224 research outputs found

    Controlling cluster synchronization by adapting the topology

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    We suggest an adaptive control scheme for the control of zero-lag and cluster synchronization in delay-coupled networks. Based on the speed-gradient method, our scheme adapts the topology of a network such that the target state is realized. It is robust towards different initial condition as well as changes in the coupling parameters. The emerging topology is characterized by a delicate interplay of excitatory and inhibitory links leading to the stabilization of the desired cluster state. As a crucial parameter determining this interplay we identify the delay time. Furthermore, we show how to construct networks such that they exhibit not only a given cluster state but also with a given oscillation frequency. We apply our method to coupled Stuart-Landau oscillators, a paradigmatic normal form that naturally arises in an expansion of systems close to a Hopf bifurcation. The successful and robust control of this generic model opens up possible applications in a wide range of systems in physics, chemistry, technology, and life science

    Attention deficits in childhood-onset schizophrenia: reaction time studies

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    The hypothesis of continuity between childhood-onset and adult schizophrenia was tested by comparing the performance of 15 patients with childhood-onset schizophrenia and 52 age-matched controls on 2 reaction time paradigms that have been used to study adult schizophrenia. On simple reaction time to tones with regular and irregular preparatory intervals of 2, 4, and 8 s, patients showed greater effects of the length of the preparatory interval in the regular condition and greater effects of the preparatory interval (girls only) and the preceding preparatory interval in the irregular series. On simple reaction time to random lights and tones, patients were faster on ipsimodal sequences than cross-modal sequences compared with controls. Overall, patients were much slower than controls in both paradigms. The results suggest similar attention dysfunction as is found in adult schizophrenia and thus are consistent with the continuity hypothesis

    A novel high accuracy model for automatic surgical workflow recognition using artificial intelligence in laparoscopic totally extraperitoneal inguinal hernia repair (TEP)

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    Introduction: Artificial intelligence and computer vision are revolutionizing the way we perceive video analysis in minimally invasive surgery. This emerging technology has increasingly been leveraged successfully for video segmentation, documentation, education, and formative assessment. New, sophisticated platforms allow pre-determined segments chosen by surgeons to be automatically presented without the need to review entire videos. This study aimed to validate and demonstrate the accuracy of the first reported AI-based computer vision algorithm that automatically recognizes surgical steps in videos of totally extraperitoneal (TEP) inguinal hernia repair. Methods: Videos of TEP procedures were manually labeled by a team of annotators trained to identify and label surgical workflow according to six major steps. For bilateral hernias, an additional change of focus step was also included. The videos were then used to train a computer vision AI algorithm. Performance accuracy was assessed in comparison to the manual annotations. Results: A total of 619 full-length TEP videos were analyzed: 371 were used to train the model, 93 for internal validation, and the remaining 155 as a test set to evaluate algorithm accuracy. The overall accuracy for the complete procedure was 88.8%. Per-step accuracy reached the highest value for the hernia sac reduction step (94.3%) and the lowest for the preperitoneal dissection step (72.2%). Conclusions: These results indicate that the novel AI model was able to provide fully automated video analysis with a high accuracy level. High-accuracy models leveraging AI to enable automation of surgical video analysis allow us to identify and monitor surgical performance, providing mathematical metrics that can be stored, evaluated, and compared. As such, the proposed model is capable of enabling data-driven insights to improve surgical quality and demonstrate best practices in TEP procedures

    Heterogeneous Delays in Neural Networks

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    We investigate heterogeneous coupling delays in complex networks of excitable elements described by the FitzHugh-Nagumo model. The effects of discrete as well as of uni- and bimodal continuous distributions are studied with a focus on different topologies, i.e., regular, small-world, and random networks. In the case of two discrete delay times resonance effects play a major role: Depending on the ratio of the delay times, various characteristic spiking scenarios, such as coherent or asynchronous spiking, arise. For continuous delay distributions different dynamical patterns emerge depending on the width of the distribution. For small distribution widths, we find highly synchronized spiking, while for intermediate widths only spiking with low degree of synchrony persists, which is associated with traveling disruptions, partial amplitude death, or subnetwork synchronization, depending sensitively on the network topology. If the inhomogeneity of the coupling delays becomes too large, global amplitude death is induced

    Dysregulated protocadherin-pathway activity as an intrinsic defect in induced pluripotent stem cell-derived cortical interneurons from subjects with schizophrenia.

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    We generated cortical interneurons (cINs) from induced pluripotent stem cells derived from 14 healthy controls and 14 subjects with schizophrenia. Both healthy control cINs and schizophrenia cINs were authentic, fired spontaneously, received functional excitatory inputs from host neurons, and induced GABA-mediated inhibition in host neurons in vivo. However, schizophrenia cINs had dysregulated expression of protocadherin genes, which lie within documented schizophrenia loci. Mice lacking protocadherin-α showed defective arborization and synaptic density of prefrontal cortex cINs and behavioral abnormalities. Schizophrenia cINs similarly showed defects in synaptic density and arborization that were reversed by inhibitors of protein kinase C, a downstream kinase in the protocadherin pathway. These findings reveal an intrinsic abnormality in schizophrenia cINs in the absence of any circuit-driven pathology. They also demonstrate the utility of homogenous and functional populations of a relevant neuronal subtype for probing pathogenesis mechanisms during development

    Sleep spindles across youth affected by schizophrenia or anti-N-methyl-D-aspartate-receptor encephalitis

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    BackgroundSleep disturbances are intertwined with the progression and pathophysiology of psychotic symptoms in schizophrenia. Reductions in sleep spindles, a major electrophysiological oscillation during non-rapid eye movement sleep, have been identified in patients with schizophrenia as a potential biomarker representing the impaired integrity of the thalamocortical network. Altered glutamatergic neurotransmission within this network via a hypofunction of the N-methyl-D-aspartate receptor (NMDAR) is one of the hypotheses at the heart of schizophrenia. This pathomechanism and the symptomatology are shared by anti-NMDAR encephalitis (NMDARE), where antibodies specific to the NMDAR induce a reduction of functional NMDAR. However, sleep spindle parameters have yet to be investigated in NMDARE and a comparison of these rare patients with young individuals with schizophrenia and healthy controls (HC) is lacking. This study aims to assess and compare sleep spindles across young patients affected by Childhood-Onset Schizophrenia (COS), Early-Onset Schizophrenia, (EOS), or NMDARE and HC. Further, the potential relationship between sleep spindle parameters in COS and EOS and the duration of the disease is examined.MethodsSleep EEG data of patients with COS (N = 17), EOS (N = 11), NMDARE (N = 8) aged 7–21 years old, and age- and sex-matched HC (N = 36) were assessed in 17 (COS, EOS) or 5 (NMDARE) electrodes. Sleep spindle parameters (sleep spindle density, maximum amplitude, and sigma power) were analyzed.ResultsCentral sleep spindle density, maximum amplitude, and sigma power were reduced when comparing all patients with psychosis to all HC. Between patient group comparisons showed no differences in central spindle density but lower central maximum amplitude and sigma power in patients with COS compared to patients with EOS or NMDARE. Assessing the topography of spindle density, it was significantly reduced over 15/17 electrodes in COS, 3/17 in EOS, and 0/5 in NMDARE compared to HC. In the pooled sample of COS and EOS, a longer duration of illness was associated with lower central sigma power.ConclusionsPatients with COS demonstrated more pronounced impairments of sleep spindles compared to patients with EOS and NMDARE. In this sample, there is no strong evidence that changes in NMDAR activity are related to spindle deficits

    The anatomical distance of functional connections predicts brain network topology in health and schizophrenia.

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    The human brain is a topologically complex network embedded in anatomical space. Here, we systematically explored relationships between functional connectivity, complex network topology, and anatomical (Euclidean) distance between connected brain regions, in the resting-state functional magnetic resonance imaging brain networks of 20 healthy volunteers and 19 patients with childhood-onset schizophrenia (COS). Normal between-subject differences in average distance of connected edges in brain graphs were strongly associated with variation in topological properties of functional networks. In addition, a club or subset of connector hubs was identified, in lateral temporal, parietal, dorsal prefrontal, and medial prefrontal/cingulate cortical regions. In COS, there was reduced strength of functional connectivity over short distances especially, and therefore, global mean connection distance of thresholded graphs was significantly greater than normal. As predicted from relationships between spatial and topological properties of normal networks, this disorder-related proportional increase in connection distance was associated with reduced clustering and modularity and increased global efficiency of COS networks. Between-group differences in connection distance were localized specifically to connector hubs of multimodal association cortex. In relation to the neurodevelopmental pathogenesis of schizophrenia, we argue that the data are consistent with the interpretation that spatial and topological disturbances of functional network organization could arise from excessive "pruning" of short-distance functional connections in schizophrenia.PEV is supported by the Medical Research Council (grant number MR/K020706/1). This work was supported by the Neuroscience in Psychiatry Network (NSPN) which is funded by a Wellcome Trust strategy award to the University of Cambridge and University College London. ETB is employed half-time by the University of Cambridge and half-time by GlaxoSmithKline; he holds stock in GSK.This is the final published version. It first appeared at http://onlinelibrary.wiley.com/doi/10.1111/jcpp.12365/full

    From phenomenology to a neurophysiological understanding of hallucinations in children and adolescents

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    Typically reported as vivid, multisensory experiences which may spontaneously resolve, hallucinations are present at high rates during childhood. The risk of associated psychopathology is a major cause of concern. On the one hand, the risk of developing further delusional ideation has been shown to be reduced by better theory of mind skills. On the other hand, ideas of reference, passivity phenomena, and misidentification syndrome have been shown to increase the risk of self-injury or heteroaggressive behaviors. Cognitive psychology and brain-imaging studies have advanced our knowledge of the mechanisms underlying these early-onset hallucinations. Notably, specific functional impairments have been associated with certain phenomenological characteristics of hallucinations in youths, including intrusiveness and the sense of reality. In this review, we provide an update of associated epidemiological and phenomenological factors (including sociocultural context, social adversity, and genetics, considered in relation to the psychosis continuum hypothesis), cognitive models, and neurophysiological findings concerning hallucinations in children and adolescents. Key issues that have interfered with progress are considered and recommendations for future studies are provided

    Defining the Specificity of Cotranslationally Acting Chaperones by Systematic Analysis of mRNAs Associated with Ribosome-Nascent Chain Complexes

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    Polypeptides exiting the ribosome must fold and assemble in the crowded environment of the cell. Chaperones and other protein homeostasis factors interact with newly translated polypeptides to facilitate their folding and correct localization. Despite the extensive efforts, little is known about the specificity of the chaperones and other factors that bind nascent polypeptides. To address this question we present an approach that systematically identifies cotranslational chaperone substrates through the mRNAs associated with ribosome-nascent chain-chaperone complexes. We here focused on two Saccharomyces cerevisiae chaperones: the Signal Recognition Particle (SRP), which acts cotranslationally to target proteins to the ER, and the Nascent chain Associated Complex (NAC), whose function has been elusive. Our results provide new insights into SRP selectivity and reveal that NAC is a general cotranslational chaperone. We found surprising differential substrate specificity for the three subunits of NAC, which appear to recognize distinct features within nascent chains. Our results also revealed a partial overlap between the sets of nascent polypeptides that interact with NAC and SRP, respectively, and showed that NAC modulates SRP specificity and fidelity in vivo. These findings give us new insight into the dynamic interplay of chaperones acting on nascent chains. The strategy we used should be generally applicable to mapping the specificity, interplay, and dynamics of the cotranslational protein homeostasis network
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