Journal of neurophysiology最新文献

{"title":"Comprehensive analysis of human dendritic spine morphology and density.","authors":"Kerstin D Schünemann, Roxanne M Hattingh, Matthijs B Verhoog, Danqing Yang, Aniella V Bak, Sabrina Peter, Karen M J van Loo, Stefan Wolking, Deborah Kronenberg-Versteeg, Yvonne Weber, Niklas Schwarz, Joseph V Raimondo, Roger Melvill, Sean A Tromp, James T Butler, Anke Höllig, Daniel Delev, Thomas V Wuttke, Björn M Kampa, Henner Koch","doi":"10.1152/jn.00622.2024","DOIUrl":"10.1152/jn.00622.2024","url":null,"abstract":"<p><p>Dendritic spines, small protrusions on neuronal dendrites, play a crucial role in brain function by changing shape and size in response to neural activity. So far, in-depth analysis of dendritic spines in human brain tissue is lacking. This study presents a comprehensive analysis of human dendritic spine morphology and density using a unique dataset from human brain tissue from 27 patients (8 females, 19 males, aged 18-71 yr) undergoing tumor or epilepsy surgery at three neurosurgery sites. We used acute slices and organotypic brain slice cultures to examine dendritic spines, classifying them into the three main morphological subtypes: mushroom, thin, and stubby, via three-dimensional (3-D) reconstruction using ZEISS arivis Pro software. A deep learning model, trained on 39 diverse datasets, automated spine segmentation and 3-D reconstruction, achieving a 74% F1-score and reducing processing time by over 50%. We show significant differences in spine density by sex, dendrite type, and tissue condition. Females had higher spine densities than males, and apical dendrites were denser in spines than basal ones. Acute tissue showed higher spine densities compared with cultured human brain tissue. With time in culture, mushroom spines decreased, whereas stubby and thin spine percentages increased, particularly from 7-9 to 14 days in vitro, reflecting potential synaptic plasticity changes. Our study underscores the importance of using human brain tissue to understand unique synaptic properties and shows that integrating deep learning with traditional methods enables efficient large-scale analysis, revealing key insights into sex- and tissue-specific dendritic spine dynamics relevant to neurological diseases.<b>NEW & NOTEWORTHY</b> This study presents a dataset of nearly 4,000 morphologically reconstructed human dendritic spines across different ages, gender, and tissue conditions. The dataset was further used to evaluate a deep learning algorithm for three-dimensional spine reconstruction, offering a scalable method for semiautomated spine analysis across various tissues and microscopy setups. The findings enhance understanding of human neurology, indicating potential connections between spine morphology, brain function, and the mechanisms of neurological and psychiatric diseases.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"1086-1102"},"PeriodicalIF":2.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515788","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":"Cerebral blood flow in Andean children and adolescents living above 5,000 m.","authors":"Connor A Howe, Samuel Verges, Daniela Nowak-Flück, Jack S Talbot, Benoit Champigneulle, Emeric Stauffer, Julien V Brugniaux, Stéphane Doutreleau, Ivan Hancco, Shailesh Niroula, Aurélien Pichon, Ali M McManus, Michael Stembridge, Philip N Ainslie","doi":"10.1152/jn.00513.2024","DOIUrl":"10.1152/jn.00513.2024","url":null,"abstract":"<p><p>A number of indigenous populations have resided at high-altitude for generations, resulting in various phenotypical adaptations promoting successful high-altitude adaptation. Although many of these adaptations have been investigated in adults, little is known regarding how children residing at high-altitudes adapt, particularly with regards to the cerebrovasculature. Under hypoxic environments, compensatory changes in cerebral blood flow (CBF) are necessary to couple oxygen delivery to metabolic demand in the face of reduced oxygen availability. In this study, we aimed to evaluate regional and global cerebral blood flow (CBF) in Andean children and adolescents living in the highest city in the world at 5,100 m. Eighteen Andeans (ages 6-17 yr) living in La Rinconada, Peru (5,100 m) were compared with sex-, age-, size-, and maturity-matched high-altitude Sherpa (3,800 m) living in the Khumbu valley of Nepal (<i>n</i> = 18) and lowlanders (44 m) living at sea-level in Cardiff, Wales (<i>n</i> = 18). Volumetric measurements of CBF were assessed using duplex ultrasound of the internal carotid and vertebral arteries to assess regional and global CBF. End-tidal gases and oxygen saturation were measured in all groups, while hemoglobin concentration was assessed in Andeans. Despite Andeans living under a more severe hypoxic environment, global CBF was similar between Andeans (687.01 ± 138.49 mL/min), Sherpa (711.27 ± 110.27 mL/min), and lowlanders (704.88 ± 59.23 mL/min). In contrast, vertebral artery blood flow was 24% lower in Andeans (72.93 ± 31.60 mL/min) compared with lowlanders (96.09 ± 19.23 mL/min). The similar global CBF in Andean children might be achieved through elevated hemoglobin concentration. However, lower posterior perfusion in Andeans requires further investigation to determine whether it represents an adaptive or maladaptive response.<b>NEW & NOTEWORTHY</b> We have, for the first time, quantified volumetric regional and global cerebral blood flow in indigenous Andean children and adolescents living above 5,000 m in the highest city in the world. Compared with Sherpa living at moderate altitude (3,800 m), and lowlanders residing at sea level, Andeans present with similar global cerebral blood flow, but lower posterior flow despite being more hypoxemic. Similar to adults, differences in high hemoglobin concentration may drive this pattern of cerebral blood flow.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"1138-1145"},"PeriodicalIF":2.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573288","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":"A novel biomechanical model of the proximal mouse forelimb predicts muscle activity in optimal control simulations of reaching movements.","authors":"Jesse I Gilmer, Susan K Coltman, Geraldine Cuenu, John R Hutchinson, Daniel Huber, Abigail L Person, Mazen Al Borno","doi":"10.1152/jn.00499.2024","DOIUrl":"10.1152/jn.00499.2024","url":null,"abstract":"<p><p>Mice are key model organisms in neuroscience and motor systems physiology. Fine motor control tasks performed by mice have become widely used in assaying neural and biophysical motor system mechanisms. Although fine motor tasks provide useful insights into behaviors that require complex multi-joint motor control, there is no previously developed physiological biomechanical model of the adult mouse forelimb available for estimating kinematics, muscle activity, or kinetics during behaviors. Here, we developed a musculoskeletal model based on high-resolution imaging of the mouse forelimb that includes muscles spanning the neck, trunk, shoulder, and limbs. Physics-based optimal control simulations of the forelimb model were used to estimate in vivo muscle activity present when constrained to the tracked kinematics during reaching movements. The activity of a subset of muscles was recorded and used to assess the accuracy of the muscle patterning in simulation. We found that the synthesized muscle patterning in the forelimb model had a strong resemblance to empirical muscle patterning, suggesting that our model has utility in providing a realistic set of estimated muscle excitations over time when given a kinematic template. The strength of the similarity between empirical muscle activity and optimal control predictions increases as mice performance improves throughout learning of the reaching task. Our computational tools are available as open-source in the OpenSim physics and modeling platform. Our model can enhance research into limb control across broad research topics and can inform analyses of motor learning, muscle synergies, neural patterning, and behavioral research that would otherwise be inaccessible.<b>NEW & NOTEWORTHY</b> Investigations into motor planning and execution lack an accurate and complete model of the forelimb, which could bolster or expand on findings. We sought to construct such a model using high-detail scans of murine anatomy and prior research into muscle physiology. We then used the model to predict muscle excitations in a set of reaching movements and found that it provided accurate estimations and provided insight into an optimal-control framework of motor learning.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"1266-1278"},"PeriodicalIF":2.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12087678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648831","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}

{"title":"Microbiome's effect on white matter in autism.","authors":"Katherine Canada, Tanya M Evans, Kevin A Pelphrey","doi":"10.1152/jn.00607.2024","DOIUrl":"10.1152/jn.00607.2024","url":null,"abstract":"<p><p>Autism spectrum disorder (ASD) is characterized by deficits in social communication and restricted, repetitive behavioral patterns. Although other physiological presentations in individuals with ASD are heterogeneous, neuroimaging studies have consistently revealed a developmental pattern of initial white matter hypermyelination followed by reduced myelination compared with typically developing peers. Multiple studies have demonstrated that core ASD symptoms, including impairments in social skills, language acquisition, learning capabilities, motor performance, and sensory processing, correlate significantly with white matter dysregulation measured through diffusion tensor imaging (DTI). Longitudinal studies have shown that decreased gut microbiome diversity, particularly reductions in beneficial bacteria such as Bifidobacterium and Lactobacillus, correlates with symptom severity. Emerging mechanistic evidence suggests bidirectional relationships between microbiome composition and white matter development, both directly through metabolites like short-chain fatty acids (SCFAs) that regulate oligodendrocyte function and subsequent myelination, and indirectly through modulation of neuroinflammatory pathways. By integrating molecular-level gut physiology findings with macro-level brain imaging data, we may identify novel therapeutic approaches targeting the gut-brain axis in ASD management.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"1150-1158"},"PeriodicalIF":2.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492435","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":"Neuroanatomical and neurochemical organization of brainstem and forebrain circuits involved in breathing regulation.","authors":"Thiago S Moreira, Ana C Takakura, Barbara Falquetto, Jan-Marino Ramirez, Luiz M Oliveira, Phelipe E Silva, Emmanuel V Araujo","doi":"10.1152/jn.00475.2024","DOIUrl":"10.1152/jn.00475.2024","url":null,"abstract":"<p><p>Breathing regulation depends on a highly intricate and precise network within the brainstem, requiring the identification of all neuronal elements in the brainstem respiratory circuits and a comprehensive understanding of their organization into distinct functional compartments. These compartments play a pivotal role by providing essential input to three main targets: cranial motoneurons that regulate airway control, spinal motoneurons that activate the inspiratory and expiratory muscles, and higher brain structures that influence breathing behavior and integrate it with other physiological and behavioral processes. This review offers a comprehensive examination of the phenotypes, connections, and functional roles of the major compartments within the brainstem and forebrain respiratory circuits. In addition, it summarizes the diverse neurotransmitters used by neurons in these regions, highlighting their contributions to the coordination and modulation of respiratory activity.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"1116-1137"},"PeriodicalIF":2.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585920","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":"Reward invigorates isometric gripping actions.","authors":"Rachel M Marbaker, Ryan C Schmad, Razan A Al-Ghamdi, Shruthi Sukumar, Alaa A Ahmed","doi":"10.1152/jn.00384.2024","DOIUrl":"10.1152/jn.00384.2024","url":null,"abstract":"<p><p>Individuals exhibit a propensity to move faster toward more rewarding stimuli. Although this phenomenon has been observed in movements, the effect of reward on implicit control of isometric actions, such as gripping or grasping, is relatively unknown. How reward-related invigoration generalizes to other effortful actions is an important question. Reward invigorates reaching movements and saccades, supporting the idea that reward pays the additional effort cost of moving faster. Effort in isometric force generation is less understood, so here we ask whether and how reward-related invigoration generalizes to isometric force gripping. And if so, what implicit characteristics of gripping change when there is a prospect of reward? Participants (<i>n</i> = 19) gripped a force transducer and the force applied was mapped to radial position of an onscreen cursor. Each trial, a target appeared in one of four locations; increasing grip force moved the cursor toward the target. The gripping action was interchangeable for all target positions. In each block of 100 trials, one target was consistently rewarded, whereas the other targets were not. When gripping to acquire the rewarded target, participants reacted faster, generated force more rapidly and to a greater extent, without increasing variance and without increasing the rising force-time integral. These findings support the generalization of reward-related invigoration in isometric force tasks, and that the brain exquisitely trades-off reward and effort costs to obtain reward more rapidly without increasing variance and without more effort costs than necessary.<b>NEW & NOTEWORTHY</b> Gripping actions are important for day-to-day tasks, for medical diagnostics like strength and force control, and for choice selection in decision-making experiments. Comparing isometric gripping responses to reward and nonreward cues, we observed reward-based invigoration mediated by selective increases in effort. These findings can be leveraged to provide additional insight into the decision making process and better understand the effect of reward on movement vigor.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"1282-1294"},"PeriodicalIF":2.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648834","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":"String-pulling by the common marmoset.","authors":"Mathilde Bertrand, Michael Karkuszewski, Rhonda Kersten, Jean-Jacques Orban de Xivry, J Andrew Pruszynski","doi":"10.1152/jn.00561.2024","DOIUrl":"10.1152/jn.00561.2024","url":null,"abstract":"<p><p>Coordinated hand movements used to grasp and manipulate objects are crucial for many daily activities, such as tying shoelaces or opening jars. Recently, the string-pulling task, which involves cyclically reaching, grasping, and pulling a string, has been used to study coordinated hand movements in rodents and humans. Here, we characterize how adult common marmosets perform the string-pulling task and describe changes in performance across the lifespan. Marmosets (<i>n</i> = 15, 7 females) performed a string-pulling task for a food reward using an instrumented apparatus attached to their home-cage. Movement kinematics were acquired using markerless video tracking and we assessed individual hand movements and bimanual coordination using standard metrics. Marmosets oriented their gaze toward the string above their hands and readily performed the task regardless of sex or age. The task required little training and animals routinely engaged in multiple pulling trials per session, despite not being under water or food control. All marmosets showed consistent pulling speed and similar hand movements regardless of age. Adult marmosets exhibited a clear hand effect, performing straighter and faster movements with their right hand despite showing idiosyncratic hand preference according to a traditional food retrieval assay. Hand effects were also evident for younger animals but seemed attenuated in the older animals. In terms of bimanual coordination, all adult marmosets demonstrated alternating movement pattern for vertical hand positions. Two younger and two older marmosets exhibited idiosyncratic coordination patterns even after substantial experience. In general, younger and older animals exhibited higher variability in bimanual coordination than adults.<b>NEW & NOTEWORTHY</b> Bimanual coordination is crucial for daily activities. In this study, we characterized how common marmosets performed the string-pulling task without extensive training, regardless of sex or age, and naturally exhibited a cyclical alternating pattern of hand movements. Although the overall behavior was similar across ages, younger and older marmosets demonstrated higher variability in bimanual coordination. These results establish the string-pulling task as a reliable tool for studying bimanual coordination and its underlying neural substrates.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"1222-1233"},"PeriodicalIF":2.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649047","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":"Volumetric mesoscopic electrophysiology: a new imaging modality for the nonhuman primate.","authors":"Tobias Teichert, László Papp, Ferenc Vincze, Nioka Burns, Baldwin Goodell, Zabir Ahmed, Andrew Holmes, Maysam Chamanzar, Kate Gurnsey","doi":"10.1152/jn.00399.2024","DOIUrl":"10.1152/jn.00399.2024","url":null,"abstract":"<p><p>The primate brain is a densely interconnected organ whose function is best understood by recording from the entire structure in parallel, rather than parts of it in sequence. However, available methods either have limited temporal resolution (functional magnetic resonance imaging; fMRI), limited spatial resolution (macroscopic electroencephalography), or a limited field of view (microscopic electrophysiology). To address this need, we developed a volumetric, mesoscopic recording approach (MePhys) by tessellating the volume of a monkey hemisphere with 992 electrode contacts that were distributed across 62 chronically implanted multielectrode shafts. We showcase the scientific promise of MePhys by describing the functional interactions of local field potentials between the more than 300,000 simultaneously recorded pairs of electrodes. We find that a subanesthetic dose of ketamine-believed to mimic certain aspects of psychosis-can create a pronounced state of functional disconnection and prevent the formation of stable large-scale intrinsic states. We conclude that MePhys provides a new and fundamentally distinct window into brain function whose unique profile of strengths and weaknesses complements existing approaches in synergistic ways.<b>NEW & NOTEWORTHY</b> We created a new imaging modality for the nonhuman primate, mesoscopic electrophysiology, or MePhys by sampling local field potentials (LFPs) in a dense three-dimensional grid from across the volume of one entire hemisphere. MePhys combines the millisecond temporal resolution of electrophysiology with the large field of view and millimeter spatial resolution of functional magnetic resonance imaging (fMRI). MePhys' unique profile of strengths and limitations makes it an ideal imaging method for the nonhuman primate brain observatories of the future.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"1034-1053"},"PeriodicalIF":2.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515795","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":"Subcortical responses to continuous speech under bimodal divided attention.","authors":"Zilong Xie","doi":"10.1152/jn.00039.2025","DOIUrl":"10.1152/jn.00039.2025","url":null,"abstract":"<p><p>Everyday speech perception often occurs in multimodal environments, requiring listeners to divide attention across sensory modalities to prioritize relevant information. Although this division of attention modestly reduces cortical encoding of natural continuous speech, its impact on subcortical processing remains unclear. To investigate this, we used an audiovisual dual-task paradigm to manipulate bimodal divided attention. Participants completed a primary visual memory task (low or high cognitive load) while simultaneously performing a secondary task of listening to audiobook segments. Sixteen young adults with normal hearing completed these tasks while their EEG signals were recorded. In a third condition, participants performed only the listening task. Subcortical responses to the audiobook segments were analyzed using temporal response functions (TRFs), which predicted EEG responses from speech predictors derived from auditory nerve models. Across all conditions, TRFs displayed a prominent peak at ∼8 ms, resembling the wave V peak of auditory brainstem responses, indicating subcortical origins. No significant differences in latencies or amplitudes of this peak, nor in TRF prediction correlations, were observed between conditions. These findings provide no evidence that bimodal divided attention affects the subcortical processing of continuous speech, indicating that its effects may be restricted to cortical levels.<b>NEW & NOTEWORTHY</b> This study shows that auditory subcortical processing of natural continuous speech remains unaffected when attention is divided across auditory and visual modalities. These findings indicate that the influence of crossmodal attention on the processing of natural continuous speech may be restricted to cortical levels.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"1216-1221"},"PeriodicalIF":2.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649194","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":"Balancing the role of the ventral posterior thalamus in pain and temperature.","authors":"Henry C Evrard, Anders Blomqvist","doi":"10.1152/jn.00009.2025","DOIUrl":"10.1152/jn.00009.2025","url":null,"abstract":"","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":"133 4","pages":"1014-1015"},"PeriodicalIF":2.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649257","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}