAA brain tissues will be visualized. Despite the close relationship between vascular and plaque Aβ deposition, the current strategy will define cross talk between neurodegenerative and cerebrovascular processes at the level of Aβ metabolism.</p>","PeriodicalId":9155,"journal":{"name":"Brain connectivity","volume":"13 6","pages":"319-333"},"PeriodicalIF":2.4,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10494909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10207425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiangliang Chen, Oezguer A Onur, Nils Richter, Ronja Fassbender, Hannes Gramespacher, Qumars Befahr, Boris von Reutern, Kim Dillen, Heidi I L Jacobs, Juraj Kukolja, Gereon R Fink, Julian Dronse
{"title":"Concordance of Intrinsic Brain Connectivity Measures Is Disrupted in Alzheimer's Disease.","authors":"Xiangliang Chen, Oezguer A Onur, Nils Richter, Ronja Fassbender, Hannes Gramespacher, Qumars Befahr, Boris von Reutern, Kim Dillen, Heidi I L Jacobs, Juraj Kukolja, Gereon R Fink, Julian Dronse","doi":"10.1089/brain.2020.0918","DOIUrl":"https://doi.org/10.1089/brain.2020.0918","url":null,"abstract":"<p><p><b><i>Background:</i></b> Recently, a new resting-state functional magnetic resonance imaging (rs-fMRI) measure to evaluate the concordance between different rs-fMRI metrics has been proposed and has not been investigated in Alzheimer's disease (AD). <b><i>Methods:</i></b> 3T rs-fMRI data were obtained from healthy young controls (YC, <i>n</i> = 26), healthy senior controls (SC, <i>n</i> = 29), and AD patients (<i>n</i> = 35). The fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity (ReHo), and degree centrality (DC) were analyzed, followed by the calculation of their concordance using Kendall's W for each brain voxel across time. Group differences in the concordance were compared globally, within seven intrinsic brain networks, and on a voxel-by-voxel basis with covariates of age, sex, head motion, and gray matter volume. <b><i>Results:</i></b> The global concordance was lowest in AD among the three groups, with similar differences for the single metrics. When comparing AD to SC, reductions of concordance were detected in each of the investigated networks apart from the limbic network. For SC in comparison to YC, lower global concordance without any network-level difference was observed. Voxel-wise analyses revealed lower concordance in the right middle temporal gyrus in AD compared to SC and lower concordance in the left middle frontal gyrus in SC compared to YC. Lower fALFF were observed in the right angular gyrus in AD in comparison to SC, but ReHo and DC showed no group differences. <b><i>Conclusions:</i></b> The concordance of resting-state measures differentiates AD from healthy aging and may represent a novel imaging marker in AD.</p>","PeriodicalId":9155,"journal":{"name":"Brain connectivity","volume":"13 6","pages":"344-355"},"PeriodicalIF":3.4,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9982586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}