{"title":"Human motor learning dynamics in high-dimensional tasks.","authors":"Ankur Kamboj, Rajiv Ranganathan, Xiaobo Tan, Vaibhav Srivastava","doi":"10.1371/journal.pcbi.1012455","DOIUrl":"10.1371/journal.pcbi.1012455","url":null,"abstract":"<p><p>Conventional approaches to enhance movement coordination, such as providing instructions and visual feedback, are often inadequate in complex motor tasks with multiple degrees of freedom (DoFs). To effectively address coordination deficits in such complex motor systems, it becomes imperative to develop interventions grounded in a model of human motor learning; however, modeling such learning processes is challenging due to the large DoFs. In this paper, we present a computational motor learning model that leverages the concept of motor synergies to extract low-dimensional learning representations in the high-dimensional motor space and the internal model theory of motor control to capture both fast and slow motor learning processes. We establish the model's convergence properties and validate it using data from a target capture game played by human participants. We study the influence of model parameters on several motor learning trade-offs such as speed-accuracy, exploration-exploitation, satisficing, and flexibility-performance, and show that the human motor learning system tunes these parameters to optimize learning and various output performance metrics.</p>","PeriodicalId":20241,"journal":{"name":"PLoS Computational Biology","volume":"20 10","pages":"e1012455"},"PeriodicalIF":3.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11501022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142472902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS Computational BiologyPub Date : 2024-10-14eCollection Date: 2024-10-01DOI: 10.1371/journal.pcbi.1012465
Philip Greulich
{"title":"Emergent order in epithelial sheets by interplay of cell divisions and cell fate regulation.","authors":"Philip Greulich","doi":"10.1371/journal.pcbi.1012465","DOIUrl":"10.1371/journal.pcbi.1012465","url":null,"abstract":"<p><p>The fate choices of stem cells between self-renewal and differentiation are often tightly regulated by juxtacrine (cell-cell contact) signalling. Here, we assess how the interplay between cell division, cell fate choices, and juxtacrine signalling can affect the macroscopic ordering of cell types in self-renewing epithelial sheets, by studying a simple spatial cell fate model with cells being arranged on a 2D lattice. We show in this model that if cells commit to their fate directly upon cell division, macroscopic patches of cells of the same type emerge, if at least a small proportion of divisions are symmetric, except if signalling interactions are laterally inhibiting. In contrast, if cells are first 'licensed' to differentiate, yet retaining the possibility to return to their naive state, macroscopic order only emerges if the signalling strength exceeds a critical threshold: if then the signalling interactions are laterally inducing, macroscopic patches emerge as well. Lateral inhibition, on the other hand, can in that case generate periodic patterns of alternating cell types (checkerboard pattern), yet only if the proportion of symmetric divisions is sufficiently low. These results can be understood theoretically by an analogy to phase transitions in spin systems known from statistical physics.</p>","PeriodicalId":20241,"journal":{"name":"PLoS Computational Biology","volume":"20 10","pages":"e1012465"},"PeriodicalIF":3.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11501039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142472900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS Computational BiologyPub Date : 2024-10-11eCollection Date: 2024-10-01DOI: 10.1371/journal.pcbi.1011986
Jessica L Gaines, Kwang S Kim, Ben Parrell, Vikram Ramanarayanan, Alvincé L Pongos, Srikantan S Nagarajan, John F Houde
{"title":"Bayesian inference of state feedback control parameters for fo perturbation responses in cerebellar ataxia.","authors":"Jessica L Gaines, Kwang S Kim, Ben Parrell, Vikram Ramanarayanan, Alvincé L Pongos, Srikantan S Nagarajan, John F Houde","doi":"10.1371/journal.pcbi.1011986","DOIUrl":"10.1371/journal.pcbi.1011986","url":null,"abstract":"<p><p>Behavioral speech tasks have been widely used to understand the mechanisms of speech motor control in typical speakers as well as in various clinical populations. However, determining which neural functions differ between typical speakers and clinical populations based on behavioral data alone is difficult because multiple mechanisms may lead to the same behavioral differences. For example, individuals with cerebellar ataxia (CA) produce atypically large compensatory responses to pitch perturbations in their auditory feedback, compared to typical speakers, but this pattern could have many explanations. Here, computational modeling techniques were used to address this challenge. Bayesian inference was used to fit a state feedback control (SFC) model of voice fundamental frequency (fo) control to the behavioral pitch perturbation responses of speakers with CA and typical speakers. This fitting process resulted in estimates of posterior likelihood distributions for five model parameters (sensory feedback delays, absolute and relative levels of auditory and somatosensory feedback noise, and controller gain), which were compared between the two groups. Results suggest that the speakers with CA may proportionally weight auditory and somatosensory feedback differently from typical speakers. Specifically, the CA group showed a greater relative sensitivity to auditory feedback than the control group. There were also large group differences in the controller gain parameter, suggesting increased motor output responses to target errors in the CA group. These modeling results generate hypotheses about how CA may affect the speech motor system, which could help guide future empirical investigations in CA. This study also demonstrates the overall proof-of-principle of using this Bayesian inference approach to understand behavioral speech data in terms of interpretable parameters of speech motor control models.</p>","PeriodicalId":20241,"journal":{"name":"PLoS Computational Biology","volume":"20 10","pages":"e1011986"},"PeriodicalIF":3.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11498721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"EEG microstate transition cost correlates with task demands.","authors":"Giacomo Barzon, Ettore Ambrosini, Antonino Vallesi, Samir Suweis","doi":"10.1371/journal.pcbi.1012521","DOIUrl":"10.1371/journal.pcbi.1012521","url":null,"abstract":"<p><p>The ability to solve complex tasks relies on the adaptive changes occurring in the spatio-temporal organization of brain activity under different conditions. Altered flexibility in these dynamics can lead to impaired cognitive performance, manifesting for instance as difficulties in attention regulation, distraction inhibition, and behavioral adaptation. Such impairments result in decreased efficiency and increased effort in accomplishing goal-directed tasks. Therefore, developing quantitative measures that can directly assess the effort involved in these transitions using neural data is of paramount importance. In this study, we propose a framework to associate cognitive effort during the performance of tasks with electroencephalography (EEG) activation patterns. The methodology relies on the identification of discrete dynamical states (EEG microstates) and optimal transport theory. To validate the effectiveness of this framework, we apply it to a dataset collected during a spatial version of the Stroop task, a cognitive test in which participants respond to one aspect of a stimulus while ignoring another, often conflicting, aspect. The Stroop task is a cognitive test where participants must respond to one aspect of a stimulus while ignoring another, often conflicting, aspect. Our findings reveal an increased cost linked to cognitive effort, thus confirming the framework's effectiveness in capturing and quantifying cognitive transitions. By utilizing a fully data-driven method, this research opens up fresh perspectives for physiologically describing cognitive effort within the brain.</p>","PeriodicalId":20241,"journal":{"name":"PLoS Computational Biology","volume":"20 10","pages":"e1012521"},"PeriodicalIF":3.8,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11495555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS Computational BiologyPub Date : 2024-10-10eCollection Date: 2024-10-01DOI: 10.1371/journal.pcbi.1012150
Amanda Craine, Adarsh Krishnamurthy, Christopher T Villongco, Kevin Vincent, David E Krummen, Sanjiv M Narayan, Roy C P Kerckhoffs, Jeffrey H Omens, Francisco Contijoch, Andrew D McCulloch
{"title":"Successful cardiac resynchronization therapy reduces negative septal work in patient-specific models of dyssynchronous heart failure.","authors":"Amanda Craine, Adarsh Krishnamurthy, Christopher T Villongco, Kevin Vincent, David E Krummen, Sanjiv M Narayan, Roy C P Kerckhoffs, Jeffrey H Omens, Francisco Contijoch, Andrew D McCulloch","doi":"10.1371/journal.pcbi.1012150","DOIUrl":"10.1371/journal.pcbi.1012150","url":null,"abstract":"<p><p>In patients with dyssynchronous heart failure (DHF), cardiac conduction abnormalities cause the regional distribution of myocardial work to be non-homogeneous. Cardiac resynchronization therapy (CRT) using an implantable, programmed biventricular pacemaker/defibrillator, can improve the synchrony of contraction between the right and left ventricles in DHF, resulting in reduced morbidity and mortality and increased quality of life. Since regional work depends on wall stress, which cannot be measured in patients, we used computational methods to investigate regional work distributions and their changes after CRT. We used three-dimensional multi-scale patient-specific computational models parameterized by anatomic, functional, hemodynamic, and electrophysiological measurements in eight patients with heart failure and left bundle branch block (LBBB) who received CRT. To increase clinical translatability, we also explored whether streamlined computational methods provide accurate estimates of regional myocardial work. We found that CRT increased global myocardial work efficiency with significant improvements in non-responders. Reverse ventricular remodeling after CRT was greatest in patients with the highest heterogeneity of regional work at baseline, however the efficacy of CRT was not related to the decrease in overall work heterogeneity or to the reduction in late-activated regions of high myocardial work. Rather, decreases in early-activated regions of myocardium performing negative myocardial work following CRT best explained patient variations in reverse remodeling. These findings were also observed when regional myocardial work was estimated using ventricular pressure as a surrogate for myocardial stress and changes in endocardial surface area as a surrogate for strain. These new findings suggest that CRT promotes reverse ventricular remodeling in human dyssynchronous heart failure by increasing regional myocardial work in early-activated regions of the ventricles, where dyssynchrony is specifically associated with hypoperfusion, late systolic stretch, and altered metabolic activity and that measurement of these changes can be performed using streamlined approaches.</p>","PeriodicalId":20241,"journal":{"name":"PLoS Computational Biology","volume":"20 10","pages":"e1012150"},"PeriodicalIF":3.8,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11495643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS Computational BiologyPub Date : 2024-10-10eCollection Date: 2024-10-01DOI: 10.1371/journal.pcbi.1012506
Marta Sampaio, Miguel Rocha, Oscar Dias
{"title":"A diel multi-tissue genome-scale metabolic model of Vitis vinifera.","authors":"Marta Sampaio, Miguel Rocha, Oscar Dias","doi":"10.1371/journal.pcbi.1012506","DOIUrl":"10.1371/journal.pcbi.1012506","url":null,"abstract":"<p><p>Vitis vinifera, also known as grapevine, is widely cultivated and commercialized, particularly to produce wine. As wine quality is directly linked to fruit quality, studying grapevine metabolism is important to understand the processes underlying grape composition. Genome-scale metabolic models (GSMMs) have been used for the study of plant metabolism and advances have been made, allowing the integration of omics datasets with GSMMs. On the other hand, Machine learning (ML) has been used to analyze and integrate omics data, and while the combination of ML with GSMMs has shown promising results, it is still scarcely used to study plants. Here, the first GSSM of V. vinifera was reconstructed and validated, comprising 7199 genes, 5399 reactions, and 5141 metabolites across 8 compartments. Tissue-specific models for the stem, leaf, and berry of the Cabernet Sauvignon cultivar were generated from the original model, through the integration of RNA-Seq data. These models have been merged into diel multi-tissue models to study the interactions between tissues at light and dark phases. The potential of combining ML with GSMMs was explored by using ML to analyze the fluxomics data generated by green and mature grape GSMMs and provide insights regarding the metabolism of grapes at different developmental stages. Therefore, the models developed in this work are useful tools to explore different aspects of grapevine metabolism and understand the factors influencing grape quality.</p>","PeriodicalId":20241,"journal":{"name":"PLoS Computational Biology","volume":"20 10","pages":"e1012506"},"PeriodicalIF":3.8,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11495577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS Computational BiologyPub Date : 2024-10-10eCollection Date: 2024-10-01DOI: 10.1371/journal.pcbi.1012414
Colby Fronk, Jaewoong Yun, Prashant Singh, Linda Petzold
{"title":"Bayesian polynomial neural networks and polynomial neural ordinary differential equations.","authors":"Colby Fronk, Jaewoong Yun, Prashant Singh, Linda Petzold","doi":"10.1371/journal.pcbi.1012414","DOIUrl":"10.1371/journal.pcbi.1012414","url":null,"abstract":"<p><p>Symbolic regression with polynomial neural networks and polynomial neural ordinary differential equations (ODEs) are two recent and powerful approaches for equation recovery of many science and engineering problems. However, these methods provide point estimates for the model parameters and are currently unable to accommodate noisy data. We address this challenge by developing and validating the following Bayesian inference methods: the Laplace approximation, Markov Chain Monte Carlo (MCMC) sampling methods, and variational inference. We have found the Laplace approximation to be the best method for this class of problems. Our work can be easily extended to the broader class of symbolic neural networks to which the polynomial neural network belongs.</p>","PeriodicalId":20241,"journal":{"name":"PLoS Computational Biology","volume":"20 10","pages":"e1012414"},"PeriodicalIF":3.8,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11476690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS Computational BiologyPub Date : 2024-10-10eCollection Date: 2024-10-01DOI: 10.1371/journal.pcbi.1012460
Alexis Bénichou, Jean-Baptiste Masson, Christian L Vestergaard
{"title":"Compression-based inference of network motif sets.","authors":"Alexis Bénichou, Jean-Baptiste Masson, Christian L Vestergaard","doi":"10.1371/journal.pcbi.1012460","DOIUrl":"10.1371/journal.pcbi.1012460","url":null,"abstract":"<p><p>Physical and functional constraints on biological networks lead to complex topological patterns across multiple scales in their organization. A particular type of higher-order network feature that has received considerable interest is network motifs, defined as statistically regular subgraphs. These may implement fundamental logical and computational circuits and are referred to as \"building blocks of complex networks\". Their well-defined structures and small sizes also enable the testing of their functions in synthetic and natural biological experiments. Here, we develop a framework for motif mining based on lossless network compression using subgraph contractions. This provides an alternative definition of motif significance which allows us to compare different motifs and select the collectively most significant set of motifs as well as other prominent network features in terms of their combined compression of the network. Our approach inherently accounts for multiple testing and correlations between subgraphs and does not rely on a priori specification of an appropriate null model. It thus overcomes common problems in hypothesis testing-based motif analysis and guarantees robust statistical inference. We validate our methodology on numerical data and then apply it on synaptic-resolution biological neural networks, as a medium for comparative connectomics, by evaluating their respective compressibility and characterize their inferred circuit motifs.</p>","PeriodicalId":20241,"journal":{"name":"PLoS Computational Biology","volume":"20 10","pages":"e1012460"},"PeriodicalIF":3.8,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11495616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS Computational BiologyPub Date : 2024-10-10eCollection Date: 2024-10-01DOI: 10.1371/journal.pcbi.1012492
George Gabriel, Faisal Mushtaq, J Ryan Morehead
{"title":"De novo sensorimotor learning through reuse of movement components.","authors":"George Gabriel, Faisal Mushtaq, J Ryan Morehead","doi":"10.1371/journal.pcbi.1012492","DOIUrl":"10.1371/journal.pcbi.1012492","url":null,"abstract":"<p><p>From tying one's shoelaces to driving a car, complex skills involving the coordination of multiple muscles are common in everyday life; yet relatively little is known about how these skills are learned. Recent studies have shown that new sensorimotor skills involving re-mapping familiar body movements to unfamiliar outputs cannot be learned by adjusting pre-existing controllers, and that new task-specific controllers must instead be learned \"de novo\". To date, however, few studies have investigated de novo learning in scenarios requiring continuous and coordinated control of relatively unpractised body movements. In this study, we used a myoelectric interface to investigate how a novel controller is learned when the task involves an unpractised combination of relatively untrained continuous muscle contractions. Over five sessions on five consecutive days, participants learned to trace a series of trajectories using a computer cursor controlled by the activation of two muscles. The timing of the generated cursor trajectory and its shape relative to the target improved for conditions trained with post-trial visual feedback. Improvements in timing transferred to all untrained conditions, but improvements in shape transferred less robustly to untrained conditions requiring the trained order of muscle activation. All muscle outputs in the final session could already be generated during the first session, suggesting that participants learned the new task by improving the selection of existing motor commands. These results suggest that the novel controllers acquired during de novo learning can, in some circumstances, be constructed from components of existing controllers.</p>","PeriodicalId":20241,"journal":{"name":"PLoS Computational Biology","volume":"20 10","pages":"e1012492"},"PeriodicalIF":3.8,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11495618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS Computational BiologyPub Date : 2024-10-07eCollection Date: 2024-10-01DOI: 10.1371/journal.pcbi.1012498
Fan Xia, Yanni Xiao, Junling Ma
{"title":"The optimal spatially-dependent control measures to effectively and economically eliminate emerging infectious diseases.","authors":"Fan Xia, Yanni Xiao, Junling Ma","doi":"10.1371/journal.pcbi.1012498","DOIUrl":"10.1371/journal.pcbi.1012498","url":null,"abstract":"<p><p>Non-pharmaceutical interventions (NPIs) are effective in mitigating infections during the early stages of an infectious disease outbreak. However, these measures incur significant economic and livelihood costs. To address this, we developed an optimal control framework aimed at identifying strategies that minimize such costs while ensuring full control of a cross-regional outbreak of emerging infectious diseases. Our approach uses a spatial SEIR model with interventions for the epidemic process, and incorporates population flow in a gravity model dependent on gross domestic product (GDP) and geographical distance. We applied this framework to identify an optimal control strategy for the COVID-19 outbreak caused by the Delta variant in Xi'an City, Shaanxi, China, between December 2021 and January 2022. The model was parameterized by fitting it to daily case data from each district of Xi'an City. Our findings indicate that an increase in the basic reproduction number, the latent period or the infectious period leads to a prolonged outbreak and a larger final size. This indicates that diseases with greater transmissibility are more challenging and costly to control, and so it is important for governments to quickly identify cases and implement control strategies. Indeed, the optimal control strategy we identified suggests that more costly control measures should be implemented as soon as they are deemed necessary. Our results demonstrate that optimal control regimes exhibit spatial, economic, and population heterogeneity. More populated and economically developed regions require a robust regular surveillance mechanism to ensure timely detection and control of imported infections. Regions with higher GDP tend to experience larger-scale epidemics and, consequently, require higher control costs. Notably, our proposed optimal strategy significantly reduced costs compared to the actual expenditures for the Xi'an outbreak.</p>","PeriodicalId":20241,"journal":{"name":"PLoS Computational Biology","volume":"20 10","pages":"e1012498"},"PeriodicalIF":3.8,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11486435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}