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Sample records for acquire neural signals

  1. Acquiring neural signals for developing a perception and cognition model

    NASA Astrophysics Data System (ADS)

    Li, Wei; Li, Yunyi; Chen, Genshe; Shen, Dan; Blasch, Erik; Pham, Khanh; Lynch, Robert

    2012-06-01

    The understanding of how humans process information, determine salience, and combine seemingly unrelated information is essential to automated processing of large amounts of information that is partially relevant, or of unknown relevance. Recent neurological science research in human perception, and in information science regarding contextbased modeling, provides us with a theoretical basis for using a bottom-up approach for automating the management of large amounts of information in ways directly useful for human operators. However, integration of human intelligence into a game theoretic framework for dynamic and adaptive decision support needs a perception and cognition model. For the purpose of cognitive modeling, we present a brain-computer-interface (BCI) based humanoid robot system to acquire brainwaves during human mental activities of imagining a humanoid robot-walking behavior. We use the neural signals to investigate relationships between complex humanoid robot behaviors and human mental activities for developing the perception and cognition model. The BCI system consists of a data acquisition unit with an electroencephalograph (EEG), a humanoid robot, and a charge couple CCD camera. An EEG electrode cup acquires brainwaves from the skin surface on scalp. The humanoid robot has 20 degrees of freedom (DOFs); 12 DOFs located on hips, knees, and ankles for humanoid robot walking, 6 DOFs on shoulders and arms for arms motion, and 2 DOFs for head yaw and pitch motion. The CCD camera takes video clips of the human subject's hand postures to identify mental activities that are correlated to the robot-walking behaviors. We use the neural signals to investigate relationships between complex humanoid robot behaviors and human mental activities for developing the perception and cognition model.

  2. Neural Network Communications Signal Processing

    DTIC Science & Technology

    1994-08-01

    This final technical report describes the research and development- results of the Neural Network Communications Signal Processing (NNCSP) Program...The objectives of the NNCSP program are to: (1) develop and implement a neural network and communications signal processing simulation system for the...purpose of exploring the applicability of neural network technology to communications signal processing; (2) demonstrate several configurations of the

  3. Signal regulators of systemic acquired resistance

    PubMed Central

    Gao, Qing-Ming; Zhu, Shifeng; Kachroo, Pradeep; Kachroo, Aardra

    2015-01-01

    Salicylic acid (SA) is an important phytohormone that plays a vital role in a number of physiological responses, including plant defense. The last two decades have witnessed a number of breakthroughs related to biosynthesis, transport, perception and signaling mediated by SA. These findings demonstrate that SA plays a crictical role in both local and systemic defense responses. Systemic acquired resistance (SAR) is one such SA-dependent response. SAR is a long distance signaling mechanism that provides broad spectrum and long-lasting resistance to secondary infections throughout the plant. This unique feature makes SAR a highly desirable trait in crop production. This review summarizes the recent advances in the role of SA in SAR and discusses its relationship to other SAR inducers. PMID:25918514

  4. Neural Network Classification of Cerebral Embolic Signals

    DTIC Science & Technology

    2007-11-02

    application of new signal processing techniques to the analysis and classification of embolic signals. We applied a Wavelet Neural Network algorithm...to approximate the embolic signals, with the parameters of the wavelet nodes being used to train a Neural Network to classify these signals as resulting from normal flow, or from gaseous or solid emboli.

  5. Neural Alterations in Acquired Age-Related Hearing Loss.

    PubMed

    Mudar, Raksha A; Husain, Fatima T

    2016-01-01

    Hearing loss is one of the most prevalent chronic health conditions in older adults. Growing evidence suggests that hearing loss is associated with reduced cognitive functioning and incident dementia. In this mini-review, we briefly examine literature on anatomical and functional alterations in the brains of adults with acquired age-associated hearing loss, which may underlie the cognitive consequences observed in this population, focusing on studies that have used structural and functional magnetic resonance imaging, diffusion tensor imaging, and event-related electroencephalography. We discuss structural and functional alterations observed in the temporal and frontal cortices and the limbic system. These neural alterations are discussed in the context of common cause, information-degradation, and sensory-deprivation hypotheses, and we suggest possible rehabilitation strategies. Although, we are beginning to learn more about changes in neural architecture and functionality related to age-associated hearing loss, much work remains to be done. Understanding the neural alterations will provide objective markers for early identification of neural consequences of age-associated hearing loss and for evaluating benefits of intervention approaches.

  6. Signal Approximation with a Wavelet Neural Network

    DTIC Science & Technology

    1992-12-01

    specialized electronic devices like the Intel Electronically Trainable Analog Neural Network (ETANN) chip. The WNN representation allows the...accurately approximated with a WNN trained with irregularly sampled data. Signal approximation, Wavelet neural network .

  7. Neural Networks Applied to Signal Processing

    DTIC Science & Technology

    1989-09-01

    DTIC FILE COpy NAVAL POSTGRADUATE SCHOOL . Monterey, California Lf 0 (0 V’ STATES 4 THESIS NEURAL NETWORKS APPLIED TO SIGNAL PROCESSING by Mark D...FUNDING NUMBERS PROGRAM PROJECT TASK WORK UNIT ELEMENT NO NO NO ACCESSION NO. 11. TITLE (Include Security Classification) NEURAL NETWORKS APPLIED TO...for public release; distribution is unlimited Neural Networks Applied to Signal Processing by Mark D. Baehre Captain, United States Army B.S., United

  8. A Neural Basis for the Acquired Capability for Suicide

    PubMed Central

    Deshpande, Gopikrishna; Baxi, Madhura; Witte, Tracy; Robinson, Jennifer L.

    2016-01-01

    The high rate of fatal suicidal behavior (SB) in men is an urgent issue as highlighted in the public eye via news sources and media outlets. In this study, we have attempted to address this issue and understand the neural substrates underlying the gender differences in the rate of fatal SB. The Interpersonal–Psychological Theory of Suicide has proposed an explanation for the seemingly paradoxical relationship between gender and SB, i.e., greater non-fatal suicide attempts by women but higher number of deaths by suicide in men. This theory states that possessing suicidal desire (due to conditions such as depression) alone is not sufficient for a lethal suicide attempt. It is imperative for an individual to have the acquired capability for suicide (ACS) along with suicidal desire in order to die by suicide. Therefore, higher levels of ACS in men may explain why men are more likely to die by suicide than women, despite being less likely to experience suicidal ideation or depression. In this study, we used activation likelihood estimation meta-analysis to investigate a potential ACS network that involves neural substrates underlying emotional stoicism, sensation-seeking, pain tolerance, and fearlessness of death, along with a potential depression network that involves neural substrates that underlie clinical depression. Brain regions commonly found in ACS and depression networks for males and females were further used as seeds to obtain regions functionally and structurally connected to them. We found that the male-specific networks were more widespread and diverse than the female-specific ones. Also, while the former involved motor regions, such as the premotor cortex and cerebellum, the latter was dominated by limbic regions. This may support the fact that suicidal desire generally leads to fatal/decisive action in males, while, in females, it manifests as depression, ideation, and generally non-fatal actions. The proposed model is a first attempt to characterize

  9. Imaging Posture Veils Neural Signals

    PubMed Central

    Thibault, Robert T.; Raz, Amir

    2016-01-01

    Whereas modern brain imaging often demands holding body positions incongruent with everyday life, posture governs both neural activity and cognitive performance. Humans commonly perform while upright; yet, many neuroimaging methodologies require participants to remain motionless and adhere to non-ecological comportments within a confined space. This inconsistency between ecological postures and imaging constraints undermines the transferability and generalizability of many a neuroimaging assay. Here we highlight the influence of posture on brain function and behavior. Specifically, we challenge the tacit assumption that brain processes and cognitive performance are comparable across a spectrum of positions. We provide an integrative synthesis regarding the increasingly prominent influence of imaging postures on autonomic function, mental capacity, sensory thresholds, and neural activity. Arguing that neuroimagers and cognitive scientists could benefit from considering the influence posture wields on both general functioning and brain activity, we examine existing imaging technologies and the potential of portable and versatile imaging devices (e.g., functional near infrared spectroscopy). Finally, we discuss ways that accounting for posture may help unveil the complex brain processes of everyday cognition. PMID:27818629

  10. Semaphorin Signaling in Vertebrate Neural Circuit Assembly

    PubMed Central

    Yoshida, Yutaka

    2012-01-01

    Neural circuit formation requires the coordination of many complex developmental processes. First, neurons project axons over long distances to find their final targets and then establish appropriate connectivity essential for the formation of neuronal circuitry. Growth cones, the leading edges of axons, navigate by interacting with a variety of attractive and repulsive axon guidance cues along their trajectories and at final target regions. In addition to guidance of axons, neuronal polarization, neuronal migration, and dendrite development must be precisely regulated during development to establish proper neural circuitry. Semaphorins consist of a large protein family, which includes secreted and cell surface proteins, and they play important roles in many steps of neural circuit formation. The major semaphorin receptors are plexins and neuropilins, however other receptors and co-receptors also mediate signaling by semaphorins. Upon semaphorin binding to their receptors, downstream signaling molecules transduce this event within cells to mediate further events, including alteration of microtubule and actin cytoskeletal dynamics. Here, I review recent studies on semaphorin signaling in vertebrate neural circuit assembly, with the goal of highlighting how this diverse family of cues and receptors imparts exquisite specificity to neural complex connectivity. PMID:22685427

  11. Distributed neural signals on parabolic cylindrical shells

    NASA Astrophysics Data System (ADS)

    Hu, S. D.; Li, H.; Tzou, H. S.

    2013-06-01

    Parabolic cylindrical shells are commonly used as key components in communication antennas, space telescopes, solar collectors, etc. This study focuses on distributed modal neural sensing signals on a flexible simply-supported parabolic cylindrical shell panel. The parabolic cylindrical shell is fully laminated with a piezoelectric layer on its outer surface and the piezoelectric layer is segmented into infinitesimal elements (neurons) to investigate the microscopic distributed neural sensing signals. Since the dominant vibration component of the shell is usually the transverse oscillation, a new transverse mode shape function is defined. Two shell cases, i.e., the ratio of the meridian height to the half span distance of a parabola at 1:4 (shallow) and 1:1 (deep), are studied to reveal the curvature effect to the neural sensing signals. Studies suggest that the membrane signal component dominates for lower natural modes and the bending signal component dominates for higher natural modes. The meridional membrane and bending signal components are mostly concentrated on the high-curvature areas, while the longitudinal bending component is mostly concentrated on the relatively flat areas. The concentration behavior becomes more prominent as the parabolic cylindrical shell deepens, primarily resulting from the enhanced membrane effect due to the increased curvature.

  12. Signal dispersion within a hippocampal neural network

    NASA Technical Reports Server (NTRS)

    Horowitz, J. M.; Mates, J. W. B.

    1975-01-01

    A model network is described, representing two neural populations coupled so that one population is inhibited by activity it excites in the other. Parameters and operations within the model represent EPSPs, IPSPs, neural thresholds, conduction delays, background activity and spatial and temporal dispersion of signals passing from one population to the other. Simulations of single-shock and pulse-train driving of the network are presented for various parameter values. Neuronal events from 100 to 300 msec following stimulation are given special consideration in model calculations.

  13. Losartan prevents acquired epilepsy via TGF-β signaling suppression

    PubMed Central

    Bar-Klein, Guy; Cacheaux, Luisa P.; Kamintsky, Lyn; Prager, Ofer; Weissberg, Itai; Schoknecht, Karl; Cheng, Paul; Kim, Soo Young; Wood, Lydia; Heinemann, Uwe; Kaufer, Daniela; Friedman, Alon

    2014-01-01

    Objective Acquired epilepsy is frequently associated with structural lesions following trauma, stroke and infections. While seizures are often difficult to treat, there is no clinically applicable strategy to prevent the development of epilepsy in patients at risk. We have recently shown that vascular injury is associated with activation of albumin-mediated transforming growth factor β (TGF-β) signaling, and followed by local inflammatory response and epileptiform activity ex vivo. Here we investigated albumin-mediated TGF-β signaling and tested the efficacy of blocking the TGF-β pathway in preventing epilepsy. Methods We addressed the role of TGF-β signaling in epiletogenesis in two different rat models of vascular injury, combining in vitro and in vivo biochemical assays, gene expression, magnetic resonance and direct optical imaging for blood-brain barrier (BBB) permeability and vascular reactivity. Long-term electrocorticographic (ECoG) recordings were acquired in freely behaving animals. Results We demonstrate that serum-derived albumin preferentially induces activation of the activin receptor-like kinase 5 (ALK5) pathway of TGF-β receptor I in astrocytes. We further show that the angiotensin II type 1 receptor antagonist (AT1), losartan, previously identified as a blocker of peripheral TGF-β signaling, effectively blocks albumin-induced TGF-β activation in the brain. Most importantly, losartan prevents the development of delayed recurrent spontaneous seizures, an effect that persists weeks after drug withdrawal. Interpretation TGF-β signaling, activated in astrocytes by serum-derived albumin, is involved in epileptogenesis. We propose losartan, an FDA-approved drug, as an efficient anti-epileptogenic therapy for epilepsy associated with vascular injury. PMID:24659129

  14. Neural systems for choice and valuation with counterfactual learning signals.

    PubMed

    Tobia, M J; Guo, R; Schwarze, U; Boehmer, W; Gläscher, J; Finckh, B; Marschner, A; Büchel, C; Obermayer, K; Sommer, T

    2014-04-01

    The purpose of this experiment was to test a computational model of reinforcement learning with and without fictive prediction error (FPE) signals to investigate how counterfactual consequences contribute to acquired representations of action-specific expected value, and to determine the functional neuroanatomy and neuromodulator systems that are involved. 80 male participants underwent dietary depletion of either tryptophan or tyrosine/phenylalanine to manipulate serotonin (5HT) and dopamine (DA), respectively. They completed 80 rounds (240 trials) of a strategic sequential investment task that required accepting interim losses in order to access a lucrative state and maximize long-term gains, while being scanned. We extended the standard Q-learning model by incorporating both counterfactual gains and losses into separate error signals. The FPE model explained the participants' data significantly better than a model that did not include counterfactual learning signals. Expected value from the FPE model was significantly correlated with BOLD signal change in the ventromedial prefrontal cortex (vmPFC) and posterior orbitofrontal cortex (OFC), whereas expected value from the standard model did not predict changes in neural activity. The depletion procedure revealed significantly different neural responses to expected value in the vmPFC, caudate, and dopaminergic midbrain in the vicinity of the substantia nigra (SN). Differences in neural activity were not evident in the standard Q-learning computational model. These findings demonstrate that FPE signals are an important component of valuation for decision making, and that the neural representation of expected value incorporates cortical and subcortical structures via interactions among serotonergic and dopaminergic modulator systems.

  15. Cerebellar granule cells acquire a widespread predictive feedback signal during motor learning.

    PubMed

    Giovannucci, Andrea; Badura, Aleksandra; Deverett, Ben; Najafi, Farzaneh; Pereira, Talmo D; Gao, Zhenyu; Ozden, Ilker; Kloth, Alexander D; Pnevmatikakis, Eftychios; Paninski, Liam; De Zeeuw, Chris I; Medina, Javier F; Wang, Samuel S-H

    2017-03-20

    Cerebellar granule cells, which constitute half the brain's neurons, supply Purkinje cells with contextual information necessary for motor learning, but how they encode this information is unknown. Here we show, using two-photon microscopy to track neural activity over multiple days of cerebellum-dependent eyeblink conditioning in mice, that granule cell populations acquire a dense representation of the anticipatory eyelid movement. Initially, granule cells responded to neutral visual and somatosensory stimuli as well as periorbital airpuffs used for training. As learning progressed, two-thirds of monitored granule cells acquired a conditional response whose timing matched or preceded the learned eyelid movements. Granule cell activity covaried trial by trial to form a redundant code. Many granule cells were also active during movements of nearby body structures. Thus, a predictive signal about the upcoming movement is widely available at the input stage of the cerebellar cortex, as required by forward models of cerebellar control.

  16. Classification of Images Acquired with Colposcopy Using Artificial Neural Networks

    PubMed Central

    Simões, Priscyla W; Izumi, Narjara B; Casagrande, Ramon S; Venson, Ramon; Veronezi, Carlos D; Moretti, Gustavo P; da Rocha, Edroaldo L; Cechinel, Cristian; Ceretta, Luciane B; Comunello, Eros; Martins, Paulo J; Casagrande, Rogério A; Snoeyer, Maria L; Manenti, Sandra A

    2014-01-01

    OBJECTIVE To explore the advantages of using artificial neural networks (ANNs) to recognize patterns in colposcopy to classify images in colposcopy. PURPOSE Transversal, descriptive, and analytical study of a quantitative approach with an emphasis on diagnosis. The training test e validation set was composed of images collected from patients who underwent colposcopy. These images were provided by a gynecology clinic located in the city of Criciúma (Brazil). The image database (n = 170) was divided; 48 images were used for the training process, 58 images were used for the tests, and 64 images were used for the validation. A hybrid neural network based on Kohonen self-organizing maps and multilayer perceptron (MLP) networks was used. RESULTS After 126 cycles, the validation was performed. The best results reached an accuracy of 72.15%, a sensibility of 69.78%, and a specificity of 68%. CONCLUSION Although the preliminary results still exhibit an average efficiency, the present approach is an innovative and promising technique that should be deeply explored in the context of the present study. PMID:25374454

  17. Correlated EEG Signals Simulation Based on Artificial Neural Networks.

    PubMed

    Tomasevic, Nikola M; Neskovic, Aleksandar M; Neskovic, Natasa J

    2016-09-30

    In recent years, simulation of the human electroencephalogram (EEG) data found its important role in medical domain and neuropsychology. In this paper, a novel approach to simulation of two cross-correlated EEG signals is proposed. The proposed method is based on the principles of artificial neural networks (ANN). Contrary to the existing EEG data simulators, the ANN-based approach was leveraged solely on the experimentally acquired EEG data. More precisely, measured EEG data were utilized to optimize the simulator which consisted of two ANN models (each model responsible for generation of one EEG sequence). In order to acquire the EEG recordings, the measurement campaign was carried out on a healthy awake adult having no cognitive, physical or mental load. For the evaluation of the proposed approach, comprehensive quantitative and qualitative statistical analysis was performed considering probability distribution, correlation properties and spectral characteristics of generated EEG processes. The obtained results clearly indicated the satisfactory agreement with the measurement data.

  18. Model for neural signaling leap statistics

    NASA Astrophysics Data System (ADS)

    Chevrollier, Martine; Oriá, Marcos

    2011-03-01

    We present a simple model for neural signaling leaps in the brain considering only the thermodynamic (Nernst) potential in neuron cells and brain temperature. We numerically simulated connections between arbitrarily localized neurons and analyzed the frequency distribution of the distances reached. We observed qualitative change between Normal statistics (with T = 37.5°C, awaken regime) and Lévy statistics (T = 35.5°C, sleeping period), characterized by rare events of long range connections.

  19. Neural correlates of success and failure signals during neurofeedback learning.

    PubMed

    Radua, Joaquim; Stoica, Teodora; Scheinost, Dustin; Pittenger, Christopher; Hampson, Michelle

    2016-04-05

    Feedback-driven learning, observed across phylogeny and of clear adaptive value, is frequently operationalized in simple operant conditioning paradigms, but it can be much more complex, driven by abstract representations of success and failure. This study investigates the neural processes involved in processing success and failure during feedback learning, which are not well understood. Data analyzed were acquired during a multisession neurofeedback experiment in which ten participants were presented with, and instructed to modulate, the activity of their orbitofrontal cortex with the aim of decreasing their anxiety. We assessed the regional blood-oxygenation-level-dependent response to the individualized neurofeedback signals of success and failure across twelve functional runs acquired in two different magnetic resonance sessions in each of ten individuals. Neurofeedback signals of failure correlated early during learning with deactivation in the precuneus/posterior cingulate and neurofeedback signals of success correlated later during learning with deactivation in the medial prefrontal/anterior cingulate cortex. The intensity of the latter deactivations predicted the efficacy of the neurofeedback intervention in the reduction of anxiety. These findings indicate a role for regulation of the default mode network during feedback learning, and suggest a higher sensitivity to signals of failure during the early feedback learning and to signals of success subsequently.

  20. Signaling pathways and tissue interactions in neural plate border formation.

    PubMed

    Schille, Carolin; Schambony, Alexandra

    2017-01-01

    The neural crest is a transient cell population that gives rise to various cell types of multiple tissues and organs in the vertebrate embryo. Neural crest cells arise from the neural plate border, a region localized at the lateral borders of the prospective neural plate. Temporally and spatially coordinated interaction with the adjacent tissues, the non-neural ectoderm, the neural plate and the prospective dorsolateral mesoderm, is required for neural plate border specification. Signaling molecules, namely BMP, Wnt and FGF ligands and corresponding antagonists are derived from these tissues and interact to induce the expression of neural plate border specific genes. The present mini-review focuses on the current understanding of how the NPB territory is formed and accentuates the need for coordinated interaction of BMP and Wnt signaling pathways and precise tissue communication that are required for the definition of the prospective NC in the competent ectoderm.

  1. Neural network-based sensor signal accelerator.

    SciTech Connect

    Vogt, M. C.

    2000-10-16

    A strategy has been developed to computationally accelerate the response time of a generic electronic sensor. The strategy can be deployed as an algorithm in a control system or as a physical interface (on an embedded microcontroller) between a slower responding external sensor and a higher-speed control system. Optional code implementations are available to adjust algorithm performance when computational capability is limited. In one option, the actual sensor signal can be sampled at the slower rate with adaptive linear neural networks predicting the sensor's future output and interpolating intermediate synthetic output values. In another option, a synchronized collection of predictors sequentially controls the corresponding synthetic output voltage. Error is adaptively corrected in both options. The core strategy has been demonstrated with automotive oxygen sensor data. A prototype interface device is under construction. The response speed increase afforded by this strategy could greatly offset the cost of developing a replacement sensor with a faster physical response time.

  2. Active voltammetric microsensors with neural signal processing.

    SciTech Connect

    Vogt, M. C.

    1998-12-11

    Many industrial and environmental processes, including bioremediation, would benefit from the feedback and control information provided by a local multi-analyte chemical sensor. For most processes, such a sensor would need to be rugged enough to be placed in situ for long-term remote monitoring, and inexpensive enough to be fielded in useful numbers. The multi-analyte capability is difficult to obtain from common passive sensors, but can be provided by an active device that produces a spectrum-type response. Such new active gas microsensor technology has been developed at Argonne National Laboratory. The technology couples an electrocatalytic ceramic-metallic (cermet) microsensor with a voltammetric measurement technique and advanced neural signal processing. It has been demonstrated to be flexible, rugged, and very economical to produce and deploy. Both narrow interest detectors and wide spectrum instruments have been developed around this technology. Much of this technology's strength lies in the active measurement technique employed. The technique involves applying voltammetry to a miniature electrocatalytic cell to produce unique chemical ''signatures'' from the analytes. These signatures are processed with neural pattern recognition algorithms to identify and quantify the components in the analyte. The neural signal processing allows for innovative sampling and analysis strategies to be employed with the microsensor. In most situations, the whole response signature from the voltammogram can be used to identify, classify, and quantify an analyte, without dissecting it into component parts. This allows an instrument to be calibrated once for a specific gas or mixture of gases by simple exposure to a multi-component standard rather than by a series of individual gases. The sampled unknown analytes can vary in composition or in concentration, the calibration, sensing, and processing methods of these active voltammetric microsensors can detect, recognize, and

  3. Neural Networks for Signal Processing and Control

    NASA Astrophysics Data System (ADS)

    Hesselroth, Ted Daniel

    Neural networks are developed for controlling a robot-arm and camera system and for processing images. The networks are based upon computational schemes that may be found in the brain. In the first network, a neural map algorithm is employed to control a five-joint pneumatic robot arm and gripper through feedback from two video cameras. The pneumatically driven robot arm employed shares essential mechanical characteristics with skeletal muscle systems. To control the position of the arm, 200 neurons formed a network representing the three-dimensional workspace embedded in a four-dimensional system of coordinates from the two cameras, and learned a set of pressures corresponding to the end effector positions, as well as a set of Jacobian matrices for interpolating between these positions. Because of the properties of the rubber-tube actuators of the arm, the position as a function of supplied pressure is nonlinear, nonseparable, and exhibits hysteresis. Nevertheless, through the neural network learning algorithm the position could be controlled to an accuracy of about one pixel (~3 mm) after two hundred learning steps. Applications of repeated corrections in each step via the Jacobian matrices leads to a very robust control algorithm since the Jacobians learned by the network have to satisfy the weak requirement that they yield a reduction of the distance between gripper and target. The second network is proposed as a model for the mammalian vision system in which backward connections from the primary visual cortex (V1) to the lateral geniculate nucleus play a key role. The application of hebbian learning to the forward and backward connections causes the formation of receptive fields which are sensitive to edges, bars, and spatial frequencies of preferred orientations. The receptive fields are learned in such a way as to maximize the rate of transfer of information from the LGN to V1. Orientational preferences are organized into a feature map in the primary visual

  4. Signal Classification Using The Mean Separator Neural Network

    DTIC Science & Technology

    2000-03-01

    and investigated. One modification involved input data preconditioning prior to neural network processing. A second modification incorporated...decision-making capacity. More data is not needed; enhanced information and knowledge are essential. This study built upon the Mean Separator Neural ... Network (MSNN) signal classification tool originally proposed by Duzenli (1998) and modified it for increased robustness. MSNN variants were developed

  5. An electroacoustic recording device for wireless sensing of neural signals.

    PubMed

    Hua Meng; Sahin, Mesut

    2013-01-01

    Elimination of wires connecting neural recording electrodes to external electronics is highly desired, particularly in survival animal studies, due to neural damage and the device failures caused by these wires. In this study, an electroacoustic device for sensing and wireless transmission of neural signals to an external unit is proposed and results from a prototype are presented. In this method, the neural signals modulate the acoustic pulse amplitudes generated by a small piezoelectric element that is implanted at the recording site. The acoustics waves are detected wirelessly outside the nervous system by another piezoelectric transducer and the neural signals are extracted by amplitude demodulation. To test the prototype, a sinusoidal signal with 100µVpp amplitude was applied in phosphate buffered saline to simulated neural signals and the external transducer was placed 10mm away from the recording element. The results show that a sinusoidal signal of the given amplitude could be wirelessly sensed and reconstructed with a signal-to-noise ratio of 14dB.

  6. Neural signal registration and analysis of axons grown in microchannels

    NASA Astrophysics Data System (ADS)

    Pigareva, Y.; Malishev, E.; Gladkov, A.; Kolpakov, V.; Bukatin, A.; Mukhina, I.; Kazantsev, V.; Pimashkin, A.

    2016-08-01

    Registration of neuronal bioelectrical signals remains one of the main physical tools to study fundamental mechanisms of signal processing in the brain. Neurons generate spiking patterns which propagate through complex map of neural network connectivity. Extracellular recording of isolated axons grown in microchannels provides amplification of the signal for detailed study of spike propagation. In this study we used neuronal hippocampal cultures grown in microfluidic devices combined with microelectrode arrays to investigate a changes of electrical activity during neural network development. We found that after 5 days in vitro after culture plating the spiking activity appears first in microchannels and on the next 2-3 days appears on the electrodes of overall neural network. We conclude that such approach provides a convenient method to study neural signal processing and functional structure development on a single cell and network level of the neuronal culture.

  7. Neural Signaling Metabolites May Modulate Energy Use in Hibernation.

    PubMed

    Drew, Kelly L; Frare, Carla; Rice, Sarah A

    2017-01-01

    Despite an epidemic in obesity and metabolic syndrome limited means exist to effect adiposity or metabolic rate other than life style changes. Here we review evidence that neural signaling metabolites may modulate thermoregulatory pathways and offer novel means to fine tune energy use. We extend prior reviews on mechanisms that regulate thermogenesis and energy use in hibernation by focusing primarily on the neural signaling metabolites adenosine, AMP and glutamate.

  8. Using pulse width modulation for wireless transmission of neural signals in multichannel neural recording systems.

    PubMed

    Yin, Ming; Ghovanloo, Maysam

    2009-08-01

    We have used a well-known technique in wireless communication, pulse width modulation (PWM) of time division multiplexed (TDM) signals, within the architecture of a novel wireless integrated neural recording (WINeR) system. We have evaluated the performance of the PWM-based architecture and indicated its accuracy and potential sources of error through detailed theoretical analysis, simulations, and measurements on a setup consisting of a 15-channel WINeR prototype as the transmitter and two types of receivers; an Agilent 89600 vector signal analyzer and a custom wideband receiver, with 36 and 75 MHz of maximum bandwidth, respectively. Furthermore, we present simulation results from a realistic MATLAB-Simulink model of the entire WINeR system to observe the system behavior in response to changes in various parameters. We have concluded that the 15-ch WINeR prototype, which is fabricated in a 0.5- mum standard CMOS process and consumes 4.5 mW from +/-1.5 V supplies, can acquire and wirelessly transmit up to 320 k-samples/s to a 75-MHz receiver with 8.4 bits of resolution, which is equivalent to a wireless data rate of approximately 2.56 Mb/s.

  9. GPCR-like signaling mediated by smoothened contributes to acquired chemoresistance through activating Gli

    PubMed Central

    2014-01-01

    Background Smoothened (Smo), which possesses a structural similarity with classic G-protein coupled receptors (GPCR), is the most important molecular target in Hedgehog (Hh) signaling system for developing anticancer drugs; however, whether Smo may transmit GPCR-like signaling to activate the canonical transcriptional factor Gli of Hh signaling system and consequently to be involved in the Gli-dependent biological events remains controversial. Results In this study, using the acquired chemoresistant cancer cell lines and their respective parental cells, we found that Smo may activate Gli through Gαi, Gβγ-JNK signaling axis, thereby promoting the Gli-dependent acquired chemoresistance. These observations were further complementarily strengthened by data obtained from chemosensitive cancer cells with artificially elevated Hh pathway activity. Conclusions Hence, our data demonstrate that GPCR-like signaling mediated by Smo contributes to the acquired chemoresistance through activating the canonical Hh transcriptional factor Gli; therefore improving our knowledge of the nature of the signal transduction of Smo and the molecular mechanisms responsible for the acquired chemoresistance maintained by Hh pathway. Moreover, our data that JNK after activated by Smo-Gβγ signaling axis may stimulate the Gli activity and consequently promotes acquired chemoresistance expose a promising and potential target for developing anti-cancer drugs aimed at Hh pathway and for combating the acquired resistance raised by using of anti-cancer drugs targeting Smo. PMID:24393163

  10. Radar signal categorization using a neural network

    NASA Technical Reports Server (NTRS)

    Anderson, James A.; Gately, Michael T.; Penz, P. Andrew; Collins, Dean R.

    1991-01-01

    Neural networks were used to analyze a complex simulated radar environment which contains noisy radar pulses generated by many different emitters. The neural network used is an energy minimizing network (the BSB model) which forms energy minima - attractors in the network dynamical system - based on learned input data. The system first determines how many emitters are present (the deinterleaving problem). Pulses from individual simulated emitters give rise to separate stable attractors in the network. Once individual emitters are characterized, it is possible to make tentative identifications of them based on their observed parameters. As a test of this idea, a neural network was used to form a small data base that potentially could make emitter identifications.

  11. Mesodermal Wnt signaling organizes the neural plate via Meis3.

    PubMed

    Elkouby, Yaniv M; Elias, Sarah; Casey, Elena S; Blythe, Shelby A; Tsabar, Nir; Klein, Peter S; Root, Heather; Liu, Karen J; Frank, Dale

    2010-05-01

    In vertebrates, canonical Wnt signaling controls posterior neural cell lineage specification. Although Wnt signaling to the neural plate is sufficient for posterior identity, the source and timing of this activity remain uncertain. Furthermore, crucial molecular targets of this activity have not been defined. Here, we identify the endogenous Wnt activity and its role in controlling an essential downstream transcription factor, Meis3. Wnt3a is expressed in a specialized mesodermal domain, the paraxial dorsolateral mesoderm, which signals to overlying neuroectoderm. Loss of zygotic Wnt3a in this region does not alter mesoderm cell fates, but blocks Meis3 expression in the neuroectoderm, triggering the loss of posterior neural fates. Ectopic Meis3 protein expression is sufficient to rescue this phenotype. Moreover, Wnt3a induction of the posterior nervous system requires functional Meis3 in the neural plate. Using ChIP and promoter analysis, we show that Meis3 is a direct target of Wnt/beta-catenin signaling. This suggests a new model for neural anteroposterior patterning, in which Wnt3a from the paraxial mesoderm induces posterior cell fates via direct activation of a crucial transcription factor in the overlying neural plate.

  12. Exploiting the 1/f structure of neural signals for the design of integrated neural amplifiers.

    PubMed

    Venkatraman, Subramaniam; Patten, Craig; Carmena, Jose M

    2009-01-01

    Neural amplifiers require a large time-constant high-pass filter at approximately 1Hz to reject large DC offsets while amplifying low frequency neural signals. This high pass filter is typically realized using large area capacitors and teraohm resistances which makes integration difficult. In this paper, we present a novel topology for a neural amplifier which exploits the (1/f)(n) power spectra of local field potentials (LFP). Using a high-pass filter at approximately 100Hz, we pre-filter the LFP before amplification. Post digitization, we can recover the LFP signal by building the inverse of the high pass filter in software. We built an array of neural amplifiers based on this principle and tested it on rats chronically implanted with microelectrode arrays. We found that we could recover the initial LFP signal and the power spectral information over time with correlation coefficient greater than 0.94.

  13. Heterotypic Signals from Neural HSF-1 Separate Thermotolerance from Longevity.

    PubMed

    Douglas, Peter M; Baird, Nathan A; Simic, Milos S; Uhlein, Sarah; McCormick, Mark A; Wolff, Suzanne C; Kennedy, Brian K; Dillin, Andrew

    2015-08-18

    Integrating stress responses across tissues is essential for the survival of multicellular organisms. The metazoan nervous system can sense protein-misfolding stress arising in different subcellular compartments and initiate cytoprotective transcriptional responses in the periphery. Several subcellular compartments possess a homotypic signal whereby the respective compartment relies on a single signaling mechanism to convey information within the affected cell to the same stress-responsive pathway in peripheral tissues. In contrast, we find that the heat shock transcription factor, HSF-1, specifies its mode of transcellular protection via two distinct signaling pathways. Upon thermal stress, neural HSF-1 primes peripheral tissues through the thermosensory neural circuit to mount a heat shock response. Independent of this thermosensory circuit, neural HSF-1 activates the FOXO transcription factor, DAF-16, in the periphery and prolongs lifespan. Thus a single transcription factor can coordinate different stress response pathways to specify its mode of protection against changing environmental conditions.

  14. Automatic Speech Recognition from Neural Signals: A Focused Review

    PubMed Central

    Herff, Christian; Schultz, Tanja

    2016-01-01

    Speech interfaces have become widely accepted and are nowadays integrated in various real-life applications and devices. They have become a part of our daily life. However, speech interfaces presume the ability to produce intelligible speech, which might be impossible due to either loud environments, bothering bystanders or incapabilities to produce speech (i.e., patients suffering from locked-in syndrome). For these reasons it would be highly desirable to not speak but to simply envision oneself to say words or sentences. Interfaces based on imagined speech would enable fast and natural communication without the need for audible speech and would give a voice to otherwise mute people. This focused review analyzes the potential of different brain imaging techniques to recognize speech from neural signals by applying Automatic Speech Recognition technology. We argue that modalities based on metabolic processes, such as functional Near Infrared Spectroscopy and functional Magnetic Resonance Imaging, are less suited for Automatic Speech Recognition from neural signals due to low temporal resolution but are very useful for the investigation of the underlying neural mechanisms involved in speech processes. In contrast, electrophysiologic activity is fast enough to capture speech processes and is therefor better suited for ASR. Our experimental results indicate the potential of these signals for speech recognition from neural data with a focus on invasively measured brain activity (electrocorticography). As a first example of Automatic Speech Recognition techniques used from neural signals, we discuss the Brain-to-text system. PMID:27729844

  15. Automatic Speech Recognition from Neural Signals: A Focused Review.

    PubMed

    Herff, Christian; Schultz, Tanja

    2016-01-01

    Speech interfaces have become widely accepted and are nowadays integrated in various real-life applications and devices. They have become a part of our daily life. However, speech interfaces presume the ability to produce intelligible speech, which might be impossible due to either loud environments, bothering bystanders or incapabilities to produce speech (i.e., patients suffering from locked-in syndrome). For these reasons it would be highly desirable to not speak but to simply envision oneself to say words or sentences. Interfaces based on imagined speech would enable fast and natural communication without the need for audible speech and would give a voice to otherwise mute people. This focused review analyzes the potential of different brain imaging techniques to recognize speech from neural signals by applying Automatic Speech Recognition technology. We argue that modalities based on metabolic processes, such as functional Near Infrared Spectroscopy and functional Magnetic Resonance Imaging, are less suited for Automatic Speech Recognition from neural signals due to low temporal resolution but are very useful for the investigation of the underlying neural mechanisms involved in speech processes. In contrast, electrophysiologic activity is fast enough to capture speech processes and is therefor better suited for ASR. Our experimental results indicate the potential of these signals for speech recognition from neural data with a focus on invasively measured brain activity (electrocorticography). As a first example of Automatic Speech Recognition techniques used from neural signals, we discuss the Brain-to-text system.

  16. A reconfigurable neural signal processor (NSP) for brain machine interfaces.

    PubMed

    Darmanjian, Shalom; Cieslewski, Grzegorz; Morrison, Scott; Dang, Benjamin; Gugel, Karl; Principe, Jose

    2006-01-01

    In this paper, we present a design for a wearable computational DSP system that alleviates the issues of a previous design and provides a much smaller and lower power solution for the overall BMI goals. The system first acquires the neural data through a high speed data bus in order to train and evaluate prediction models. Then it wirelessly transmits the predicted results to a simulated robot arm. This system has been built and successfully tested with real and simulated data.

  17. Measuring entropy in continuous and digitally filtered neural signals.

    PubMed

    French, Andrew S; Pfeiffer, Keram

    2011-03-15

    Neurons receive, process and transmit information using two distinct types of signaling methods: analog signals, such as graded changes in membrane potential, and binary digital action potentials. Quantitative estimates of information in neural signals have been based either on information capacity, which measures the theoretical maximum information flow through a communication channel, or on entropy, the amount of information that is required to describe or reproduce a signal. Measurement of entropy is straightforward for digital signals, including action potentials, but is more difficult for analog signals. This problem compromises attempts to estimate information in many neural signals, particularly when there is conversion between the two signal formats. We extended an established method for action potential entropy estimation to provide entropy estimation of analog signals. Our approach is based on context-independent data compression of analog signals, which we call analog compression. Although compression of analog signals is computationally intensive, we describe an algorithm that provides practical, efficient and reliable entropy estimation via analog compression. Implementation of the algorithm is demonstrated at two stages of sensory processing by a mechanoreceptor.

  18. Ion fluxes and neurotransmitters signaling in neural development.

    PubMed

    Andäng, Michael; Lendahl, Urban

    2008-06-01

    The brain develops and functions in a complex ionic milieu, which is a prerequisite for neurotransmitter function and neuronal signaling. Neurotransmitters and ion fluxes are, however, important not only in neuronal signaling, but also in the control of neural differentiation, and in this review, we highlight the recent advances in our understanding of how the gamma-amino butyric acid (GABA) neurotransmitter and ion fluxes are relevant for cell cycle control and neural differentiation. Conversely, proteins previously associated with ion transport across membranes have been endowed with novel ion-independent functions, and we discuss this in the context of gap junctions in cell adhesion and of the neuron-specific K(+)-Cl(-) cotransporter KCC2 in dendritic spine development. Collectively, these findings provide a richer and more complex picture of when ion fluxes are needed in neural development and when they are not.

  19. Gamma oscillations of spiking neural populations enhance signal discrimination.

    PubMed

    Masuda, Naoki; Doiron, Brent

    2007-11-01

    Selective attention is an important filter for complex environments where distractions compete with signals. Attention increases both the gamma-band power of cortical local field potentials and the spike-field coherence within the receptive field of an attended object. However, the mechanisms by which gamma-band activity enhances, if at all, the encoding of input signals are not well understood. We propose that gamma oscillations induce binomial-like spike-count statistics across noisy neural populations. Using simplified models of spiking neurons, we show how the discrimination of static signals based on the population spike-count response is improved with gamma induced binomial statistics. These results give an important mechanistic link between the neural correlates of attention and the discrimination tasks where attention is known to enhance performance. Further, they show how a rhythmicity of spike responses can enhance coding schemes that are not temporally sensitive.

  20. Plasmodesmata localizing proteins regulate transport and signaling during systemic acquired immunity in plants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Systemic acquired resistance (SAR) in plants is mediated by the signaling molecules azelaic acid (AzA),glycerol-3-phosphate (G3P), and salicylic acid (SA).Here, we show that AzA and G3P transport occurs via the symplastic route, which is regulated by channels known as plasmodesmata (PD). In contrast...

  1. Major transcriptome re-organisation and abrupt changes in signalling, cell cycle and chromatin regulation at neural differentiation in vivo.

    PubMed

    Olivera-Martinez, Isabel; Schurch, Nick; Li, Roman A; Song, Junfang; Halley, Pamela A; Das, Raman M; Burt, Dave W; Barton, Geoffrey J; Storey, Kate G

    2014-08-01

    Here, we exploit the spatial separation of temporal events of neural differentiation in the elongating chick body axis to provide the first analysis of transcriptome change in progressively more differentiated neural cell populations in vivo. Microarray data, validated against direct RNA sequencing, identified: (1) a gene cohort characteristic of the multi-potent stem zone epiblast, which contains neuro-mesodermal progenitors that progressively generate the spinal cord; (2) a major transcriptome re-organisation as cells then adopt a neural fate; and (3) increasing diversity as neural patterning and neuron production begin. Focussing on the transition from multi-potent to neural state cells, we capture changes in major signalling pathways, uncover novel Wnt and Notch signalling dynamics, and implicate new pathways (mevalonate pathway/steroid biogenesis and TGFβ). This analysis further predicts changes in cellular processes, cell cycle, RNA-processing and protein turnover as cells acquire neural fate. We show that these changes are conserved across species and provide biological evidence for reduced proteasome efficiency and a novel lengthening of S phase. This latter step may provide time for epigenetic events to mediate large-scale transcriptome re-organisation; consistent with this, we uncover simultaneous downregulation of major chromatin modifiers as the neural programme is established. We further demonstrate that transcription of one such gene, HDAC1, is dependent on FGF signalling, making a novel link between signals that control neural differentiation and transcription of a core regulator of chromatin organisation. Our work implicates new signalling pathways and dynamics, cellular processes and epigenetic modifiers in neural differentiation in vivo, identifying multiple new potential cellular and molecular mechanisms that direct differentiation.

  2. A neural microcircuit for cognitive conflict detection and signaling.

    PubMed

    Cohen, Michael X

    2014-09-01

    During human response conflict - competition between multiple conflicting actions when a mistake could be made - a specific pattern of brain electrical activity occurs over the medial frontal cortex (MFC), characterized by modulations of ongoing theta-band (∼6Hz) oscillations and synchronization with task-relevant brain regions. Despite the replicable and robust findings linking MFC theta to conflict processing, the significance of MFC theta for how neural microcircuits actually detect conflict and broadcast that signal is unknown. A neural MFC microcircuit model is proposed for processing conflict and generating theta oscillations. The model makes several novel predictions for the causes and consequences of MFC theta and conflict processing, and may be relevant for understanding the neural implementations of related cognitive processes.

  3. Neural signals encoding shifts in beliefs

    PubMed Central

    Schwartenbeck, Philipp; FitzGerald, Thomas H.B.; Dolan, Ray

    2016-01-01

    Dopamine is implicated in a diverse range of cognitive functions including cognitive flexibility, task switching, signalling novel or unexpected stimuli as well as advance information. There is also longstanding line of thought that links dopamine with belief formation and, crucially, aberrant belief formation in psychosis. Integrating these strands of evidence would suggest that dopamine plays a central role in belief updating and more specifically in encoding of meaningful information content in observations. The precise nature of this relationship has remained unclear. To directly address this question we developed a paradigm that allowed us to decompose two distinct types of information content, information-theoretic surprise that reflects the unexpectedness of an observation, and epistemic value that induces shifts in beliefs or, more formally, Bayesian surprise. Using functional magnetic-resonance imaging in humans we show that dopamine-rich midbrain regions encode shifts in beliefs whereas surprise is encoded in prefrontal regions, including the pre-supplementary motor area and dorsal cingulate cortex. By linking putative dopaminergic activity to belief updating these data provide a link to false belief formation that characterises hyperdopaminergic states associated with idiopathic and drug induced psychosis. PMID:26520774

  4. Neural mechanisms of spatiotemporal signal processing

    NASA Astrophysics Data System (ADS)

    Khanbabaie Shoub, Shaban (Reza)

    We have studied the synaptic, dendritic, and network mechanisms of spatiotemporal signal processing underlying the computation of visual motion in the avian tectum. Such mechanisms are critical for information processing in all vertebrates, but have been difficult to elucidate in mammals because of anatomical limitations. We have therefore developed a chick tectal slice preparation, which has features that help us circumvent these limitations. Using single-electrode multi-pulse synaptic stimulation experiments we found that the SGC-I cell responds to synaptic stimulation in a binary manner and its response is phasic in a time dependent probabilistic manner over large time scales. Synaptic inputs at two locations typically interact in a mutually exclusive manner when delivered within the "interaction time" of approximately 30 ms. Then we constructed a model of SGC-I cell and the retinal inputs to examine the role of the observed non-linear cellular properties in shaping the response of SGC-I neurons to assumed retinal representations of dynamic spatiotemporal visual stimuli. We found that by these properties, SGC-I cells can classify different stimuli. Especially without the phasic synaptic signal transfer the model SGC-I cell fails to distinguish between the static stationary stimuli and dynamic spatiotemporal stimuli. Based on one-site synaptic response probability and the assumption of independent neighboring dendritic endings we predicted the response probability of SGC-I cells to multiple synaptic inputs. We tested this independence-based model prediction and found that the independency assumption is not valid. The measured SGC-I response probability to multiple synaptic inputs does not increase with the number of synaptic inputs. The presence of GABAergic horizontal cells in layer 5 suggest an inhibitory effect of these cells on the SGC-I retino-tectal synaptic responses. In our experiment we found that the measured SGC-I response probability to multiple

  5. In vivo optical modulation of neural signals using monolithically integrated two-dimensional neural probe arrays

    NASA Astrophysics Data System (ADS)

    Son, Yoojin; Jenny Lee, Hyunjoo; Kim, Jeongyeon; Shin, Hyogeun; Choi, Nakwon; Justin Lee, C.; Yoon, Eui-Sung; Yoon, Euisik; Wise, Kensall D.; Geun Kim, Tae; Cho, Il-Joo

    2015-10-01

    Integration of stimulation modalities (e.g. electrical, optical, and chemical) on a large array of neural probes can enable an investigation of important underlying mechanisms of brain disorders that is not possible through neural recordings alone. Furthermore, it is important to achieve this integration of multiple functionalities in a compact structure to utilize a large number of the mouse models. Here we present a successful optical modulation of in vivo neural signals of a transgenic mouse through our compact 2D MEMS neural array (optrodes). Using a novel fabrication method that embeds a lower cladding layer in a silicon substrate, we achieved a thin silicon 2D optrode array that is capable of delivering light to multiple sites using SU-8 as a waveguide core. Without additional modification to the microelectrodes, the measured impedance of the multiple microelectrodes was below 1 MΩ at 1 kHz. In addition, with a low background noise level (±25 μV), neural spikes from different individual neurons were recorded on each microelectrode. Lastly, we successfully used our optrodes to modulate the neural activity of a transgenic mouse through optical stimulation. These results demonstrate the functionality of the 2D optrode array and its potential as a next-generation tool for optogenetic applications.

  6. In vivo optical modulation of neural signals using monolithically integrated two-dimensional neural probe arrays

    PubMed Central

    Son, Yoojin; Jenny Lee, Hyunjoo; Kim, Jeongyeon; Shin, Hyogeun; Choi, Nakwon; Justin Lee, C.; Yoon, Eui-Sung; Yoon, Euisik; Wise, Kensall D.; Geun Kim, Tae; Cho, Il-Joo

    2015-01-01

    Integration of stimulation modalities (e.g. electrical, optical, and chemical) on a large array of neural probes can enable an investigation of important underlying mechanisms of brain disorders that is not possible through neural recordings alone. Furthermore, it is important to achieve this integration of multiple functionalities in a compact structure to utilize a large number of the mouse models. Here we present a successful optical modulation of in vivo neural signals of a transgenic mouse through our compact 2D MEMS neural array (optrodes). Using a novel fabrication method that embeds a lower cladding layer in a silicon substrate, we achieved a thin silicon 2D optrode array that is capable of delivering light to multiple sites using SU-8 as a waveguide core. Without additional modification to the microelectrodes, the measured impedance of the multiple microelectrodes was below 1 MΩ at 1 kHz. In addition, with a low background noise level (±25 μV), neural spikes from different individual neurons were recorded on each microelectrode. Lastly, we successfully used our optrodes to modulate the neural activity of a transgenic mouse through optical stimulation. These results demonstrate the functionality of the 2D optrode array and its potential as a next-generation tool for optogenetic applications. PMID:26494437

  7. Fate Specification of Neural Plate Border by Canonical Wnt Signaling and Grhl3 is Crucial for Neural Tube Closure.

    PubMed

    Kimura-Yoshida, Chiharu; Mochida, Kyoko; Ellwanger, Kristina; Niehrs, Christof; Matsuo, Isao

    2015-06-01

    During primary neurulation, the separation of a single-layered ectodermal sheet into the surface ectoderm (SE) and neural tube specifies SE and neural ectoderm (NE) cell fates. The mechanisms underlying fate specification in conjunction with neural tube closure are poorly understood. Here, by comparing expression profiles between SE and NE lineages, we observed that uncommitted progenitor cells, expressing stem cell markers, are present in the neural plate border/neural fold prior to neural tube closure. Our results also demonstrated that canonical Wnt and its antagonists, DKK1/KREMEN1, progressively specify these progenitors into SE or NE fates in accord with the progress of neural tube closure. Additionally, SE specification of the neural plate border via canonical Wnt signaling is directed by the grainyhead-like 3 (Grhl3) transcription factor. Thus, we propose that the fate specification of uncommitted progenitors in the neural plate border by canonical Wnt signaling and its downstream effector Grhl3 is crucial for neural tube closure. This study implicates that failure in critical genetic factors controlling fate specification of progenitor cells in the neural plate border/neural fold coordinated with neural tube closure may be potential causes of human neural tube defects.

  8. Stochastic resonance with colored noise for neural signal detection.

    PubMed

    Duan, Fabing; Chapeau-Blondeau, François; Abbott, Derek

    2014-01-01

    We analyze signal detection with nonlinear test statistics in the presence of colored noise. In the limits of small signal and weak noise correlation, the optimal test statistic and its performance are derived under general conditions, especially concerning the type of noise. We also analyze, for a threshold nonlinearity-a key component of a neural model, the conditions for noise-enhanced performance, establishing that colored noise is superior to white noise for detection. For a parallel array of nonlinear elements, approximating neurons, we demonstrate even broader conditions allowing noise-enhanced detection, via a form of suprathreshold stochastic resonance.

  9. Oscillation-Induced Signal Transmission and Gating in Neural Circuits

    PubMed Central

    Jahnke, Sven; Memmesheimer, Raoul-Martin; Timme, Marc

    2014-01-01

    Reliable signal transmission constitutes a key requirement for neural circuit function. The propagation of synchronous pulse packets through recurrent circuits is hypothesized to be one robust form of signal transmission and has been extensively studied in computational and theoretical works. Yet, although external or internally generated oscillations are ubiquitous across neural systems, their influence on such signal propagation is unclear. Here we systematically investigate the impact of oscillations on propagating synchrony. We find that for standard, additive couplings and a net excitatory effect of oscillations, robust propagation of synchrony is enabled in less prominent feed-forward structures than in systems without oscillations. In the presence of non-additive coupling (as mediated by fast dendritic spikes), even balanced oscillatory inputs may enable robust propagation. Here, emerging resonances create complex locking patterns between oscillations and spike synchrony. Interestingly, these resonances make the circuits capable of selecting specific pathways for signal transmission. Oscillations may thus promote reliable transmission and, in co-action with dendritic nonlinearities, provide a mechanism for information processing by selectively gating and routing of signals. Our results are of particular interest for the interpretation of sharp wave/ripple complexes in the hippocampus, where previously learned spike patterns are replayed in conjunction with global high-frequency oscillations. We suggest that the oscillations may serve to stabilize the replay. PMID:25503492

  10. Neural network analysis of oxygenation signals in infants during sleep.

    PubMed

    Taktak, A F; Simpson, S; Patel, S; Meyer, G

    2000-08-01

    The use of artificial neural networks (ANNs) to interpret sleep monitoring signals is described. Recordings from ten infants with apparent life threatening episodes were assigned into training feedforward R-PROP networks. In order to separate good signal from artefact, 60 second time frames of SaO2 and TcPO2 signals were processed and the mean and standard deviation values were used as inputs to the networks. Intra-human errors were minimized using this method whilst inter-human errors remained significant. To decrease the latter, the number of hidden units was increased to eight. Sensitivity figures of the SaO2 network were 0.93 and 0.9 for the training and test sets respectively whilst the specificity figures were 0.7 and 0.65 respectively. For the TcPO2 signals the above figures were 0.92, 0.85, 0.77 and 0.61 respectively.

  11. Artificial neural network-based classification of body movements in ambulatory ECG signal.

    PubMed

    Darji, Sachin T; Kher, Rahul K

    2013-11-01

    Abstract Ambulatory ECG monitoring provides electrical activity of the heart when a person is involved in doing normal routine activities. Thus, the recorded ECG signal consists of cardiac signal along with motion artifacts introduced due to a person's body movements during routine activities. Detection of motion artifacts due to different physical activities might help in further cardiac diagnosis. Ambulatory ECG signal analysis for detection of various motion artifacts using adaptive filtering approach is addressed in this paper. We have used BIOPAC MP 36 system for acquiring ECG signal. The ECG signals of five healthy subjects (aged between 22-30 years) were recorded while the person performed various body movements like up and down movement of the left hand, up and down movement of the right hand, waist twisting movement while standing and change from sitting down on a chair to standing up movement in lead I configuration. An adaptive filter-based approach has been used to extract the motion artifact component from the ambulatory ECG signal. The features of motion artifact signal, extracted using Gabor transform, have been used to train the artificial neural network (ANN) for classifying body movements.

  12. Rapid Exact Signal Scanning With Deep Convolutional Neural Networks

    NASA Astrophysics Data System (ADS)

    Thom, Markus; Gritschneder, Franz

    2017-03-01

    A rigorous formulation of the dynamics of a signal processing scheme aimed at dense signal scanning without any loss in accuracy is introduced and analyzed. Related methods proposed in the recent past lack a satisfactory analysis of whether they actually fulfill any exactness constraints. This is improved through an exact characterization of the requirements for a sound sliding window approach. The tools developed in this paper are especially beneficial if Convolutional Neural Networks are employed, but can also be used as a more general framework to validate related approaches to signal scanning. The proposed theory helps to eliminate redundant computations and renders special case treatment unnecessary, resulting in a dramatic boost in efficiency particularly on massively parallel processors. This is demonstrated both theoretically in a computational complexity analysis and empirically on modern parallel processors.

  13. Signal Processing in Periodically Forced Gradient Frequency Neural Networks.

    PubMed

    Kim, Ji Chul; Large, Edward W

    2015-01-01

    Oscillatory instability at the Hopf bifurcation is a dynamical phenomenon that has been suggested to characterize active non-linear processes observed in the auditory system. Networks of oscillators poised near Hopf bifurcation points and tuned to tonotopically distributed frequencies have been used as models of auditory processing at various levels, but systematic investigation of the dynamical properties of such oscillatory networks is still lacking. Here we provide a dynamical systems analysis of a canonical model for gradient frequency neural networks driven by a periodic signal. We use linear stability analysis to identify various driven behaviors of canonical oscillators for all possible ranges of model and forcing parameters. The analysis shows that canonical oscillators exhibit qualitatively different sets of driven states and transitions for different regimes of model parameters. We classify the parameter regimes into four main categories based on their distinct signal processing capabilities. This analysis will lead to deeper understanding of the diverse behaviors of neural systems under periodic forcing and can inform the design of oscillatory network models of auditory signal processing.

  14. Signal Processing in Periodically Forced Gradient Frequency Neural Networks

    PubMed Central

    Kim, Ji Chul; Large, Edward W.

    2015-01-01

    Oscillatory instability at the Hopf bifurcation is a dynamical phenomenon that has been suggested to characterize active non-linear processes observed in the auditory system. Networks of oscillators poised near Hopf bifurcation points and tuned to tonotopically distributed frequencies have been used as models of auditory processing at various levels, but systematic investigation of the dynamical properties of such oscillatory networks is still lacking. Here we provide a dynamical systems analysis of a canonical model for gradient frequency neural networks driven by a periodic signal. We use linear stability analysis to identify various driven behaviors of canonical oscillators for all possible ranges of model and forcing parameters. The analysis shows that canonical oscillators exhibit qualitatively different sets of driven states and transitions for different regimes of model parameters. We classify the parameter regimes into four main categories based on their distinct signal processing capabilities. This analysis will lead to deeper understanding of the diverse behaviors of neural systems under periodic forcing and can inform the design of oscillatory network models of auditory signal processing. PMID:26733858

  15. Altered Death Receptor Signaling Promotes Epithelial-to-Mesenchymal Transition and Acquired Chemoresistance

    PubMed Central

    Antoon, James W.; Lai, Rongye; Struckhoff, Amanda P.; Nitschke, Ashley M.; Elliott, Steven; Martin, Elizabeth C.; Rhodes, Lyndsay V.; Yoon, Nam Seung; Salvo, Virgilio A.; Shan, Bin; Beckman, Barbara S.; Nephew, Kenneth P.; Burow, Matthew E.

    2012-01-01

    Altered death receptor signaling and resistance to subsequent apoptosis is an important clinical resistance mechanism. Here, we investigated the role of death receptor resistance in breast cancer progression. Resistance of the estrogen receptor alpha (ER)-positive, chemosensitive MCF7 breast cancer cell line to tumor necrosis factor (TNF) was associated with loss of ER expression and a multi-drug resistant phenotype. Changes in three major pathways were involved in this transition to a multidrug resistance phenotype: ER, Death Receptor and epithelial to mesenchymal transition (EMT). Resistant cells exhibited altered ER signaling, resulting in decreased ER target gene expression. The death receptor pathway was significantly altered, blocking extrinsic apoptosis and increasing NF-kappaB survival signaling. TNF resistance promoted EMT changes, resulting in a more aggressive phenotype. This first report identifying specific mechanisms underlying acquired resistance to TNF could lead to a better understanding of the progression of breast cancer in response to chemotherapy treatment. PMID:22844580

  16. Wnt signaling: role in LTP, neural networks and memory.

    PubMed

    Oliva, Carolina A; Vargas, Jessica Y; Inestrosa, Nibaldo C

    2013-06-01

    Wnt components are key regulators of a variety of developmental processes, including embryonic patterning, cell specification, and cell polarity. The Wnt signaling pathway participates in the development of the central nervous system and growing evidence indicates that Wnts also regulates the function of the adult nervous system. In fact, most of the key components including Wnts and Frizzled receptors are expressed in the adult brain. Wnt ligands have been implicated in the regulation of synaptic assembly as well as in neurotransmission and synaptic plasticity. Deregulation of Wnt signaling has been associated with several pathologies, and more recently has been related to neurodegenerative diseases and to mental and mood disorders. In this review, we focus our attention on the Wnt signaling cascade in postnatal life and we review in detail the presence of Wnt signaling components in pre- and postsynaptic regions. Due to the important role of Wnt proteins in wiring neural circuits, we discuss recent findings about the role of Wnt pathways both in basal spontaneous activities as well as in activity-dependent processes that underlie synaptic plasticity. Finally, we review the role of Wnt in vivo and we finish with the most recent data in literature that involves the effect of components of the Wnt signaling pathway in neurological and mental disorders, including a special emphasis on in vivo studies that relate behavioral abnormalities to deficiencies in Wnt signaling, as well as the data that support a neuroprotective role of Wnt proteins in relation to the pathogenesis of Alzheimer's disease.

  17. Levels of complexity in scale-invariant neural signals

    NASA Astrophysics Data System (ADS)

    Ivanov, Plamen Ch.; Ma, Qianli D. Y.; Bartsch, Ronny P.; Hausdorff, Jeffrey M.; Nunes Amaral, Luís A.; Schulte-Frohlinde, Verena; Stanley, H. Eugene; Yoneyama, Mitsuru

    2009-04-01

    Many physical and physiological signals exhibit complex scale-invariant features characterized by 1/f scaling and long-range power-law correlations, indicating a possibly common control mechanism. Specifically, it has been suggested that dynamical processes, influenced by inputs and feedback on multiple time scales, may be sufficient to give rise to 1/f scaling and scale invariance. Two examples of physiologic signals that are the output of hierarchical multiscale physiologic systems under neural control are the human heartbeat and human gait. Here we show that while both cardiac interbeat interval and gait interstride interval time series under healthy conditions have comparable 1/f scaling, they still may belong to different complexity classes. Our analysis of the multifractal scaling exponents of the fluctuations in these two signals demonstrates that in contrast to the multifractal behavior found in healthy heartbeat dynamics, gait time series exhibit less complex, close to monofractal behavior. Further, we find strong anticorrelations in the sign and close to random behavior for the magnitude of gait fluctuations at short and intermediate time scales, in contrast to weak anticorrelations in the sign and strong positive correlation for the magnitude of heartbeat interval fluctuations—suggesting that the neural mechanisms of cardiac and gait control exhibit different linear and nonlinear features. These findings are of interest because they underscore the limitations of traditional two-point correlation methods in fully characterizing physiological and physical dynamics. In addition, these results suggest that different mechanisms of control may be responsible for varying levels of complexity observed in physiological systems under neural regulation and in physical systems that possess similar 1/f scaling.

  18. Levels of complexity in scale-invariant neural signals.

    PubMed

    Ivanov, Plamen Ch; Ma, Qianli D Y; Bartsch, Ronny P; Hausdorff, Jeffrey M; Nunes Amaral, Luís A; Schulte-Frohlinde, Verena; Stanley, H Eugene; Yoneyama, Mitsuru

    2009-04-01

    Many physical and physiological signals exhibit complex scale-invariant features characterized by 1/f scaling and long-range power-law correlations, indicating a possibly common control mechanism. Specifically, it has been suggested that dynamical processes, influenced by inputs and feedback on multiple time scales, may be sufficient to give rise to 1/f scaling and scale invariance. Two examples of physiologic signals that are the output of hierarchical multiscale physiologic systems under neural control are the human heartbeat and human gait. Here we show that while both cardiac interbeat interval and gait interstride interval time series under healthy conditions have comparable 1/f scaling, they still may belong to different complexity classes. Our analysis of the multifractal scaling exponents of the fluctuations in these two signals demonstrates that in contrast to the multifractal behavior found in healthy heartbeat dynamics, gait time series exhibit less complex, close to monofractal behavior. Further, we find strong anticorrelations in the sign and close to random behavior for the magnitude of gait fluctuations at short and intermediate time scales, in contrast to weak anticorrelations in the sign and strong positive correlation for the magnitude of heartbeat interval fluctuations-suggesting that the neural mechanisms of cardiac and gait control exhibit different linear and nonlinear features. These findings are of interest because they underscore the limitations of traditional two-point correlation methods in fully characterizing physiological and physical dynamics. In addition, these results suggest that different mechanisms of control may be responsible for varying levels of complexity observed in physiological systems under neural regulation and in physical systems that possess similar 1/f scaling.

  19. Neural Networks for Signal Processing VII Proceeding of the 1997 IEEE Workshop

    DTIC Science & Technology

    2007-11-02

    Fu, Hsin-Chia and Xu, Y. Y. 626 Neural Networks for Engine Fault Diagnostics Dong, Dawei W., Hopfield , John J., and Unnikrishnan, K. P. 636...June 98 REPORT TYPE AND DATES COVERED Final \\^Q\\ Cf\\ - M DteC ^ TITLE AND SUBTITLE Neural Networks for Signal Processing VII Proceeding...sponsored by the Neural Networks Technical Committee of the IEEE Signal Processing Society, in cooperation with the IEEE Neural Networks Council and

  20. Low-Cutoff, High-Pass Digital Filtering of Neural Signals

    NASA Technical Reports Server (NTRS)

    Mojarradi,Mohammad; Johnson, Travis; Ortiz, Monico; Cunningham, Thomas; Andersen, Richard

    2004-01-01

    The figure depicts the major functional blocks of a system, now undergoing development, for conditioning neural signals acquired by electrodes implanted in a brain. The overall functions to be performed by this system can be summarized as preamplification, multiplexing, digitization, and high-pass filtering. Other systems under development for recording neural signals typically contain resistor-capacitor analog low-pass filters characterized by cutoff frequencies in the vicinity of 100 Hz. In the application for which this system is being developed, there is a requirement for a cutoff frequency of 5 Hz. Because the resistors needed to obtain such a low cutoff frequency would be impractically large, it was decided to perform low-pass filtering by use of digital rather than analog circuitry. In addition, it was decided to timemultiplex the digitized signals from the multiple input channels into a single stream of data in a single output channel. The signal in each input channel is first processed by a preamplifier having a voltage gain of approximately 50. Embedded in each preamplifier is a low-pass anti-aliasing filter having a cutoff frequency of approximately 10 kHz. The anti-aliasing filters make it possible to couple the outputs of the preamplifiers to the input ports of a multiplexer. The output of the multiplexer is a single stream of time-multiplexed samples of analog signals. This stream is processed by a main differential amplifier, the output of which is sent to an analog-to-digital converter (ADC). The output of the ADC is sent to a digital signal processor (DSP).

  1. Dynamic neural activity during stress signals resilient coping

    PubMed Central

    Sinha, Rajita; Lacadie, Cheryl M.; Constable, R. Todd; Seo, Dongju

    2016-01-01

    Active coping underlies a healthy stress response, but neural processes supporting such resilient coping are not well-known. Using a brief, sustained exposure paradigm contrasting highly stressful, threatening, and violent stimuli versus nonaversive neutral visual stimuli in a functional magnetic resonance imaging (fMRI) study, we show significant subjective, physiologic, and endocrine increases and temporally related dynamically distinct patterns of neural activation in brain circuits underlying the stress response. First, stress-specific sustained increases in the amygdala, striatum, hypothalamus, midbrain, right insula, and right dorsolateral prefrontal cortex (DLPFC) regions supported the stress processing and reactivity circuit. Second, dynamic neural activation during stress versus neutral runs, showing early increases followed by later reduced activation in the ventrolateral prefrontal cortex (VLPFC), dorsal anterior cingulate cortex (dACC), left DLPFC, hippocampus, and left insula, suggested a stress adaptation response network. Finally, dynamic stress-specific mobilization of the ventromedial prefrontal cortex (VmPFC), marked by initial hypoactivity followed by increased VmPFC activation, pointed to the VmPFC as a key locus of the emotional and behavioral control network. Consistent with this finding, greater neural flexibility signals in the VmPFC during stress correlated with active coping ratings whereas lower dynamic activity in the VmPFC also predicted a higher level of maladaptive coping behaviors in real life, including binge alcohol intake, emotional eating, and frequency of arguments and fights. These findings demonstrate acute functional neuroplasticity during stress, with distinct and separable brain networks that underlie critical components of the stress response, and a specific role for VmPFC neuroflexibility in stress-resilient coping. PMID:27432990

  2. Living ordered neural networks as model systems for signal processing

    NASA Astrophysics Data System (ADS)

    Villard, C.; Amblard, P. O.; Becq, G.; Gory-Fauré, S.; Brocard, J.; Roth, S.

    2007-06-01

    Neural circuit architecture is a fundamental characteristic of the brain, and how architecture is bound to biological functions is still an open question. Some neuronal geometries seen in the retina or the cochlea are intriguing: information is processed in parallel by several entities like in "pooling" networks which have recently drawn the attention of signal processing scientists. These systems indeed exhibit the noise-enhanced processing effect, which is also actively discussed in the neuroscience community at the neuron scale. The aim of our project is to use in-vitro ordered neuron networks as living paradigms to test ideas coming from the computational science. The different technological bolts that have to be solved are enumerated and the first results are presented. A neuron is a polarised cell, with an excitatory axon and a receiving dendritic tree. We present how soma confinement and axon differentiation can be induced by surface functionalization techniques. The recording of large neuron networks, ordered or not, is also detailed and biological signals shown. The main difficulty to access neural noise in the case of weakly connected networks grown on micro electrode arrays is explained. This open the door to a new detection technology suitable for sub-cellular analysis and stimulation, whose development will constitute the next step of this project.

  3. Respiratory rate derived from smartphone-camera-acquired pulse photoplethysmographic signals.

    PubMed

    Lázaro, Jesús; Nam, Yunyoung; Gil, Eduardo; Laguna, Pablo; Chon, Ki H

    2015-11-01

    A method for deriving respiratory rate from smartphone-camera-acquired pulse photoplethysmographic (SCPPG) signal is presented. Our method exploits respiratory information by examining the pulse wave velocity and dispersion from the SCPPG waveform and we term these indices as the pulse width variability (PWV). A method to combine information from several derived respiration signals is also presented and it is used to combine PWV information with other methods such as pulse amplitude variability (PAV), pulse rate variability (PRV), and respiration-induced amplitude and frequency modulations (AM and FM) in SCPPG signals.Evaluation is performed on a database containing SCPPG signals recorded from 30 subjects during controlled respiration experiments at rates from 0.2 to 0.6 Hz with an increment of 0.1 Hz, using three different devices: iPhone 4S, iPod 5, and HTC One M8. Results suggest that spontaneous respiratory rates (0.2-0.4 Hz) can be estimated from SCPPG signals by the PWV- and PRV-based methods with low relative error (median of order 0.5% and interquartile range of order 2.5%). The accuracy can be improved by combining PWV and PRV with other methods such as PAV, AM and/or FM methods. Combination of these methods yielded low relative error for normal respiratory rates, and maintained good performance at higher rates (0.5-0.6 Hz) when using the iPhone 4S or iPod 5 devices.

  4. Neural network approach to classification of infrasound signals

    NASA Astrophysics Data System (ADS)

    Lee, Dong-Chang

    As part of the International Monitoring Systems of the Preparatory Commissions for the Comprehensive Nuclear Test-Ban Treaty Organization, the Infrasound Group at the University of Alaska Fairbanks maintains and operates two infrasound stations to monitor global nuclear activity. In addition, the group specializes in detecting and classifying the man-made and naturally produced signals recorded at both stations by computing various characterization parameters (e.g. mean of the cross correlation maxima, trace velocity, direction of arrival, and planarity values) using the in-house developed weighted least-squares algorithm. Classifying commonly observed low-frequency (0.015--0.1 Hz) signals at out stations, namely mountain associated waves and high trace-velocity signals, using traditional approach (e.g. analysis of power spectral density) presents a problem. Such signals can be separated statistically by setting a window to the trace-velocity estimate for each signal types, and the feasibility of such technique is demonstrated by displaying and comparing various summary plots (e.g. universal, seasonal and azimuthal variations) produced by analyzing infrasound data (2004--2007) from the Fairbanks and Antarctic arrays. Such plots with the availability of magnetic activity information (from the College International Geophysical Observatory located at Fairbanks, Alaska) leads to possible physical sources of the two signal types. Throughout this thesis a newly developed robust algorithm (sum of squares of variance ratios) with improved detection quality (under low signal to noise ratios) over two well-known detection algorithms (mean of the cross correlation maxima and Fisher Statistics) are investigated for its efficacy as a new detector. A neural network is examined for its ability to automatically classify the two signals described above against clutter (spurious signals with common characteristics). Four identical perceptron networks are trained and validated (with

  5. An FGF3-BMP Signaling Axis Regulates Caudal Neural Tube Closure, Neural Crest Specification and Anterior-Posterior Axis Extension.

    PubMed

    Anderson, Matthew J; Schimmang, Thomas; Lewandoski, Mark

    2016-05-01

    During vertebrate axis extension, adjacent tissue layers undergo profound morphological changes: within the neuroepithelium, neural tube closure and neural crest formation are occurring, while within the paraxial mesoderm somites are segmenting from the presomitic mesoderm (PSM). Little is known about the signals between these tissues that regulate their coordinated morphogenesis. Here, we analyze the posterior axis truncation of mouse Fgf3 null homozygotes and demonstrate that the earliest role of PSM-derived FGF3 is to regulate BMP signals in the adjacent neuroepithelium. FGF3 loss causes elevated BMP signals leading to increased neuroepithelium proliferation, delay in neural tube closure and premature neural crest specification. We demonstrate that elevated BMP4 depletes PSM progenitors in vitro, phenocopying the Fgf3 mutant, suggesting that excessive BMP signals cause the Fgf3 axis defect. To test this in vivo we increased BMP signaling in Fgf3 mutants by removing one copy of Noggin, which encodes a BMP antagonist. In such mutants, all parameters of the Fgf3 phenotype were exacerbated: neural tube closure delay, premature neural crest specification, and premature axis termination. Conversely, genetically decreasing BMP signaling in Fgf3 mutants, via loss of BMP receptor activity, alleviates morphological defects. Aberrant apoptosis is observed in the Fgf3 mutant tailbud. However, we demonstrate that cell death does not cause the Fgf3 phenotype: blocking apoptosis via deletion of pro-apoptotic genes surprisingly increases all Fgf3 defects including causing spina bifida. We demonstrate that this counterintuitive consequence of blocking apoptosis is caused by the increased survival of BMP-producing cells in the neuroepithelium. Thus, we show that FGF3 in the caudal vertebrate embryo regulates BMP signaling in the neuroepithelium, which in turn regulates neural tube closure, neural crest specification and axis termination. Uncovering this FGF3-BMP signaling axis is

  6. An FGF3-BMP Signaling Axis Regulates Caudal Neural Tube Closure, Neural Crest Specification and Anterior-Posterior Axis Extension

    PubMed Central

    Anderson, Matthew J.; Schimmang, Thomas; Lewandoski, Mark

    2016-01-01

    During vertebrate axis extension, adjacent tissue layers undergo profound morphological changes: within the neuroepithelium, neural tube closure and neural crest formation are occurring, while within the paraxial mesoderm somites are segmenting from the presomitic mesoderm (PSM). Little is known about the signals between these tissues that regulate their coordinated morphogenesis. Here, we analyze the posterior axis truncation of mouse Fgf3 null homozygotes and demonstrate that the earliest role of PSM-derived FGF3 is to regulate BMP signals in the adjacent neuroepithelium. FGF3 loss causes elevated BMP signals leading to increased neuroepithelium proliferation, delay in neural tube closure and premature neural crest specification. We demonstrate that elevated BMP4 depletes PSM progenitors in vitro, phenocopying the Fgf3 mutant, suggesting that excessive BMP signals cause the Fgf3 axis defect. To test this in vivo we increased BMP signaling in Fgf3 mutants by removing one copy of Noggin, which encodes a BMP antagonist. In such mutants, all parameters of the Fgf3 phenotype were exacerbated: neural tube closure delay, premature neural crest specification, and premature axis termination. Conversely, genetically decreasing BMP signaling in Fgf3 mutants, via loss of BMP receptor activity, alleviates morphological defects. Aberrant apoptosis is observed in the Fgf3 mutant tailbud. However, we demonstrate that cell death does not cause the Fgf3 phenotype: blocking apoptosis via deletion of pro-apoptotic genes surprisingly increases all Fgf3 defects including causing spina bifida. We demonstrate that this counterintuitive consequence of blocking apoptosis is caused by the increased survival of BMP-producing cells in the neuroepithelium. Thus, we show that FGF3 in the caudal vertebrate embryo regulates BMP signaling in the neuroepithelium, which in turn regulates neural tube closure, neural crest specification and axis termination. Uncovering this FGF3-BMP signaling axis is

  7. Neural decoding of treadmill walking from noninvasive electroencephalographic signals.

    PubMed

    Presacco, Alessandro; Goodman, Ronald; Forrester, Larry; Contreras-Vidal, Jose Luis

    2011-10-01

    Chronic recordings from ensembles of cortical neurons in primary motor and somatosensory areas in rhesus macaques provide accurate information about bipedal locomotion (Fitzsimmons NA, Lebedev MA, Peikon ID, Nicolelis MA. Front Integr Neurosci 3: 3, 2009). Here we show that the linear and angular kinematics of the ankle, knee, and hip joints during both normal and precision (attentive) human treadmill walking can be inferred from noninvasive scalp electroencephalography (EEG) with decoding accuracies comparable to those from neural decoders based on multiple single-unit activities (SUAs) recorded in nonhuman primates. Six healthy adults were recorded. Participants were asked to walk on a treadmill at their self-selected comfortable speed while receiving visual feedback of their lower limbs (i.e., precision walking), to repeatedly avoid stepping on a strip drawn on the treadmill belt. Angular and linear kinematics of the left and right hip, knee, and ankle joints and EEG were recorded, and neural decoders were designed and optimized with cross-validation procedures. Of note, the optimal set of electrodes of these decoders were also used to accurately infer gait trajectories in a normal walking task that did not require subjects to control and monitor their foot placement. Our results indicate a high involvement of a fronto-posterior cortical network in the control of both precision and normal walking and suggest that EEG signals can be used to study in real time the cortical dynamics of walking and to develop brain-machine interfaces aimed at restoring human gait function.

  8. Neural decoding of treadmill walking from noninvasive electroencephalographic signals

    PubMed Central

    Presacco, Alessandro; Goodman, Ronald; Forrester, Larry

    2011-01-01

    Chronic recordings from ensembles of cortical neurons in primary motor and somatosensory areas in rhesus macaques provide accurate information about bipedal locomotion (Fitzsimmons NA, Lebedev MA, Peikon ID, Nicolelis MA. Front Integr Neurosci 3: 3, 2009). Here we show that the linear and angular kinematics of the ankle, knee, and hip joints during both normal and precision (attentive) human treadmill walking can be inferred from noninvasive scalp electroencephalography (EEG) with decoding accuracies comparable to those from neural decoders based on multiple single-unit activities (SUAs) recorded in nonhuman primates. Six healthy adults were recorded. Participants were asked to walk on a treadmill at their self-selected comfortable speed while receiving visual feedback of their lower limbs (i.e., precision walking), to repeatedly avoid stepping on a strip drawn on the treadmill belt. Angular and linear kinematics of the left and right hip, knee, and ankle joints and EEG were recorded, and neural decoders were designed and optimized with cross-validation procedures. Of note, the optimal set of electrodes of these decoders were also used to accurately infer gait trajectories in a normal walking task that did not require subjects to control and monitor their foot placement. Our results indicate a high involvement of a fronto-posterior cortical network in the control of both precision and normal walking and suggest that EEG signals can be used to study in real time the cortical dynamics of walking and to develop brain-machine interfaces aimed at restoring human gait function. PMID:21768121

  9. Pattern recognition for electroencephalographic signals based on continuous neural networks.

    PubMed

    Alfaro-Ponce, M; Argüelles, A; Chairez, I

    2016-07-01

    This study reports the design and implementation of a pattern recognition algorithm to classify electroencephalographic (EEG) signals based on artificial neural networks (NN) described by ordinary differential equations (ODEs). The training method for this kind of continuous NN (CNN) was developed according to the Lyapunov theory stability analysis. A parallel structure with fixed weights was proposed to perform the classification stage. The pattern recognition efficiency was validated by two methods, a generalization-regularization and a k-fold cross validation (k=5). The classifier was applied on two different databases. The first one was made up by signals collected from patients suffering of epilepsy and it is divided in five different classes. The second database was made up by 90 single EEG trials, divided in three classes. Each class corresponds to a different visual evoked potential. The pattern recognition algorithm achieved a maximum correct classification percentage of 97.2% using the information of the entire database. This value was similar to some results previously reported when this database was used for testing pattern classification. However, these results were obtained when only two classes were considered for the testing. The result reported in this study used the whole set of signals (five different classes). In comparison with similar pattern recognition methods that even considered less number of classes, the proposed CNN proved to achieve the same or even better correct classification results.

  10. Real-Time Neural Signals Decoding onto Off-the-Shelf DSP Processors for Neuroprosthetic Applications.

    PubMed

    Pani, Danilo; Barabino, Gianluca; Citi, Luca; Meloni, Paolo; Raspopovic, Stanisa; Micera, Silvestro; Raffo, Luigi

    2016-09-01

    The control of upper limb neuroprostheses through the peripheral nervous system (PNS) can allow restoring motor functions in amputees. At present, the important aspect of the real-time implementation of neural decoding algorithms on embedded systems has been often overlooked, notwithstanding the impact that limited hardware resources have on the efficiency/effectiveness of any given algorithm. Present study is addressing the optimization of a template matching based algorithm for PNS signals decoding that is a milestone for its real-time, full implementation onto a floating-point digital signal processor (DSP). The proposed optimized real-time algorithm achieves up to 96% of correct classification on real PNS signals acquired through LIFE electrodes on animals, and can correctly sort spikes of a synthetic cortical dataset with sufficiently uncorrelated spike morphologies (93% average correct classification) comparably to the results obtained with top spike sorter (94% on average on the same dataset). The power consumption enables more than 24 h processing at the maximum load, and latency model has been derived to enable a fair performance assessment. The final embodiment demonstrates the real-time performance onto a low-power off-the-shelf DSP, opening to experiments exploiting the efferent signals to control a motor neuroprosthesis.

  11. Sensory signals in neural populations underlying tactile perception and manipulation.

    PubMed

    Goodwin, Antony W; Wheat, Heather E

    2004-01-01

    For humans to manipulate an object successfully, the motor control system must have accurate information about parameters such as the shape of the stimulus, its position of contact on the skin, and the magnitude and direction of contact force. The same information is required for perception during haptic exploration of an object. Much of these data are relayed by the mechanoreceptive afferents innervating the glabrous skin of the digits. Single afferent responses are modulated by all the relevant stimulus parameters. Thus, only in complete population reconstructions is it clear how each of the parameters can be signaled to the brain independently when many are changing simultaneously, as occurs in most normal movements or haptic exploration. Modeling population responses reveals how resolution is affected by neural noise and intrinsic properties of the population such as the pattern and density of innervation and the covariance of response variability.

  12. TREM-2 promotes acquired cholesteatoma-induced bone destruction by modulating TLR4 signaling pathway and osteoclasts activation

    PubMed Central

    Jiang, Huaili; Si, Yu; Li, Zhuohao; Huang, Xi; Chen, Suijun; Zheng, Yiqing; Xu, Guo; Chen, Ximing; Chen, Yubin; Liu, Yi; Xiong, Hao; Huang, Qiuhong; Liang, Maojin; Zhang, Zhigang

    2016-01-01

    Triggering receptor expressed on myeloid cells (TREM) has been broadly studied in inflammatory disease. However, the expression and function of TREM-2 remain undiscovered in acquired cholesteatoma. The expression of TREM-2 was significantly higher in human acquired cholesteatoma than in normal skin from the external auditory canal, and its expression level was positively correlated with the severity of bone destruction. Furthermore, TREM-2 was mainly expressed on dendritic cells (DCs). In human acquired cholesteatoma, the expression of proinflammatory cytokines (IL-1β, TNF-α and IL-6) and matrix metalloproteinases (MMP-2, MMP-8 and MMP-9) were up-regulated, and their expression levels were positively correlated with TREM-2 expression. Osteoclasts were activated in human acquired cholesteatoma. In an animal model, TREM-2 was up-regulated in mice with experimentally acquired cholesteatoma. TREM-2 deficiency impaired the maturation of experimentally acquired cholesteatoma and protected against bone destruction induced by experimentally acquired cholesteatoma. Additional data showed that TREM-2 up-regulated IL-1β and IL-6 expression via TLR4 instead of the TLR2 signaling pathway and promoted MMP-2 and MMP-8 secretion and osteoclast activation in experimentally acquired cholesteatoma. Therefore, TREM-2 might enhance acquired cholesteatoma-induced bone destruction by amplifying the inflammatory response via TLR4 signaling pathways and promoting MMP secretion and osteoclast activation. PMID:27934908

  13. Role of TGF-β signaling in inherited and acquired myopathies

    PubMed Central

    2011-01-01

    The transforming growth factor-beta (TGF-β) superfamily consists of a variety of cytokines expressed in many different cell types including skeletal muscle. Members of this superfamily that are of particular importance in skeletal muscle are TGF-β1, mitogen-activated protein kinases (MAPKs), and myostatin. These signaling molecules play important roles in skeletal muscle homeostasis and in a variety of inherited and acquired neuromuscular disorders. Expression of these molecules is linked to normal processes in skeletal muscle such as growth, differentiation, regeneration, and stress response. However, chronic elevation of TGF-β1, MAPKs, and myostatin is linked to various features of muscle pathology, including impaired regeneration and atrophy. In this review, we focus on the aberrant signaling of TGF-β in various disorders such as Marfan syndrome, muscular dystrophies, sarcopenia, and critical illness myopathy. We also discuss how the inhibition of several members of the TGF-β signaling pathway has been implicated in ameliorating disease phenotypes, opening up novel therapeutic avenues for a large group of neuromuscular disorders. PMID:21798096

  14. Method for acquiring extended real-time kinetic signals in nanosecond laser flash photolysis experiments

    NASA Astrophysics Data System (ADS)

    Banderini, Andrea; Sottini, Silvia; Viappiani, Cristiano

    2004-07-01

    We report a data acquisition method for detecting transient absorbance signals extended in time which require nanosecond resolution and need to span several decades in time up to the hundreds of milliseconds. A microprocessor is used to generate a sequence of up to 100, 2.120 μs wide radio frequency signals at 500 MHz which are used to trigger the analog-to-digital conversion on a digital oscilloscope, operating in the external clock mode. During these radio frequency bursts the data are sampled at a sampling rate of 500 Ms/s. The delay of each sampling burst can be set at arbitrary values with respect to the first signal, with a minimum delay of 0.96 μs for the second pulse, and 1.2 μs for all other pulses. The microprocessor provides accessory synchronization outputs for laser triggering and for shutter opening and closing. This data acquisition system allows measuring the complete time course of extended kinetics after each laser shot, thus reducing acquisition times and data size. We prove the complete equivalence of the proposed acquisition method with standard methods, where several time bases are acquired to cover the complete kinetic trace for the ligand rebinding to myoglobin after photolysis of a gel embedded myoglobin-CO complex.

  15. Neural Network Prediction of Failure of Damaged Composite Pressure Vessels from Strain Field Data Acquired by a Computer Vision Method

    NASA Technical Reports Server (NTRS)

    Russell, Samuel S.; Lansing, Matthew D.

    1997-01-01

    This effort used a new and novel method of acquiring strains called Sub-pixel Digital Video Image Correlation (SDVIC) on impact damaged Kevlar/epoxy filament wound pressure vessels during a proof test. To predict the burst pressure, the hoop strain field distribution around the impact location from three vessels was used to train a neural network. The network was then tested on additional pressure vessels. Several variations on the network were tried. The best results were obtained using a single hidden layer. SDVIC is a fill-field non-contact computer vision technique which provides in-plane deformation and strain data over a load differential. This method was used to determine hoop and axial displacements, hoop and axial linear strains, the in-plane shear strains and rotations in the regions surrounding impact sites in filament wound pressure vessels (FWPV) during proof loading by internal pressurization. The relationship between these deformation measurement values and the remaining life of the pressure vessels, however, requires a complex theoretical model or numerical simulation. Both of these techniques are time consuming and complicated. Previous results using neural network methods had been successful in predicting the burst pressure for graphite/epoxy pressure vessels based upon acoustic emission (AE) measurements in similar tests. The neural network associates the character of the AE amplitude distribution, which depends upon the extent of impact damage, with the burst pressure. Similarly, higher amounts of impact damage are theorized to cause a higher amount of strain concentration in the damage effected zone at a given pressure and result in lower burst pressures. This relationship suggests that a neural network might be able to find an empirical relationship between the SDVIC strain field data and the burst pressure, analogous to the AE method, with greater speed and simplicity than theoretical or finite element modeling. The process of testing SDVIC

  16. Stage-specific roles of FGF2 signaling in human neural development.

    PubMed

    Grabiec, Marta; Hříbková, Hana; Vařecha, Miroslav; Střítecká, Dana; Hampl, Aleš; Dvořák, Petr; Sun, Yuh-Man

    2016-09-01

    This study elucidated the stage-specific roles of FGF2 signaling during neural development using in-vitro human embryonic stem cell-based developmental modeling. We found that the dysregulation of FGF2 signaling prior to the onset of neural induction resulted in the malformation of neural rosettes (a neural tube-like structure), despite cells having undergone neural induction. The aberrant neural rosette formation may be attributed to the misplacement of ZO-1, which is a polarized tight junction protein and shown co-localized with FGF2/FGFR1 in the apical region of neural rosettes, subsequently led to abnormal neurogenesis. Moreover, the FGF2 signaling inhibition at the stage of neural rosettes caused a reduction in cell proliferation, an increase in numbers of cells with cell-cycle exit, and premature neurogenesis. These effects may be mediated by NUMB, to which expression was observed enriched in the apical region of neural rosettes after FGF2 signaling inhibition coinciding with the disappearance of PAX6(+)/Ki67(+) neural stem cells and the emergence of MAP2(+) neurons. Moreover, our results suggested that the hESC-based developmental system reserved a similar neural stem cell niche in vivo.

  17. Classification of Communication Signals and Detection of Unknown Formats Using Artificial Neural Networks

    DTIC Science & Technology

    2006-12-01

    Using Artificial Neural Networks Alexander Iversen, Nicholas K. Taylor and Keith E. Brown Intelligent Systems Laboratory Heriot-Watt University...Brown, K.E. (2006) Classification of Communication Signals and Detection of Unknown Formats Using Artificial Neural Networks . In Military...Classification of Communication Signals and Detection of Unknown Formats Using Artificial Neural Networks 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM

  18. Signal transduction of the physical environment in the neural differentiation of stem cells

    PubMed Central

    Thompson, Ryan; Chan, Christina

    2016-01-01

    Neural differentiation is largely dependent on extracellular signals within the cell microenvironment. These extracellular signals are mainly in the form of soluble factors that activate intracellular signaling cascades that drive changes in the cell nucleus. However, it is becoming increasingly apparent that the physical microenvironment provides signals that can also influence lineage commitment and very low modulus surfaces has been repeatedly demonstrated to promote neurogenesis. The molecular mechanisms governing mechano-induced neural differentiation are still largely uncharacterized; however, a growing body of evidence indicates that physical stimuli can regulate known signaling cascades and transcription factors involved in neural differentiation. Understanding how the physical environment affects neural differentiation at the molecular level will enable research and design of materials that will eventually enhance neural stem cell (NSC) differentiation, homogeneity and specificity. PMID:27785459

  19. Neural network classification of myoelectric signal for prosthesis control.

    PubMed

    Kelly, M F; Parker, P A; Scott, R N

    1991-12-01

    An alternate approach to deriving control for multidegree of freedom prosthetic arms is considered. By analyzing a single-channel myoelectric signal (MES), we can extract information that can be used to identify different contraction patterns in the upper arm. These contraction patterns are generated by subjects without previous training and are naturally associated with specific functions. Using a set of normalized MES spectral features, we can identify contraction patterns for four arm functions, specifically extension and flexion of the elbow and pronation and supination of the forearm. Performing identification independent of signal power is advantageous because this can then be used as a means for deriving proportional rate control for a prosthesis. An artificial neural network implementation is applied in the classification task. By using three single-layer perceptron networks, the MES is classified, with the spectral representations as input features. Trials performed on five subjects with normal limbs resulted in an average classification performance level of 85% for the four functions.

  20. Slit/Robo1 signaling regulates neural tube development by balancing neuroepithelial cell proliferation and differentiation

    SciTech Connect

    Wang, Guang; Li, Yan; Wang, Xiao-yu; Han, Zhe; Chuai, Manli; Wang, Li-jing; Ho Lee, Kenneth Ka; Geng, Jian-guo; Yang, Xuesong

    2013-05-01

    Formation of the neural tube is the morphological hallmark for development of the embryonic central nervous system (CNS). Therefore, neural tube development is a crucial step in the neurulation process. Slit/Robo signaling was initially identified as a chemo-repellent that regulated axon growth cone elongation, but its role in controlling neural tube development is currently unknown. To address this issue, we investigated Slit/Robo1 signaling in the development of chick neCollege of Life Sciences Biocentre, University of Dundee, Dundee DD1 5EH, UKural tube and transgenic mice over-expressing Slit2. We disrupted Slit/Robo1 signaling by injecting R5 monoclonal antibodies into HH10 neural tubes to block the Robo1 receptor. This inhibited the normal development of the ventral body curvature and caused the spinal cord to curl up into a S-shape. Next, Slit/Robo1 signaling on one half-side of the chick embryo neural tube was disturbed by electroporation in ovo. We found that the morphology of the neural tube was dramatically abnormal after we interfered with Slit/Robo1 signaling. Furthermore, we established that silencing Robo1 inhibited cell proliferation while over-expressing Robo1 enhanced cell proliferation. We also investigated the effects of altering Slit/Robo1 expression on Sonic Hedgehog (Shh) and Pax7 expression in the developing neural tube. We demonstrated that over-expressing Robo1 down-regulated Shh expression in the ventral neural tube and resulted in the production of fewer HNK-1{sup +} migrating neural crest cells (NCCs). In addition, Robo1 over-expression enhanced Pax7 expression in the dorsal neural tube and increased the number of Slug{sup +} pre-migratory NCCs. Conversely, silencing Robo1 expression resulted in an enhanced Shh expression and more HNK-1{sup +} migrating NCCs but reduced Pax7 expression and fewer Slug{sup +} pre-migratory NCCs were observed. In conclusion, we propose that Slit/Robo1 signaling is involved in regulating neural tube

  1. Neural Signaling of Food Healthiness Associated with Emotion Processing

    PubMed Central

    Herwig, Uwe; Dhum, Matthias; Hittmeyer, Anna; Opialla, Sarah; Scherpiet, Sigrid; Keller, Carmen; Brühl, Annette B.; Siegrist, Michael

    2016-01-01

    The ability to differentiate healthy from unhealthy foods is important in order to promote good health. Food, however, may have an emotional connotation, which could be inversely related to healthiness. The neurobiological background of differentiating healthy and unhealthy food and its relations to emotion processing are not yet well understood. We addressed the neural activations, particularly considering the single subject level, when one evaluates a food item to be of a higher, compared to a lower grade of healthiness with a particular view on emotion processing brain regions. Thirty-seven healthy subjects underwent functional magnetic resonance imaging while evaluating the healthiness of food presented as photographs with a subsequent rating on a visual analog scale. We compared individual evaluations of high and low healthiness of food items and also considered gender differences. We found increased activation when food was evaluated to be healthy in the left dorsolateral prefrontal cortex and precuneus in whole brain analyses. In ROI analyses, perceived and rated higher healthiness was associated with lower amygdala activity and higher ventral striatal and orbitofrontal cortex activity. Females exerted a higher activation in midbrain areas when rating food items as being healthy. Our results underline the close relationship between food and emotion processing, which makes sense considering evolutionary aspects. Actively evaluating and deciding whether food is healthy is accompanied by neural signaling associated with reward and self-relevance, which could promote salutary nutrition behavior. The involved brain regions may be amenable to mechanisms of emotion regulation in the context of psychotherapeutic regulation of food intake. PMID:26903859

  2. Neural timing signal for precise tactile timing judgments

    PubMed Central

    Watanabe, Junji; Nishida, Shin'ya

    2016-01-01

    The brain can precisely encode the temporal relationship between tactile inputs. While behavioural studies have demonstrated precise interfinger temporal judgments, the underlying neural mechanism remains unknown. Computationally, two kinds of neural responses can act as the information source. One is the phase-locked response to the phase of relatively slow inputs, and the other is the response to the amplitude change of relatively fast inputs. To isolate the contributions of these components, we measured performance of a synchrony judgment task for sine wave and amplitude-modulation (AM) wave stimuli. The sine wave stimulus was a low-frequency sinusoid, with the phase shifted in the asynchronous stimulus. The AM wave stimulus was a low-frequency sinusoidal AM of a 250-Hz carrier, with only the envelope shifted in the asynchronous stimulus. In the experiment, three stimulus pairs, two synchronous ones and one asynchronous one, were sequentially presented to neighboring fingers, and participants were asked to report which one was the asynchronous pair. We found that the asynchrony of AM waves could be detected as precisely as single impulse pair, with the threshold asynchrony being ∼20 ms. On the other hand, the asynchrony of sine waves could not be detected at all in the range from 5 to 30 Hz. Our results suggest that the timing signal for tactile judgments is provided not by the stimulus phase information but by the envelope of the response of the high-frequency-sensitive Pacini channel (PC), although they do not exclude a possible contribution of the envelope of non-PCs. PMID:26843600

  3. Neural responses in songbird forebrain reflect learning rates, acquired salience, and stimulus novelty after auditory discrimination training.

    PubMed

    Bell, Brittany A; Phan, Mimi L; Vicario, David S

    2015-03-01

    How do social interactions form and modulate the neural representations of specific complex signals? This question can be addressed in the songbird auditory system. Like humans, songbirds learn to vocalize by imitating tutors heard during development. These learned vocalizations are important in reproductive and social interactions and in individual recognition. As a model for the social reinforcement of particular songs, male zebra finches were trained to peck for a food reward in response to one song stimulus (GO) and to withhold responding for another (NoGO). After performance reached criterion, single and multiunit neural responses to both trained and novel stimuli were obtained from multiple electrodes inserted bilaterally into two songbird auditory processing areas [caudomedial mesopallium (CMM) and caudomedial nidopallium (NCM)] of awake, restrained birds. Neurons in these areas undergo stimulus-specific adaptation to repeated song stimuli, and responses to familiar stimuli adapt more slowly than to novel stimuli. The results show that auditory responses differed in NCM and CMM for trained (GO and NoGO) stimuli vs. novel song stimuli. When subjects were grouped by the number of training days required to reach criterion, fast learners showed larger neural responses and faster stimulus-specific adaptation to all stimuli than slow learners in both areas. Furthermore, responses in NCM of fast learners were more strongly left-lateralized than in slow learners. Thus auditory responses in these sensory areas not only encode stimulus familiarity, but also reflect behavioral reinforcement in our paradigm, and can potentially be modulated by social interactions.

  4. Tbx2 regulates anterior neural specification by repressing FGF signaling pathway.

    PubMed

    Cho, Gun-Sik; Park, Dong-Seok; Choi, Sun-Cheol; Han, Jin-Kwan

    2017-01-15

    During early embryogenesis, FGF signals regulate the antero-posterior (AP) patterning of the neural plate by promoting posterior cell fates. In particular, BMP signal-mediated attenuation of FGF pathway plays a critical role in the determination of the anterior neural region. Here we show that Tbx2, a T-box transcriptional repressor regulates anterior neural specification by suppressing FGF8 signaling pathway in Xenopus embryo. Tbx2 is expressed in the anterior edge of the neural plate in early neurulae. Overexpression and knockdown of Tbx2 induce expansion and reduction in the expression of anterior neural markers, respectively. It also suppresses FGF8-induced ERK phosphorylation and neural caudalization. Tbx2, which is a target gene of BMP signal, down-regulates FGF8 signaling by inhibiting the expression of Flrt3, a positive regulator of this pathway. We found that Tbx2 binds directly to the T-box element located in the promoter region of Flrt3 gene, thereby interfering with the activity of the promoter. Consistently, Tbx2 augmentation of anterior neural formation is inhibited by co-expression of Flrt3. Furthermore, disruption of the anterior-most structures such as eyes in Tbx2-depleted embryos can be rescued by inhibition of Flrt3 function or FGF signaling. Taken together, our results suggest that Tbx2 mediates BMP signal to down-regulate FGF signaling pathway by repressing Flrt3 expression for anterior tissue formation.

  5. Signal processing using artificial neural network for BOTDA sensor system.

    PubMed

    Azad, Abul Kalam; Wang, Liang; Guo, Nan; Tam, Hwa-Yaw; Lu, Chao

    2016-03-21

    We experimentally demonstrate the use of artificial neural network (ANN) to process sensing signals obtained from Brillouin optical time domain analyzer (BOTDA). The distributed temperature information is extracted directly from the local Brillouin gain spectra (BGSs) along the fiber under test without the process of determination of Brillouin frequency shift (BFS) and hence conversion from BFS to temperature. Unlike our previous work for short sensing distance where ANN is trained by measured BGSs, here we employ ideal BGSs with different linewidths to train the ANN in order to take the linewidth variation due to different conditions from the training and testing phases into account, making it feasible for long distance sensing. Moreover, the performance of ANN is compared with other two techniques, Lorentzian curve fitting and cross-correlation method, and our results show that ANN has higher accuracy and larger tolerance to measurement error, especially at large frequency scanning step. We also show that the temperature extraction from BOTDA measurements employing ANN is significantly faster than the other two approaches. Hence ANN can be an excellent alternative tool to process BGSs measured by BOTDA and obtain temperature distribution along the fiber, especially when large frequency scanning step is adopted to significantly reduce the measurement time but without sacrifice of sensing accuracy.

  6. Is Salicylic Acid a Translocated Signal of Systemic Acquired Resistance in Tobacco?

    PubMed Central

    Shulaev, V.; Leon, J.; Raskin, I.

    1995-01-01

    Salicylic acid (SA) is a likely endogenous signal in the development of systemic acquired resistance (SAR) in some dicotyledonous plants. In tobacco mosaic virus (TMV)-resistant Xanthi-nc tobacco, SA levels increase systemically following the inoculation of a single leaf with TMV. To determine the extent to which systemic increases in SA result from SA export from the inoculated leaf, SA produced in TMV-inoculated or healthy leaves was noninvasively labeled with 18O2. Spatial and temporal distribution of 18O-SA indicated that most of the SA detected in the healthy tissues was synthesized in the inoculated leaf. No significant increase in the activity of benzoic acid 2-hydroxylase, the last enzyme involved in SA biosynthesis, was detected in upper uninoculated leaves, although the basal level of enzyme activity was relatively high. No increases in SA level, pathogenesis-related PR-1 gene expression, or TMV resistance in the upper uninoculated leaf were observed if the TMV-inoculated leaf was detached up to 60 hr after inoculation. Apart from the inoculated tissues, the highest increase in SA was observed in the leaf located directly above the inoculated leaf. The systemic SA increase observed during SAR may be explained by phloem transport of SA from the inoculation sites. PMID:12242358

  7. Microelectronic neural bridge for signal regeneration and function rebuilding over two separate nerves

    NASA Astrophysics Data System (ADS)

    Xiaoyan, Shen; Zhigong, Wang; Xiaoying, Lü; Shushan, Xie; Zonghao, Huang

    2011-06-01

    According to the feature of neural signals, a micro-electronic neural bridge (MENB) has been designed. It consists of two electrode arrays for neural signal detection and functional electrical stimulation (FES), and a microelectronic circuit for signal amplifying, processing, and FES driving. The core of the system is realized in 0.5-μm CMOS technology and used in animal experiments. A special experimental strategy has been designed to demonstrate the feasibility of the system. With the help of the MENB, the withdrawal reflex function of the left/right leg of one spinal toad has been rebuilt in the corresponding leg of another spinal toad. According to the coherence analysis between the source and regenerated neural signals, the controlled spinal toad's sciatic nerve signal is delayed by 0.72 ms in relation to the sciatic nerve signal of the source spinal toad and the cross-correlation function reaches a value of 0.73. This shows that the regenerated signal is correlated with the source sciatic signal significantly and the neural activities involved in reflex function have been regenerated. The experiment demonstrates that the MENB is useful in rebuilding the neural function between nerves of different bodies.

  8. Wireless instrumentation system based on dry electrodes for acquiring EEG signals.

    PubMed

    Dias, Nuno Sérgio; Carmo, João Paulo; Mendes, Paulo Mateus; Correia, José Higino

    2012-09-01

    This paper presents a complete non-invasive Wireless acquisition system based on dry electrodes for electroencephalograms (WiDE-EEG) with emphasis in the electronic system design. The WiDE-EEG is composed by a 2.4 GHz radio-frequency (RF) transceiver, biopotential acquisition electronics and dry electrodes. The WiDE-EEG can acquire electroencephalogram (EEG) signals from 5 unipolar channels, with a resolution of 16 bits and minimum analog amplitude of 9.98 μV(pp), at a sampling rate of 1000 samples/s/channel and sends them to a processing unit through RF in a 10 m range. The analog channels were optimized for EEG signals (with amplitudes in the range 70-100 μV) and present the following characteristics: a signal gain of 66 dB and a common mode rejection ratio of 56.5 dB. Each electrode is composed by 16 microtip structures that were fabricated through bulk micromachining of a <100>-type silicon substrate in a potassium hydroxide (KOH) solution. The microtips present solid angles of 54.7°, a height of 100-200 μm and 2 μm spaced apart. The electrodes have a thin layer (obtained by sputtering) of iridium oxide (IrO) to guaranty their biocompatibility and improve the contact with the skin. These dry electrodes are in direct contact with the electrolyte fluids of the inner skin layers, and avoid the use of conductive gels. The complete WiDE-EEG occupies a volume of 9 cm×8.5 cm×1 cm, which makes it suitable for true mobility of the subjects and at the same time allows high data transfer rates. Since the WiDE-EEG is battery-powered, it overcomes the need of galvanic isolation for ensuring patient safety observed on conventional EEG instrumentation systems. The WiDE-EEG presents a total power consumption of 107 mW, divided as follows: the acquisition system contributes with 10 mW per channel, whereas the commercial MICAz module contributes with 57 mW (e.g., 24 mW from the microcontroller and 33 mW from the RF chip). The WiDE-EEG also presents autonomy of about 25 h

  9. The neural subjective frame: from bodily signals to perceptual consciousness.

    PubMed

    Park, Hyeong-Dong; Tallon-Baudry, Catherine

    2014-05-05

    The report 'I saw the stimulus' operationally defines visual consciousness, but where does the 'I' come from? To account for the subjective dimension of perceptual experience, we introduce the concept of the neural subjective frame. The neural subjective frame would be based on the constantly updated neural maps of the internal state of the body and constitute a neural referential from which first person experience can be created. We propose to root the neural subjective frame in the neural representation of visceral information which is transmitted through multiple anatomical pathways to a number of target sites, including posterior insula, ventral anterior cingulate cortex, amygdala and somatosensory cortex. We review existing experimental evidence showing that the processing of external stimuli can interact with visceral function. The neural subjective frame is a low-level building block of subjective experience which is not explicitly experienced by itself which is necessary but not sufficient for perceptual experience. It could also underlie other types of subjective experiences such as self-consciousness and emotional feelings. Because the neural subjective frame is tightly linked to homeostatic regulations involved in vigilance, it could also make a link between state and content consciousness.

  10. Application of Neural Networks to Seismic Signal Discrimination Research Findings

    DTIC Science & Technology

    1994-04-11

    waveforms, and the training and testing of neural networks for seismic event classification. It was necessary to utilize seismic events that had a high...degree of reliability for accurate training of the neural networks . The seismic waveforms were obtained from the Center for Seismic Studies and were

  11. Bayesian model of signal rewiring reveals mechanisms of gene dysregulation in acquired drug resistance in breast cancer

    PubMed Central

    Azad, A. K. M.; Keith, Jonathan M.

    2017-01-01

    Small molecule inhibitors, such as lapatinib, are effective against breast cancer in clinical trials, but tumor cells ultimately acquire resistance to the drug. Maintaining sensitization to drug action is essential for durable growth inhibition. Recently, adaptive reprogramming of signaling circuitry has been identified as a major cause of acquired resistance. We developed a computational framework using a Bayesian statistical approach to model signal rewiring in acquired resistance. We used the p1-model to infer potential aberrant gene-pairs with differential posterior probabilities of appearing in resistant-vs-parental networks. Results were obtained using matched gene expression profiles under resistant and parental conditions. Using two lapatinib-treated ErbB2-positive breast cancer cell-lines: SKBR3 and BT474, our method identified similar dysregulated signaling pathways including EGFR-related pathways as well as other receptor-related pathways, many of which were reported previously as compensatory pathways of EGFR-inhibition via signaling cross-talk. A manual literature survey provided strong evidence that aberrant signaling activities in dysregulated pathways are closely related to acquired resistance in EGFR tyrosine kinase inhibitors. Our approach predicted literature-supported dysregulated pathways complementary to both node-centric (SPIA, DAVID, and GATHER) and edge-centric (ESEA and PAGI) methods. Moreover, by proposing a novel pattern of aberrant signaling called V-structures, we observed that genes were dysregulated in resistant-vs-sensitive conditions when they were involved in the switch of dependencies from targeted to bypass signaling events. A literature survey of some important V-structures suggested they play a role in breast cancer metastasis and/or acquired resistance to EGFR-TKIs, where the mRNA changes of TGFBR2, LEF1 and TP53 in resistant-vs-sensitive conditions were related to the dependency switch from targeted to bypass signaling links

  12. Bayesian model of signal rewiring reveals mechanisms of gene dysregulation in acquired drug resistance in breast cancer.

    PubMed

    Azad, A K M; Lawen, Alfons; Keith, Jonathan M

    2017-01-01

    Small molecule inhibitors, such as lapatinib, are effective against breast cancer in clinical trials, but tumor cells ultimately acquire resistance to the drug. Maintaining sensitization to drug action is essential for durable growth inhibition. Recently, adaptive reprogramming of signaling circuitry has been identified as a major cause of acquired resistance. We developed a computational framework using a Bayesian statistical approach to model signal rewiring in acquired resistance. We used the p1-model to infer potential aberrant gene-pairs with differential posterior probabilities of appearing in resistant-vs-parental networks. Results were obtained using matched gene expression profiles under resistant and parental conditions. Using two lapatinib-treated ErbB2-positive breast cancer cell-lines: SKBR3 and BT474, our method identified similar dysregulated signaling pathways including EGFR-related pathways as well as other receptor-related pathways, many of which were reported previously as compensatory pathways of EGFR-inhibition via signaling cross-talk. A manual literature survey provided strong evidence that aberrant signaling activities in dysregulated pathways are closely related to acquired resistance in EGFR tyrosine kinase inhibitors. Our approach predicted literature-supported dysregulated pathways complementary to both node-centric (SPIA, DAVID, and GATHER) and edge-centric (ESEA and PAGI) methods. Moreover, by proposing a novel pattern of aberrant signaling called V-structures, we observed that genes were dysregulated in resistant-vs-sensitive conditions when they were involved in the switch of dependencies from targeted to bypass signaling events. A literature survey of some important V-structures suggested they play a role in breast cancer metastasis and/or acquired resistance to EGFR-TKIs, where the mRNA changes of TGFBR2, LEF1 and TP53 in resistant-vs-sensitive conditions were related to the dependency switch from targeted to bypass signaling links

  13. [Principles of design of neural-network analog-to-digital converters of bioelectric signals].

    PubMed

    Loktiukhin, V N; Chelebaev, S V

    2007-01-01

    A design principle and a procedure for synthesis of neural-network analog-to-digital converters of bioelectric signals are suggested. An example of implementation of an FPGA-based neural-network converter for classification of bioparameters is presented.

  14. The neural basis of the blood-oxygen-level-dependent functional magnetic resonance imaging signal.

    PubMed Central

    Logothetis, Nikos K

    2002-01-01

    Magnetic resonance imaging (MRI) has rapidly become an important tool in clinical medicine and biological research. Its functional variant (functional magnetic resonance imaging; fMRI) is currently the most widely used method for brain mapping and studying the neural basis of human cognition. While the method is widespread, there is insufficient knowledge of the physiological basis of the fMRI signal to interpret the data confidently with respect to neural activity. This paper reviews the basic principles of MRI and fMRI, and subsequently discusses in some detail the relationship between the blood-oxygen-level-dependent (BOLD) fMRI signal and the neural activity elicited during sensory stimulation. To examine this relationship, we conducted the first simultaneous intracortical recordings of neural signals and BOLD responses. Depending on the temporal characteristics of the stimulus, a moderate to strong correlation was found between the neural activity measured with microelectrodes and the BOLD signal averaged over a small area around the microelectrode tips. However, the BOLD signal had significantly higher variability than the neural activity, indicating that human fMRI combined with traditional statistical methods underestimates the reliability of the neuronal activity. To understand the relative contribution of several types of neuronal signals to the haemodynamic response, we compared local field potentials (LFPs), single- and multi-unit activity (MUA) with high spatio-temporal fMRI responses recorded simultaneously in monkey visual cortex. At recording sites characterized by transient responses, only the LFP signal was significantly correlated with the haemodynamic response. Furthermore, the LFPs had the largest magnitude signal and linear systems analysis showed that the LFPs were better than the MUAs at predicting the fMRI responses. These findings, together with an analysis of the neural signals, indicate that the BOLD signal primarily measures the input

  15. Paracrine sonic hedgehog signaling contributes significantly to acquired steroidogenesis in the prostate tumor microenvironment.

    PubMed

    Lubik, Amy A; Nouri, Mannan; Truong, Sarah; Ghaffari, Mazyar; Adomat, Hans H; Corey, Eva; Cox, Michael E; Li, Na; Guns, Emma S; Yenki, Parvin; Pham, Steven; Buttyan, Ralph

    2017-01-15

    Despite the substantial benefit of androgen deprivation therapy (ADT) for metastatic prostate cancer, patients often progress to castration-resistant disease (CRPC) that is more difficult to treat. CRPC is associated with renewed androgen receptor activity in tumor cells and restoration of tumor androgen levels through acquired intratumoral steroidogenesis (AIS). Although prostate cancer (PCa) cells have been shown to have steroidogenic capability in vitro, we previously found that benign prostate stromal cells (PrSCs) can also synthesize testosterone (T) from an adrenal precursor, DHEA, when stimulated with a hedgehog (Hh) pathway agonist, SAG. Here, we show exposure of PrSCs to a different Smoothened (Smo) agonist, Ag1.5, or to conditioned medium from sonic hedgehog overexpressing LNCaP cells induces steroidogenic enzyme expression in PrSCs and significantly increases production of T and its precursor steroids in a Smo-dependent manner from 22-OH-cholesterol substrate. Hh agonist-/ligand-treated PrSCs produced androgens at a rate similar to or greater than that of PCa cell lines. Likewise, primary bone marrow stromal cells became more steroidogenic and produced T under the influence of Smo agonist. Treatment of mice bearing LNCaP xenografts with a Smo antagonist, TAK-441, delayed the onset of CRPC after castration and substantially reduced androgen levels in residual tumors. These outcomes support the idea that stromal cells in ADT-treated primary or metastatic prostate tumors can contribute to AIS as a consequence of a paracrine Hh signaling microenvironment. As such, Smo antagonists may be useful for targeting prostate tumor stromal cell-derived AIS and delaying the onset of CRPC after ADT.

  16. Dangerous mating systems: signal complexity, signal content and neural capacity in spiders.

    PubMed

    Herberstein, M E; Wignall, A E; Hebets, E A; Schneider, J M

    2014-10-01

    Spiders are highly efficient predators in possession of exquisite sensory capacities for ambushing prey, combined with machinery for launching rapid and determined attacks. As a consequence, any sexually motivated approach carries a risk of ending up as prey rather than as a mate. Sexual selection has shaped courtship to effectively communicate the presence, identity, motivation and/or quality of potential mates, which help ameliorate these risks. Spiders communicate this information via several sensory channels, including mechanical (e.g. vibrational), visual and/or chemical, with examples of multimodal signalling beginning to emerge in the literature. The diverse environments that spiders inhabit have further shaped courtship content and form. While our understanding of spider neurobiology remains in its infancy, recent studies are highlighting the unique and considerable capacities of spiders to process and respond to complex sexual signals. As a result, the dangerous mating systems of spiders are providing important insights into how ecology shapes the evolution of communication systems, with future work offering the potential to link this complex communication with its neural processes.

  17. Neural retina identity is specified by lens-derived BMP signals.

    PubMed

    Pandit, Tanushree; Jidigam, Vijay K; Patthey, Cedric; Gunhaga, Lena

    2015-05-15

    The eye has served as a classical model to study cell specification and tissue induction for over a century. Nevertheless, the molecular mechanisms that regulate the induction and maintenance of eye-field cells, and the specification of neural retina cells are poorly understood. Moreover, within the developing anterior forebrain, how prospective eye and telencephalic cells are differentially specified is not well defined. In the present study, we have analyzed these issues by manipulating signaling pathways in intact chick embryo and explant assays. Our results provide evidence that at blastula stages, BMP signals inhibit the acquisition of eye-field character, but from neural tube/optic vesicle stages, BMP signals from the lens are crucial for the maintenance of eye-field character, inhibition of dorsal telencephalic cell identity and specification of neural retina cells. Subsequently, our results provide evidence that a Rax2-positive eye-field state is not sufficient for the progress to a neural retina identity, but requires BMP signals. In addition, our results argue against any essential role of Wnt or FGF signals during the specification of neural retina cells, but provide evidence that Wnt signals together with BMP activity are sufficient to induce cells of retinal pigment epithelial character. We conclude that BMP activity emanating from the lens ectoderm maintains eye-field identity, inhibits telencephalic character and induces neural retina cells. Our findings link the requirement of the lens ectoderm for neural retina specification with the molecular mechanism by which cells in the forebrain become specified as neural retina by BMP activity.

  18. Effects of social sustainability signaling on neural valuation signals and taste-experience of food products.

    PubMed

    Enax, Laura; Krapp, Vanessa; Piehl, Alexandra; Weber, Bernd

    2015-01-01

    Value-based decision making occurs when individuals choose between different alternatives and place a value on each alternative and its attributes. Marketing actions frequently manipulate product attributes, by adding, e.g., health claims on the packaging. A previous imaging study found that an emblem for organic products increased willingness to pay (WTP) and activity in the ventral striatum (VS). The current study investigated neural and behavioral processes underlying the influence of Fair Trade (FT) labeling on food valuation and choice. Sustainability is an important product attribute for many consumers, with FT signals being one way to highlight ethically sustainable production. Forty participants valuated products in combination with an FT emblem or no emblem and stated their WTP in a bidding task while in an MRI scanner. After that, participants tasted-objectively identical-chocolates, presented either as "FT" or as "conventionally produced". In the fMRI task, WTP was significantly higher for FT products. FT labeling increased activity in regions important for reward-processing and salience, that is, in the VS, anterior and posterior cingulate, as well as superior frontal gyrus. Subjective value, that is, WTP was correlated with activity in the ventromedial prefrontal cortex (vmPFC). We find that the anterior cingulate, VS and superior frontal gyrus exhibit task-related increases in functional connectivity to the vmPFC when an FT product was evaluated. Effective connectivity analyses revealed a highly probable directed modulation of the vmPFC by those three regions, suggesting a network which alters valuation processes. We also found a significant taste-placebo effect, with higher experienced taste pleasantness and intensity for FT labeled chocolates. Our results reveal a possible neural mechanism underlying valuation processes of certified food products. The results are important in light of understanding current marketing trends as well as designing

  19. Effects of social sustainability signaling on neural valuation signals and taste-experience of food products

    PubMed Central

    Enax, Laura; Krapp, Vanessa; Piehl, Alexandra; Weber, Bernd

    2015-01-01

    Value-based decision making occurs when individuals choose between different alternatives and place a value on each alternative and its attributes. Marketing actions frequently manipulate product attributes, by adding, e.g., health claims on the packaging. A previous imaging study found that an emblem for organic products increased willingness to pay (WTP) and activity in the ventral striatum (VS). The current study investigated neural and behavioral processes underlying the influence of Fair Trade (FT) labeling on food valuation and choice. Sustainability is an important product attribute for many consumers, with FT signals being one way to highlight ethically sustainable production. Forty participants valuated products in combination with an FT emblem or no emblem and stated their WTP in a bidding task while in an MRI scanner. After that, participants tasted—objectively identical—chocolates, presented either as “FT” or as “conventionally produced”. In the fMRI task, WTP was significantly higher for FT products. FT labeling increased activity in regions important for reward-processing and salience, that is, in the VS, anterior and posterior cingulate, as well as superior frontal gyrus. Subjective value, that is, WTP was correlated with activity in the ventromedial prefrontal cortex (vmPFC). We find that the anterior cingulate, VS and superior frontal gyrus exhibit task-related increases in functional connectivity to the vmPFC when an FT product was evaluated. Effective connectivity analyses revealed a highly probable directed modulation of the vmPFC by those three regions, suggesting a network which alters valuation processes. We also found a significant taste-placebo effect, with higher experienced taste pleasantness and intensity for FT labeled chocolates. Our results reveal a possible neural mechanism underlying valuation processes of certified food products. The results are important in light of understanding current marketing trends as well as

  20. G-protein-coupled receptor signaling and neural tube closure defects.

    PubMed

    Shimada, Issei S; Mukhopadhyay, Saikat

    2017-01-30

    Disruption of the normal mechanisms that mediate neural tube closure can result in neural tube defects (NTDs) with devastating consequences in affected patients. With the advent of next-generation sequencing, we are increasingly detecting mutations in multiple genes in NTD cases. However, our ability to determine which of these genes contribute to the malformation is limited by our understanding of the pathways controlling neural tube closure. G-protein-coupled receptors (GPCRs) comprise the largest family of transmembrane receptors in humans and have been historically favored as drug targets. Recent studies implicate several GPCRs and downstream signaling pathways in neural tube development and closure. In this review, we will discuss our current understanding of GPCR signaling pathways in pathogenesis of NTDs. Notable examples include the orphan primary cilia-localized GPCR, Gpr161 that regulates the basal suppression machinery of sonic hedgehog pathway by means of activation of cAMP-protein kinase A signaling in the neural tube, and protease-activated receptors that are activated by a local network of membrane-tethered proteases during neural tube closure involving the surface ectoderm. Understanding the role of these GPCR-regulated pathways in neural tube development and closure is essential toward identification of underlying genetic causes to prevent NTDs. Birth Defects Research 109:129-139, 2017. © 2016 Wiley Periodicals, Inc.

  1. Canonical Wnt signaling transiently stimulates proliferation and enhances neurogenesis in neonatal neural progenitor cultures

    SciTech Connect

    Hirsch, Cordula; Campano, Louise M.; Woehrle, Simon; Hecht, Andreas . E-mail: andreas.hecht@mol-med.uni-freiburg.de

    2007-02-01

    Canonical Wnt signaling triggers the formation of heterodimeric transcription factor complexes consisting of {beta}-catenin and T cell factors, and thereby controls the execution of specific genetic programs. During the expansion and neurogenic phases of embryonic neural development canonical Wnt signaling initially controls proliferation of neural progenitor cells, and later neuronal differentiation. Whether Wnt growth factors affect neural progenitor cells postnatally is not known. Therefore, we have analyzed the impact of Wnt signaling on neural progenitors isolated from cerebral cortices of newborn mice. Expression profiling of pathway components revealed that these cells are fully equipped to respond to Wnt signals. However, Wnt pathway activation affected only a subset of neonatal progenitors and elicited a limited increase in proliferation and neuronal differentiation in distinct subsets of cells. Moreover, Wnt pathway activation only transiently stimulated S-phase entry but did not support long-term proliferation of progenitor cultures. The dampened nature of the Wnt response correlates with the predominant expression of inhibitory pathway components and the rapid actuation of negative feedback mechanisms. Interestingly, in differentiating cell cultures activation of canonical Wnt signaling reduced Hes1 and Hes5 expression suggesting that during postnatal neural development, Wnt/{beta}-catenin signaling enhances neurogenesis from progenitor cells by interfering with Notch pathway activity.

  2. Neural signal processing and closed-loop control algorithm design for an implanted neural recording and stimulation system.

    PubMed

    Hamilton, Lei; McConley, Marc; Angermueller, Kai; Goldberg, David; Corba, Massimiliano; Kim, Louis; Moran, James; Parks, Philip D; Sang Chin; Widge, Alik S; Dougherty, Darin D; Eskandar, Emad N

    2015-08-01

    A fully autonomous intracranial device is built to continually record neural activities in different parts of the brain, process these sampled signals, decode features that correlate to behaviors and neuropsychiatric states, and use these features to deliver brain stimulation in a closed-loop fashion. In this paper, we describe the sampling and stimulation aspects of such a device. We first describe the signal processing algorithms of two unsupervised spike sorting methods. Next, we describe the LFP time-frequency analysis and feature derivation from the two spike sorting methods. Spike sorting includes a novel approach to constructing a dictionary learning algorithm in a Compressed Sensing (CS) framework. We present a joint prediction scheme to determine the class of neural spikes in the dictionary learning framework; and, the second approach is a modified OSort algorithm which is implemented in a distributed system optimized for power efficiency. Furthermore, sorted spikes and time-frequency analysis of LFP signals can be used to generate derived features (including cross-frequency coupling, spike-field coupling). We then show how these derived features can be used in the design and development of novel decode and closed-loop control algorithms that are optimized to apply deep brain stimulation based on a patient's neuropsychiatric state. For the control algorithm, we define the state vector as representative of a patient's impulsivity, avoidance, inhibition, etc. Controller parameters are optimized to apply stimulation based on the state vector's current state as well as its historical values. The overall algorithm and software design for our implantable neural recording and stimulation system uses an innovative, adaptable, and reprogrammable architecture that enables advancement of the state-of-the-art in closed-loop neural control while also meeting the challenges of system power constraints and concurrent development with ongoing scientific research designed

  3. A portable system for acquiring and removing motion artefact from ECG signals

    NASA Astrophysics Data System (ADS)

    Griffiths, A.; Das, A.; Fernandes, B.; Gaydecki, P.

    2007-07-01

    A novel electrocardiograph (ECG) signal acquisition and display system is under development. It is designed for patients ranging from the elderly to athletes. The signals are obtained from electrodes integrated into a vest, amplified, digitally processed and transmitted via Bluetooth to a PC with a Labview ® interface. Digital signal processing is performed to remove movement artefact and electromyographic (EMG) noise, which severely distorts signal morphology and complicates clinical diagnosis. Independent component analysis (ICA) is also used to improve the signal quality. The complete system will integrate the electronics into a single module which will be embedded in the vest.

  4. Uncoupling High Light Responses from Singlet Oxygen Retrograde Signaling and Spatial-Temporal Systemic Acquired Acclimation1[OPEN

    PubMed Central

    Gordon, Matthew; Havaux, Michel; Albrecht-Borth, Verónica

    2016-01-01

    Distinct ROS signaling pathways initiated by singlet oxygen (1O2) or superoxide and hydrogen peroxide have been attributed to either cell death or acclimation, respectively. Recent studies have revealed that more complex antagonistic and synergistic relationships exist within and between these pathways. As specific chloroplastic ROS signals are difficult to study, rapid systemic signaling experiments using localized high light (HL) stress or ROS treatments were used in this study to uncouple signals required for direct HL and ROS perception and distal systemic acquired acclimation (SAA). A qPCR approach was chosen to determine local perception and distal signal reception. Analysis of a thylakoidal ascorbate peroxidase mutant (tapx), the 1O2-retrograde signaling double mutant (ex1/ex2), and an apoplastic signaling double mutant (rbohD/F) revealed that tAPX and EXECUTER 1 are required for both HL and systemic acclimation stress perception. Apoplastic membrane-localized RBOHs were required for systemic spread of the signal but not for local signal induction in directly stressed tissues. Endogenous ROS treatments revealed a very strong systemic response induced by a localized 1 h induction of 1O2 using the conditional flu mutant. A qPCR time course of 1O2 induced systemic marker genes in directly and indirectly connected leaves revealed a direct vascular connection component of both immediate and longer term SAA signaling responses. These results reveal the importance of an EXECUTER-dependent 1O2 retrograde signal for both local and long distance RBOH-dependent acclimation signaling that is distinct from other HL signaling pathways, and that direct vascular connections have a role in spatial-temporal SAA induction. PMID:27288360

  5. Slit/Robo1 signaling regulates neural tube development by balancing neuroepithelial cell proliferation and differentiation.

    PubMed

    Wang, Guang; Li, Yan; Wang, Xiao-yu; Han, Zhe; Chuai, Manli; Wang, Li-jing; Ho Lee, Kenneth Ka; Geng, Jian-guo; Yang, Xuesong

    2013-05-01

    Formation of the neural tube is the morphological hallmark for development of the embryonic central nervous system (CNS). Therefore, neural tube development is a crucial step in the neurulation process. Slit/Robo signaling was initially identified as a chemo-repellent that regulated axon growth cone elongation, but its role in controlling neural tube development is currently unknown. To address this issue, we investigated Slit/Robo1 signaling in the development of chick neCollege of Life Sciences Biocentre, University of Dundee, Dundee DD1 5EH, UKural tube and transgenic mice over-expressing Slit2. We disrupted Slit/Robo1 signaling by injecting R5 monoclonal antibodies into HH10 neural tubes to block the Robo1 receptor. This inhibited the normal development of the ventral body curvature and caused the spinal cord to curl up into a S-shape. Next, Slit/Robo1 signaling on one half-side of the chick embryo neural tube was disturbed by electroporation in ovo. We found that the morphology of the neural tube was dramatically abnormal after we interfered with Slit/Robo1 signaling. Furthermore, we established that silencing Robo1 inhibited cell proliferation while over-expressing Robo1 enhanced cell proliferation. We also investigated the effects of altering Slit/Robo1 expression on Sonic Hedgehog (Shh) and Pax7 expression in the developing neural tube. We demonstrated that over-expressing Robo1 down-regulated Shh expression in the ventral neural tube and resulted in the production of fewer HNK-1(+) migrating neural crest cells (NCCs). In addition, Robo1 over-expression enhanced Pax7 expression in the dorsal neural tube and increased the number of Slug(+) pre-migratory NCCs. Conversely, silencing Robo1 expression resulted in an enhanced Shh expression and more HNK-1(+) migrating NCCs but reduced Pax7 expression and fewer Slug(+) pre-migratory NCCs were observed. In conclusion, we propose that Slit/Robo1 signaling is involved in regulating neural tube development by tightly

  6. Neural network committees for finger joint angle estimation from surface EMG signals

    PubMed Central

    Shrirao, Nikhil A; Reddy, Narender P; Kosuri, Durga R

    2009-01-01

    Background In virtual reality (VR) systems, the user's finger and hand positions are sensed and used to control the virtual environments. Direct biocontrol of VR environments using surface electromyography (SEMG) signals may be more synergistic and unconstraining to the user. The purpose of the present investigation was to develop a technique to predict the finger joint angle from the surface EMG measurements of the extensor muscle using neural network models. Methodology SEMG together with the actual joint angle measurements were obtained while the subject was performing flexion-extension rotation of the index finger at three speeds. Several neural networks were trained to predict the joint angle from the parameters extracted from the SEMG signals. The best networks were selected to form six committees. The neural network committees were evaluated using data from new subjects. Results There was hysteresis in the measured SMEG signals during the flexion-extension cycle. However, neural network committees were able to predict the joint angle with reasonable accuracy. RMS errors ranged from 0.085 ± 0.036 for fast speed finger-extension to 0.147 ± 0.026 for slow speed finger extension, and from 0.098 ± 0.023 for the fast speed finger flexion to 0.163 ± 0.054 for slow speed finger flexion. Conclusion Although hysteresis was observed in the measured SEMG signals, the committees of neural networks were able to predict the finger joint angle from SEMG signals. PMID:19154615

  7. Purinergic signaling and human immunodeficiency virus/acquired immune deficiency syndrome: From viral entry to therapy.

    PubMed

    Passos, Daniela F; Schetinger, Maria Rosa C; Leal, Daniela Br

    2015-08-12

    Human immunodeficiency virus (HIV) infection is a serious condition associated to severe immune dysfunction and immunodeficiency. Mechanisms involved in HIV-associated immune activation, inflammation and loss of CD4+ T cells have been extensively studied, including those concerning purinergic signaling pathways. Purinergic signaling components are involved in viral entry and replication and disease progression. Research involving the participation of purinergic signaling in HIV infection has been not only important to elucidate disease mechanisms but also to introduce new approaches to therapy. The involvement of purinergic signaling in the pathogenesis of HIV infection and its implications in the control of the HIV infection are reviewed in this paper.

  8. A fully integrated mixed-signal neural processor for implantable multichannel cortical recording.

    PubMed

    Sodagar, Amir M; Wise, Kensall D; Najafi, Khalil

    2007-06-01

    A 64-channel neural processor has been developed for use in an implantable neural recording microsystem. In the Scan Mode, the processor is capable of detecting neural spikes by programmable positive, negative, or window thresholding. Spikes are tagged with their associated channel addresses and formed into 18-bit data words that are sent serially to the external host. In the Monitor Mode, two channels can be selected and viewed at high resolution for studies where the entire signal is of interest. The processor runs from a 3-V supply and a 2-MHz clock, with a channel scan rate of 64 kS/s and an output bit rate of 2 Mbps.

  9. Microbe-Induced Inflammatory Signals Triggering Acquired Bone Marrow Failure Syndromes

    PubMed Central

    Espinoza, J. Luis; Kotecha, Ritesh; Nakao, Shinji

    2017-01-01

    Acquired bone marrow failure syndromes encompass a unique set of disorders characterized by a reduction in the effective production of mature cells by the bone marrow (BM). In the majority of cases, these syndromes are the result of the immune-mediated destruction of hematopoietic stem cells or their progenitors at various stages of differentiation. Microbial infection has also been associated with hematopoietic stem cell injury and may lead to associated transient or persistent BM failure, and recent evidence has highlighted the potential impact of commensal microbes and their metabolites on hematopoiesis. We summarize the interactions between microorganisms and the host immune system and emphasize how they may impact the development of acquired BM failure. PMID:28286502

  10. Amphioxus SARM involved in neural development may function as a suppressor of TLR signaling.

    PubMed

    Yuan, Shaochun; Wu, Kui; Yang, Manyi; Xu, Liqun; Huang, Ling; Liu, Huiling; Tao, Xin; Huang, Shengfeng; Xu, Anlong

    2010-06-15

    Among five Toll/IL-1R resistance adaptors, sterile alpha and Toll/IL-1R resistance motif containing protein (SARM) is the only one conserved from Caenorhabditis elegans to human. However, its physiologic roles are hardly understood, and its involvement in TLR signaling remains debatable. In this study, we first demonstrated a predominant expression of amphioxus SARM (Branchiostoma belcheri tsingtauense SARM) in neural cells during embryogenesis and its predominant expression in the digestive system from larva to adult, suggesting its primitive role in neural development and a potential physiologic role in immunity. We further found that B. belcheri tsingtauense SARM was localized in mitochondria and could attenuate the TLR signaling via interacting with amphioxus MyD88 and tumor necrosis receptor associated factor 6. Thus, amphioxus SARM appears unique in that it may play dual functions in neural development and innate immunity by targeting amphioxus TLR signaling.

  11. SoxB1-driven transcriptional network underlies neural-specific interpretation of morphogen signals.

    PubMed

    Oosterveen, Tony; Kurdija, Sanja; Ensterö, Mats; Uhde, Christopher W; Bergsland, Maria; Sandberg, Magnus; Sandberg, Rickard; Muhr, Jonas; Ericson, Johan

    2013-04-30

    The reiterative deployment of a small cadre of morphogen signals underlies patterning and growth of most tissues during embyogenesis, but how such inductive events result in tissue-specific responses remains poorly understood. By characterizing cis-regulatory modules (CRMs) associated with genes regulated by Sonic hedgehog (Shh), retinoids, or bone morphogenetic proteins in the CNS, we provide evidence that the neural-specific interpretation of morphogen signaling reflects a direct integration of these pathways with SoxB1 proteins at the CRM level. Moreover, expression of SoxB1 proteins in the limb bud confers on mesodermal cells the potential to activate neural-specific target genes upon Shh, retinoid, or bone morphogenetic protein signaling, and the collocation of binding sites for SoxB1 and morphogen-mediatory transcription factors in CRMs faithfully predicts neural-specific gene activity. Thus, an unexpectedly simple transcriptional paradigm appears to conceptually explain the neural-specific interpretation of pleiotropic signaling during vertebrate development. Importantly, genes induced in a SoxB1-dependent manner appear to constitute repressive gene regulatory networks that are directly interlinked at the CRM level to constrain the regional expression of patterning genes. Accordingly, not only does the topology of SoxB1-driven gene regulatory networks provide a tissue-specific mode of gene activation, but it also determines the spatial expression pattern of target genes within the developing neural tube.

  12. ETOH inhibits embryonic neural stem/precursor cell proliferation via PLD signaling

    SciTech Connect

    Fujita, Yuko; Hiroyama, Masami; Sanbe, Atsushi Yamauchi, Junji; Murase, Shoko; Tanoue, Akito

    2008-05-23

    While a mother's excessive alcohol consumption during pregnancy is known to have adverse effects on fetal neural development, little is known about the underlying mechanism of these effects. In order to investigate these mechanisms, we investigated the toxic effect of ethanol (ETOH) on neural stem/precursor cell (NSC) proliferation. In cultures of NSCs, phospholipase D (PLD) is activated following stimulation with epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF2). Exposure of NSCs to ETOH suppresses cell proliferation, while it has no effect on cell death. Phosphatidic acid (PA), which is a signaling messenger produced by PLD, reverses ETOH inhibition of NSC proliferation. Blocking the PLD signal by 1-butanol suppresses the proliferation. ETOH-induced suppression of NSC proliferation and the protective effect of PA for ETOH-induced suppression are mediated through extracellular signal-regulated kinase signaling. These results indicate that exposure to ETOH impairs NSC proliferation by altering the PLD signaling pathway.

  13. ETOH inhibits embryonic neural stem/precursor cell proliferation via PLD signaling.

    PubMed

    Fujita, Yuko; Hiroyama, Masami; Sanbe, Atsushi; Yamauchi, Junji; Murase, Shoko; Tanoue, Akito

    2008-05-23

    While a mother's excessive alcohol consumption during pregnancy is known to have adverse effects on fetal neural development, little is known about the underlying mechanism of these effects. In order to investigate these mechanisms, we investigated the toxic effect of ethanol (ETOH) on neural stem/precursor cell (NSC) proliferation. In cultures of NSCs, phospholipase D (PLD) is activated following stimulation with epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF2). Exposure of NSCs to ETOH suppresses cell proliferation, while it has no effect on cell death. Phosphatidic acid (PA), which is a signaling messenger produced by PLD, reverses ETOH inhibition of NSC proliferation. Blocking the PLD signal by 1-butanol suppresses the proliferation. ETOH-induced suppression of NSC proliferation and the protective effect of PA for ETOH-induced suppression are mediated through extracellular signal-regulated kinase signaling. These results indicate that exposure to ETOH impairs NSC proliferation by altering the PLD signaling pathway.

  14. Dynamical system modeling via signal reduction and neural network simulation

    SciTech Connect

    Paez, T.L.; Hunter, N.F.

    1997-11-01

    Many dynamical systems tested in the field and the laboratory display significant nonlinear behavior. Accurate characterization of such systems requires modeling in a nonlinear framework. One construct forming a basis for nonlinear modeling is that of the artificial neural network (ANN). However, when system behavior is complex, the amount of data required to perform training can become unreasonable. The authors reduce the complexity of information present in system response measurements using decomposition via canonical variate analysis. They describe a method for decomposing system responses, then modeling the components with ANNs. A numerical example is presented, along with conclusions and recommendations.

  15. Neural Source Localization Using Advanced Sensor Array Signal Processing Techniques

    DTIC Science & Technology

    2001-10-25

    Singular Value Decomposition ( SVD ) of the spatial covariance matrix MxMjYR ℜ∈ of jY [7]. From a theoretic viewpoint, the information about the neural...source’s spatial amplitude distribution or “footprint” on the array side is contained in this covariance matrix. The SVD allows one to assess the P...Abstract unclassified Limitation of Abstract UU Number of Pages 4 2 of the SVD stage. The last step consists of selecting certain subbands from the full

  16. Bone Morphogenetic Protein 4 Signalling in Neural Stem and Progenitor Cells during Development and after Injury

    PubMed Central

    Cole, Alistair E.; Murray, Simon S.; Xiao, Junhua

    2016-01-01

    Substantial progress has been made in identifying the extracellular signalling pathways that regulate neural stem and precursor cell biology in the central nervous system (CNS). The bone morphogenetic proteins (BMPs), in particular BMP4, are key players regulating neuronal and glial cell development from neural precursor cells in the embryonic, postnatal, and injured CNS. Here we review recent studies on BMP4 signalling in the generation of neurons, astrocytes, and oligodendroglial cells in the CNS. We also discuss putative mechanisms that BMP4 may utilise to influence glial cell development following CNS injury and highlight some questions for further research. PMID:27293450

  17. Vegetation Fraction Mapping with Artificial Neural Network and High Resolution Multispectral Aerial Imagery Acquired During BEAREX07

    NASA Astrophysics Data System (ADS)

    Kersh, K. L.; Gowda, P. H.; Basu, S.; Howell, T. A.; O'Shaughnessy, S.; Rajan, N.; Akasheh, O. Z.

    2009-12-01

    Land surface models use vegetation fraction to more accurately partition latent, sensible and soil heat fluxes for a partial vegetated surface as it affects energy and moisture exchanges between the earth’s surface and atmosphere. In recent years, there is interest to integrate vegetation fraction data into intelligent irrigation scheduling systems to avoid false positive signals to irrigate. Remote sensing can facilitate the rapid collection of vegetation fraction information on individual fields over large areas in a timely and cost-effective manner. In this study, we developed a set of vegetation fraction models using least square regression and artificial neural network (ANN) techniques and evaluated using the data collected during Bushland Evapotranspiration and Agricultural Remote sensing Experiment 2007 (BEAREX07). During the BEAREX07, six aircraft campaigns were made covering bare soil to full crop cover conditions. High resolution multispectral data include 0.5-m visible (green and red) and near infrared images and 1.8-m thermal infrared images over the USDA-ARS-Conservation and Production Research Laboratory in Bushland, Texas [350 11' N, 1020 06' W; 1,170 m elevation MSL]. Atmospheric corrections were applied on these images before extracting spectral signatures for 40 ground truth locations. Field data collection in ground truth locations during the aircraft campaigns included digital pictures of crop cover using a Red/Infrared camera. Vegetation fraction information was derived from digital photos using a supervised classification. Comparison of performance statistics indicate that ANN performed slightly better than least square regression models. Newly developed fraction vegetation models will be used in the evaluation of land surface energy balance based evapotranspiration models.

  18. Neural basis of impaired safety signaling in Obsessive Compulsive Disorder.

    PubMed

    Apergis-Schoute, Annemieke M; Gillan, Claire M; Fineberg, Naomi A; Fernandez-Egea, Emilio; Sahakian, Barbara J; Robbins, Trevor W

    2017-03-06

    The ability to assign safety to stimuli in the environment is integral to everyday functioning. A key brain region for this evaluation is the ventromedial prefrontal cortex (vmPFC). To investigate the importance of vmPFC safety signaling, we used neuroimaging of Pavlovian fear reversal, a paradigm that involves flexible updating when the contingencies for a threatening (CS+) and safe (CS-) stimulus reverse, in a prototypical disorder of inflexible behavior influenced by anxiety, Obsessive Compulsive Disorder (OCD). Skin conductance responses in OCD patients (n = 43) failed to differentiate during reversal compared with healthy controls (n = 35), although significant differentiation did occur during early conditioning and amygdala BOLD signaling was unaffected in these patients. Increased vmPFC activation (for CS+ > CS-) during early conditioning predicted the degree of generalization in OCD patients during reversal, whereas vmPFC safety signals were absent throughout learning in these patients. Regions of the salience network (dorsal anterior cingulate, insula, and thalamus) showed early learning task-related hyperconnectivity with the vmPFC in OCD, consistent with biased processing of the CS+. Our findings reveal an absence of vmPFC safety signaling in OCD, undermining flexible threat updating and explicit contingency knowledge. Although differential threat learning can occur to some extent in the absence of vmPFC safety signals, effective CS- signaling becomes crucial during conflicting threat and safety cues. These results promote further investigation of vmPFC safety signaling in other anxiety disorders, with potential implications for the development of exposure-based therapies, in which safety signaling is likely to play a key role.

  19. Irrational exuberance and neural crash warning signals during endogenous experimental market bubbles.

    PubMed

    Smith, Alec; Lohrenz, Terry; King, Justin; Montague, P Read; Camerer, Colin F

    2014-07-22

    Groups of humans routinely misassign value to complex future events, especially in settings involving the exchange of resources. If properly structured, experimental markets can act as excellent probes of human group-level valuation mechanisms during pathological overvaluations--price bubbles. The connection between the behavioral and neural underpinnings of such phenomena has been absent, in part due to a lack of enabling technology. We used a multisubject functional MRI paradigm to measure neural activity in human subjects participating in experimental asset markets in which endogenous price bubbles formed and crashed. Although many ideas exist about how and why such bubbles may form and how to identify them, our experiment provided a window on the connection between neural responses and behavioral acts (buying and selling) that created the bubbles. We show that aggregate neural activity in the nucleus accumbens (NAcc) tracks the price bubble and that NAcc activity aggregated within a market predicts future price changes and crashes. Furthermore, the lowest-earning subjects express a stronger tendency to buy as a function of measured NAcc activity. Conversely, we report a signal in the anterior insular cortex in the highest earners that precedes the impending price peak, is associated with a higher propensity to sell in high earners, and that may represent a neural early warning signal in these subjects. Such markets could be a model system to understand neural and behavior mechanisms in other settings where emergent group-level activity exhibits mistaken belief or valuation.

  20. Irrational exuberance and neural crash warning signals during endogenous experimental market bubbles

    PubMed Central

    Smith, Alec; Lohrenz, Terry; King, Justin; Montague, P. Read; Camerer, Colin F.

    2014-01-01

    Groups of humans routinely misassign value to complex future events, especially in settings involving the exchange of resources. If properly structured, experimental markets can act as excellent probes of human group-level valuation mechanisms during pathological overvaluations—price bubbles. The connection between the behavioral and neural underpinnings of such phenomena has been absent, in part due to a lack of enabling technology. We used a multisubject functional MRI paradigm to measure neural activity in human subjects participating in experimental asset markets in which endogenous price bubbles formed and crashed. Although many ideas exist about how and why such bubbles may form and how to identify them, our experiment provided a window on the connection between neural responses and behavioral acts (buying and selling) that created the bubbles. We show that aggregate neural activity in the nucleus accumbens (NAcc) tracks the price bubble and that NAcc activity aggregated within a market predicts future price changes and crashes. Furthermore, the lowest-earning subjects express a stronger tendency to buy as a function of measured NAcc activity. Conversely, we report a signal in the anterior insular cortex in the highest earners that precedes the impending price peak, is associated with a higher propensity to sell in high earners, and that may represent a neural early warning signal in these subjects. Such markets could be a model system to understand neural and behavior mechanisms in other settings where emergent group-level activity exhibits mistaken belief or valuation. PMID:25002476

  1. [Development of a digital EEG signal acquiring system based on virtual instrument technology].

    PubMed

    Ying, Jun; Chen, Guang-Fei; He, Shi-Lin

    2009-09-01

    This paper introduces an 16-lead digital EEG signal acquisition system, which applies MCU MSP430 as central control unit with high performance analog devices and high speed multi-channel, multi-bit analog-to-digital converter as peripheral to retrench analog circuit. Data is transferred to PC by USART interface. Software on PC based on virtual instrument technology realizes real-time detection, display and storage. The system has many advantages such as high precision, stable performance, small volume and low power dissipation, thus provides a new means for digital EEG signal acquisition.

  2. Evaluating the lower-body electromyogram signal acquired from the feet as a noise reference for standing ballistocardiogram measurements.

    PubMed

    Inan, Omer T; Kovacs, Gregory T A; Giovangrandi, Laurent

    2010-09-01

    The ballistocardiogram (BCG) is a measure of the reaction force of the body to cardiac ejection of blood. A variety of systems can be used for BCG detection, including beds, tables, chairs, and weighing scales. Weighing scales, in particular, have several practical advantages over the alternatives: low cost, small size, unobtrusiveness, and familiarity to the user; one disadvantage is that the subject must stand during the recording, rather than sit or lay supine, resulting in a higher susceptibility to motion artifacts in the measured signal. This paper evaluates the electromyogram (EMG) signal acquired from the feet of the subject during BCG recording as a noise reference for standing BCG measurements. As a subject moves while standing on the scale, muscle contractions in the feet are detected by the EMG signal, and used to flag segments of the BCG signal that are corrupted by elevated noise. For the purposes of evaluating this method, estimates of the BCG noise-to-signal ratio (NSR) were independently calculated with an ensemble average method, using the R-wave of a simultaneously-acquired chest ECG as a timing reference. The linear correlation between EMG power alone and BCG NSR from 14 subjects was found to be moderate ( r = 0.58, F-statistic p -value 0.05); combined with body-mass index (BMI), multiple linear regression yielded a stronger correlation ( r = 0.73, F -statistic p-value = 0.01). Additionally, an example usage of the lower-leg EMG for improving BCG measurement robustness is provided.

  3. Semi-physical neural modeling for linear signal restoration.

    PubMed

    Bourgois, Laurent; Roussel, Gilles; Benjelloun, Mohammed

    2013-02-01

    This paper deals with the design methodology of an Inverse Neural Network (INN) model. The basic idea is to carry out a semi-physical model gathering two types of information: the a priori knowledge of the deterministic rules which govern the studied system and the observation of the actual conduct of this system obtained from experimental data. This hybrid model is elaborated by being inspired by the mechanisms of a neuromimetic network whose structure is constrained by the discrete reverse-time state-space equations. In order to validate the approach, some tests are performed on two dynamic models. The first suggested model is a dynamic system characterized by an unspecified r-order Ordinary Differential Equation (ODE). The second one concerns in particular the mass balance equation for a dispersion phenomenon governed by a Partial Differential Equation (PDE) discretized on a basic mesh. The performances are numerically analyzed in terms of generalization, regularization and training effort.

  4. Mate call as reward: Acoustic communication signals can acquire positive reinforcing values during adulthood in female zebra finches (Taeniopygia guttata).

    PubMed

    Hernandez, Alexandra M; Perez, Emilie C; Mulard, Hervé; Mathevon, Nicolas; Vignal, Clémentine

    2016-02-01

    Social stimuli can have rewarding properties and promote learning. In birds, conspecific vocalizations like song can act as a reinforcer, and specific song variants can acquire particular rewarding values during early life exposure. Here we ask if, during adulthood, an acoustic signal simpler and shorter than song can become a reward for a female songbird because of its particular social value. Using an operant choice apparatus, we showed that female zebra finches display a preferential response toward their mate's calls. This reinforcing value of mate's calls could be involved in the maintenance of the monogamous pair-bond of the zebra finch.

  5. Reading Between the Spikes: Real-Time Signal Processing in Neural Systems

    NASA Astrophysics Data System (ADS)

    Warland, David Karsten

    This thesis discusses biological strategies for real-time signal processing in neural systems. Nearly all creatures encode information about the world as patterns of identically shaped action potentials, or "spikes". As a result, all the animal's knowledge of the world is contained in the occurrence times of these discrete events. Traditional approaches to the study of neural coding emphasize the encoding process, resulting in predictions of average neural responses to a limited class of stimuli. However, these studies fail to address the relevant biological question: What can the organism "learn" about the outside world from real-time observations of its own spike trains? Therefore, this thesis approaches neural coding from the point of view of the organism itself: We learn to decode neural spike trains to obtain real-time estimates of sensory stimuli. In particular, this ability to extract continuous signals from spiking cells, together with the definition of an equivalent spectral noise level for a spiking neuron allows characterization of the information contained in patterns of neural response as well as forming the basis for the prediction of optimal neural computation strategies with spike trains. These methods are applied to the design and analysis of experiments on a single wide field, movement -sensitive neuron (H1) in the visual system of the blowfly Calliphora erythrocephela and to the filiform hair receptors of the wind-sensing system of the cricket Acheta domestica. This thesis also discusses the generalization of these strategies to collections of neurons and the applications to future work in the context of neural computation in the retina.

  6. G protein-coupled receptor signaling through Gq and JNK negatively regulates neural progenitor cell migration

    PubMed Central

    Mizuno, Norikazu; Kokubu, Hiroshi; Sato, Maiko; Nishimura, Akiyuki; Yamauchi, Junji; Kurose, Hitoshi; Itoh, Hiroshi

    2005-01-01

    In the early development of the central nervous system, neural progenitor cells divide in an asymmetric manner and migrate along the radial glia cells. The radial migration is an important process for the proper lamination of the cerebral cortex. Recently, a new mode of the radial migration was found at the intermediate zone where the neural progenitor cells become multipolar and reduce the migration rate. However, the regulatory signals for the radial migration are unknown. Using the migration assay in vitro, we examined how neural progenitor cell migration is regulated. Neural progenitor cells derived from embryonic mouse telencephalon migrated on laminin-coated dishes. Endothelin (ET)-1 inhibited the neural progenitor cell migration. This ET-1 effect was blocked by BQ788, a specific inhibitor of the ETB receptor, and by the expression of a carboxyl-terminal peptide of Gαq but not Gαi. The expression of constitutively active mutant of Gαq, GαqR183C, inhibited the migration of neural progenitor cells. Moreover, the inhibitory effect of ET-1 was suppressed by the c-Jun N-terminal kinase (JNK) inhibitor SP600125 and the expression of the JNK-binding domain of JNK-interacting protein-1, a specific inhibitor of the JNK pathway. Using the slice culture system of embryonic brain, we demonstrated that ET-1 and the constitutively active mutant of Gαq caused the retention of the neural progenitor cells in the intermediate zone and JNK-binding domain of JNK-interacting protein-1 abrogated the effect of ET-1. These results indicated that G protein-coupled receptor signaling negatively regulates neural progenitor cell migration through Gq and JNK. PMID:16116085

  7. Knowledge-directed electroencephalography (EEG) signal analysis with recurrent context-learning neural networks

    NASA Astrophysics Data System (ADS)

    Fu, Li-Min

    1994-06-01

    EEG signal analysis is a key to the understanding of brain activities. Traditionally, this process involves quantifying the signal in terms of frequency and amplitude, on which basis a number of waveforms have been identified. The complexity of EEG signals warrants the construction of a computer program for automatic interpretation. Symbolic knowledge is being built up for correlating the quantity of certain waveforms and brain behavior, and this knowledge can be readily programmed into a knowledge-based system (expert system) for various purposes such as cognitive research, neurological evaluation, and clinical diagnosis. The presented approach employs a knowledge-based neural network in conjunction with a recurrent neural network model as a memory deice which conducts context processing. This research emphasizes the need for the exploitation of `knowledge' and `context' in signal analysis.

  8. dNSP: a biologically inspired dynamic Neural network approach to Signal Processing.

    PubMed

    Cano-Izquierdo, José Manuel; Ibarrola, Julio; Pinzolas, Miguel; Almonacid, Miguel

    2008-09-01

    The arriving order of data is one of the intrinsic properties of a signal. Therefore, techniques dealing with this temporal relation are required for identification and signal processing tasks. To perform a classification of the signal according with its temporal characteristics, it would be useful to find a feature vector in which the temporal attributes were embedded. The correlation and power density spectrum functions are suitable tools to manage this issue. These functions are usually defined with statistical formulation. On the other hand, in biology there can be found numerous processes in which signals are processed to give a feature vector; for example, the processing of sound by the auditory system. In this work, the dNSP (dynamic Neural Signal Processing) architecture is proposed. This architecture allows representing a time-varying signal by a spatial (thus statical) vector. Inspired by the aforementioned biological processes, the dNSP performs frequency decomposition using an analogical parallel algorithm carried out by simple processing units. The architecture has been developed under the paradigm of a multilayer neural network, where the different layers are composed by units whose activation functions have been extracted from the theory of Neural Dynamic [Grossberg, S. (1988). Nonlinear neural networks principles, mechanisms and architectures. Neural Networks, 1, 17-61]. A theoretical study of the behavior of the dynamic equations of the units and their relationship with some statistical functions allows establishing a parallelism between the unit activations and correlation and power density spectrum functions. To test the capabilities of the proposed approach, several testbeds have been employed, i.e. the frequencial study of mathematical functions. As a possible application of the architecture, a highly interesting problem in the field of automatic control is addressed: the recognition of a controlled DC motor operating state.

  9. Hybrid digital signal processing and neural networks for automated diagnostics using NDE methods

    SciTech Connect

    Upadhyaya, B.R.; Yan, W.

    1993-11-01

    The primary purpose of the current research was to develop an integrated approach by combining information compression methods and artificial neural networks for the monitoring of plant components using nondestructive examination data. Specifically, data from eddy current inspection of heat exchanger tubing were utilized to evaluate this technology. The focus of the research was to develop and test various data compression methods (for eddy current data) and the performance of different neural network paradigms for defect classification and defect parameter estimation. Feedforward, fully-connected neural networks, that use the back-propagation algorithm for network training, were implemented for defect classification and defect parameter estimation using a modular network architecture. A large eddy current tube inspection database was acquired from the Metals and Ceramics Division of ORNL. These data were used to study the performance of artificial neural networks for defect type classification and for estimating defect parameters. A PC-based data preprocessing and display program was also developed as part of an expert system for data management and decision making. The results of the analysis showed that for effective (low-error) defect classification and estimation of parameters, it is necessary to identify proper feature vectors using different data representation methods. The integration of data compression and artificial neural networks for information processing was established as an effective technique for automation of diagnostics using nondestructive examination methods.

  10. Classification of Acousto-Optic Correlation Signatures of Spread Spectrum Signals Using Artificial Neural Networks

    DTIC Science & Technology

    1989-12-01

    Ohio ’aPw iorlipuab muo i 0I2, AFIT/GE/ENG/89D-10 CLASSIFICATION OF ACOUSTO - OPTIC CORRELATION SIGNATURES OF SPREAD SPECTRUM SIGNALS USING ARTIFICIAL...ENG/89D- 10 CLASSIFICATION OF ACOUSTO - OPTIC CORRELATION SIGNATURES OF SPREAD SPECTRUM SIGNALS USING ARTIFICIAL NEURAL NETWORKS THESIS John W. DeBerry...Captain, USAF AFIT/GE/ENG/89D- 10 Approved for public release; distribution unlimited. AFIT/GE/ENG/89D-10 CLASSIFICATION OF ACOUSTO - OPTIC CORRELATION

  11. A New High-Resolution Direction Finding Architecture Using Photonics and Neural Network Signal Processing for Miniature Air Vehicle Applications

    DTIC Science & Technology

    2015-09-01

    RESOLUTION DIRECTION FINDING ARCHITECTURE USING PHOTONICS AND NEURAL NETWORK SIGNAL PROCESSING FOR MINIATURE AIR VEHICLE APPLICATIONS by Robert...RESOLUTION DIRECTION FINDING ARCHITECTURE USING PHOTONICS AND NEURAL NETWORK SIGNAL PROCESSING FOR MINIATURE AIR VEHICLE APPLICATIONS 5. FUNDING...unlimited 12b. DISTRIBUTION CODE 13. ABSTRACT (maximum 200 words) This paper investigates the design of an interferometric direction finding receiver

  12. System identification: a multi-signal approach for probing neural cardiovascular regulation.

    PubMed

    Xiao, Xinshu; Mullen, Thomas J; Mukkamala, Ramakrishna

    2005-06-01

    Short-term, beat-to-beat cardiovascular variability reflects the dynamic interplay between ongoing perturbations to the circulation and the compensatory response of neurally mediated regulatory mechanisms. This physiologic information may be deciphered from the subtle, beat-to-beat variations by using digital signal processing techniques. While single signal analysis techniques (e.g., power spectral analysis) may be employed to quantify the variability itself, the multi-signal approach of system identification permits the dynamic characterization of the neural regulatory mechanisms responsible for coupling the variability between signals. In this review, we provide an overview of applications of system identification to beat-to-beat variability for the quantitative characterization of cardiovascular regulatory mechanisms. After briefly summarizing the history of the field and basic principles, we take a didactic approach to describe the practice of system identification in the context of probing neural cardiovascular regulation. We then review studies in the literature over the past two decades that have applied system identification for characterizing the dynamical properties of the sinoatrial node, respiratory sinus arrhythmia, and the baroreflex control of sympathetic nerve activity, heart rate and total peripheral resistance. Based on this literature review, we conclude by advocating specific methods of practice and that future research should focus on nonlinear and time-varying behaviors, validation of identification methods, and less understood neural regulatory mechanisms. Ultimately, we hope that this review stimulates such future investigations by both new and experienced system identification researchers.

  13. Ror2 signaling is required for local upregulation of GDF6 and activation of BMP signaling at the neural plate border.

    PubMed

    Schille, Carolin; Bayerlová, Michaela; Bleckmann, Annalen; Schambony, Alexandra

    2016-09-01

    The receptor tyrosine kinase Ror2 is a major Wnt receptor that activates β-catenin-independent signaling and plays a conserved role in the regulation of convergent extension movements and planar cell polarity in vertebrates. Mutations in the ROR2 gene cause recessive Robinow syndrome in humans, a short-limbed dwarfism associated with craniofacial malformations. Here, we show that Ror2 is required for local upregulation of gdf6 at the neural plate border in Xenopus embryos. Ror2 morphant embryos fail to upregulate neural plate border genes and show defects in the induction of neural crest cell fate. These embryos lack the spatially restricted activation of BMP signaling at the neural plate border at early neurula stages, which is required for neural crest induction. Ror2-dependent planar cell polarity signaling is required in the dorsolateral marginal zone during gastrulation indirectly to upregulate the BMP ligand Gdf6 at the neural plate border and Gdf6 is sufficient to rescue neural plate border specification in Ror2 morphant embryos. Thereby, Ror2 links Wnt/planar cell polarity signaling to BMP signaling in neural plate border specification and neural crest induction.

  14. Ubenimex attenuates acquired sorafenib resistance in renal cell carcinoma by inhibiting Akt signaling in a lipophagy associated mechanism

    PubMed Central

    Liu, Shuai; Gao, Mingwei; Wang, Xiaoqing; Ding, Sentai; Lv, Jiaju; Gao, Dexuan; Wang, Zhiyang; Niu, Zhihong

    2016-01-01

    Sorafenib is used as first line treatment of renal cell carcinoma (RCC) due to the poor sensitivity to radiotherapy and chemotherapy of this malignancy; however, acquired resistance limits the application of sorafenib and its analogues. In this study, we explored a new strategy to overcome acquired resistance to sorafenib. The RCC cell lines 786-O and ACHN were cultured in presence of increasing concentrations of sorafenib to generate sorafenib-resistant cell lines, 786-O-R and ACHN-R. Interestingly, treatment with ubenimex (0.25 mg/ml) and 3-MA (2 mM) restored the sensitivity of resistant cell lines to sorafenib, indicating the involvement of autophagy in acquired resistance. High levels of autophagy flux were observed in resistant cells, and the opposite effects of ubenimex and 3-MA suggested a complex role for autophagy. While 3-MA abolished protection in sorafenib-resistant cells, ubenimex induced uncontrolled autophagy and autophagic cell death. Lipophagy, characterized by a lipid droplet cargo, was observed in RCC tissues and cells. In sorafenib-resistant cells, ubenimex inhibited the Akt signaling pathway that regulates autophagy. In summary, lipophagy participates in sorafenib-resistance of RCC, which could be reversed by interventions targeting the Akt pathway. PMID:27816967

  15. Early neural crest induction requires an initial inhibition of Wnt signals.

    PubMed

    Steventon, Ben; Mayor, Roberto

    2012-05-01

    Neural crest (NC) induction is a long process that continues through gastrula and neurula stages. In order to reveal additional stages of NC induction we performed a series of explants where different known inducing tissues were taken along with the prospective NC. Interestingly the dorso-lateral marginal zone (DLMZ) is only able to promote the expression of a subset of neural plate border (NPB) makers without the presence of specific NC markers. We then analysed the temporal requirement for BMP and Wnt signals for the NPB genes Hairy2a and Dlx5, compared to the expression of neural plate (NP) and NC genes. Although the NP is sensitive to BMP levels at early gastrula stages, Hairy2a/Dlx5 expression is unaffected. Later, the NP becomes insensitive to BMP levels at late gastrulation when NC markers require an inhibition. The NP requires an inhibition of Wnt signals prior to gastrulation, but becomes insensitive during early gastrula stages when Hairy2a/Dlx5 requires an inhibition of Wnt signalling. An increase in Wnt signalling is then important for the switch from NPB to NC at late gastrula stages. In addition to revealing an additional distinct signalling event in NC induction, this work emphasizes the importance of integrating both timing and levels of signalling activity during the patterning of complex tissues such as the vertebrate ectoderm.

  16. Myoelectric Signal Segmentation and Classification Using Wavelets Based Neural Networks

    DTIC Science & Technology

    2007-11-02

    MES are signals recorded using surface electrodes that reflect the localized neuromuscular activity. They have been used in various aspects of medical ...and biomedical applications [1]. For example, they are used for the diagnosis of neuromuscular diseases such as polymyositics [2]. One of the uses...training patterns and N is the number of output nodes. dk and zk are the desired and actual responses for output node k, respectively. Arm movement

  17. FGF Signalling Regulates Chromatin Organisation during Neural Differentiation via Mechanisms that Can Be Uncoupled from Transcription

    PubMed Central

    Patel, Nishal S.; Rhinn, Muriel; Semprich, Claudia I.; Halley, Pamela A.; Dollé, Pascal; Bickmore, Wendy A.; Storey, Kate G.

    2013-01-01

    Changes in higher order chromatin organisation have been linked to transcriptional regulation; however, little is known about how such organisation alters during embryonic development or how it is regulated by extrinsic signals. Here we analyse changes in chromatin organisation as neural differentiation progresses, exploiting the clear spatial separation of the temporal events of differentiation along the elongating body axis of the mouse embryo. Combining fluorescence in situ hybridisation with super-resolution structured illumination microscopy, we show that chromatin around key differentiation gene loci Pax6 and Irx3 undergoes both decompaction and displacement towards the nuclear centre coincident with transcriptional onset. Conversely, down-regulation of Fgf8 as neural differentiation commences correlates with a more peripheral nuclear position of this locus. During normal neural differentiation, fibroblast growth factor (FGF) signalling is repressed by retinoic acid, and this vitamin A derivative is further required for transcription of neural genes. We show here that exposure to retinoic acid or inhibition of FGF signalling promotes precocious decompaction and central nuclear positioning of differentiation gene loci. Using the Raldh2 mutant as a model for retinoid deficiency, we further find that such changes in higher order chromatin organisation are dependent on retinoid signalling. In this retinoid deficient condition, FGF signalling persists ectopically in the elongating body, and importantly, we find that inhibiting FGF receptor (FGFR) signalling in Raldh2−/− embryos does not rescue differentiation gene transcription, but does elicit both chromatin decompaction and nuclear position change. These findings demonstrate that regulation of higher order chromatin organisation during differentiation in the embryo can be uncoupled from the machinery that promotes transcription and, for the first time, identify FGF as an extrinsic signal that can direct

  18. A Decline in Response Variability Improves Neural Signal Detection during Auditory Task Performance.

    PubMed

    von Trapp, Gardiner; Buran, Bradley N; Sen, Kamal; Semple, Malcolm N; Sanes, Dan H

    2016-10-26

    The detection of a sensory stimulus arises from a significant change in neural activity, but a sensory neuron's response is rarely identical to successive presentations of the same stimulus. Large trial-to-trial variability would limit the central nervous system's ability to reliably detect a stimulus, presumably affecting perceptual performance. However, if response variability were to decrease while firing rate remained constant, then neural sensitivity could improve. Here, we asked whether engagement in an auditory detection task can modulate response variability, thereby increasing neural sensitivity. We recorded telemetrically from the core auditory cortex of gerbils, both while they engaged in an amplitude-modulation detection task and while they sat quietly listening to the identical stimuli. Using a signal detection theory framework, we found that neural sensitivity was improved during task performance, and this improvement was closely associated with a decrease in response variability. Moreover, units with the greatest change in response variability had absolute neural thresholds most closely aligned with simultaneously measured perceptual thresholds. Our findings suggest that the limitations imposed by response variability diminish during task performance, thereby improving the sensitivity of neural encoding and potentially leading to better perceptual sensitivity.

  19. Influence of Mobile Phones on the Quality of ECG Signal Acquired by Medical Devices

    NASA Astrophysics Data System (ADS)

    Buczkowski, T.; Janusek, D.; Zavala-Fernandez, H.; Skrok, M.; Kania, M.; Liebert, A.

    2013-10-01

    Health aspects of the use of radiating devices, like mobile phones, are still a public concern. Stand-alone electrocardiographic systems and those built-in, more sophisticated, medical devices have become a standard tool used in everyday medical practice. GSM mobile phones might be a potential source of electromagnetic interference (EMI) which may affect reliability of medical appliances. Risk of such event is particularly high in places remote from GSM base stations in which the signal received by GSM mobile phone is weak. In such locations an increase in power of transmitted radio signal is necessary to enhance quality of the communication. In consequence, the risk of interference of electronic devices increases because of the high level of EMI. In the present paper the spatial, temporal, and spectral characteristics of the interference have been examined. The influence of GSM mobile phone on multilead ECG recordings was studied. It was observed that the electrocardiographic system was vulnerable to the interference generated by the GSM mobile phone working with maximum transmit power and in DTX mode when the device was placed in a distance shorter than 7.5 cm from the ECG electrode located on the surface of the chest. Negligible EMI was encountered at any longer distance.

  20. Wavelet transform for real-time detection of action potentials in neural signals.

    PubMed

    Quotb, Adam; Bornat, Yannick; Renaud, Sylvie

    2011-01-01

    We present a study on wavelet detection methods of neuronal action potentials (APs). Our final goal is to implement the selected algorithms on custom integrated electronics for on-line processing of neural signals; therefore we take real-time computing as a hard specification and silicon area as a price to pay. Using simulated neural signals including APs, we characterize an efficient wavelet method for AP extraction by evaluating its detection rate and its implementation cost. We compare software implementation for three methods: adaptive threshold, discrete wavelet transform (DWT), and stationary wavelet transform (SWT). We evaluate detection rate and implementation cost for detection functions dynamically comparing a signal with an adaptive threshold proportional to its SD, where the signal is the raw neural signal, respectively: (i) non-processed; (ii) processed by a DWT; (iii) processed by a SWT. We also use different mother wavelets and test different data formats to set an optimal compromise between accuracy and silicon cost. Detection accuracy is evaluated together with false negative and false positive detections. Simulation results show that for on-line AP detection implemented on a configurable digital integrated circuit, APs underneath the noise level can be detected using SWT with a well-selected mother wavelet, combined to an adaptive threshold.

  1. Hippo signaling is required for Notch-dependent smooth muscle differentiation of neural crest

    PubMed Central

    Manderfield, Lauren J.; Aghajanian, Haig; Engleka, Kurt A.; Lim, Lillian Y.; Liu, Feiyan; Jain, Rajan; Li, Li; Olson, Eric N.; Epstein, Jonathan A.

    2015-01-01

    Notch signaling has well-defined roles in the assembly of arterial walls and in the development of the endothelium and smooth muscle of the vasculature. Hippo signaling regulates cellular growth in many tissues, and contributes to regulation of organ size, in addition to other functions. Here, we show that the Notch and Hippo pathways converge to regulate smooth muscle differentiation of the neural crest, which is crucial for normal development of the aortic arch arteries and cranial vasculature during embryonic development. Neural crest-specific deletion of the Hippo effectors Yap and Taz produces neural crest precursors that migrate normally, but fail to produce vascular smooth muscle, and Notch target genes such as Jagged1 fail to activate normally. We show that Yap is normally recruited to a tissue-specific Jagged1 enhancer by directly interacting with the Notch intracellular domain (NICD). The Yap-NICD complex is recruited to chromatin by the DNA-binding protein Rbp-J in a Tead-independent fashion. Thus, Hippo signaling can modulate Notch signaling outputs, and components of the Hippo and Notch pathways physically interact. Convergence of Hippo and Notch pathways by the mechanisms described here might be relevant for the function of these signaling cascades in many tissues and in diseases such as cancer. PMID:26253400

  2. Neural network based near- lossless compression of EEG signals with non uniform quantization.

    PubMed

    Sriraam, N

    2007-01-01

    Efficient compression technique is highly essential for the transmission and storage of large amount of biomedical signals. In this paper, a near- lossless scheme for the compression of EEG signals using artificial neural networks is proposed. The error (residue) signals which is obtained due to the difference between the original and the predicted EEG signals are thresolded based on a term referred as absolute error limit (AEL) such that, any error samples above the limit require more number of bits than the samples below the limit that require less number of bits. The thresholded error samples are quantized in a non-uniform manner by varying the actual bits assigned to the error samples. An arithmetic encoder is further used to improve the compression efficiency. Three adaptive neural network models, namely, single and multilayer perceptrons and Elman neural network and two classical adaptive predictors such as autoregressive model(AR) and normalized least mean-square FIR filter are used. EEG signals recorded under different physiological conditions are considered and the performance of the proposed scheme is evaluated in terms of compression ratio and the fidelity parameter, percent of root-mean-square-difference (PRD). It is found from the experimental results that the variation of error limit and quantization step decides the overall compression performance. Single- layer perceptron yields the best compression results in terms of utilizing less bit rate as well achieving low PRD values compared to other predictors.

  3. Forecast of TEXT plasma disruptions using soft X rays as input signal in a neural network

    NASA Astrophysics Data System (ADS)

    Vannucci, A.; Oliveira, K. A.; Tajima, T.

    1999-02-01

    A feedforward neural network with two hidden layers is used to forecast major and minor disruptive instabilities in TEXT tokamak discharges. Using the experimental data of soft X ray signals as input data, the neural network is trained with one disruptive plasma discharge, and a different disruptive discharge is used for validation. After being properly trained, the networks, with the same set of weights, are used to forecast disruptions in two other plasma discharges. It is observed that the neural network is able to predict the occurrence of a disruption more than 3 ms in advance. This time interval is almost 3 times longer than the one already obtained previously when a magnetic signal from a Mirnov coil was used to feed the neural networks. Visually no indication of an upcoming disruption is seen from the experimental data this far back from the time of disruption. Finally, by observing the predictive behaviour of the network for the disruptive discharges analysed and comparing the soft X ray data with the corresponding magnetic experimental signal, it is conjectured about where inside the plasma column the disruption first started.

  4. A preferential design approach for energy-efficient and robust implantable neural signal processing hardware.

    PubMed

    Narasimhan, Seetharam; Chiel, Hillel J; Bhunia, Swarup

    2009-01-01

    For implantable neural interface applications, it is important to compress data and analyze spike patterns across multiple channels in real time. Such a computational task for online neural data processing requires an innovative circuit-architecture level design approach for low-power, robust and area-efficient hardware implementation. Conventional microprocessor or Digital Signal Processing (DSP) chips would dissipate too much power and are too large in size for an implantable system. In this paper, we propose a novel hardware design approach, referred to as "Preferential Design" that exploits the nature of the neural signal processing algorithm to achieve a low-voltage, robust and area-efficient implementation using nanoscale process technology. The basic idea is to isolate the critical components with respect to system performance and design them more conservatively compared to the noncritical ones. This allows aggressive voltage scaling for low power operation while ensuring robustness and area efficiency. We have applied the proposed approach to a neural signal processing algorithm using the Discrete Wavelet Transform (DWT) and observed significant improvement in power and robustness over conventional design.

  5. Vangl-dependent planar cell polarity signalling is not required for neural crest migration in mammals

    PubMed Central

    Pryor, Sophie E.; Massa, Valentina; Savery, Dawn; Andre, Philipp; Yang, Yingzi; Greene, Nicholas D. E.; Copp, Andrew J.

    2014-01-01

    The role of planar cell polarity (PCP) signalling in neural crest (NC) development is unclear. The PCP dependence of NC cell migration has been reported in Xenopus and zebrafish, but NC migration has not been studied in mammalian PCP mutants. Vangl2Lp/Lp mouse embryos lack PCP signalling and undergo almost complete failure of neural tube closure. Here we show, however, that NC specification, migration and derivative formation occur normally in Vangl2Lp/Lp embryos. The gene family member Vangl1 was not expressed in NC nor ectopically expressed in Vangl2Lp/Lp embryos, and doubly homozygous Vangl1/Vangl2 mutants exhibited normal NC migration. Acute downregulation of Vangl2 in the NC lineage did not prevent NC migration. In vitro, Vangl2Lp/Lp neural tube explants generated emigrating NC cells, as in wild type. Hence, PCP signalling is not essential for NC migration in mammals, in contrast to its essential role in neural tube closure. PCP mutations are thus unlikely to mediate NC-related birth defects in humans. PMID:25038043

  6. The NHR domains of Neuralized and related proteins: Beyond Notch signalling.

    PubMed

    Liu, Sili; Boulianne, Gabrielle L

    2017-01-01

    Neuralized Homology Repeats (NHRs) were first identified in Neuralized, an E3-ubiquitin ligase that plays a key role in the Notch signalling pathway. Since their original discovery, NHR domains have been shown to regulate protein-protein interactions in a broad range of developmental processes and in a wide variety of species from flies to humans. The NHR family of proteins can be categorized into three groups: (1) those that contain a RING finger, (2) those that contain a SOCS box and, (3) those that only have NHR domains. Here we review the structure and function of NHR domains in various cellular and developmental processes.

  7. Internal signal correlates neural populations and biases perceptual decision reports

    PubMed Central

    Carnevale, Federico; de Lafuente, Victor; Romo, Ranulfo; Parga, Néstor

    2012-01-01

    In perceptual decision-making tasks the activity of neurons in frontal and posterior parietal cortices covaries more with perceptual reports than with the physical properties of stimuli. This relationship is revealed when subjects have to make behavioral choices about weak or uncertain stimuli. If knowledge about stimulus onset time is available, decision making can be based on accumulation of sensory evidence. However, the time of stimulus onset or even its very presence is often ambiguous. By analyzing firing rates and correlated variability of frontal lobe neurons while monkeys perform a vibrotactile detection task, we show that behavioral outcomes are crucially affected by the state of cortical networks before stimulus onset times. The results suggest that sensory detection is partly due to a purely internal signal whereas the stimulus, if finally applied, adds a contribution to this initial processing later on. The probability to detect or miss the stimulus can thus be explained as the combined effect of this variable internal signal and the sensory evidence. PMID:23112203

  8. Gating of neural error signals during motor learning

    PubMed Central

    Kimpo, Rhea R; Rinaldi, Jacob M; Kim, Christina K; Payne, Hannah L; Raymond, Jennifer L

    2014-01-01

    Cerebellar climbing fiber activity encodes performance errors during many motor learning tasks, but the role of these error signals in learning has been controversial. We compared two motor learning paradigms that elicited equally robust putative error signals in the same climbing fibers: learned increases and decreases in the gain of the vestibulo-ocular reflex (VOR). During VOR-increase training, climbing fiber activity on one trial predicted changes in cerebellar output on the next trial, and optogenetic activation of climbing fibers to mimic their encoding of performance errors was sufficient to implant a motor memory. In contrast, during VOR-decrease training, there was no trial-by-trial correlation between climbing fiber activity and changes in cerebellar output, and climbing fiber activation did not induce VOR-decrease learning. Our data suggest that the ability of climbing fibers to induce plasticity can be dynamically gated in vivo, even under conditions where climbing fibers are robustly activated by performance errors. DOI: http://dx.doi.org/10.7554/eLife.02076.001 PMID:24755290

  9. Aging neural progenitors lose competence to respond to mitogenic Notch signaling

    PubMed Central

    Farnsworth, Dylan R.; Bayraktar, Omer Ali; Doe, Chris Q.

    2015-01-01

    Drosophila neural stem cells (neuroblasts) are a powerful model system for investigating stem cell self-renewal, specification of temporal identity, and progressive restriction in competence. Notch signaling is a conserved cue that is an important determinant of cell fate in many contexts across animal development; for example mammalian T cell differentiation in the thymus and neuroblast specification in Drosophila are both regulated by Notch signaling. However, Notch also functions as a mitogen, and constitutive Notch signaling potentiates T cell leukemia as well as Drosophila neuroblast tumors. While the role of Notch signaling has been studied in these and other cell types, it remains unclear how stem cells and progenitors change competence to respond to Notch over time. Notch is required in type II neuroblasts for normal development of their transit amplifying progeny, intermediate neural progenitors (INPs). Here we find that aging INPs lose competence to respond to constitutively active Notch signaling. Moreover, we show that reducing the levels of the old INP temporal transcription factor Eyeless/Pax6 allows Notch signaling to promote the de-differentiation of INP progeny into ectopic INPs, thereby creating a proliferative mass of ectopic progenitors in the brain. These findings provide a new system for studying progenitor competence, and identify a novel role for the conserved transcription factor Eyeless/Pax6 in blocking Notch signaling during development. PMID:26585279

  10. Noise in Neural Networks: Thresholds, Hysteresis, and Neuromodulation of Signal-To-Noise

    NASA Astrophysics Data System (ADS)

    Keeler, James D.; Pichler, Elgar E.; Ross, John

    1989-03-01

    We study a neural-network model including Gaussian noise, higher-order neuronal interactions, and neuromodulation. For a first-order network, there is a threshold in the noise level (phase transition) above which the network displays only disorganized behavior and critical slowing down near the noise threshold. The network can tolerate more noise if it has higher-order feedback interactions, which also lead to hysteresis and multistability in the network dynamics. The signal-to-noise ratio can be adjusted in a biological neural network by neuromodulators such as norepinephrine. Comparisons are made to experimental results and further investigations are suggested to test the effects of hysteresis and neuromodulation in pattern recognition and learning. We propose that norepinephrine may ``quench'' the neural patterns of activity to enhance the ability to learn details.

  11. Human Age Recognition by Electrocardiogram Signal Based on Artificial Neural Network

    NASA Astrophysics Data System (ADS)

    Dasgupta, Hirak

    2016-12-01

    The objective of this work is to make a neural network function approximation model to detect human age from the electrocardiogram (ECG) signal. The input vectors of the neural network are the Katz fractal dimension of the ECG signal, frequencies in the QRS complex, male or female (represented by numeric constant) and the average of successive R-R peak distance of a particular ECG signal. The QRS complex has been detected by short time Fourier transform algorithm. The successive R peak has been detected by, first cutting the signal into periods by auto-correlation method and then finding the absolute of the highest point in each period. The neural network used in this problem consists of two layers, with Sigmoid neuron in the input and linear neuron in the output layer. The result shows the mean of errors as -0.49, 1.03, 0.79 years and the standard deviation of errors as 1.81, 1.77, 2.70 years during training, cross validation and testing with unknown data sets, respectively.

  12. Innate signals overcome acquired TCR signaling pathway regulation and govern the fate of human CD161(hi) CD8α⁺ semi-invariant T cells.

    PubMed

    Turtle, Cameron J; Delrow, Jeff; Joslyn, Rochelle C; Swanson, Hillary M; Basom, Ryan; Tabellini, Laura; Delaney, Colleen; Heimfeld, Shelly; Hansen, John A; Riddell, Stanley R

    2011-09-08

    Type 17 programmed CD161(hi)CD8α(+) T cells contribute to mucosal immunity to bacteria and yeast. In early life, microbial colonization induces proliferation of CD161(hi) cells that is dependent on their expression of a semi-invariant Vα7.2(+) TCR. Although prevalent in adults, CD161(hi)CD8α(+) cells exhibit weak proliferative and cytokine responses to TCR ligation. The mechanisms responsible for the dichotomous response of neonatal and adult CD161(hi) cells, and the signals that enable their effector function, have not been established. We describe acquired regulation of TCR signaling in adult memory CD161(hi)CD8α(+) T cells that is absent in cord CD161(hi) cells and adult CD161(lo) cells. Regulated TCR signaling in CD161(hi) cells was due to profound alterations in TCR signaling pathway gene expression and could be overcome by costimulation through CD28 or innate cytokine receptors, which dictated the fate of their progeny. Costimulation with IL-1β during TCR ligation markedly increased proinflammatory IL-17 production, while IL-12-induced Tc1-like function and restored the response to TCR ligation without costimulation. CD161(hi) cells from umbilical cord blood and granulocyte colony stimulating factor-mobilized leukaphereses differed in frequency and function, suggesting future evaluation of the contribution of CD161(hi) cells in hematopoietic stem cell grafts to transplant outcomes is warranted.

  13. Constitutive cyclic GMP accumulation in Arabidopsis thaliana compromises systemic acquired resistance induced by an avirulent pathogen by modulating local signals.

    PubMed

    Hussain, Jamshaid; Chen, Jian; Locato, Vittoria; Sabetta, Wilma; Behera, Smrutisanjita; Cimini, Sara; Griggio, Francesca; Martínez-Jaime, Silvia; Graf, Alexander; Bouneb, Mabrouk; Pachaiappan, Raman; Fincato, Paola; Blanco, Emanuela; Costa, Alex; De Gara, Laura; Bellin, Diana; de Pinto, Maria Concetta; Vandelle, Elodie

    2016-11-04

    The infection of Arabidopsis thaliana plants with avirulent pathogens causes the accumulation of cGMP with a biphasic profile downstream of nitric oxide signalling. However, plant enzymes that modulate cGMP levels have yet to be identified, so we generated transgenic A. thaliana plants expressing the rat soluble guanylate cyclase (GC) to increase genetically the level of cGMP and to study the function of cGMP in plant defence responses. Once confirmed that cGMP levels were higher in the GC transgenic lines than in wild-type controls, the GC transgenic plants were then challenged with bacterial pathogens and their defence responses were characterized. Although local resistance was similar in the GC transgenic and wild-type lines, differences in the redox state suggested potential cross-talk between cGMP and the glutathione redox system. Furthermore, large-scale transcriptomic and proteomic analysis highlighted the significant modulation of both gene expression and protein abundance at the infection site, inhibiting the establishment of systemic acquired resistance. Our data indicate that cGMP plays a key role in local responses controlling the induction of systemic acquired resistance in plants challenged with avirulent pathogens.

  14. Constitutive cyclic GMP accumulation in Arabidopsis thaliana compromises systemic acquired resistance induced by an avirulent pathogen by modulating local signals

    PubMed Central

    Hussain, Jamshaid; Chen, Jian; Locato, Vittoria; Sabetta, Wilma; Behera, Smrutisanjita; Cimini, Sara; Griggio, Francesca; Martínez-Jaime, Silvia; Graf, Alexander; Bouneb, Mabrouk; Pachaiappan, Raman; Fincato, Paola; Blanco, Emanuela; Costa, Alex; De Gara, Laura; Bellin, Diana; de Pinto, Maria Concetta; Vandelle, Elodie

    2016-01-01

    The infection of Arabidopsis thaliana plants with avirulent pathogens causes the accumulation of cGMP with a biphasic profile downstream of nitric oxide signalling. However, plant enzymes that modulate cGMP levels have yet to be identified, so we generated transgenic A. thaliana plants expressing the rat soluble guanylate cyclase (GC) to increase genetically the level of cGMP and to study the function of cGMP in plant defence responses. Once confirmed that cGMP levels were higher in the GC transgenic lines than in wild-type controls, the GC transgenic plants were then challenged with bacterial pathogens and their defence responses were characterized. Although local resistance was similar in the GC transgenic and wild-type lines, differences in the redox state suggested potential cross-talk between cGMP and the glutathione redox system. Furthermore, large-scale transcriptomic and proteomic analysis highlighted the significant modulation of both gene expression and protein abundance at the infection site, inhibiting the establishment of systemic acquired resistance. Our data indicate that cGMP plays a key role in local responses controlling the induction of systemic acquired resistance in plants challenged with avirulent pathogens. PMID:27811978

  15. Vorinostat-induced autophagy switches from a death-promoting to a cytoprotective signal to drive acquired resistance.

    PubMed

    Dupéré-Richer, D; Kinal, M; Ménasché, V; Nielsen, T H; Del Rincon, S; Pettersson, F; Miller, W H

    2013-02-07

    Histone deacetylase inhibitors (HDACi) have shown promising activity against hematological malignancies in clinical trials and have led to the approval of vorinostat for the treatment of cutaneous T-cell lymphoma. However, de novo or acquired resistance to HDACi therapy is inevitable, and their molecular mechanisms are still unclear. To gain insight into HDACi resistance, we developed vorinostat-resistant clones from the hematological cell lines U937 and SUDHL6. Although cross-resistant to some but not all HDACi, the resistant cell lines exhibit dramatically increased sensitivity toward chloroquine, an inhibitor of autophagy. Consistent with this, resistant cells growing in vorinostat show increased autophagy. Inhibition of autophagy in vorinostat-resistant U937 cells by knockdown of Beclin-1 or Lamp-2 (lysosome-associated membrane protein 2) restores sensitivity to vorinostat. Interestingly, autophagy is also activated in parental U937 cells by de novo treatment with vorinostat. However, in contrast to the resistant cells, inhibition of autophagy decreases sensitivity to vorinostat. These results indicate that autophagy can switch from a proapoptotic signal to a prosurvival function driving acquired resistance. Moreover, inducers of autophagy (such as mammalian target of rapamycin inhibitors) synergize with vorinostat to induce cell death in parental cells, whereas the resistant cells remain insensitive. These data highlight the complexity of the design of combination strategies using modulators of autophagy and HDACi for the treatment of hematological malignancies.

  16. Synaptopathy in the noise-exposed and aging cochlea: Primary neural degeneration in acquired sensorineural hearing loss.

    PubMed

    Kujawa, Sharon G; Liberman, M Charles

    2015-12-01

    The classic view of sensorineural hearing loss (SNHL) is that the "primary" targets are hair cells, and that cochlear-nerve loss is "secondary" to hair cell degeneration. Our recent work in mouse and guinea pig has challenged that view. In noise-induced hearing loss, exposures causing only reversible threshold shifts (and no hair cell loss) nevertheless cause permanent loss of >50% of cochlear-nerve/hair-cell synapses. Similarly, in age-related hearing loss, degeneration of cochlear synapses precedes both hair cell loss and threshold elevation. This primary neural degeneration has remained hidden for three reasons: 1) the spiral ganglion cells, the cochlear neural elements commonly assessed in studies of SNHL, survive for years despite loss of synaptic connection with hair cells, 2) the synaptic terminals of cochlear nerve fibers are unmyelinated and difficult to see in the light microscope, and 3) the degeneration is selective for cochlear-nerve fibers with high thresholds. Although not required for threshold detection in quiet (e.g. threshold audiometry or auditory brainstem response threshold), these high-threshold fibers are critical for hearing in noisy environments. Our research suggests that 1) primary neural degeneration is an important contributor to the perceptual handicap in SNHL, and 2) in cases where the hair cells survive, neurotrophin therapies can elicit neurite outgrowth from spiral ganglion neurons and re-establishment of their peripheral synapses. This article is part of a Special Issue entitled .

  17. Reward Motivation Accelerates the Onset of Neural Novelty Signals in Humans to 85 Milliseconds

    PubMed Central

    Bunzeck, Nico; Doeller, Christian F.; Fuentemilla, Lluis; Dolan, Raymond J.; Duzel, Emrah

    2009-01-01

    Summary The neural responses that distinguish novel from familiar items in recognition memory tasks are remarkably fast in both humans and nonhuman primates. In humans, the earliest onsets of neural novelty effects emerge at about ∼150–200 ms after stimulus onset [1–5]. However, in recognition memory studies with nonhuman primates, novelty effects can arise at as early as 70–80 ms [6, 7]. Here, we address the possibility that this large species difference in onset latencies is caused experimentally by the necessity of using reward reinforcement to motivate the detection of novel or familiar items in nonhuman primates but not in humans. Via magnetoencephalography in humans, we show in two experiments that the onset of neural novelty signals is accelerated from ∼200 ms to ∼85 ms if correct recognition memory for either novel or familiar items is rewarded. Importantly, this acceleration is independent of whether the detection of the novel or the familiar scenes is rewarded. Furthermore, this early novelty effect contributed to memory retrieval because neural reward responses, which were contingent upon novelty detection, followed ∼100 ms later. Thus, under the contextual influence of reward motivation, behaviorally relevant novelty signals emerge much faster than previously held possible in humans. PMID:19576774

  18. Recognition Method of Limb Motor Imagery EEG Signals Based on Integrated Back-propagation Neural Network.

    PubMed

    Li, Mingyang; Chen, Wanzhong; Cui, Bingyi; Tian, Yantao

    2015-01-01

    In this paper, in order to solve the existing problems of the low recognition rate and poor real-time performance in limb motor imagery, the integrated back-propagation neural network (IBPNN) was applied to the pattern recognition research of motor imagery EEG signals (imagining left-hand movement, imagining right-hand movement and imagining no movement). According to the motor imagery EEG data categories to be recognized, the IBPNN was designed to consist of 3 single three-layer back-propagation neural networks (BPNN), and every single neural network was dedicated to recognizing one kind of motor imagery. It simplified the complicated classification problems into three mutually independent two-class classifications by the IBPNN. The parallel computing characteristic of IBPNN not only improved the generation ability for network, but also shortened the operation time. The experimental results showed that, while comparing the single BPNN and Elman neural network, IBPNN was more competent in recognizing limb motor imagery EEG signals. Also among these three networks, IBPNN had the least number of iterations, the shortest operation time and the best consistency of actual output and expected output, and had lifted the success recognition rate above 97 percent while other single network is around 93 percent.

  19. Reciprocal projections in hierarchically organized evolvable neural circuits affect EEG-like signals.

    PubMed

    Shaposhnyk, Vladyslav; Villa, Alessandro E P

    2012-01-24

    Modular architecture is a hallmark of many brain circuits. In the cerebral cortex, in particular, it has been observed that reciprocal connections are often present between functionally interconnected areas that are hierarchically organized. We investigate the effect of reciprocal connections in a network of modules of simulated spiking neurons. The neural activity is recorded by means of virtual electrodes and EEG-like signals, called electrochipograms (EChG), analyzed by time- and frequency-domain methods. A major feature of our approach is the implementation of important bio-inspired processes that affect the connectivity within a neural module: synaptogenesis, cell death, spike-timing-dependent plasticity and synaptic pruning. These bio-inspired processes drive the build-up of auto-associative links within each module, which generate an areal activity, recorded by EChG, that reflect the changes in the corresponding functional connectivity within and between neuronal modules. We found that circuits with intra-layer reciprocal projections exhibited enhanced stimulus-locked response. We show evidence that all networks of modules are able to process and maintain patterns of activity associated with the stimulus after its offset. The presence of feedback and horizontal projections was necessary to evoke cross-layer coherence in bursts of -frequency at regular intervals. These findings bring new insights to the understanding of the relation between the functional organization of neural circuits and the electrophysiological signals generated by large cell assemblies. This article is part of a Special Issue entitled "Neural Coding".

  20. FGF signaling in gastrulation and neural development in Nematostella vectensis, an anthozoan cnidarian.

    PubMed

    Matus, David Q; Thomsen, Gerald H; Martindale, Mark Q

    2007-02-01

    The fibroblast growth factor (FGF) signal transduction pathway serves as one of the key regulators of early metazoan development, displaying conserved roles in the specification of endodermal, mesodermal, and neural fates during vertebrate development. FGF signals also regulate gastrulation, in part, by triggering epithelial to mesenchymal transitions in embryos of both vertebrates and invertebrates. Thus, FGF signals coordinate gastrulation movements across many different phyla. To help understand the breadth of FGF signaling deployment across the animal kingdom, we have examined the presence and expression of genes encoding FGF pathway components in the anthozoan cnidarian Nematostella vectensis. We isolated three FGF ligands (NvFGF8A, NvFGF8B, and NvFGF1A), two FGF receptors (NvFGFRa and NvFGFRb), and two orthologs of vertebrate FGF responsive genes, Sprouty (NvSprouty), an inhibitor of FGF signaling, and Churchill (NvChurchill), a Zn finger transcription factor. We found these FGF ligands, receptors, and response gene expressed asymmetrically along the oral/aboral axis during gastrulation and in a developing chemosensory structure of planula stages known as the apical tuft. These results suggest a conserved role for FGF signaling molecules in coordinating both gastrulation and neural induction that predates the Cambrian explosion and the origins of the Bilateria.

  1. Quality-on-Demand Compression of EEG Signals for Telemedicine Applications Using Neural Network Predictors

    PubMed Central

    Sriraam, N.

    2011-01-01

    A telemedicine system using communication and information technology to deliver medical signals such as ECG, EEG for long distance medical services has become reality. In either the urgent treatment or ordinary healthcare, it is necessary to compress these signals for the efficient use of bandwidth. This paper discusses a quality on demand compression of EEG signals using neural network predictors for telemedicine applications. The objective is to obtain a greater compression gains at a low bit rate while preserving the clinical information content. A two-stage compression scheme with a predictor and an entropy encoder is used. The residue signals obtained after prediction is first thresholded using various levels of thresholds and are further quantized and then encoded using an arithmetic encoder. Three neural network models, single-layer and multi-layer perceptrons and Elman network are used and the results are compared with linear predictors such as FIR filters and AR modeling. The fidelity of the reconstructed EEG signal is assessed quantitatively using parameters such as PRD, SNR, cross correlation and power spectral density. It is found from the results that the quality of the reconstructed signal is preserved at a low PRD thereby yielding better compression results compared to results obtained using lossless scheme. PMID:21785587

  2. Inhibition of FGF signaling accelerates neural crest cell differentiation of human pluripotent stem cells.

    PubMed

    Jaroonwitchawan, Thiranut; Muangchan, Pattamon; Noisa, Parinya

    2016-12-02

    Neural crest (NC) is a transient population, arising during embryonic development and capable of differentiating into various somatic cells. The defects of neural crest development leads to neurocristopathy. Several signaling pathways were revealed their significance in NC cell specification. Fibroblast growth factor (FGF) is recognized as an important signaling during NC development, for instance Xenopus and avian; however, its contributions in human species are remained elusive. Here we used human pluripotent stem cells (hPSCs) to investigate the consequences of FGF inhibition during NC cell differentiation. The specific-FGF receptor inhibitor, SU5402, was used in this investigation. The inhibition of FGF did not found to affect the proliferation or death of hPSC-derived NC cells, but promoted hPSCs to commit NC cell fate. NC-specific genes, including PAX3, SLUG, and TWIST1, were highly upregulated, while hPSC genes, such as OCT4, and E-CAD, rapidly reduced upon FGF signaling blockage. Noteworthy, TFAP-2α, a marker of migratory NC cells, abundantly presented in SU5402-induced cells. This accelerated NC cell differentiation could be due to the activation of Notch signaling upon the blockage of ERK1/2 phosphorylation, since NICD was increased by SU5402. Altogether, this study proposed the contributions of FGF signaling in controlling human NC cell differentiation from hPSCs, the crosstalk between FGF and Notch, and might imply to the influences of FGF signaling in neurocristophatic diseases.

  3. Neural network classifier with analytic translation and scaling capabilities for optimal signal viewing

    SciTech Connect

    Vilim, R.B.; Wegerich, S.W.

    1995-12-31

    A neural network originally proposed by Szu for performing pattern recognition has been modified for use in a noisy manufacturing environment. Signals from the factory floor are frequently affine transformed and, as a consequence, a signal may not be properly aligned with respect to the input node that corresponds to the signal leading edge or with respect to the number of nodes representing the time varying part. Rater than translate and scale the presented signal, an operation which because of noise can be prone to numerical error since the signal is not smoothly varying, the network in this paper has the capability to analytically translate and scale its internal representation of the signal so that it overlays the presented signal. A response surface in the neighborhood of the stored reference signal is built during, training, and covers the range of translate and scale parameter values expected. A genetic algorithm is used to search over this hilly terrain to find the optimal values of these parameters so that the reference signal overlays the presented signal. The procedure is repeated over all hypothesized pattern classes with the best fit identifying the class.

  4. Global exponential stability and dissipativity of generalized neural networks with time-varying delay signals.

    PubMed

    Manivannan, R; Samidurai, R; Cao, Jinde; Alsaedi, Ahmed; Alsaadi, Fuad E

    2017-03-01

    This paper investigates the problems of exponential stability and dissipativity of generalized neural networks (GNNs) with time-varying delay signals. By constructing a novel Lyapunov-Krasovskii functionals (LKFs) with triple integral terms that contain more advantages of the state vectors of the neural networks, and the upper bound on the time-varying delay signals are formulated. We employ a new integral inequality technique (IIT), free-matrix-based (FMB) integral inequality approach, and Wirtinger double integral inequality (WDII) technique together with the reciprocally convex combination (RCC) approach to bound the time derivative of the LKFs. An improved exponential stability and strictly (Q,S,R)-γ-dissipative conditions of the addressed systems are represented by the linear matrix inequalities (LMIs). Finally, four interesting numerical examples are developed to verify the usefulness of the proposed method with a practical application to a biological network.

  5. Recovery of noisy pyroelectric-detector signals through neural-network processing

    NASA Astrophysics Data System (ADS)

    González, Martín G.; Peuriot, Alejandro L.; Slezak, Verónica B.; Santiago, Guillermo D.

    2005-05-01

    We introduce a neural-network-based filter devised to extend the dynamic range of pyroelectric detectors which otherwise would only be useful for medium-to-high energy measurements. To accomplish this task, we trained a multilayer perceptron through the back-propagation method using the theoretical signal derived from the detector equivalent electric circuit. We tested the performance of the neural-network filter both numerically and experimentally. In the former case we recovered theoretical signals corrupted with white and impulse noise and compared the results with those obtained through the use of standard filtering methods. In the latter case, we applied the filter to measure pulses from a Nd:YAG laser whose energy was below the detector noise-equivalent energy. With this processing technique in a standard PC we have been able to accurately measure laser energy values as low as one-tenth the detector's noise-equivalent energy and at 10-20Hz repetition rate.

  6. Anomalous Signal Detection in ELF Band Electromagnetic Wave using Multi-layer Neural Network with Wavelet Decomposition

    NASA Astrophysics Data System (ADS)

    Itai, Akitoshi; Yasukawa, Hiroshi; Takumi, Ichi; Hata, Masayasu

    It is well known that electromagnetic waves radiated from the earth's crust are useful for predicting earthquakes. We analyze the electromagnetic waves received at the extremely low frequency band of 223Hz. These observed signals contain the seismic radiation from the earth's crust, but also include several undesired signals. Our research focuses on the signal detection technique to identify an anomalous signal corresponding to the seismic radiation in the observed signal. Conventional anomalous signal detections lack a wide applicability due to their assumptions, e.g. the digital data have to be observed at the same time or the same sensor. In order to overcome the limitation related to the observed signal, we proposed the anomalous signals detection based on a multi-layer neural network which is trained by digital data observed during a span of a day. In the neural network approach, training data do not need to be recorded at the same place or the same time. However, some noises, which have a large amplitude, are detected as the anomalous signal. This paper develops a multi-layer neural network to decrease the false detection of the anomalous signal from the electromagnetic wave. The training data for the proposed network is the decomposed signal of the observed signal during several days, since the seismic radiations are often recorded from several days to a couple of weeks. Results show that the proposed neural network is useful to achieve the accurate detection of the anomalous signal that indicates seismic activity.

  7. Wireless Telemetry of In-Flight Collision Avoidance Neural Signals in Insects

    DTIC Science & Technology

    2010-09-01

    AFRL-RW-EG-TR-2010-110 Wireless Telemetry of In-Flight Collision Avoidance Neural Signals in Insects Reid R. Harrison Fabrizio...in Insects 5b. GRANT NUMBER FA8651-07-1-0007 5c. PROGRAM ELEMENT NUMBER 62602F 6. AUTHOR(S) Reid R. Harrison Fabrizio Gabbiani Ryan J...14. ABSTRACT Modern neuroscience research often relies on experiments using small animals such as mice and insects . For example, flying insects

  8. Comparison of Near Infrared Spectroscopy (NIRS) Signal Quantitation by Multilinear Regression and Neural Networks

    DTIC Science & Technology

    2007-11-02

    aim of this study was to compare NIRS signal quantitation by conventional multiple regression to artificial neural networks. Sixteen adult sheep were...Electrocardiography was monitored with electrodes clipped to the extremities. Surgery After wool was removed from the neck and thigh area, incisions...network was trained with results obtained from three sheep and validated in one. Initially, network weight matrices were randomly assigned. After training

  9. Neural crest cell signaling pathways critical to cranial bone development and pathology.

    PubMed

    Mishina, Yuji; Snider, Taylor Nicholas

    2014-07-15

    Neural crest cells appear early during embryogenesis and give rise to many structures in the mature adult. In particular, a specific population of neural crest cells migrates to and populates developing cranial tissues. The ensuing differentiation of these cells via individual complex and often intersecting signaling pathways is indispensible to growth and development of the craniofacial complex. Much research has been devoted to this area of development with particular emphasis on cell signaling events required for physiologic development. Understanding such mechanisms will allow researchers to investigate ways in which they can be exploited in order to treat a multitude of diseases affecting the craniofacial complex. Knowing how these multipotent cells are driven towards distinct fates could, in due course, allow patients to receive regenerative therapies for tissues lost to a variety of pathologies. In order to realize this goal, nucleotide sequencing advances allowing snapshots of entire genomes and exomes are being utilized to identify molecular entities associated with disease states. Once identified, these entities can be validated for biological significance with other methods. A crucial next step is the integration of knowledge gleaned from observations in disease states with normal physiology to generate an explanatory model for craniofacial development. This review seeks to provide a current view of the landscape on cell signaling and fate determination of the neural crest and to provide possible avenues of approach for future research.

  10. On the use of information theory for the analysis of the relationship between neural and imaging signals.

    PubMed

    Panzeri, Stefano; Magri, Cesare; Logothetis, Nikos K

    2008-09-01

    Functional magnetic resonance imaging (fMRI) is a widely used method for studying the neural basis of cognition and of sensory function. A potential problem in the interpretation of fMRI data is that fMRI measures neural activity only indirectly, as a local change of deoxyhemoglobin concentration due to the metabolic demands of neural function. To build correct sensory and cognitive maps in the human brain, it is thus crucial to understand whether fMRI and neural activity convey the same type of information about external correlates. While a substantial experimental effort has been devoted to the simultaneous recordings of hemodynamic and neural signals, so far, the development of analysis methods that elucidate how neural and hemodynamic signals represent sensory information has received less attention. In this article, we critically review why the analytical framework of information theory, the mathematical theory of communication, is ideally suited to this purpose. We review the principles of information theory and explain how they could be applied to the analysis of fMRI and neural signals. We show that a critical advantage of information theory over more traditional analysis paradigms commonly used in the fMRI literature is that it can elucidate, within a single framework, whether an empirically observed correlation between neural and fMRI signals reflects either a similar stimulus tuning or a common source of variability unrelated to the external stimuli. In addition, information theory determines the extent to which these shared sources of stimulus signal and of variability lead fMRI and neural signals to convey similar information about external correlates. We then illustrate the formalism by applying it to the analysis of the information carried by different bands of the local field potential. We conclude by discussing the current methodological challenges that need to be addressed to make the information-theoretic approach more robustly applicable to the

  11. EEG signal classification based on artificial neural networks and amplitude spectra features

    NASA Astrophysics Data System (ADS)

    Chojnowski, K.; FrÄ czek, J.

    BCI (called Brain-Computer Interface) is an interface that allows direct communication between human brain and an external device. It bases on EEG signal collection, processing and classification. In this paper a complete BCI system is presented which classifies EEG signal using artificial neural networks. For this purpose we used a multi-layered perceptron architecture trained with the RProp algorithm. Furthermore a simple multi-threaded method for automatic network structure optimizing was shown. We presented the results of our system in the opening and closing eyes recognition task. We also showed how our system could be used for controlling devices basing on imaginary hand movements.

  12. Primary cilium and sonic hedgehog signaling during neural tube patterning: role of GPCRs and second messengers.

    PubMed

    Pal, Kasturi; Mukhopadhyay, Saikat

    2015-04-01

    The ventral neural tube in vertebrates is patterned by a gradient of sonic hedgehog (Shh) secreted from the notochord and floor plate. Forward genetic screens first pointed to the role of the primary cilium in ventral neural tube patterning. Further research has shown that most components of the Shh pathway localize to or shuttle through the primary cilium. In the absence of Shh, the bifunctional Gli transcription factors are proteolytically processed into repressor forms in a protein kinase A (PKA)- and cilium-dependent manner. Recent work suggests that the orphan G-protein-coupled receptor (GPCR) Gpr161 localizes to cilia, and functions as a negative regulator of Shh signaling by determining Gli processing via cAMP signaling. The primary cilium also functions as a signaling compartment for calcium in the Shh pathway. A better understanding of the role of the cilium as a signaling compartment, and the interplay of second messenger systems that regulate PKA activation and Gli amplification during signaling is critical for deciphering the role of Shh during development, neuronal differentiation, and tumorigenesis.

  13. Genetic algorithm for the optimization of features and neural networks in ECG signals classification

    NASA Astrophysics Data System (ADS)

    Li, Hongqiang; Yuan, Danyang; Ma, Xiangdong; Cui, Dianyin; Cao, Lu

    2017-01-01

    Feature extraction and classification of electrocardiogram (ECG) signals are necessary for the automatic diagnosis of cardiac diseases. In this study, a novel method based on genetic algorithm-back propagation neural network (GA-BPNN) for classifying ECG signals with feature extraction using wavelet packet decomposition (WPD) is proposed. WPD combined with the statistical method is utilized to extract the effective features of ECG signals. The statistical features of the wavelet packet coefficients are calculated as the feature sets. GA is employed to decrease the dimensions of the feature sets and to optimize the weights and biases of the back propagation neural network (BPNN). Thereafter, the optimized BPNN classifier is applied to classify six types of ECG signals. In addition, an experimental platform is constructed for ECG signal acquisition to supply the ECG data for verifying the effectiveness of the proposed method. The GA-BPNN method with the MIT-BIH arrhythmia database achieved a dimension reduction of nearly 50% and produced good classification results with an accuracy of 97.78%. The experimental results based on the established acquisition platform indicated that the GA-BPNN method achieved a high classification accuracy of 99.33% and could be efficiently applied in the automatic identification of cardiac arrhythmias.

  14. Detection and identification of seismic signals recorded at Krakatau volcano (Indonesia) using artificial neural networks

    NASA Astrophysics Data System (ADS)

    Ibs-von Seht, M.

    2008-10-01

    The Anak Krakatau volcano (Indonesia) has been monitored by a multi-parametric system since 2005. A variety of signal types can be observed in the records of the seismic stations installed on the island volcano. These include volcano-induced signals such as LP, VT, and tremor-type events as well as signals not originating from the volcano such as regional tectonic earthquakes and transient noise signals. The work presented here aims at the realization of a system that automatically detects and identifies the signals in order to estimate and monitor current activity states of the volcano. An artificial neural network approach was chosen for the identification task. A set of parameters was defined, describing waveform and spectrogram properties of events detected by an amplitude-ratio-based (STA/LTA) algorithm. The parameters are fed into a neural network which is, after a training phase, able to generalize input data and identify corresponding event types. The success of the identification depends on the network architecture and training strategy. Several tests have been performed in order to determine appropriate network layout and training for the given problem. The performance of the final system is found to be well suited to get an overview of the seismic activity recorded at the volcano. The reliability of the network classifier, as well as general drawbacks of the methods used, are discussed.

  15. Genetic algorithm for the optimization of features and neural networks in ECG signals classification

    PubMed Central

    Li, Hongqiang; Yuan, Danyang; Ma, Xiangdong; Cui, Dianyin; Cao, Lu

    2017-01-01

    Feature extraction and classification of electrocardiogram (ECG) signals are necessary for the automatic diagnosis of cardiac diseases. In this study, a novel method based on genetic algorithm-back propagation neural network (GA-BPNN) for classifying ECG signals with feature extraction using wavelet packet decomposition (WPD) is proposed. WPD combined with the statistical method is utilized to extract the effective features of ECG signals. The statistical features of the wavelet packet coefficients are calculated as the feature sets. GA is employed to decrease the dimensions of the feature sets and to optimize the weights and biases of the back propagation neural network (BPNN). Thereafter, the optimized BPNN classifier is applied to classify six types of ECG signals. In addition, an experimental platform is constructed for ECG signal acquisition to supply the ECG data for verifying the effectiveness of the proposed method. The GA-BPNN method with the MIT-BIH arrhythmia database achieved a dimension reduction of nearly 50% and produced good classification results with an accuracy of 97.78%. The experimental results based on the established acquisition platform indicated that the GA-BPNN method achieved a high classification accuracy of 99.33% and could be efficiently applied in the automatic identification of cardiac arrhythmias. PMID:28139677

  16. Embryonic requirements for ErbB signaling in neural crest development and adult pigment pattern formation

    PubMed Central

    Budi, Erine H.; Patterson, Larissa B.; Parichy, David M.

    2009-01-01

    SUMMARY Vertebrate pigment cells are derived from neural crest cells and are a useful system for studying neural crest-derived traits during post-embryonic development. In zebrafish, neural crest-derived melanophores differentiate during embryogenesis to produce stripes in the early larva. Dramatic changes to the pigment pattern occur subsequently during the larva-to-adult transformation, or metamorphosis. At this time, embryonic melanophores are replaced by newly differentiating metamorphic melanophores that form the adult stripes. Mutants with normal embryonic/early larval pigment patterns but defective adult patterns identify factors required uniquely to establish, maintain, or recruit the latent precursors to metamorphic melanophores. We show that one such mutant, picasso, lacks most metamorphic melanophores and results from mutations in the ErbB gene erbb3b, encoding an EGFR-like receptor tyrosine kinase. To identify critical periods for ErbB activities, we treated fish with pharmacological ErbB inhibitors and also knocked-down erbb3b by morpholino injection. These analyses reveal an embryonic critical period for ErbB signaling in promoting later pigment pattern metamorphosis, despite the normal patterning of embryonic/early larval melanophores. We further demonstrate a peak requirement during neural crest migration that correlates with early defects in neural crest pathfinding and peripheral ganglion formation. Finally, we show that erbb3b activities are both autonomous and non-autonomous to the metamorphic melanophore lineage. These data identify a very early, embryonic, requirement for erbb3b in the development of much later metamorphic melanophores, and suggest complex modes by which ErbB signals promote adult pigment pattern development. PMID:18508863

  17. Differential requirements of BMP and Wnt signalling during gastrulation and neurulation define two steps in neural crest induction.

    PubMed

    Steventon, Ben; Araya, Claudio; Linker, Claudia; Kuriyama, Sei; Mayor, Roberto

    2009-03-01

    The neural crest is induced by a combination of secreted signals. Although previous models of neural crest induction have proposed a step-wise activation of these signals, the actual spatial and temporal requirement has not been analysed. Through analysing the role of the mesoderm we show for the first time that specification of neural crest requires two temporally and chemically different steps: first, an induction at the gastrula stage dependent on signals arising from the dorsolateral mesoderm; and second, a maintenance step at the neurula stage dependent on signals from tissues adjacent to the neural crest. By performing tissue recombination experiments and using specific inhibitors of different inductive signals, we show that the first inductive step requires Wnt activation and BMP inhibition, whereas the later maintenance step requires activation of both pathways. This change in BMP necessity from BMP inhibition at gastrula to BMP activation at neurula stages is further supported by the dynamic expression of BMP4 and its antagonists, and is confirmed by direct measurements of BMP activity in the neural crest cells. The differential requirements of BMP activity allow us to propose an explanation for apparently discrepant results between chick and frog experiments. The demonstration that Wnt signals are required for neural crest induction by mesoderm solves an additional long-standing controversy. Finally, our results emphasise the importance of considering the order of exposure to signals during an inductive event.

  18. RBF neural network prediction on weak electrical signals in Aloe vera var. chinensis

    NASA Astrophysics Data System (ADS)

    Wang, Lanzhou; Zhao, Jiayin; Wang, Miao

    2008-10-01

    A Gaussian radial base function (RBF) neural network forecast on signals in the Aloe vera var. chinensis by the wavelet soft-threshold denoised as the time series and using the delayed input window chosen at 50, is set up to forecast backward. There was the maximum amplitude at 310.45μV, minimum -75.15μV, average value -2.69μV and <1.5Hz at frequency in Aloe vera var. chinensis respectively. The electrical signal in Aloe vera var. chinensis is a sort of weak, unstable and low frequency signals. A result showed that it is feasible to forecast plant electrical signals for the timing by the RBF. The forecast data can be used as the preferences for the intelligent autocontrol system based on the adaptive characteristic of plants to achieve the energy saving on the agricultural production in the plastic lookum or greenhouse.

  19. A probablistic neural network classification system for signal and image processing

    SciTech Connect

    Bowman, B.

    1994-11-15

    The Acoustical Heart Valve Analysis Package is a system for signal and image processing and classification. It is being developed in both Matlab and C, to provide an interactive, interpreted environment, and has been optimized for large scale matrix operations. It has been used successfully to classify acoustic signals from implanted prosthetic heart valves in human patients, and will be integrated into a commercial Heart Valve Screening Center. The system uses several standard signal processing algorithms, as well as supervised learning techniques using the probabilistic neural network (PNN). Although currently used for the acoustic heart valve application, the algorithms and modular design allow it to be used for other applications, as well. We will describe the signal classification system, and show results from a set of test valves.

  20. Intra-day signal instabilities affect decoding performance in an intracortical neural interface system

    NASA Astrophysics Data System (ADS)

    Perge, János A.; Homer, Mark L.; Malik, Wasim Q.; Cash, Sydney; Eskandar, Emad; Friehs, Gerhard; Donoghue, John P.; Hochberg, Leigh R.

    2013-06-01

    Objective. Motor neural interface systems (NIS) aim to convert neural signals into motor prosthetic or assistive device control, allowing people with paralysis to regain movement or control over their immediate environment. Effector or prosthetic control can degrade if the relationship between recorded neural signals and intended motor behavior changes. Therefore, characterizing both biological and technological sources of signal variability is important for a reliable NIS. Approach. To address the frequency and causes of neural signal variability in a spike-based NIS, we analyzed within-day fluctuations in spiking activity and action potential amplitude recorded with silicon microelectrode arrays implanted in the motor cortex of three people with tetraplegia (BrainGate pilot clinical trial, IDE). Main results. 84% of the recorded units showed a statistically significant change in apparent firing rate (3.8 ± 8.71 Hz or 49% of the mean rate) across several-minute epochs of tasks performed on a single session, and 74% of the units showed a significant change in spike amplitude (3.7 ± 6.5 µV or 5.5% of mean spike amplitude). 40% of the recording sessions showed a significant correlation in the occurrence of amplitude changes across electrodes, suggesting array micro-movement. Despite the relatively frequent amplitude changes, only 15% of the observed within-day rate changes originated from recording artifacts such as spike amplitude change or electrical noise, while 85% of the rate changes most likely emerged from physiological mechanisms. Computer simulations confirmed that systematic rate changes of individual neurons could produce a directional ‘bias’ in the decoded neural cursor movements. Instability in apparent neuronal spike rates indeed yielded a directional bias in 56% of all performance assessments in participant cursor control (n = 2 participants, 108 and 20 assessments over two years), resulting in suboptimal performance in these sessions

  1. Modeling Neural Immune Signaling of Episodic and Chronic Migraine Using Spreading Depression In Vitro

    PubMed Central

    Mitchell, Heidi M.; Kraig, Richard P.

    2011-01-01

    Migraine and its transformation to chronic migraine are healthcare burdens in need of improved treatment options. We seek to define how neural immune signaling modulates the susceptibility to migraine, modeled in vitro using spreading depression (SD), as a means to develop novel therapeutic targets for episodic and chronic migraine. SD is the likely cause of migraine aura and migraine pain. It is a paroxysmal loss of neuronal function triggered by initially increased neuronal activity, which slowly propagates within susceptible brain regions. Normal brain function is exquisitely sensitive to, and relies on, coincident low-level immune signaling. Thus, neural immune signaling likely affects electrical activity of SD, and therefore migraine. Pain perception studies of SD in whole animals are fraught with difficulties, but whole animals are well suited to examine systems biology aspects of migraine since SD activates trigeminal nociceptive pathways. However, whole animal studies alone cannot be used to decipher the cellular and neural circuit mechanisms of SD. Instead, in vitro preparations where environmental conditions can be controlled are necessary. Here, it is important to recognize limitations of acute slices and distinct advantages of hippocampal slice cultures. Acute brain slices cannot reveal subtle changes in immune signaling since preparing the slices alone triggers: pro-inflammatory changes that last days, epileptiform behavior due to high levels of oxygen tension needed to vitalize the slices, and irreversible cell injury at anoxic slice centers. In contrast, we examine immune signaling in mature hippocampal slice cultures since the cultures closely parallel their in vivo counterpart with mature trisynaptic function; show quiescent astrocytes, microglia, and cytokine levels; and SD is easily induced in an unanesthetized preparation. Furthermore, the slices are long-lived and SD can be induced on consecutive days without injury, making this preparation the

  2. Signal processing and neural network toolbox and its application to failure diagnosis and prognosis

    NASA Astrophysics Data System (ADS)

    Tu, Fang; Wen, Fang; Willett, Peter K.; Pattipati, Krishna R.; Jordan, Eric H.

    2001-07-01

    Many systems are comprised of components equipped with self-testing capability; however, if the system is complex involving feedback and the self-testing itself may occasionally be faulty, tracing faults to a single or multiple causes is difficult. Moreover, many sensors are incapable of reliable decision-making on their own. In such cases, a signal processing front-end that can match inference needs will be very helpful. The work is concerned with providing an object-oriented simulation environment for signal processing and neural network-based fault diagnosis and prognosis. In the toolbox, we implemented a wide range of spectral and statistical manipulation methods such as filters, harmonic analyzers, transient detectors, and multi-resolution decomposition to extract features for failure events from data collected by data sensors. Then we evaluated multiple learning paradigms for general classification, diagnosis and prognosis. The network models evaluated include Restricted Coulomb Energy (RCE) Neural Network, Learning Vector Quantization (LVQ), Decision Trees (C4.5), Fuzzy Adaptive Resonance Theory (FuzzyArtmap), Linear Discriminant Rule (LDR), Quadratic Discriminant Rule (QDR), Radial Basis Functions (RBF), Multiple Layer Perceptrons (MLP) and Single Layer Perceptrons (SLP). Validation techniques, such as N-fold cross-validation and bootstrap techniques, are employed for evaluating the robustness of network models. The trained networks are evaluated for their performance using test data on the basis of percent error rates obtained via cross-validation, time efficiency, generalization ability to unseen faults. Finally, the usage of neural networks for the prediction of residual life of turbine blades with thermal barrier coatings is described and the results are shown. The neural network toolbox has also been applied to fault diagnosis in mixed-signal circuits.

  3. Nitric Oxide Signaling and Neural Stem Cell Differentiation in Peripheral Nerve Regeneration

    PubMed Central

    Tao Li, Jessica; Somasundaram, Chandra; Bian, Ka; Xiong, Weijun; Mahmooduddin, Faiz; Nath, Rahul K.; Murad, Ferid

    2010-01-01

    Objective: The objective was to examine whether nitric oxide signaling plays a role in human embryonic stem cell differentiation into neural cells. This article reviews current literature on nitric oxide signaling and neural stem cell differentiation for potential therapeutic application to peripheral nerve regeneration. Methods: Human embryonic H9-stem cells were grown, maintained on mitomycin C–treated mouse embryonic fibroblast feeder layer, cultured on Matrigel to be feeder-free, and used for all the experiments. Fluorescent dual-immunolabeling and confocal image analysis were used to detect the presence of the neural precursor cell markers nestin and nitric oxide synthase-1. Fluorescence-activated cell sorting analysis was used to determine the percentage of expression. Results: We have shown the confocal image of stage 1 human embryonic stem cells coexpressing nestin and nitric oxide synthase-1. Fluorescence-activated cell sorting analysis indicated 24.3% positive labeling of nitric oxide synthase-1. Adding retinoic acid (10−6 M) to the culture medium increased the percent of nitric oxide synthase-1 positive cells to 33.9%. Combining retinoic acid (10−6 M) with 8-brom cyclic guanosine monophosphate (10−5 M), the fluorescence-activated cell sorting analysis demonstrated a further increase of nitric oxide synthase-1 positive cells to 45.4%. Our current results demonstrate a prodifferentiation potency of nitric oxide synthase-1, stimulated by retinoic acid with and without cyclic guanosine monophosphate. Conclusion: We demonstrated for the first time how nitric oxide/cyclic guanosine monophosphate signaling contributes to the development of neural precursors derived from human embryonic stem cells and enhances the differentiation of precursors toward functional neurons for peripheral nerve regeneration. PMID:20563304

  4. Integration of signals along orthogonal axes of the vertebrate neural tube controls progenitor competence and increases cell diversity.

    PubMed

    Sasai, Noriaki; Kutejova, Eva; Briscoe, James

    2014-07-01

    A relatively small number of signals are responsible for the variety and pattern of cell types generated in developing embryos. In part this is achieved by exploiting differences in the concentration or duration of signaling to increase cellular diversity. In addition, however, changes in cellular competence-temporal shifts in the response of cells to a signal-contribute to the array of cell types generated. Here we investigate how these two mechanisms are combined in the vertebrate neural tube to increase the range of cell types and deliver spatial control over their location. We provide evidence that FGF signaling emanating from the posterior of the embryo controls a change in competence of neural progenitors to Shh and BMP, the two morphogens that are responsible for patterning the ventral and dorsal regions of the neural tube, respectively. Newly generated neural progenitors are exposed to FGF signaling, and this maintains the expression of the Nk1-class transcription factor Nkx1.2. Ventrally, this acts in combination with the Shh-induced transcription factor FoxA2 to specify floor plate cells and dorsally in combination with BMP signaling to induce neural crest cells. As development progresses, the intersection of FGF with BMP and Shh signals is interrupted by axis elongation, resulting in the loss of Nkx1.2 expression and allowing the induction of ventral and dorsal interneuron progenitors by Shh and BMP signaling to supervene. Hence a similar mechanism increases cell type diversity at both dorsal and ventral poles of the neural tube. Together these data reveal that tissue morphogenesis produces changes in the coincidence of signals acting along orthogonal axes of the neural tube and this is used to define spatial and temporal transitions in the competence of cells to interpret morphogen signaling.

  5. Social discounting involves modulation of neural value signals by temporoparietal junction.

    PubMed

    Strombach, Tina; Weber, Bernd; Hangebrauk, Zsofia; Kenning, Peter; Karipidis, Iliana I; Tobler, Philippe N; Kalenscher, Tobias

    2015-02-03

    Most people are generous, but not toward everyone alike: generosity usually declines with social distance between individuals, a phenomenon called social discounting. Despite the pervasiveness of social discounting, social distance between actors has been surprisingly neglected in economic theory and neuroscientific research. We used functional magnetic resonance imaging (fMRI) to study the neural basis of this process to understand the neural underpinnings of social decision making. Participants chose between selfish and generous alternatives, yielding either a large reward for the participant alone, or smaller rewards for the participant and another individual at a particular social distance. We found that generous choices engaged the temporoparietal junction (TPJ). In particular, the TPJ activity was scaled to the social-distance-dependent conflict between selfish and generous motives during prosocial choice, consistent with ideas that the TPJ promotes generosity by facilitating overcoming egoism bias. Based on functional coupling data, we propose and provide evidence for a biologically plausible neural model according to which the TPJ supports social discounting by modulating basic neural value signals in the ventromedial prefrontal cortex to incorporate social-distance-dependent other-regarding preferences into an otherwise exclusively own-reward value representation.

  6. Social discounting involves modulation of neural value signals by temporoparietal junction

    PubMed Central

    Strombach, Tina; Weber, Bernd; Hangebrauk, Zsofia; Kenning, Peter; Karipidis, Iliana I.; Tobler, Philippe N.; Kalenscher, Tobias

    2015-01-01

    Most people are generous, but not toward everyone alike: generosity usually declines with social distance between individuals, a phenomenon called social discounting. Despite the pervasiveness of social discounting, social distance between actors has been surprisingly neglected in economic theory and neuroscientific research. We used functional magnetic resonance imaging (fMRI) to study the neural basis of this process to understand the neural underpinnings of social decision making. Participants chose between selfish and generous alternatives, yielding either a large reward for the participant alone, or smaller rewards for the participant and another individual at a particular social distance. We found that generous choices engaged the temporoparietal junction (TPJ). In particular, the TPJ activity was scaled to the social-distance–dependent conflict between selfish and generous motives during prosocial choice, consistent with ideas that the TPJ promotes generosity by facilitating overcoming egoism bias. Based on functional coupling data, we propose and provide evidence for a biologically plausible neural model according to which the TPJ supports social discounting by modulating basic neural value signals in the ventromedial prefrontal cortex to incorporate social-distance–dependent other-regarding preferences into an otherwise exclusively own-reward value representation. PMID:25605887

  7. Performance evaluation of neural network and linear predictors for near-lossless compression of EEG signals.

    PubMed

    Sriraam, N; Eswaran, C

    2008-01-01

    This paper presents a comparison of the performances of neural network and linear predictors for near-lossless compression of EEG signals. Three neural network predictors, namely, single-layer perceptron (SLP), multilayer perceptron (MLP), and Elman network (EN), and two linear predictors, namely, autoregressive model (AR) and finite-impulse response filter (FIR) are used. For all the predictors, uniform quantization is applied on the residue signals obtained as the difference between the original and the predicted values. The maximum allowable reconstruction error delta is varied to determine the theoretical bound delta 0 for near-lossless compression and the corresponding bit rate rp. It is shown that among all the predictors, the SLP yields the best results in achieving the lowest values for delta 0 and rp. The corresponding values of the fidelity parameters, namely, percent of root-mean-square difference, peak SNR and cross correlation are also determined. A compression efficiency of 82.8% is achieved using the SLP with a near-lossless bound delta 0 = 3, with the diagnostic quality of the reconstructed EEG signal preserved. Thus, the proposed near-lossless scheme facilitates transmission of real time as well as offline EEG signals over network to remote interpretation center economically with less bandwidth utilization compared to other known lossless and near-lossless schemes.

  8. Altered neural reward and loss processing and prediction error signalling in depression.

    PubMed

    Ubl, Bettina; Kuehner, Christine; Kirsch, Peter; Ruttorf, Michaela; Diener, Carsten; Flor, Herta

    2015-08-01

    Dysfunctional processing of reward and punishment may play an important role in depression. However, functional magnetic resonance imaging (fMRI) studies have shown heterogeneous results for reward processing in fronto-striatal regions. We examined neural responsivity associated with the processing of reward and loss during anticipation and receipt of incentives and related prediction error (PE) signalling in depressed individuals. Thirty medication-free depressed persons and 28 healthy controls performed an fMRI reward paradigm. Regions of interest analyses focused on neural responses during anticipation and receipt of gains and losses and related PE-signals. Additionally, we assessed the relationship between neural responsivity during gain/loss processing and hedonic capacity. When compared with healthy controls, depressed individuals showed reduced fronto-striatal activity during anticipation of gains and losses. The groups did not significantly differ in response to reward and loss outcomes. In depressed individuals, activity increases in the orbitofrontal cortex and nucleus accumbens during reward anticipation were associated with hedonic capacity. Depressed individuals showed an absence of reward-related PEs but encoded loss-related PEs in the ventral striatum. Depression seems to be linked to blunted responsivity in fronto-striatal regions associated with limited motivational responses for rewards and losses. Alterations in PE encoding might mirror blunted reward- and enhanced loss-related associative learning in depression.

  9. Diverse ETS transcription factors mediate FGF signaling in the Ciona anterior neural plate.

    PubMed

    Gainous, T Blair; Wagner, Eileen; Levine, Michael

    2015-03-15

    The ascidian Ciona intestinalis is a marine invertebrate belonging to the sister group of the vertebrates, the tunicates. Its compact genome and simple, experimentally tractable embryos make Ciona well-suited for the study of cell-fate specification in chordates. Tunicate larvae possess a characteristic chordate body plan, and many developmental pathways are conserved between tunicates and vertebrates. Previous studies have shown that FGF signals are essential for neural induction and patterning at sequential steps of Ciona embryogenesis. Here we show that two different ETS family transcription factors, Ets1/2 and Elk1/3/4, have partially redundant activities in the anterior neural plate of gastrulating embryos. Whereas Ets1/2 promotes pigment cell formation in lateral lineages, both Ets1/2 and Elk1/3/4 are involved in the activation of Myt1L in medial lineages and the restriction of Six3/6 expression to the anterior-most regions of the neural tube. We also provide evidence that photoreceptor cells arise from posterior regions of the presumptive sensory vesicle, and do not depend on FGF signaling. Cells previously identified as photoreceptor progenitors instead form ependymal cells and neurons of the larval brain. Our results extend recent findings on FGF-dependent patterning of anterior-posterior compartments in the Ciona central nervous system.

  10. Prediction of density limit disruption boundaries from diagnostic signals using neural networks

    NASA Astrophysics Data System (ADS)

    Sengupta, A.; Ranjan, P.

    2001-05-01

    An attempt is made to make a prediction of the disruption boundaries for the density limit disruption case using a neural network. Using experimental signals as input, the network should, in the long run, be able to provide information to the real time control systems about the density limit at which a discharge is likely to disrupt, so that the density can be kept below that limit. Several diagnostic signals are used from the ADITYA tokamak and are presented at selected time instants to the neural network inputs, in order to predict, at each of these instants, the density boundary. A disruption threshold has been established in order to examine the possibility of using the network as a real time disruption alarm. For most of the discharges this threshold is reached much before the actual disruption. The neural network is also used to make an optimization of the particular set of diagnostics in order to obtain the ones most crucial for predicting the density limit. The results of optimization have some of the features of the scaling laws of Murakami and Hugill. The optimized network compares well with the original one.

  11. Pulse-coupled neural nets: translation, rotation, scale, distortion, and intensity signal invariance for images.

    PubMed

    Johnson, J L

    1994-09-10

    The linking-field neural network model of Eckhorn et al. [Neural Comput. 2, 293-307 (1990)] was introduced to explain the experimentally observed synchronous activity among neural assemblies in the cat cortex induced by feature-dependent visual activity. The model produces synchronous bursts of pulses from neurons with similar activity, effectively grouping them by phase and pulse frequency. It gives a basic new function: grouping by similarity. The synchronous bursts are obtained in the limit of strong linking strengths. The linking-field model in the limit of moderate-to-weak linking characterized by few if any multiple bursts is investigated. In this limit dynamic, locally periodic traveling waves exist whose time signal encodes the geometrical structure of a two-dimensional input image. The signal can be made insensitive to translation, scale, rotation, distortion, and intensity. The waves transmit information beyond the physical interconnect distance. The model is implemented in an optical hybrid demonstration system. Results of the simulations and the optical system are presented.

  12. A mixed-signal implementation of a polychronous spiking neural network with delay adaptation

    PubMed Central

    Wang, Runchun M.; Hamilton, Tara J.; Tapson, Jonathan C.; van Schaik, André

    2014-01-01

    We present a mixed-signal implementation of a re-configurable polychronous spiking neural network capable of storing and recalling spatio-temporal patterns. The proposed neural network contains one neuron array and one axon array. Spike Timing Dependent Delay Plasticity is used to fine-tune delays and add dynamics to the network. In our mixed-signal implementation, the neurons and axons have been implemented as both analog and digital circuits. The system thus consists of one FPGA, containing the digital neuron array and the digital axon array, and one analog IC containing the analog neuron array and the analog axon array. The system can be easily configured to use different combinations of each. We present and discuss the experimental results of all combinations of the analog and digital axon arrays and the analog and digital neuron arrays. The test results show that the proposed neural network is capable of successfully recalling more than 85% of stored patterns using both analog and digital circuits. PMID:24672422

  13. Altered neural reward and loss processing and prediction error signalling in depression

    PubMed Central

    Ubl, Bettina; Kuehner, Christine; Kirsch, Peter; Ruttorf, Michaela

    2015-01-01

    Dysfunctional processing of reward and punishment may play an important role in depression. However, functional magnetic resonance imaging (fMRI) studies have shown heterogeneous results for reward processing in fronto-striatal regions. We examined neural responsivity associated with the processing of reward and loss during anticipation and receipt of incentives and related prediction error (PE) signalling in depressed individuals. Thirty medication-free depressed persons and 28 healthy controls performed an fMRI reward paradigm. Regions of interest analyses focused on neural responses during anticipation and receipt of gains and losses and related PE-signals. Additionally, we assessed the relationship between neural responsivity during gain/loss processing and hedonic capacity. When compared with healthy controls, depressed individuals showed reduced fronto-striatal activity during anticipation of gains and losses. The groups did not significantly differ in response to reward and loss outcomes. In depressed individuals, activity increases in the orbitofrontal cortex and nucleus accumbens during reward anticipation were associated with hedonic capacity. Depressed individuals showed an absence of reward-related PEs but encoded loss-related PEs in the ventral striatum. Depression seems to be linked to blunted responsivity in fronto-striatal regions associated with limited motivational responses for rewards and losses. Alterations in PE encoding might mirror blunted reward- and enhanced loss-related associative learning in depression. PMID:25567763

  14. The phenomenon of acquired resistance to metformin in breast cancer cells: The interaction of growth pathways and estrogen receptor signaling.

    PubMed

    Scherbakov, Alexander M; Sorokin, Danila V; Tatarskiy, Victor V; Prokhorov, Nikolay S; Semina, Svetlana E; Berstein, Lev M; Krasil'nikov, Mikhail A

    2016-04-01

    Metformin, a biguanide antidiabetic drug, is used to decrease hyperglycemia in patients with type 2 diabetes. Recently, the epidemiological studies revealed the potential of metformin as an anti-tumor drug for several types of cancer, including breast cancer. Anti-tumor metformin action was found to be mediated, at least in part, via activation of adenosine monophosphate-activated protein kinase (AMPK)-intracellular energy sensor, which inhibits the mammalian target of rapamycin (mTOR) and some other signaling pathways. Nevertheless, some patients can be non-sensitive or resistant to metformin action. Here we analyzed the mechanism of the formation of metformin-resistant phenotype in breast cancer cells and its role in estrogen receptor (ER) regulation. The experiments were performed on the ER-positive MCF-7 breast cancer cells and metformin-resistant MCF-7 subline (MCF-7/M) developed due to long-term metformin treatment. The transcriptional activity of NF-κB and ER was measured by the luciferase reporter gene analysis. The protein expression was determined by immunoblotting (Snail1, (phospho)AMPK, (phospho)IκBα, (phospho)mTOR, cyclin D1, (phospho)Akt and ERα) and immunohistochemical analysis (E-cadherin). We have found that: 1) metformin treatment of MCF-7 cells is accompanied with the stimulation of AMPK and inhibition of growth-related proteins including IκBα, NF-κB, cyclin D1 and ERα; 2) long-term metformin treatment lead to the appearance and progression of cross-resistance to metformin and tamoxifen; the resistant cells are characterized with the unaffected AMPK activity, but the irreversible ER suppression and constitutive activation of Akt/Snail1 signaling; 3) Akt/Snail1 signaling is involved into progression of metformin resistance. The results presented may be considered as the first evidence of the progression of cross-resistance to metformin and tamoxifen in breast cancer cells. Importantly, the acquired resistance to both drugs is based on the

  15. Implantable neurotechnologies: a review of integrated circuit neural amplifiers.

    PubMed

    Ng, Kian Ann; Greenwald, Elliot; Xu, Yong Ping; Thakor, Nitish V

    2016-01-01

    Neural signal recording is critical in modern day neuroscience research and emerging neural prosthesis programs. Neural recording requires the use of precise, low-noise amplifier systems to acquire and condition the weak neural signals that are transduced through electrode interfaces. Neural amplifiers and amplifier-based systems are available commercially or can be designed in-house and fabricated using integrated circuit (IC) technologies, resulting in very large-scale integration or application-specific integrated circuit solutions. IC-based neural amplifiers are now used to acquire untethered/portable neural recordings, as they meet the requirements of a miniaturized form factor, light weight and low power consumption. Furthermore, such miniaturized and low-power IC neural amplifiers are now being used in emerging implantable neural prosthesis technologies. This review focuses on neural amplifier-based devices and is presented in two interrelated parts. First, neural signal recording is reviewed, and practical challenges are highlighted. Current amplifier designs with increased functionality and performance and without penalties in chip size and power are featured. Second, applications of IC-based neural amplifiers in basic science experiments (e.g., cortical studies using animal models), neural prostheses (e.g., brain/nerve machine interfaces) and treatment of neuronal diseases (e.g., DBS for treatment of epilepsy) are highlighted. The review concludes with future outlooks of this technology and important challenges with regard to neural signal amplification.

  16. Implantable neurotechnologies: a review of integrated circuit neural amplifiers

    PubMed Central

    Greenwald, Elliot; Xu, Yong Ping; Thakor, Nitish V.

    2016-01-01

    Neural signal recording is critical in modern day neuroscience research and emerging neural prosthesis programs. Neural recording requires the use of precise, low-noise amplifier systems to acquire and condition the weak neural signals that are transduced through electrode interfaces. Neural amplifiers and amplifier-based systems are available commercially or can be designed in-house and fabricated using integrated circuit (IC) technologies, resulting in very large-scale integration or application-specific integrated circuit solutions. IC-based neural amplifiers are now used to acquire untethered/portable neural recordings, as they meet the requirements of a miniaturized form factor, light weight and low power consumption. Furthermore, such miniaturized and low-power IC neural amplifiers are now being used in emerging implantable neural prosthesis technologies. This review focuses on neural amplifier-based devices and is presented in two interrelated parts. First, neural signal recording is reviewed, and practical challenges are highlighted. Current amplifier designs with increased functionality and performance and without penalties in chip size and power are featured. Second, applications of IC-based neural amplifiers in basic science experiments (e.g., cortical studies using animal models), neural prostheses (e.g., brain/nerve machine interfaces) and treatment of neuronal diseases (e.g., DBS for treatment of epilepsy) are highlighted. The review concludes with future outlooks of this technology and important challenges with regard to neural signal amplification. PMID:26798055

  17. Neural crest-derived mesenchymal cells require Wnt signaling for their development and drive invagination of the telencephalic midline.

    PubMed

    Choe, Youngshik; Zarbalis, Konstantinos S; Pleasure, Samuel J

    2014-01-01

    Embryonic neural crest cells contribute to the development of the craniofacial mesenchyme, forebrain meninges and perivascular cells. In this study, we investigated the function of ß-catenin signaling in neural crest cells abutting the dorsal forebrain during development. In the absence of ß-catenin signaling, neural crest cells failed to expand in the interhemispheric region and produced ectopic smooth muscle cells instead of generating dermal and calvarial mesenchyme. In contrast, constitutive expression of stabilized ß-catenin in neural crest cells increased the number of mesenchymal lineage precursors suggesting that ß-catenin signaling is necessary for the expansion of neural crest-derived mesenchymal cells. Interestingly, the loss of neural crest-derived mesenchymal stem cells (MSCs) leads to failure of telencephalic midline invagination and causes ventricular system defects. This study shows that ß-catenin signaling is required for the switch of neural crest cells to MSCs and mediates the expansion of MSCs to drive the formation of mesenchymal structures of the head. Furthermore, loss of these structures causes striking defects in forebrain morphogenesis.

  18. Controlled levels of canonical Wnt signaling are required for neural crest migration.

    PubMed

    Maj, Ewa; Künneke, Lutz; Loresch, Elisabeth; Grund, Anita; Melchert, Juliane; Pieler, Tomas; Aspelmeier, Timo; Borchers, Annette

    2016-09-01

    Canonical Wnt signaling plays a dominant role in the development of the neural crest (NC), a highly migratory cell population that generates a vast array of cell types. Canonical Wnt signaling is required for NC induction as well as differentiation, however its role in NC migration remains largely unknown. Analyzing nuclear localization of β-catenin as readout for canonical Wnt activity, we detect nuclear β-catenin in premigratory but not migratory Xenopus NC cells suggesting that canonical Wnt activity has to decrease to basal levels to enable NC migration. To define a possible function of canonical Wnt signaling in Xenopus NC migration, canonical Wnt signaling was modulated at different time points after NC induction. This was accomplished using either chemical modulators affecting β-catenin stability or inducible glucocorticoid fusion constructs of Lef/Tcf transcription factors. In vivo analysis of NC migration by whole mount in situ hybridization demonstrates that ectopic activation of canonical Wnt signaling inhibits cranial NC migration. Further, NC transplantation experiments confirm that this effect is tissue-autonomous. In addition, live-cell imaging in combination with biophysical data analysis of explanted NC cells confirms the in vivo findings and demonstrates that modulation of canonical Wnt signaling affects the ability of NC cells to perform single cell migration. Thus, our data support the hypothesis that canonical Wnt signaling needs to be tightly controlled to enable migration of NC cells.

  19. Transmission of wireless neural signals through a 0.18 µm CMOS low-power amplifier.

    PubMed

    Gazziro, M; Braga, C F R; Moreira, D A; Carvalho, A C P L F; Rodrigues, J F; Navarro, J S; Ardila, J C M; Mioni, D P; Pessatti, M; Fabbro, P; Freewin, C; Saddow, S E

    2015-01-01

    In the field of Brain Machine Interfaces (BMI) researchers still are not able to produce clinically viable solutions that meet the requirements of long-term operation without the use of wires or batteries. Another problem is neural compatibility with the electrode probes. One of the possible ways of approaching these problems is the use of semiconductor biocompatible materials (silicon carbide) combined with an integrated circuit designed to operate with low power consumption. This paper describes a low-power neural signal amplifier chip, named Cortex, fabricated using 0.18 μm CMOS process technology with all electronics integrated in an area of 0.40 mm(2). The chip has 4 channels, total power consumption of only 144 μW, and is impedance matched to silicon carbide biocompatible electrodes.

  20. Neural networks for automated classification of ionospheric irregularities in HF radar backscattered signals

    NASA Astrophysics Data System (ADS)

    Wing, S.; Greenwald, R. A.; Meng, C.-I.; Sigillito, V. G.; Hutton, L. V.

    2003-08-01

    The classification of high frequency (HF) radar backscattered signals from the ionospheric irregularities (clutters) into those suitable, or not, for further analysis, is a time-consuming task even by experts in the field. We tested several different feedforward neural networks on this task, investigating the effects of network type (single layer versus multilayer) and number of hidden nodes upon performance. As expected, the multilayer feedforward networks (MLFNs) outperformed the single-layer networks. The MLFNs achieved performance levels of 100% correct on the training set and up to 98% correct on the testing set. Comparable figures for the single-layer networks were 94.5% and 92%, respectively. When measures of sensitivity, specificity, and proportion of variance accounted for by the model are considered, the superiority of the MLFNs over the single-layer networks is much more striking. Our results suggest that such neural networks could aid many HF radar operations such as frequency search, space weather, etc.

  1. Single-cell transcriptome analyses reveal signals to activate dormant neural stem cells.

    PubMed

    Luo, Yuping; Coskun, Volkan; Liang, Aibing; Yu, Juehua; Cheng, Liming; Ge, Weihong; Shi, Zhanping; Zhang, Kunshan; Li, Chun; Cui, Yaru; Lin, Haijun; Luo, Dandan; Wang, Junbang; Lin, Connie; Dai, Zachary; Zhu, Hongwen; Zhang, Jun; Liu, Jie; Liu, Hailiang; deVellis, Jean; Horvath, Steve; Sun, Yi Eve; Li, Siguang

    2015-05-21

    The scarcity of tissue-specific stem cells and the complexity of their surrounding environment have made molecular characterization of these cells particularly challenging. Through single-cell transcriptome and weighted gene co-expression network analysis (WGCNA), we uncovered molecular properties of CD133(+)/GFAP(-) ependymal (E) cells in the adult mouse forebrain neurogenic zone. Surprisingly, prominent hub genes of the gene network unique to ependymal CD133(+)/GFAP(-) quiescent cells were enriched for immune-responsive genes, as well as genes encoding receptors for angiogenic factors. Administration of vascular endothelial growth factor (VEGF) activated CD133(+) ependymal neural stem cells (NSCs), lining not only the lateral but also the fourth ventricles and, together with basic fibroblast growth factor (bFGF), elicited subsequent neural lineage differentiation and migration. This study revealed the existence of dormant ependymal NSCs throughout the ventricular surface of the CNS, as well as signals abundant after injury for their activation.

  2. Insulin acts as a myogenic differentiation signal for neural stem cells with multilineage differentiation potential.

    PubMed

    Bani-Yaghoub, Mahmud; Kendall, Stephen E; Moore, Daniel P; Bellum, Stephen; Cowling, Rebecca A; Nikopoulos, George N; Kubu, Chris J; Vary, Calvin; Verdi, Joseph M

    2004-09-01

    Reports of non-neural differentiation of neural stem cells (NSCs) have been challenged by alternative explanations for expanded differentiation potentials. In an attempt to demonstrate the plasticity of NSC, neurospheres were generated from single retrovirally labeled embryonic cortical precursors. In a defined serum-free insulin-containing media, 40% of the neurospheres contained both myogenic and neurogenic differentiated progeny. The number of NSCs displaying multilineage differentiation potential declines through gestation but does exist in the adult animal. In this system, insulin appears to function as a survival and dose-dependent myogenic differentiation signal for multilineage NSCs (MLNSC). MLNSC-derived cardiomyocytes contract synchronously, respond to sympathetic and parasympathetic stimulation, and regenerate injured heart tissues. These studies provide support for the hypothesis that MLNSCs exist throughout the lifetime of the animal, and potentially provide a population of stem cells for cell-based regenerative medicine strategies inside and outside of the nervous system.

  3. Instrumentation to evaluate neural signal recording properties of micromachined microelectrodes inserted in invertebrate nerve.

    PubMed

    Banks, D J; Balachandran, W; Richards, P R; Ewins, D

    2002-05-01

    The design and characterization of instrumentation for application in evaluating the neural signal recording properties of probe-type microelectrodes, micromachined from silicon, are reported. Key aspects include the close matching of gain and frequency response between channels (better than 1%), flexibility in signal conditioning options, the ability to operate with a wide range of (microelectrode) recording site dimensions (4 microm x 4 micrm to 50 microm x 50 microm), and hence impedances, and the facility to monitor and store instrumentation settings on computer along with the recorded signals. Noise levels ranged from 3.7 microV rms for a 50 microm site, to 11.7 microV rms for a microm site, measured in saline. Close matching between channels was required to enable comparisons between different sites and different probes to be made with confidence; however, the instrumentation could be readily applied to less demanding applications.

  4. PAPR Reduction of OFDM Signal by Neural Networks without Side Information and its FPGA Implementation

    NASA Astrophysics Data System (ADS)

    Ohta, Masaya; Ueda, Yasuo; Yamashita, Katsumi

    A major drawback of orthogonal frequency division multiplexing (OFDM) is the high peak-to-average power ratio (PAPR) of the transmitted signal. PAPR reduction techniques by using neural networks have been proposed to reduce the PAPR problem in OFDM transmitter. These techniques require side information to be transmitted from the transmitter to the receiver in order to recover the original data symbol from the received signal. In this paper, we propose a novel technique to reduce PAPR of OFDM signal. Proposed technique is based on Tone Injection(TI) and dose not use any side information to be transmitted from the transmitter to the receiver. Moreover, the proposed model is designed with VHDL for a FPGA device, and evaluated the performance.

  5. Subcellular Imaging of Voltage and Calcium Signals Reveals Neural Processing In Vivo.

    PubMed

    Yang, Helen H; St-Pierre, François; Sun, Xulu; Ding, Xiaozhe; Lin, Michael Z; Clandinin, Thomas R

    2016-06-30

    A mechanistic understanding of neural computation requires determining how information is processed as it passes through neurons and across synapses. However, it has been challenging to measure membrane potential changes in axons and dendrites in vivo. We use in vivo, two-photon imaging of novel genetically encoded voltage indicators, as well as calcium imaging, to measure sensory stimulus-evoked signals in the Drosophila visual system with subcellular resolution. Across synapses, we find major transformations in the kinetics, amplitude, and sign of voltage responses to light. We also describe distinct relationships between voltage and calcium signals in different neuronal compartments, a substrate for local computation. Finally, we demonstrate that ON and OFF selectivity, a key feature of visual processing across species, emerges through the transformation of membrane potential into intracellular calcium concentration. By imaging voltage and calcium signals to map information flow with subcellular resolution, we illuminate where and how critical computations arise.

  6. Modeling fMRI signals can provide insights into neural processing in the cerebral cortex.

    PubMed

    Vanni, Simo; Sharifian, Fariba; Heikkinen, Hanna; Vigário, Ricardo

    2015-08-01

    Every stimulus or task activates multiple areas in the mammalian cortex. These distributed activations can be measured with functional magnetic resonance imaging (fMRI), which has the best spatial resolution among the noninvasive brain imaging methods. Unfortunately, the relationship between the fMRI activations and distributed cortical processing has remained unclear, both because the coupling between neural and fMRI activations has remained poorly understood and because fMRI voxels are too large to directly sense the local neural events. To get an idea of the local processing given the macroscopic data, we need models to simulate the neural activity and to provide output that can be compared with fMRI data. Such models can describe neural mechanisms as mathematical functions between input and output in a specific system, with little correspondence to physiological mechanisms. Alternatively, models can be biomimetic, including biological details with straightforward correspondence to experimental data. After careful balancing between complexity, computational efficiency, and realism, a biomimetic simulation should be able to provide insight into how biological structures or functions contribute to actual data processing as well as to promote theory-driven neuroscience experiments. This review analyzes the requirements for validating system-level computational models with fMRI. In particular, we study mesoscopic biomimetic models, which include a limited set of details from real-life networks and enable system-level simulations of neural mass action. In addition, we discuss how recent developments in neurophysiology and biophysics may significantly advance the modelling of fMRI signals.

  7. Modeling fMRI signals can provide insights into neural processing in the cerebral cortex

    PubMed Central

    Sharifian, Fariba; Heikkinen, Hanna; Vigário, Ricardo

    2015-01-01

    Every stimulus or task activates multiple areas in the mammalian cortex. These distributed activations can be measured with functional magnetic resonance imaging (fMRI), which has the best spatial resolution among the noninvasive brain imaging methods. Unfortunately, the relationship between the fMRI activations and distributed cortical processing has remained unclear, both because the coupling between neural and fMRI activations has remained poorly understood and because fMRI voxels are too large to directly sense the local neural events. To get an idea of the local processing given the macroscopic data, we need models to simulate the neural activity and to provide output that can be compared with fMRI data. Such models can describe neural mechanisms as mathematical functions between input and output in a specific system, with little correspondence to physiological mechanisms. Alternatively, models can be biomimetic, including biological details with straightforward correspondence to experimental data. After careful balancing between complexity, computational efficiency, and realism, a biomimetic simulation should be able to provide insight into how biological structures or functions contribute to actual data processing as well as to promote theory-driven neuroscience experiments. This review analyzes the requirements for validating system-level computational models with fMRI. In particular, we study mesoscopic biomimetic models, which include a limited set of details from real-life networks and enable system-level simulations of neural mass action. In addition, we discuss how recent developments in neurophysiology and biophysics may significantly advance the modelling of fMRI signals. PMID:25972586

  8. Regulator of G protein signaling 2 (Rgs2) regulates neural crest development through Pparδ-Sox10 cascade.

    PubMed

    Lin, Sheng-Jia; Chiang, Ming-Chang; Shih, Hung-Yu; Hsu, Li-Sung; Yeh, Tu-Hsueh; Huang, Yin-Cheng; Lin, Ching-Yu; Cheng, Yi-Chuan

    2017-03-01

    Neural crest cells are multipotent progenitors that migrate extensively and differentiate into numerous derivatives. The developmental plasticity and migratory ability of neural crest cells render them an attractive model for studying numerous aspects of cell progression. We observed that zebrafish rgs2 was expressed in neural crest cells. Disrupting Rgs2 expression by using a dominant negative rgs2 construct or rgs2 morpholinos reduced GTPase-activating protein activity, induced the formation of neural crest progenitors, increased the proliferation of nonectomesenchymal neural crest cells, and inhibited the formation of ectomesenchymal neural crest derivatives. The transcription of pparda (which encodes Pparδ, a Wnt-activated transcription factor) was upregulated in Rgs2-deficient embryos, and Pparδ inhibition using a selective antagonist in the Rgs2-deficient embryos repaired neural crest defects. Our results clarify the mechanism through which the Rgs2-Pparδ cascade regulates neural crest development; specifically, Pparδ directly binds to the promoter and upregulates the transcription of the neural crest specifier sox10. This study reveals a unique regulatory mechanism, the Rgs2-Pparδ-Sox10 signaling cascade, and defines a key molecular regulator, Rgs2, in neural crest development.

  9. Auditory detection and discrimination in deaf cats: psychophysical and neural thresholds for intracochlear electrical signals.

    PubMed

    Vollmer, M; Beitel, R E; Snyder, R L

    2001-11-01

    More than 30,000 hearing-impaired human subjects have learned to use cochlear implants for speech perception and speech discrimination. To understand the basic mechanisms underlying the successful application of contemporary speech processing strategies, it is important to investigate how complex electrical stimuli delivered to the cochlea are processed and represented in the central auditory system. A deaf animal model has been developed that allows direct comparison of psychophysical thresholds with central auditory neuronal thresholds to temporally modulated intracochlear electrical signals in the same animals. Behavioral detection thresholds were estimated in neonatally deafened cats for unmodulated pulse trains (e.g., 30 pulses/s or pps) and sinusoidal amplitude-modulated (SAM) pulse trains (e.g., 300 pps, SAM at 30 Hz; 300/30 AM). Animals were trained subsequently in a discrimination task to respond to changes in the modulation frequency of successive SAM signals (e.g., 300/8 AM vs. 300/30 AM). During acute physiological experiments, neural thresholds to pulse trains were estimated in the inferior colliculus (IC) and the primary auditory cortex (A1) of the anesthetized animals. Psychophysical detection thresholds for unmodulated and SAM pulse trains were virtually identical. Single IC neuron thresholds for SAM pulse trains showed a small but significant increase in threshold (0.4 dB or 15.5 microA) when compared with thresholds for unmodulated pulse trains. The mean difference between psychophysical and minimum neural thresholds within animals was not significant (mean = 0.3 dB). Importantly, cats also successfully discriminated changes in the modulation frequencies of the SAM signals. Performance on the discrimination task was not affected by carrier rate (100, 300, 500, 1,000, or 1,500 pps). These findings indicate that 1) behavioral and neural response thresholds are based on detection of the peak pulse amplitudes of the modulated and unmodulated signals

  10. Neural Mechanisms for Acoustic Signal Detection under Strong Masking in an Insect

    PubMed Central

    Römer, Heiner

    2015-01-01

    species produces an extremely noisy sound, yet the second species still detects its own song. Using intracellular recording techniques we identified two neural mechanisms underlying the surprising behavioral signal detection at the level of single identified interneurons. These neural mechanisms for signal detection are likely to be important for other sensory modalities as well, where noise in the communication channel creates similar problems. Also, they may be used for the development of algorithms for the filtering of specific signals in technical microphones or hearing aids. PMID:26203150

  11. Endocytic recycling protein EHD1 regulates primary cilia morphogenesis and SHH signaling during neural tube development.

    PubMed

    Bhattacharyya, Sohinee; Rainey, Mark A; Arya, Priyanka; Dutta, Samikshan; George, Manju; Storck, Matthew D; McComb, Rodney D; Muirhead, David; Todd, Gordon L; Gould, Karen; Datta, Kaustubh; Gelineau-van Waes, Janee; Band, Vimla; Band, Hamid

    2016-02-17

    Members of the four-member C-terminal EPS15-Homology Domain-containing (EHD) protein family play crucial roles in endocytic recycling of cell surface receptors from endosomes to the plasma membrane. In this study, we show that Ehd1 gene knockout in mice on a predominantly B6 background is embryonic lethal. Ehd1-null embryos die at mid-gestation with a failure to complete key developmental processes including neural tube closure, axial turning and patterning of the neural tube. We found that Ehd1-null embryos display short and stubby cilia on the developing neuroepithelium at embryonic day 9.5 (E9.5). Loss of EHD1 also deregulates the ciliary SHH signaling with Ehd1-null embryos displaying features indicative of increased SHH signaling, including a significant downregulation in the formation of the GLI3 repressor and increase in the ventral neuronal markers specified by SHH. Using Ehd1-null MEFS we found that EHD1 protein co-localizes with the SHH receptor Smoothened in the primary cilia upon ligand stimulation. Under the same conditions, EHD1 was shown to co-traffic with Smoothened into the developing primary cilia and we identify EHD1 as a direct binding partner of Smoothened. Overall, our studies identify the endocytic recycling regulator EHD1 as a novel regulator of the primary cilium-associated trafficking of Smoothened and Hedgehog signaling.

  12. Endocytic recycling protein EHD1 regulates primary cilia morphogenesis and SHH signaling during neural tube development

    PubMed Central

    Bhattacharyya, Sohinee; Rainey, Mark A; Arya, Priyanka; Dutta, Samikshan; George, Manju; Storck, Matthew D.; McComb, Rodney D.; Muirhead, David; Todd, Gordon L.; Gould, Karen; Datta, Kaustubh; Waes, Janee Gelineau-van; Band, Vimla; Band, Hamid

    2016-01-01

    Members of the four-member C-terminal EPS15-Homology Domain-containing (EHD) protein family play crucial roles in endocytic recycling of cell surface receptors from endosomes to the plasma membrane. In this study, we show that Ehd1 gene knockout in mice on a predominantly B6 background is embryonic lethal. Ehd1-null embryos die at mid-gestation with a failure to complete key developmental processes including neural tube closure, axial turning and patterning of the neural tube. We found that Ehd1-null embryos display short and stubby cilia on the developing neuroepithelium at embryonic day 9.5 (E9.5). Loss of EHD1 also deregulates the ciliary SHH signaling with Ehd1-null embryos displaying features indicative of increased SHH signaling, including a significant downregulation in the formation of the GLI3 repressor and increase in the ventral neuronal markers specified by SHH. Using Ehd1-null MEFS we found that EHD1 protein co-localizes with the SHH receptor Smoothened in the primary cilia upon ligand stimulation. Under the same conditions, EHD1 was shown to co-traffic with Smoothened into the developing primary cilia and we identify EHD1 as a direct binding partner of Smoothened. Overall, our studies identify the endocytic recycling regulator EHD1 as a novel regulator of the primary cilium-associated trafficking of Smoothened and Hedgehog signaling. PMID:26884322

  13. Leg Motion Classification with Artificial Neural Networks Using Wavelet-Based Features of Gyroscope Signals

    PubMed Central

    Ayrulu-Erdem, Birsel; Barshan, Billur

    2011-01-01

    We extract the informative features of gyroscope signals using the discrete wavelet transform (DWT) decomposition and provide them as input to multi-layer feed-forward artificial neural networks (ANNs) for leg motion classification. Since the DWT is based on correlating the analyzed signal with a prototype wavelet function, selection of the wavelet type can influence the performance of wavelet-based applications significantly. We also investigate the effect of selecting different wavelet families on classification accuracy and ANN complexity and provide a comparison between them. The maximum classification accuracy of 97.7% is achieved with the Daubechies wavelet of order 16 and the reverse bi-orthogonal (RBO) wavelet of order 3.1, both with similar ANN complexity. However, the RBO 3.1 wavelet is preferable because of its lower computational complexity in the DWT decomposition and reconstruction. PMID:22319378

  14. Leg motion classification with artificial neural networks using wavelet-based features of gyroscope signals.

    PubMed

    Ayrulu-Erdem, Birsel; Barshan, Billur

    2011-01-01

    We extract the informative features of gyroscope signals using the discrete wavelet transform (DWT) decomposition and provide them as input to multi-layer feed-forward artificial neural networks (ANNs) for leg motion classification. Since the DWT is based on correlating the analyzed signal with a prototype wavelet function, selection of the wavelet type can influence the performance of wavelet-based applications significantly. We also investigate the effect of selecting different wavelet families on classification accuracy and ANN complexity and provide a comparison between them. The maximum classification accuracy of 97.7% is achieved with the Daubechies wavelet of order 16 and the reverse bi-orthogonal (RBO) wavelet of order 3.1, both with similar ANN complexity. However, the RBO 3.1 wavelet is preferable because of its lower computational complexity in the DWT decomposition and reconstruction.

  15. Recognition of aging effect from cardiomechanical signals using novel SF-ART neural network.

    PubMed

    Akhbardeh, Alireza; Tavakolian, Kouhyar; Kaminska, Bozena

    2008-01-01

    In this study we applied Haar wavelets to extract essential features of cardiac mechanical signals classified them using a novel neural network so called, Supervised Fuzzy Adaptive Resonance Theory (SF-ART). Initial tests with sternal signals of cardiac vibration from six young, middle-aged and old subjects indicate that SF-ART can classify the subjects into three classes with a high accuracy, fast learning speed, and low computational load. The method is insensitive to latency and non-linear disturbance. Moreover, the applied wavelet transform requires no prior knowledge of the statistical distribution of data samples. This can offer a novel method for the analysis of the effects of aging on the heart and assessment of the physiological age of the heart.

  16. Encoding physiological signals as images for affective state recognition using convolutional neural networks.

    PubMed

    Yu, Guangliang; Li, Xiang; Song, Dawei; Zhao, Xiaozhao; Zhang, Peng; Hou, Yuexian; Hu, Bin; Guangliang Yu; Xiang Li; Dawei Song; Xiaozhao Zhao; Peng Zhang; Yuexian Hou; Bin Hu; Zhao, Xiaozhao; Hou, Yuexian; Li, Xiang; Hu, Bin; Zhang, Peng; Song, Dawei; Yu, Guangliang

    2016-08-01

    Affective state recognition based on multiple modalities of physiological signals has been a hot research topic. Traditional methods require designing hand-crafted features based on domain knowledge, which is time-consuming and has not achieved a satisfactory performance. On the other hand, conducting classification on raw signals directly can also cause some problems, such as the interference of noise and the curse of dimensionality. To address these problems, we propose a novel approach that encodes different modalities of data as images and use convolutional neural networks (CNN) to perform the affective state recognition task. We validate our aproach on the DECAF dataset in comparison with two state-of-the-art methods, i.e., the Support Vector Machines (SVM) and Random Forest (RF). Experimental results show that our aproach outperforms the baselines by 5% to 9%.

  17. Proneural gene self-stimulation in neural precursors: an essential mechanism for sense organ development that is regulated by Notch signaling.

    PubMed

    Culí, J; Modolell, J

    1998-07-01

    To learn about the acquisition of neural fate by ectodermal cells, we have analyzed a very early sign of neural commitment in Drosophila, namely the specific accumulation of achaete-scute complex (AS-C) proneural proteins in the cell that becomes a sensory organ mother cell (SMC). We have characterized an AS-C enhancer that directs expression specifically in SMCs. This enhancer promotes Scute protein accumulation in these cells, an event essential for sensory organ development in the absence of other AS-C genes. Interspecific sequence comparisons and site-directed mutagenesis show the presence of several conserved motifs necessary for enhancer action, some of them binding sites for proneural proteins. These and other data indicate that the enhancer mediates scute self-stimulation, although only in the presence of additional activating factors, which most likely interact with conserved motifs reminiscent of NF-kappaB-binding sites. Cells neighboring the SMC do not acquire the neural fate because the Notch signaling pathway effectors, the Enhancer of split bHLH proteins, block this proneural gene self-stimulatory loop, possibly by antagonizing the action on the enhancer of the NF-kappaB-like factors or the proneural proteins. These data suggest a mechanism for SMC committment.

  18. Time-Course Gene Expression Profiling Reveals a Novel Role of Non-Canonical WNT Signaling During Neural Induction

    PubMed Central

    Huang, Cindy Tzu-Ling; Tao, Yunlong; Lu, Jianfeng; Jones, Jeffrey R.; Fowler, Lucas; Weick, Jason P.; Zhang, Su-Chun

    2016-01-01

    The process of neuroepithelial differentiation from human pluripotent stem cells (PSCs) resembles in vivo neuroectoderm induction in the temporal course, morphogenesis, and biochemical changes. This in vitro model is therefore well-suited to reveal previously unknown molecular mechanisms underlying neural induction in humans. By transcriptome analysis of cells along PSC differentiation to early neuroepithelia at day 6 and definitive neuroepithelia at day 10, we found downregulation of genes that are associated with TGF-β and canonical WNT/β-CATENIN signaling, confirming the roles of classical signaling in human neural induction. Interestingly, WNT/Ca2+ signaling was upregulated. Pharmacological inhibition of the downstream effector of WNT/Ca2+ pathway, Ca2+/calmodulin-dependent protein kinase II (CaMKII), led to an inhibition of the neural marker PAX6 and upregulation of epidermal marker K18, suggesting that Ca2+/CaMKII signaling promotes neural induction by preventing the alternative epidermal fate. In addition, our analyses revealed known and novel expression patterns of genes that are involved in DNA methylation, histone modification, as well as epithelial-mesenchymal transition, highlighting potential roles of those genes and signaling pathways during neural differentiation. PMID:27600186

  19. Extruded Bread Classification on the Basis of Acoustic Emission Signal With Application of Artificial Neural Networks

    NASA Astrophysics Data System (ADS)

    Świetlicka, Izabela; Muszyński, Siemowit; Marzec, Agata

    2015-04-01

    The presented work covers the problem of developing a method of extruded bread classification with the application of artificial neural networks. Extruded flat graham, corn, and rye breads differening in water activity were used. The breads were subjected to the compression test with simultaneous registration of acoustic signal. The amplitude-time records were analyzed both in time and frequency domains. Acoustic emission signal parameters: single energy, counts, amplitude, and duration acoustic emission were determined for the breads in four water activities: initial (0.362 for rye, 0.377 for corn, and 0.371 for graham bread), 0.432, 0.529, and 0.648. For classification and the clustering process, radial basis function, and self-organizing maps (Kohonen network) were used. Artificial neural networks were examined with respect to their ability to classify or to cluster samples according to the bread type, water activity value, and both of them. The best examination results were achieved by the radial basis function network in classification according to water activity (88%), while the self-organizing maps network yielded 81% during bread type clustering.

  20. Neural network based fault detection using different signal processing techniques as pre-processor

    SciTech Connect

    Petrilli, O.; Paya, B.; Esat, I.I.; Badi, M.N.M.

    1995-09-01

    The purpose of vibration monitoring is to detect faults occurring in machinery, in order to maintain safety and minimize the breakdown cost. The authors of this paper monitored the condition of two meshing spur gears with the ratio of 1:2, where intentionally a gear fault (a welded blip) was introduced on the loaded driven gear. The signals obtained from the faulty gear and the good or reference gear were preprocessed by using three spectral analysis techniques: Fourier transform, Power Cepstrum, and Wavelet transform. For each type of preprocessing a separate artificial neural network was trained and tested to distinguish the faulty gear from the good gear. Although similar work has been done before, the authors of this paper has expanded the work on to the transient signals by using Wavelet on the whole transformation rather than the amplitude of the meshing frequency. In order to achieve this the whole transformation was discretized for the artificial neural networks (ANNs) inputs. This is different from the commonly practiced method which selects the meshing frequency band.

  1. SDF-1/CXCR4 Signaling Maintains Stemness Signature in Mouse Neural Stem/Progenitor Cells

    PubMed Central

    Ling, Thai-Yen; Lin, Hsing-Yu; Liou, Jeffrey Tsai-Jui; Liu, Fei-Chih; Chen, I-Chun; Lee, Sue-Wei; Hsu, Yu

    2017-01-01

    SDF-1 and its primary receptor, CXCR4, are highly expressed in the embryonic central nervous system (CNS) and play a crucial role in brain architecture. Loss of SDF-1/CXCR4 signaling causes abnormal development of neural stem/progenitor cells (NSCs/NPCs) in the cerebellum, hippocampus, and cortex. However, the mechanism of SDF-1/CXCR4 axis in NSCs/NPCs regulation remains unknown. In this study, we found that elimination of SDF-1/CXCR4 transduction caused NSCs/NPCs to lose their stemness characteristics and to encounter neurogenic differentiation. Moreover, Notch and RE1 silencing transcription factor (REST) both play an essential role in NSCs/NPCs maintenance and neuronal differentiation and were dramatically downregulated following SDF-1/CXCR4 cascade inhibition. Finally, we demonstrated that the expression of achaete-scute homolog 1 (Ascl1), a proneural gene, and p27, an antiproliferative gene, were significantly increased after genetic elimination of SDF-1 alleles. Our results support that the loss of functional SDF-1/CXCR4 signaling pathway in NSCs/NPCs induces exit of cell cycle and promotes premature neural differentiation.

  2. Improvement in Neural Respiratory Drive Estimation From Diaphragm Electromyographic Signals Using Fixed Sample Entropy.

    PubMed

    Estrada, Luis; Torres, Abel; Sarlabous, Leonardo; Jané, Raimon

    2016-03-01

    Diaphragm electromyography is a valuable technique for the recording of electrical activity of the diaphragm. The analysis of diaphragm electromyographic (EMGdi) signal amplitude is an alternative approach for the quantification of the neural respiratory drive (NRD). The EMGdi signal is, however, corrupted by electrocardiographic (ECG) activity, and this presence of cardiac activity can make the EMGdi interpretation more difficult. Traditionally, the EMGdi amplitude has been estimated using the average rectified value (ARV) and the root mean square (RMS). In this study, surface EMGdi signals were analyzed using the fixed sample entropy (fSampEn) algorithm, and compared to the traditional ARV and RMS methods. The fSampEn is calculated using a tolerance value fixed and independent of the standard deviation of the analysis window. Thus, this method quantifies the amplitude of the complex components of stochastic signals (such as EMGdi), and being less affected by changes in amplitude due to less complex components (such as ECG). The proposed method was tested in synthetic and recorded EMGdi signals. fSampEn was less sensitive to the effect of cardiac activity on EMGdi signals with different levels of NRD than ARV and RMS amplitude parameters. The mean and standard deviation of the Pearson's correlation values between inspiratory mouth pressure (an indirect measure of the respiratory muscle activity) and fSampEn, ARV, and RMS parameters, estimated in the recorded EMGdi signal at tidal volume (without inspiratory load), were 0.38±0.12, 0.27±0.11 , and 0.11±0.13, respectively. Whereas at 33 cmH2O (maximum inspiratory load) were 0.83±0.02, 0.76±0.07, and 0.61±0.19 , respectively. Our findings suggest that the proposed method may improve the evaluation of NRD.

  3. USP9X deubiquitylating enzyme maintains RAPTOR protein levels, mTORC1 signalling and proliferation in neural progenitors.

    PubMed

    Bridges, Caitlin R; Tan, Men-Chee; Premarathne, Susitha; Nanayakkara, Devathri; Bellette, Bernadette; Zencak, Dusan; Domingo, Deepti; Gecz, Jozef; Murtaza, Mariyam; Jolly, Lachlan A; Wood, Stephen A

    2017-03-24

    USP9X, is highly expressed in neural progenitors and, essential for neural development in mice. In humans, mutations in USP9X are associated with neurodevelopmental disorders. To understand USP9X's role in neural progenitors, we studied the effects of altering its expression in both the human neural progenitor cell line, ReNcell VM, as well as neural stem and progenitor cells derived from Nestin-cre conditionally deleted Usp9x mice. Decreasing USP9X resulted in ReNcell VM cells arresting in G0 cell cycle phase, with a concomitant decrease in mTORC1 signalling, a major regulator of G0/G1 cell cycle progression. Decreased mTORC1 signalling was also observed in Usp9x-null neurospheres and embryonic mouse brains. Further analyses revealed, (i) the canonical mTORC1 protein, RAPTOR, physically associates with Usp9x in embryonic brains, (ii) RAPTOR protein level is directly proportional to USP9X, in both loss- and gain-of-function experiments in cultured cells and, (iii) USP9X deubiquitlyating activity opposes the proteasomal degradation of RAPTOR. EdU incorporation assays confirmed Usp9x maintains the proliferation of neural progenitors similar to Raptor-null and rapamycin-treated neurospheres. Interestingly, loss of Usp9x increased the number of sphere-forming cells consistent with enhanced neural stem cell self-renewal. To our knowledge, USP9X is the first deubiquitylating enzyme shown to stabilize RAPTOR.

  4. Artificial Neural Network for the Prediction of Tyrosine-Based Sorting Signal Recognition by Adaptor Complexes

    PubMed Central

    Mukherjee, Debarati; Hanna, Claudia B.; Aguilar, R. Claudio

    2012-01-01

    Sorting of transmembrane proteins to various intracellular compartments depends on specific signals present within their cytosolic domains. Among these sorting signals, the tyrosine-based motif (YXXØ) is one of the best characterized and is recognized by μ-subunits of the four clathrin-associated adaptor complexes (AP-1 to AP-4). Despite their overlap in specificity, each μ-subunit has a distinct sequence preference dependent on the nature of the X-residues. Moreover, combinations of these residues exert cooperative or inhibitory effects towards interaction with the various APs. This complexity makes it impossible to predict a priori, the specificity of a given tyrosine-signal for a particular μ-subunit. Here, we describe the results obtained with a computational approach based on the Artificial Neural Network (ANN) paradigm that addresses the issue of tyrosine-signal specificity, enabling the prediction of YXXØ-μ interactions with accuracies over 90%. Therefore, this approach constitutes a powerful tool to help predict mechanisms of intracellular protein sorting. PMID:22505811

  5. Automatic Detection and Identification of Seismic Signals Recorded at Krakatau Volcano (Indonesia) Using Artificial Neural Networks

    NASA Astrophysics Data System (ADS)

    Ibs-von Seht, M.; Kniess, R.

    2006-12-01

    A number of different event types can be observed in the records of seismic stations operated on Krakatau volcano (Indonesia). These include volcano-induced signals such as LP, VT, and hybrid-type events as well as signals not originating from the volcano such as local and regional tectonic earthquakes and transient noise signals. The work presented here aims at the realization of a system that automatically detects and identifies the signals in order to estimate and monitor current activity states of the volcano. An artificial neural network (ANN) approach was chosen for the identification task. A set of parameters were defined, describing waveform and spectrogram properties of events detected by an STA/LTA algorithm. The parameters are fed into an ANN which is, after a training phase, able to generalize input data and identify corresponding event types. The success of the identification depends on the network architecture and training strategy. Several tests have been performed in order to determine an appropriate network layout and training intensity for the given problem. The resulting network shows a good performance. A practical implementation of the system for the volcano observatory routine is sketched.

  6. History influences signal recognition: neural network models of túngara frogs.

    PubMed

    Phelps, S M; Ryan, M J

    2000-08-22

    Animals often attend to only a few of the cues provided by the complex displays of conspecifics. We suggest that these perceptual biases are influenced by mechanisms of signal recognition inherited from antecedent species. We tested this hypothesis by manipulating the evolutionary history of artificial neural networks, observing how the resulting networks respond to many novel stimuli and comparing these responses to the behaviour of females in phonotaxis experiments. Networks with different evolutionary histories proved equally capable of evolving to recognize the call of the túngara frog, Physalaemus pustulosus, but exhibited distinct responses to novel stimuli. History influenced the ability of networks to predict known responses of túngara frogs; network accuracy was determined by how closely the network history approximated the hypothesized history of the túngara frog. Our findings emphasize the influence of past selection pressures on current perceptual mechanisms, and demonstrate how neural network models can be used to address behavioural questions that are intractable through traditional methods.

  7. Linear-phase delay filters for ultra-low-power signal processing in neural recording implants.

    PubMed

    Gosselin, Benoit; Sawan, Mohamad; Kerherve, Eric

    2010-06-01

    We present the design and implementation of linear-phase delay filters for ultra-low-power signal processing in neural recording implants. We use these filters as low-distortion delay elements along with an automatic biopotential detector to perform integral waveform extraction and efficient power management. The presented delay elements are realized employing continuous-time OTA-C filters featuring 9th-order equiripple transfer functions with constant group delay. Such analog delay enables processing neural waveforms with reduced overhead compared to a digital delay since it does not requires sampling and digitization. It uses an allpass transfer function for achieving wider constant-delay bandwidth than all-pole does. Two filters realizations are compared for implementing the delay element: the Cascaded structure and the Inverse follow-the-leader feedback filter. Their respective strengths and drawbacks are assessed by modeling parasitics and non-idealities of OTAs, and by transistor-level simulations. A budget of 200 nA is used in both filters. Experimental measurements with the chosen filter topology are presented and discussed.

  8. Immersive audiomotor game play enhances neural and perceptual salience of weak signals in noise.

    PubMed

    Whitton, Jonathon P; Hancock, Kenneth E; Polley, Daniel B

    2014-06-24

    All sensory systems face the fundamental challenge of encoding weak signals in noisy backgrounds. Although discrimination abilities can improve with practice, these benefits rarely generalize to untrained stimulus dimensions. Inspired by recent findings that action video game training can impart a broader spectrum of benefits than traditional perceptual learning paradigms, we trained adult humans and mice in an immersive audio game that challenged them to forage for hidden auditory targets in a 2D soundscape. Both species learned to modulate their angular search vectors and target approach velocities based on real-time changes in the level of a weak tone embedded in broadband noise. In humans, mastery of this tone in noise task generalized to an improved ability to comprehend spoken sentences in speech babble noise. Neural plasticity in the auditory cortex of trained mice supported improved decoding of low-intensity sounds at the training frequency and an enhanced resistance to interference from background masking noise. These findings highlight the potential to improve the neural and perceptual salience of degraded sensory stimuli through immersive computerized games.

  9. A pain-mediated neural signal induces relapse in murine autoimmune encephalomyelitis, a multiple sclerosis model

    PubMed Central

    Arima, Yasunobu; Kamimura, Daisuke; Atsumi, Toru; Harada, Masaya; Kawamoto, Tadafumi; Nishikawa, Naoki; Stofkova, Andrea; Ohki, Takuto; Higuchi, Kotaro; Morimoto, Yuji; Wieghofer, Peter; Okada, Yuka; Mori, Yuki; Sakoda, Saburo; Saika, Shizuya; Yoshioka, Yoshichika; Komuro, Issei; Yamashita, Toshihide; Hirano, Toshio; Prinz, Marco; Murakami, Masaaki

    2015-01-01

    Although pain is a common symptom of various diseases and disorders, its contribution to disease pathogenesis is not well understood. Here we show using murine experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis (MS), that pain induces EAE relapse. Mechanistic analysis showed that pain induction activates a sensory-sympathetic signal followed by a chemokine-mediated accumulation of MHC class II+CD11b+ cells that showed antigen-presentation activity at specific ventral vessels in the fifth lumbar cord of EAE-recovered mice. Following this accumulation, various immune cells including pathogenic CD4+ T cells recruited in the spinal cord in a manner dependent on a local chemokine inducer in endothelial cells, resulting in EAE relapse. Our results demonstrate that a pain-mediated neural signal can be transformed into an inflammation reaction at specific vessels to induce disease relapse, thus making this signal a potential therapeutic target. DOI: http://dx.doi.org/10.7554/eLife.08733.001 PMID:26193120

  10. BMP2-SMAD signaling represses the proliferation of embryonic neural stem cells through YAP.

    PubMed

    Yao, Minghui; Wang, Yadong; Zhang, Peng; Chen, Hong; Xu, Zhiheng; Jiao, Jianwei; Yuan, Zengqiang

    2014-09-03

    Previous studies have shown that the Hippo pathway effector yes-associated protein (YAP) plays an important role in maintaining stem cell proliferation. However, the precise molecular mechanism of YAP in regulating murine embryonic neural stem cells (NSCs) remains largely unknown. Here, we show that bone morphogenetic protein-2 (BMP2) treatment inhibited the proliferation of mouse embryonic NSCs, that YAP was critical for mouse NSC proliferation, and that BMP2 treatment-induced inhibition of mouse NSC proliferation was abrogated by YAP knockdown, indicating that the YAP protein mediates the inhibitory effect of BMP2 signaling. Additionally, we found that BMP2 treatment reduced YAP nuclear translocation, YAP-TEAD interaction, and YAP-mediated transactivation. BMP2 treatment inhibited YAP/TEAD-mediated Cyclin D1 (ccnd1) expression, and knockdown of ccnd1 abrogated the BMP2-mediated inhibition of mouse NSC proliferation. Mechanistically, we found that Smad1/4, effectors of BMP2 signaling, competed with YAP for the interaction with TAED1 and inhibited YAP's cotranscriptional activity. Our data reveal mechanistic cross talk between BMP2 signaling and the Hippo-YAP pathway in murine NSC proliferation, which may be exploited as a therapeutic target in neurodegenerative diseases and aging.

  11. Human neural stem cell-induced endothelial morphogenesis requires autocrine/paracrine and juxtacrine signaling

    PubMed Central

    Chou, Chung-Hsing; Modo, Michel

    2016-01-01

    Transplanted neural stem cells (NSC) interact with the host brain microenvironment. A neovascularization is commonly observed in the vicinity of the cell deposit, which is correlated with behavioral improvements. To elucidate the signaling mechanisms between human NSCs and endothelial cells (ECs), these were cocultured in an in vitro model in which NSC-induced endothelial morphogenesis produced a neurovascular environment. Soluble (autocrine/paracrine) and contact–mediated (juxtacrine) signaling molecules were evaluated for two conditionally immortalized fetal NSC lines derived from the cortical anlage (CTXOE03) and ganglionic eminence (STROC05), as well as an adult EC line (D3) derived from the cerebral microvasculature of a hippocampal biopsy. STROC05 were 4 times as efficient to induce endothelial morphogenesis compared to CTXOE03. The cascade of reciprocal interactions between NSCs and ECs in this process was determined by quantifying soluble factors, receptor mapping, and immunocytochemistry for extracellular matrix molecules. The mechanistic significance of these was further evaluated by pharmacological blockade. The sequential cell-specific regulation of autocrine/paracrine and juxtacrine signaling accounted for the differential efficiency of NSCs to induce endothelial morphogenesis. These in vitro studies shed new light on the reciprocal interactions between NSCs and ECs, which are pivotal for our mechanistic understanding of the efficacy of NSC transplantation. PMID:27374240

  12. BLOS2 negatively regulates Notch signaling during neural and hematopoietic stem and progenitor cell development

    PubMed Central

    Zhou, Wenwen; He, Qiuping; Zhang, Chunxia; He, Xin; Cui, Zongbin; Liu, Feng; Li, Wei

    2016-01-01

    Notch signaling plays a crucial role in controling the proliferation and differentiation of stem and progenitor cells during embryogenesis or organogenesis, but its regulation is incompletely understood. BLOS2, encoded by the Bloc1s2 gene, is a shared subunit of two lysosomal trafficking complexes, biogenesis of lysosome-related organelles complex-1 (BLOC-1) and BLOC-1-related complex (BORC). Bloc1s2−/− mice were embryonic lethal and exhibited defects in cortical development and hematopoiesis. Loss of BLOS2 resulted in elevated Notch signaling, which consequently increased the proliferation of neural progenitor cells and inhibited neuronal differentiation in cortices. Likewise, ablation of bloc1s2 in zebrafish or mice led to increased hematopoietic stem and progenitor cell production in the aorta-gonad-mesonephros region. BLOS2 physically interacted with Notch1 in endo-lysosomal trafficking of Notch1. Our findings suggest that BLOS2 is a novel negative player in regulating Notch signaling through lysosomal trafficking to control multiple stem and progenitor cell homeostasis in vertebrates. DOI: http://dx.doi.org/10.7554/eLife.18108.001 PMID:27719760

  13. Segregating neural and mechanosensory fates in the developing ear: patterning, signaling, and transcriptional control.

    PubMed

    Raft, Steven; Groves, Andrew K

    2015-01-01

    The vertebrate inner ear is composed of multiple sensory receptor epithelia, each of which is specialized for detection of sound, gravity, or angular acceleration. Each receptor epithelium contains mechanosensitive hair cells, which are connected to the brainstem by bipolar sensory neurons. Hair cells and their associated neurons are derived from the embryonic rudiment of the inner ear epithelium, but the precise spatial and temporal patterns of their generation, as well as the signals that coordinate these events, have only recently begun to be understood. Gene expression, lineage tracing, and mutant analyses suggest that both neurons and hair cells are generated from a common domain of neural and sensory competence in the embryonic inner ear rudiment. Members of the Shh, Wnt, and FGF families, together with retinoic acid signals, regulate transcription factor genes within the inner ear rudiment to establish the axial identity of the ear and regionalize neurogenic activity. Close-range signaling, such as that of the Notch pathway, specifies the fate of sensory regions and individual cell types. We also describe positive and negative interactions between basic helix-loop-helix and SoxB family transcription factors that specify either neuronal or sensory fates in a context-dependent manner. Finally, we review recent work on inner ear development in zebrafish, which demonstrates that the relative timing of neurogenesis and sensory epithelial formation is not phylogenetically constrained.

  14. Physical and perceptual factors shape the neural mechanisms that integrate audiovisual signals in speech comprehension.

    PubMed

    Lee, HweeLing; Noppeney, Uta

    2011-08-03

    Face-to-face communication challenges the human brain to integrate information from auditory and visual senses with linguistic representations. Yet the role of bottom-up physical (spectrotemporal structure) input and top-down linguistic constraints in shaping the neural mechanisms specialized for integrating audiovisual speech signals are currently unknown. Participants were presented with speech and sinewave speech analogs in visual, auditory, and audiovisual modalities. Before the fMRI study, they were trained to perceive physically identical sinewave speech analogs as speech (SWS-S) or nonspeech (SWS-N). Comparing audiovisual integration (interactions) of speech, SWS-S, and SWS-N revealed a posterior-anterior processing gradient within the left superior temporal sulcus/gyrus (STS/STG): Bilateral posterior STS/STG integrated audiovisual inputs regardless of spectrotemporal structure or speech percept; in left mid-STS, the integration profile was primarily determined by the spectrotemporal structure of the signals; more anterior STS regions discarded spectrotemporal structure and integrated audiovisual signals constrained by stimulus intelligibility and the availability of linguistic representations. In addition to this "ventral" processing stream, a "dorsal" circuitry encompassing posterior STS/STG and left inferior frontal gyrus differentially integrated audiovisual speech and SWS signals. Indeed, dynamic causal modeling and Bayesian model comparison provided strong evidence for a parallel processing structure encompassing a ventral and a dorsal stream with speech intelligibility training enhancing the connectivity between posterior and anterior STS/STG. In conclusion, audiovisual speech comprehension emerges in an interactive process with the integration of auditory and visual signals being progressively constrained by stimulus intelligibility along the STS and spectrotemporal structure in a dorsal fronto-temporal circuitry.

  15. The effects of methylmercury on Notch signaling during embryonic neural development in Drosophila melanogaster

    PubMed Central

    Engel, GL; Delwig, A; Rand, MD

    2012-01-01

    Methylmercury (MeHg) is a ubiquitous toxicant that targets the developing fetal nervous system. MeHg interacts with the Notch signaling pathway, a highly-conserved intercellular signaling mechanism required for normal development. Notch signaling is conveyed by activation of the genes in the Enhancer of Split (E(spl)) locus in Drosophila. We have previously shown that acute high doses of MeHg upregulate several E(spl) genes in Drosophila neural-derived C6 cells. Furthermore, MeHg induction of E(spl) can occur independent of the Notch receptor itself. We now show that MeHg, unlike inorganic mercury (HgCl2), preferentially upregulates E(spl)mδ and E(spl)mγ in Drosophila C6 cells. This is distinct from Delta ligand-induced Notch signaling in which no induction of E(spl)mδ is seen. MeHg is also seen to specifically upregulate E(spl)mδ in Drosophila embryos where HgCl2 showed no such effect. Additionally, treatment of embryos with MeHg caused a consistent failure in axonal outgrowth of the intersegmental nerve (ISN). This ISN phenotype was partially replicated by genetic activation of the Notch pathway, but was not replicated by increasing expression of E(spl)mδ. These data suggest a role for Notch signaling and the E(spl)mδ target gene in MeHg toxicity, however, the site of action for E(spl)mδ in this system remains to be elucidated. PMID:22230562

  16. Endogenous Repair Signaling after Brain Injury and Complementary Bioengineering Approaches to Enhance Neural Regeneration

    PubMed Central

    Addington, Caroline P; Roussas, Adam; Dutta, Dipankar; Stabenfeldt, Sarah E

    2015-01-01

    Traumatic brain injury (TBI) affects 5.3 million Americans annually. Despite the many long-term deficits associated with TBI, there currently are no clinically available therapies that directly address the underlying pathologies contributing to these deficits. Preclinical studies have investigated various therapeutic approaches for TBI: two such approaches are stem cell transplantation and delivery of bioactive factors to mitigate the biochemical insult affiliated with TBI. However, success with either of these approaches has been limited largely due to the complexity of the injury microenvironment. As such, this review outlines the many factors of the injury microenvironment that mediate endogenous neural regeneration after TBI and the corresponding bioengineering approaches that harness these inherent signaling mechanisms to further amplify regenerative efforts. PMID:25983552

  17. The Hippo signalling pathway maintains quiescence in Drosophila neural stem cells.

    PubMed

    Ding, Rouven; Weynans, Kevin; Bossing, Torsten; Barros, Claudia S; Berger, Christian

    2016-01-29

    Stem cells control their mitotic activity to decide whether to proliferate or to stay in quiescence. Drosophila neural stem cells (NSCs) are quiescent at early larval stages, when they are reactivated in response to metabolic changes. Here we report that cell-contact inhibition of growth through the canonical Hippo signalling pathway maintains NSC quiescence. Loss of the core kinases hippo or warts leads to premature nuclear localization of the transcriptional co-activator Yorkie and initiation of growth and proliferation in NSCs. Yorkie is necessary and sufficient for NSC reactivation, growth and proliferation. The Hippo pathway activity is modulated via inter-cellular transmembrane proteins Crumbs and Echinoid that are both expressed in a nutrient-dependent way in niche glial cells and NSCs. Loss of crumbs or echinoid in the niche only is sufficient to reactivate NSCs. Finally, we provide evidence that the Hippo pathway activity discriminates quiescent from non-quiescent NSCs in the Drosophila nervous system.

  18. The Hippo signalling pathway maintains quiescence in Drosophila neural stem cells

    PubMed Central

    Ding, Rouven; Weynans, Kevin; Bossing, Torsten; Barros, Claudia S.; Berger, Christian

    2016-01-01

    Stem cells control their mitotic activity to decide whether to proliferate or to stay in quiescence. Drosophila neural stem cells (NSCs) are quiescent at early larval stages, when they are reactivated in response to metabolic changes. Here we report that cell-contact inhibition of growth through the canonical Hippo signalling pathway maintains NSC quiescence. Loss of the core kinases hippo or warts leads to premature nuclear localization of the transcriptional co-activator Yorkie and initiation of growth and proliferation in NSCs. Yorkie is necessary and sufficient for NSC reactivation, growth and proliferation. The Hippo pathway activity is modulated via inter-cellular transmembrane proteins Crumbs and Echinoid that are both expressed in a nutrient-dependent way in niche glial cells and NSCs. Loss of crumbs or echinoid in the niche only is sufficient to reactivate NSCs. Finally, we provide evidence that the Hippo pathway activity discriminates quiescent from non-quiescent NSCs in the Drosophila nervous system. PMID:26821647

  19. Novel association of VACTERL, neural tube defect and crossed renal ectopia: sonic hedgehog signaling: a point of coherence?

    PubMed

    Vaze, Dhananjay; Mahalik, Santosh; Rao, Katragadda L N

    2012-12-01

    The present case report describes two patients with a novel combination of VACTERL (vertebral, anorectal, cardiac, tracheoesophageal, renal, limb), neural tube defect and crossed renal ectopia. Though cases of VACTERL associated with crossed renal ectopia have been described, the present case report is the first to describe its combination with neural tube defect. The cases reported here are significant because central nervous system manifestations are scarce in VACTERL syndrome. The role of sonic hedgehog pathway has been proposed in VACTERL association and neural tube defects. Axial Sonic hedgehog signaling has also been implicated in the mediolateral positioning of the renal parenchyma. With this knowledge, the etiopathogenesis of this novel combination is discussed to highlight the role of sonic hedgehog signaling as a point of coherence.

  20. G-protein-coupled receptors and localized signaling in the primary cilium during ventral neural tube patterning.

    PubMed

    Hwang, Sun-Hee; Mukhopadhyay, Saikat

    2015-01-01

    The primary cilium is critical in sonic hedgehog (Shh)-dependent ventral patterning of the vertebrate neural tube. Most mutants that cause disruption of the cilium result in decreased Shh signaling in the neural tube. In contrast, mutations in the intraflagellar complex A (IFT-A) and the tubby family protein, Tulp3, result in increased Shh signaling in the neural tube. Proteomic analysis of Tulp3-binding proteins first pointed to the role of the IFT-A complex in trafficking Tulp3 into the cilia. Tulp3 directs trafficking of rhodopsin family G-protein-coupled receptors (GPCRs) to the cilia, suggesting the role of a GPCR in mediating the paradoxical effects of the Tulp3/IFT-A complex in causing increased Shh signaling. Gpr161 has recently been identified as a Tulp3/IFT-A-regulated GPCR that localizes to the primary cilium. A null knock-out mouse model of Gpr161 phenocopies Tulp3 and IFT-A mutants, and causes increased Shh signaling throughout the neural tube. In the absence of Shh, the bifunctional Gli transcription factors are proteolytically processed into repressor forms in a protein kinase A (PKA) -dependent and cilium-dependent manner. Gpr161 activity results in increased cAMP levels in a Gαs -coupled manner, and determines processing of Gli3. Shh signaling also results in removal of Gpr161 from the cilia, suggesting that Gpr161 functions in a positive feedback loop in the Shh pathway. As PKA-null and Gαs mutant embryos also exhibit increased Shh signaling in the neural tube, Gpr161 is a strong candidate for a GPCR that regulates ciliary cAMP levels, and activates PKA in close proximity to the cilia.

  1. Brain Tissue Responses to Neural Implants Impact Signal Sensitivity and Intervention Strategies

    PubMed Central

    2015-01-01

    Implantable biosensors are valuable scientific tools for basic neuroscience research and clinical applications. Neurotechnologies provide direct readouts of neurological signal and neurochemical processes. These tools are generally most valuable when performance capacities extend over months and years to facilitate the study of memory, plasticity, and behavior or to monitor patients’ conditions. These needs have generated a variety of device designs from microelectrodes for fast scan cyclic voltammetry (FSCV) and electrophysiology to microdialysis probes for sampling and detecting various neurochemicals. Regardless of the technology used, the breaching of the blood–brain barrier (BBB) to insert devices triggers a cascade of biochemical pathways resulting in complex molecular and cellular responses to implanted devices. Molecular and cellular changes in the microenvironment surrounding an implant include the introduction of mechanical strain, activation of glial cells, loss of perfusion, secondary metabolic injury, and neuronal degeneration. Changes to the tissue microenvironment surrounding the device can dramatically impact electrochemical and electrophysiological signal sensitivity and stability over time. This review summarizes the magnitude, variability, and time course of the dynamic molecular and cellular level neural tissue responses induced by state-of-the-art implantable devices. Studies show that insertion injuries and foreign body response can impact signal quality across all implanted central nervous system (CNS) sensors to varying degrees over both acute (seconds to minutes) and chronic periods (weeks to months). Understanding the underlying biological processes behind the brain tissue response to the devices at the cellular and molecular level leads to a variety of intervention strategies for improving signal sensitivity and longevity. PMID:25546652

  2. Lingo-1 shRNA and Notch signaling inhibitor DAPT promote differentiation of neural stem/progenitor cells into neurons.

    PubMed

    Wang, Jue; Ye, Zhizhong; Zheng, Shuhui; Chen, Luming; Wan, Yong; Deng, Yubin; Yang, Ruirui

    2016-03-01

    Determination of the exogenous factors that regulate differentiation of neural stem/progenitor cells into neurons, oligodendrocytes and astrocytes is an important step in the clinical therapy of spinal cord injury (SCI). The Notch pathway inhibits the differentiation of neural stem/progenitor cells and Lingo-1 is a strong negative regulator for myelination and axon growth. While Lingo-1 shRNA and N-[N-(3, 5-difluorophenacetyl)-1-alanyl]-S-Phenylglycinet-butylester (DAPT), a Notch pathway inhibitor, have been used separately to help repair SCI, the results have been unsatisfactory. Here we investigated and elucidated the preliminary mechanism for the effect of Lingo-1 shRNA and DAPT on neural stem/progenitor cells differentiation. We found that neural stem/progenitor cells from E14 rat embryos expressed Nestin, Sox-2 and Lingo-1, and we optimized the transduction of neural stem/progenitor cells using lentiviral vectors encoding Lingo-1 shRNA. The addition of DAPT decreased the expression of Notch intracellular domain (NICD) as well as the downstream genes Hes1 and Hes5. Expression of NeuN, CNPase and GFAP in DAPT treated cells and expression of NeuN in Lingo-1 shRNA treated cells confirmed differentiation of neural stem/progenitor cells into neurons, oligodendrocytes and astrocytes. These results revealed that while Lingo-1 shRNA and Notch signaling inhibitor DAPT both promoted differentiation of neural stem cells into neurons, only DAPT was capable of driving neural stem/progenitor cells differentiation into oligodendrocytes and astrocytes. Since we were able to show that both Lingo-1 shRNA and DAPT could drive neural stem/progenitor cells differentiation, our data might aid the development of more effective SCI therapies using Lingo-1 shRNA and DAPT.

  3. Targeting the AKT/GSK3{beta}/Cyclin D1/Cdk4 Survival Signaling Pathway for Eradication of Tumor Radioresistance Acquired by Fractionated Radiotherapy

    SciTech Connect

    Shimura, Tsutomu; Kakuda, Satoshi; Ochiai, Yasushi; Kuwahara, Yoshikazu; Takai, Yoshihiro; Fukumoto, Manabu

    2011-06-01

    Purpose: Radioresistance is a major cause of treatment failure of radiotherapy (RT) in human cancer. We have recently revealed that acquired radioresistance of tumor cells induced by fractionated radiation is attributable to cyclin D1 overexpression as a consequence of the downregulation of GSK3{beta}-dependent cyclin D1 proteolysis mediated by a constitutively activated serine-threonine kinase, AKT. This prompted us to hypothesize that targeting the AKT/GSK3{beta}/cyclin D1 pathway may improve fractionated RT by suppressing acquired radioresistance of tumor cells. Methods and Materials: Two human tumor cell lines with acquired radioresistance were exposed to X-rays after incubation with either an AKT inhibitor, AKT/PKB signaling inhibitor-2 (API-2), or a Cdk4 inhibitor (Cdk4-I). Cells were then subjected to immunoblotting, clonogenic survival assay, cell growth analysis, and cell death analysis with TUNEL and annexin V staining. In vivo radiosensitivity was assessed by growth of human tumors xenografted into nude mice. Results: Treatment with API-2 resulted in downregulation of cyclin D1 expression in cells with acquired radioresistance. Cellular radioresistance disappeared completely both in vitro and in vivo with accompanying apoptosis when treated with API-2. Furthermore, inhibition of cyclin D1/Cdk4 by Cdk4-I was sufficient for abolishing radioresistance. Treatment with either API-2 or Cdk4-I was also effective in suppressing resistance to cis-platinum (II)-diamine-dichloride in the cells with acquired radioresistance. Interestingly, the radiosensitizing effect of API-2 was canceled by overexpression of cyclin D1 whereas Cdk4-I was still able to sensitize cells with cyclin D1 overexpression. Conclusion: Cyclin D1/Cdk4 is a critical target of the AKT survival signaling pathway responsible for tumor radioresistance. Targeting the AKT/GSK3{beta}/cyclin D1/Cdk4 pathway would provide a novel approach to improve fractionated RT and would have an impact on tumor

  4. Correlation between stimulation strength and onset time of signal traveling within the neocortical neural circuits under caffeine application.

    PubMed

    Yoshimura, Hiroshi; Honjo, Miho; Sugai, Tokio; Kaneyama, Keiseki; Segami, Natsuki; Kato, Nobuo

    2011-08-01

    In general, strength of input to neocortical neural circuits affects the amplitude of postsynaptic potentials (PSPs), thereby modulating the way signals are transmitted within the circuits. Caffeine is one of the pharmacological agents able to modulate synaptic activities. The present study investigated how strength of input affects signal propagation in neocortical circuits under the application of caffeine. Spatio-temporal neural activities were observed from visual cortical slices of rats using optical recording methods with voltage-sensitive dye. Electrical stimulations were applied to white matter in the primary visual cortex with bath-application of caffeine. When the strength of stimulation was 0.3mA, signals propagated from the site of stimulation in the primary visual cortex toward the secondary visual cortex along vertical and horizontal pathways. When stimulation strength was reduced from 0.3mA to 0.07mA, start of signal propagation was delayed about 25ms without affecting field PSP amplitude or the manner of signal propagation. Conversely, co-application of caffeine and d-2-amino-5-phosphonovaleric acid (d-AP5) did not induce delays in signal start. These findings suggest that conversion of neural code from amplitude code to temporal code is inducible at the level of neocortical circuits in an N-methyl-d-aspartate (NMDA) receptor activity-dependent manner.

  5. Classification of a Driver's cognitive workload levels using artificial neural network on ECG signals.

    PubMed

    Tjolleng, Amir; Jung, Kihyo; Hong, Wongi; Lee, Wonsup; Lee, Baekhee; You, Heecheon; Son, Joonwoo; Park, Seikwon

    2017-03-01

    An artificial neural network (ANN) model was developed in the present study to classify the level of a driver's cognitive workload based on electrocardiography (ECG). ECG signals were measured on 15 male participants while they performed a simulated driving task as a primary task with/without an N-back task as a secondary task. Three time-domain ECG measures (mean inter-beat interval (IBI), standard deviation of IBIs, and root mean squared difference of adjacent IBIs) and three frequencydomain ECG measures (power in low frequency, power in high frequency, and ratio of power in low and high frequencies) were calculated. To compensate for individual differences in heart response during the driving tasks, a three-step data processing procedure was performed to ECG signals of each participant: (1) selection of two most sensitive ECG measures, (2) definition of three (low, medium, and high) cognitive workload levels, and (3) normalization of the selected ECG measures. An ANN model was constructed using a feed-forward network and scaled conjugate gradient as a back-propagation learning rule. The accuracy of the ANN classification model was found satisfactory for learning data (95%) and testing data (82%).

  6. Wnt signaling pathway participates in valproic acid-induced neuronal differentiation of neural stem cells.

    PubMed

    Wang, Li; Liu, Yuan; Li, Sen; Long, Zai-Yun; Wu, Ya-Min

    2015-01-01

    Neural stem cells (NSCs) are multipotent cells that have the capacity for differentiation into the major cell types of the nervous system, i.e. neurons, astrocytes and oligodendrocytes. Valproic acid (VPA) is a widely prescribed drug for seizures and bipolar disorder in clinic. Previously, a number of researches have been shown that VPA has differential effects on growth, proliferation and differentiation in many types of cells. However, whether VPA can induce NSCs from embryonic cerebral cortex differentiate into neurons and its possible molecular mechanism is also not clear. Wnt signaling is implicated in the control of cell growth and differentiation during CNS development in animal model, but its action at the cellular level has been poorly understood. In this experiment, we examined neuronal differentiation of NSCs induced by VPA culture media using vitro immunochemistry assay. The neuronal differentiation of NSCs was examined after treated with 0.75 mM VPA for three, seven and ten days. RT-PCR assay was employed to examine the level of Wnt-3α and β-catenin. The results indicated that there were more β-tublin III positive cells in NSCs treated with VPA medium compared to the control group. The expression of Wnt-3α and β-catenin in NSCs treated with VPA medium was significantly greater compared to that of control media. In conclusion, these findings indicated that VPA could induce neuronal differentiation of NSCs by activating Wnt signal pathway.

  7. Classification of RF transients in space using digital signal processing and neural network techniques

    SciTech Connect

    Moore, K.R.; Blain, P.C.; Briles, S.D.; Jones, R.G.

    1995-02-01

    The FORTE{prime} (Fast On-Orbit Recording of Transient Events) small satellite experiment scheduled for launch in October, 1995 will attempt to measure and classify electromagnetic transients as sensed from space. The FORTE{prime} payload will employ an Event Classifier to perform onboard classification of radio frequency transients from terrestrial sources such as lightning. These transients are often dominated by a constantly changing assortment of man-made ``clutter`` such as TV, FM, and radar signals. The FORTE{prime} Event Classifier, or EC, uses specialized hardware to implement various signal processing and neural network algorithms. The resulting system can process and classify digitized records of several thousand samples onboard the spacecraft at rates of about a second per record. In addition to reducing dowlink rates, the EC minimizes command uplink data by normally using uploaded algorithm sequences rather than full code modules (although it is possible for full code modules to be uploaded from the ground). The FORTE{prime} Event Classifier experiment combines science and engineering in an evolutionary step toward useful and robust adaptive processing systems in space.

  8. Weak signal detection and propagation in diluted feed-forward neural network with recurrent excitation and inhibition

    NASA Astrophysics Data System (ADS)

    Wang, Jiang; Han, Ruixue; Wei, Xilei; Qin, Yingmei; Yu, Haitao; Deng, Bin

    2016-12-01

    Reliable signal propagation across distributed brain areas provides the basis for neural circuit function. Modeling studies on cortical circuits have shown that multilayered feed-forward networks (FFNs), if strongly and/or densely connected, can enable robust signal propagation. However, cortical networks are typically neither densely connected nor have strong synapses. This paper investigates under which conditions spiking activity can be propagated reliably across diluted FFNs. Extending previous works, we model each layer as a recurrent sub-network constituting both excitatory (E) and inhibitory (I) neurons and consider the effect of interactions between local excitation and inhibition on signal propagation. It is shown that elevation of cellular excitation-inhibition (EI) balance in the local sub-networks (layers) softens the requirement for dense/strong anatomical connections and thereby promotes weak signal propagation in weakly connected networks. By means of iterated maps, we show how elevated local excitability state compensates for the decreased gain of synchrony transfer function that is due to sparse long-range connectivity. Finally, we report that modulations of EI balance and background activity provide a mechanism for selectively gating and routing neural signal. Our results highlight the essential role of intrinsic network states in neural computation.

  9. Application of artificial neural network to search for gravitational-wave signals associated with short gamma-ray bursts

    NASA Astrophysics Data System (ADS)

    Kim, Kyungmin; Harry, Ian W.; Hodge, Kari A.; Kim, Young-Min; Lee, Chang-Hwan; Lee, Hyun Kyu; Oh, John J.; Oh, Sang Hoon; Son, Edwin J.

    2015-12-01

    We apply a machine learning algorithm, the artificial neural network, to the search for gravitational-wave signals associated with short gamma-ray bursts (GRBs). The multi-dimensional samples consisting of data corresponding to the statistical and physical quantities from the coherent search pipeline are fed into the artificial neural network to distinguish simulated gravitational-wave signals from background noise artifacts. Our result shows that the data classification efficiency at a fixed false alarm probability (FAP) is improved by the artificial neural network in comparison to the conventional detection statistic. Specifically, the distance at 50% detection probability at a fixed false positive rate is increased about 8%-14% for the considered waveform models. We also evaluate a few seconds of the gravitational-wave data segment using the trained networks and obtain the FAP. We suggest that the artificial neural network can be a complementary method to the conventional detection statistic for identifying gravitational-wave signals related to the short GRBs.

  10. STAT3 signal that mediates the neural plasticity is involved in willed-movement training in focal ischemic rats*

    PubMed Central

    Tang, Qing-ping; Shen, Qin; Wu, Li-xiang; Feng, Xiang-ling; Liu, Hui; Wu, Bei; Huang, Xiao-song; Wang, Gai-qing; Li, Zhong-hao; Liu, Zun-jing

    2016-01-01

    Willed-movement training has been demonstrated to be a promising approach to increase motor performance and neural plasticity in ischemic rats. However, little is known regarding the molecular signals that are involved in neural plasticity following willed-movement training. To investigate the potential signals related to neural plasticity following willed-movement training, littermate rats were randomly assigned into three groups: middle cerebral artery occlusion, environmental modification, and willed-movement training. The infarct volume was measured 18 d after occlusion of the right middle cerebral artery. Reverse transcription-polymerase chain reaction (PCR) and immunofluorescence staining were used to detect the changes in the signal transducer and activator of transcription 3 (STAT3) mRNA and protein, respectively. A chromatin immunoprecipitation was used to investigate whether STAT3 bound to plasticity-related genes, such as brain-derived neurotrophic factor (BDNF), synaptophysin, and protein interacting with C kinase 1 (PICK1). In this study, we demonstrated that STAT3 mRNA and protein were markedly increased following 15-d willed-movement training in the ischemic hemispheres of the treated rats. STAT3 bound to BDNF, PICK1, and synaptophysin promoters in the neocortical cells of rats. These data suggest that the increased STAT3 levels after willed-movement training might play critical roles in the neural plasticity by directly regulating plasticity-related genes. PMID:27381726

  11. Integration of auditory and somatosensory error signals in the neural control of speech movements.

    PubMed

    Feng, Yongqiang; Gracco, Vincent L; Max, Ludo

    2011-08-01

    We investigated auditory and somatosensory feedback contributions to the neural control of speech. In task I, sensorimotor adaptation was studied by perturbing one of these sensory modalities or both modalities simultaneously. The first formant (F1) frequency in the auditory feedback was shifted up by a real-time processor and/or the extent of jaw opening was increased or decreased with a force field applied by a robotic device. All eight subjects lowered F1 to compensate for the up-shifted F1 in the feedback signal regardless of whether or not the jaw was perturbed. Adaptive changes in subjects' acoustic output resulted from adjustments in articulatory movements of the jaw or tongue. Adaptation in jaw opening extent in response to the mechanical perturbation occurred only when no auditory feedback perturbation was applied or when the direction of adaptation to the force was compatible with the direction of adaptation to a simultaneous acoustic perturbation. In tasks II and III, subjects' auditory and somatosensory precision and accuracy were estimated. Correlation analyses showed that the relationships 1) between F1 adaptation extent and auditory acuity for F1 and 2) between jaw position adaptation extent and somatosensory acuity for jaw position were weak and statistically not significant. Taken together, the combined findings from this work suggest that, in speech production, sensorimotor adaptation updates the underlying control mechanisms in such a way that the planning of vowel-related articulatory movements takes into account a complex integration of error signals from previous trials but likely with a dominant role for the auditory modality.

  12. Kin rejection: social signals, neural response and perceived distress during social exclusion.

    PubMed

    Sreekrishnan, Anirudh; Herrera, Tania A; Wu, Jia; Borelli, Jessica L; White, Lars O; Rutherford, Helena J V; Mayes, Linda C; Crowley, Michael J

    2014-11-01

    Across species, kin bond together to promote survival. We sought to understand the dyadic effect of exclusion by kin (as opposed to non-kin strangers) on brain activity of the mother and her child and their subjective distress. To this end, we probed mother-child relationships with a computerized ball-toss game Cyberball. When excluded by one another, rather than by a stranger, both mothers and children exhibited a significantly pronounced frontal P2. Moreover, upon kin rejection versus stranger rejection, both mothers and children showed incremented left frontal positive slow waves for rejection events. Children reported more distress upon exclusion than their own mothers. Similar to past work, relatively augmented negative frontal slow wave activity predicted greater self-reported ostracism distress. This effect, generalized to the P2, was limited to mother- or child-rejection by kin, with comparable magnitude of effect across kin identity (mothers vs. children). For both mothers and children, the frontal P2 peak was significantly pronounced for kin rejection versus stranger rejection. Taken together, our results document the rapid categorization of social signals as kin relevant and the specificity of early and late neural markers for predicting felt ostracism.

  13. β-Neurexins Control Neural Circuits by Regulating Synaptic Endocannabinoid Signaling

    PubMed Central

    Anderson, Garret R.; Aoto, Jason; Tabuchi, Katsuhiko; Földy, Csaba; Covy, Jason; Yee, Ada Xin; Wu, Dick; Lee, Sung-Jin; Chen, Lu; Malenka, Robert C.; Südhof, Thomas C.

    2015-01-01

    α- and β-neurexins are presynaptic cell-adhesion molecules implicated in autism and schizophrenia. We find that although β-neurexins are expressed at much lower levels than α-neurexins, conditional knockout of β-neurexins with continued expression of α-neurexins dramatically decreased neurotransmitter release at excitatory synapses in cultured cortical neurons. The β-neurexin knockout phenotype was attenuated by CB1-receptor inhibition which blocks presynaptic endocannabinoid signaling or by 2-arachidonoylglycerol synthesis inhibition which impairs postsynaptic endocannabinoid release. In synapses formed by CA1-region pyramidal neurons onto burst-firing subiculum neurons, presynaptic in vivo knockout of β-neurexins aggravated endocannabinoid-mediated inhibition of synaptic transmission and blocked LTP; presynaptic CB1-receptor antagonists or postsynaptic 2-arachidonoylglycerol synthesis inhibition again reversed this block. Moreover, conditional knockout of β-neurexins in CA1-region neurons impaired contextual fear memories. Thus, our data suggest that presynaptic β-neurexins control synaptic strength in excitatory synapses by regulating postsynaptic 2-arachidonoylglycerol synthesis, revealing an unexpected role for β-neurexins in the endocannabinoid-dependent regulation of neural circuits. PMID:26213384

  14. The effects of life stress and neural learning signals on fluid intelligence.

    PubMed

    Friedel, Eva; Schlagenhauf, Florian; Beck, Anne; Dolan, Raymond J; Huys, Quentin J M; Rapp, Michael A; Heinz, Andreas

    2015-02-01

    Fluid intelligence (fluid IQ), defined as the capacity for rapid problem solving and behavioral adaptation, is known to be modulated by learning and experience. Both stressful life events (SLES) and neural correlates of learning [specifically, a key mediator of adaptive learning in the brain, namely the ventral striatal representation of prediction errors (PE)] have been shown to be associated with individual differences in fluid IQ. Here, we examine the interaction between adaptive learning signals (using a well-characterized probabilistic reversal learning task in combination with fMRI) and SLES on fluid IQ measures. We find that the correlation between ventral striatal BOLD PE and fluid IQ, which we have previously reported, is quantitatively modulated by the amount of reported SLES. Thus, after experiencing adversity, basic neuronal learning signatures appear to align more closely with a general measure of flexible learning (fluid IQ), a finding complementing studies on the effects of acute stress on learning. The results suggest that an understanding of the neurobiological correlates of trait variables like fluid IQ needs to take socioemotional influences such as chronic stress into account.

  15. Eph/Ephrin signalling maintains eye field segregation from adjacent neural plate territories during forebrain morphogenesis

    PubMed Central

    Cavodeassi, Florencia; Ivanovitch, Kenzo; Wilson, Stephen W.

    2013-01-01

    During forebrain morphogenesis, there is extensive reorganisation of the cells destined to form the eyes, telencephalon and diencephalon. Little is known about the molecular mechanisms that regulate region-specific behaviours and that maintain the coherence of cell populations undergoing specific morphogenetic processes. In this study, we show that the activity of the Eph/Ephrin signalling pathway maintains segregation between the prospective eyes and adjacent regions of the anterior neural plate during the early stages of forebrain morphogenesis in zebrafish. Several Ephrins and Ephs are expressed in complementary domains in the prospective forebrain and combinatorial abrogation of their activity results in incomplete segregation of the eyes and telencephalon and in defective evagination of the optic vesicles. Conversely, expression of exogenous Ephs or Ephrins in regions of the prospective forebrain where they are not usually expressed changes the adhesion properties of the cells, resulting in segregation to the wrong domain without changing their regional fate. The failure of eye morphogenesis in rx3 mutants is accompanied by a loss of complementary expression of Ephs and Ephrins, suggesting that this pathway is activated downstream of the regional fate specification machinery to establish boundaries between domains undergoing different programmes of morphogenesis. PMID:24026122

  16. Soft implantable microelectrodes for future medicine: prosthetics, neural signal recording and neuromodulation.

    PubMed

    Lee, Joong Hoon; Kim, Hanseop; Kim, Jeong Hun; Lee, Sang-Hoon

    2016-03-21

    Implantable devices have provided various potential diagnostic options and therapeutic methods in diverse medical fields. A variety of hard-material-based implantable electrodes have been developed. However, several limitations for their chronic implantation remain, including mechanical mismatches at the interface between the electrode and the soft tissue, and biocompatibility. Soft-material-based implantable devices are suitable candidates for complementing the limitations of hard electrodes. Advances in microtechnology and materials science have largely solved many challenges, such as optimization of shape, minimization of infection, enhancement of biocompatibility and integration with components for diverse functions. Significant strides have also been made in mechanical matching of electrodes to soft tissue. In this review, we provide an overview of recent advances in soft-material-based implantable electrodes for medical applications, categorized according to their implantation site and material composition. We then review specific applications in three categories: neuroprosthetics, neural signal recording, and neuromodulation. Finally, we describe various strategies for the future development and application of implantable, soft-material-based devices.

  17. Time-Domain Frequency Correction Method for Averaging Low-Field NMR Signals Acquired in Urban Laboratory Environment

    NASA Astrophysics Data System (ADS)

    Qiu, Long-Qing; Liu, Chao; Dong, Hui; Xu, Lu; Zhang, Yi; Hans-Joachim, Krause; Xie, Xiao-Ming; Andreas, Offenhäusser

    2012-10-01

    Using a second-order helium-cooled superconducting quantum interference device gradiometer as the detector, ultra-low-field nuclear magnetic resonance (ULF-NMR) signals of protons are recorded in an urban environment without magnetic shielding. The homogeneity and stability of the measurement field are investigated. NMR signals of protons are studied at night and during working hours. The Larmor frequency variation caused by the fluctuation of the external magnetic field during daytime reaches around 5 Hz when performing multiple measurements for about 10 min, which seriously affects the results of averaging. In order to improve the performance of the averaged data, we suggest the use of a data processor, i.e. the so-called time-domain frequency correction (TFC). For a 50-times averaged signal spectrum, the signal-to-noise ratio is enhanced from 30 to 120 when applying TFC while preserving the NMR spectrum linewidth. The TFC is also applied successfully to the measurement data of the hetero-nuclear J-coupling in 2,2,2-trifluoroethanol.

  18. Electric signals regulate directional migration of ventral midbrain derived dopaminergic neural progenitor cells via Wnt/GSK3β signaling.

    PubMed

    Liu, Jia; Zhu, Bangfu; Zhang, Gaofeng; Wang, Jian; Tian, Weiming; Ju, Gong; Wei, Xiaoqing; Song, Bing

    2015-01-01

    Neural progenitor cell (NPC) replacement therapy is a promising treatment for neurodegenerative disorders including Parkinson's disease (PD). It requires a controlled directional migration and integration of NPCs, for example dopaminergic (DA) progenitor cells, into the damaged host brain tissue. There is, however, only limited understanding of how to regulate the directed migration of NPCs to the diseased or damaged brain tissues for repair and regeneration. The aims of this study are to explore the possibility of using a physiological level of electrical stimulation to regulate the directed migration of ventral midbrain NPCs (NPCs(vm)), and to investigate their potential regulation via GSK3β and associated downstream effectors. We tested the effects of direct-current (DC) electric fields (EFs) on the migration behavior of the NPCs(vm). A DC EF induced directional cell migration toward the cathode, namely electrotaxis. Reversal of the EF polarity triggered a sharp reversal of the NPC(vm) electrotaxis. The electrotactic response was both time and EF voltage dependent. Pharmacologically inhibiting the canonical Wnt/GSK3β pathway significantly reduced the electrotactic response of NPCs(vm), which is associated with the down-regulation of GSK3β phosphorylation, β-catenin activation and CLASP2 expression. This was further proved by RNA interference of GSK3β, which also showed a significantly reduced electrotactic response in association with reduced β-catenin activation and CLASP2 expression. In comparison, RNA interference of β-catenin slightly reduced electrotactic response and CLASP2 expression. Both pharmacological inhibition of Wnt/GSK3β and RNA interference of GSK3β/β-catenin clearly reduced the asymmetric redistribution of CLASP2 and its co-localization with α-tubulin. These results suggest that Wnt/GSK3β signaling contributes to the electrotactic response of NPCs(vm) through the coordination of GSK3β phosphorylation, β-catenin activation, CLASP2

  19. Lymphotropic Virions Affect Chemokine Receptor-Mediated Neural Signaling and Apoptosis: Implications for Human Immunodeficiency Virus Type 1-Associated Dementia

    PubMed Central

    Zheng, Jialin; Ghorpade, Anuja; Niemann, Douglas; Cotter, Robin L.; Thylin, Michael R.; Epstein, Leon; Swartz, Jennifer M.; Shepard, Robin B.; Liu, Xiaojuan; Nukuna, Adeline; Gendelman, Howard E.

    1999-01-01

    Chemokine receptors pivotal for human immunodeficiency virus type 1 (HIV-1) infection in lymphocytes and macrophages (CCR3, CCR5, and CXCR4) are expressed on neural cells (microglia, astrocytes, and/or neurons). It is these cells which are damaged during progressive HIV-1 infection of the central nervous system. We theorize that viral coreceptors could effect neural cell damage during HIV-1-associated dementia (HAD) without simultaneously affecting viral replication. To these ends, we studied the ability of diverse viral strains to affect intracellular signaling and apoptosis of neurons, astrocytes, and monocyte-derived macrophages. Inhibition of cyclic AMP, activation of inositol 1,4,5-trisphosphate, and apoptosis were induced by diverse HIV-1 strains, principally in neurons. Virions from T-cell-tropic (T-tropic) strains (MN, IIIB, and Lai) produced the most significant alterations in signaling of neurons and astrocytes. The HIV-1 envelope glycoprotein, gp120, induced markedly less neural damage than purified virions. Macrophage-tropic (M-tropic) strains (ADA, JR-FL, Bal, MS-CSF, and DJV) produced the least neural damage, while 89.6, a dual-tropic HIV-1 strain, elicited intermediate neural cell damage. All T-tropic strain-mediated neuronal impairments were blocked by the CXCR4 antibody, 12G5. In contrast, the M-tropic strains were only partially blocked by 12G5. CXCR4-mediated neuronal apoptosis was confirmed in pure populations of rat cerebellar granule neurons and was blocked by HA1004, an inhibitor of calcium/calmodulin-dependent protein kinase II, protein kinase A, and protein kinase C. Taken together, these results suggest that progeny HIV-1 virions can influence neuronal signal transduction and apoptosis. This process occurs, in part, through CXCR4 and is independent of CD4 binding. T-tropic viruses that traffic in and out of the brain during progressive HIV-1 disease may play an important role in HAD neuropathogenesis. PMID:10482576

  20. Forcast of TEXT plasma disruptions using soft X-rays as input signal in a neural network

    SciTech Connect

    Vannucci, A.; Oliveira, K.A.; Tajima, T.

    1998-03-03

    A feed-forward neural network with two hidden layers is used in this work to forecast major and minor disruptive instabilities in TEXT discharges. Using soft X-ray signals as input data, the neural net is trained with one disruptive plasma pulse, and a different disruptive discharge is used for validation. After being properly trained the networks, with the same set of weights. is then used to forecast disruptions in two others different plasma pulses. It is observed that the neural net is able to predict the incoming of a disruption more than 3 ms in advance. This time interval is almost three times longer than the one already obtained previously when magnetic signal from a Mirnov coil was used to feed the neural networks with. To our own eye we fail to see any indication of an upcoming disruption from the experimental data this far back from the time of disruption. Finally, from what we observe in the predictive behavior of our network, speculations are made whether the disruption triggering mechanism would be associated to an increase of the m = 2 magnetic island, that disturbs the central part of the plasma column afterwards or, in face of the results from this work, the initial perturbation would have occurred first in the central part of the plasma column, within the q = 1 magnetic surface, and then the m = 2 MHD mode would be destabilized afterwards.

  1. Neural activity in macaque parietal cortex reflects temporal integration of visual motion signals during perceptual decision making.

    PubMed

    Huk, Alexander C; Shadlen, Michael N

    2005-11-09

    Decision-making often requires the accumulation and maintenance of evidence over time. Although the neural signals underlying sensory processing have been studied extensively, little is known about how the brain accrues and holds these sensory signals to guide later actions. Previous work has suggested that neural activity in the lateral intraparietal area (LIP) of the monkey brain reflects the formation of perceptual decisions in a random dot direction-discrimination task in which monkeys communicate their decisions with eye-movement responses. We tested the hypothesis that decision-related neural activity in LIP represents the time integral of the momentary motion "evidence." By briefly perturbing the strength of the visual motion stimulus during the formation of perceptual decisions, we tested whether this LIP activity reflected a persistent, integrated "memory" of these brief sensory events. We found that the responses of LIP neurons reflected substantial temporal integration. Brief pulses had persistent effects on both the monkeys' choices and the responses of neurons in LIP, lasting up to 800 ms after appearance. These results demonstrate that LIP is involved in neural time integration underlying the accumulation of evidence in this task. Additional analyses suggest that decision-related LIP responses, as well as behavioral choices and reaction times, can be explained by near-perfect time integration that stops when a criterion amount of evidence has been accumulated. Temporal integration may be a fundamental computation underlying higher cognitive functions that are dissociated from immediate sensory inputs or motor outputs.

  2. Neural network feature detector for real-time video signal processing.

    PubMed

    Naylor, D; Jones, S; Myers, D; Vincent, J

    1993-12-01

    The application of artificial neural networks to real-time image processing tasks requires the use of dedicated, high performance hardware. A linear array processor called HANNIBAL has been developed which implements the backpropagation neural learning algorithm on-chip. This paper considers the design of a complete neural system which integrates HANNIBAL into an existing image processing environment. The goals for the design of the system have been set partly by the primary application, namely feature recognition, but mainly by the desire for a flexible, high performance hardware tool for the study and evaluation of range of neural image processing applications.

  3. β-Catenin Signaling Biases Multipotent Lingual Epithelial Progenitors to Differentiate and Acquire Specific Taste Cell Fates.

    PubMed

    Gaillard, Dany; Xu, Mingang; Liu, Fei; Millar, Sarah E; Barlow, Linda A

    2015-05-01

    Continuous taste bud cell renewal is essential to maintain taste function in adults; however, the molecular mechanisms that regulate taste cell turnover are unknown. Using inducible Cre-lox technology, we show that activation of β-catenin signaling in multipotent lingual epithelial progenitors outside of taste buds diverts daughter cells from a general epithelial to a taste bud fate. Moreover, while taste buds comprise 3 morphological types, β-catenin activation drives overproduction of primarily glial-like Type I taste cells in both anterior fungiform (FF) and posterior circumvallate (CV) taste buds, with a small increase in Type II receptor cells for sweet, bitter and umami, but does not alter Type III sour detector cells. Beta-catenin activation in post-mitotic taste bud precursors likewise regulates cell differentiation; forced activation of β-catenin in these Shh+ cells promotes Type I cell fate in both FF and CV taste buds, but likely does so non-cell autonomously. Our data are consistent with a model where β-catenin signaling levels within lingual epithelial progenitors dictate cell fate prior to or during entry of new cells into taste buds; high signaling induces Type I cells, intermediate levels drive Type II cell differentiation, while low levels may drive differentiation of Type III cells.

  4. β-Catenin Signaling Biases Multipotent Lingual Epithelial Progenitors to Differentiate and Acquire Specific Taste Cell Fates

    PubMed Central

    Gaillard, Dany; Xu, Mingang; Liu, Fei; Millar, Sarah E.; Barlow, Linda A.

    2015-01-01

    Continuous taste bud cell renewal is essential to maintain taste function in adults; however, the molecular mechanisms that regulate taste cell turnover are unknown. Using inducible Cre-lox technology, we show that activation of β-catenin signaling in multipotent lingual epithelial progenitors outside of taste buds diverts daughter cells from a general epithelial to a taste bud fate. Moreover, while taste buds comprise 3 morphological types, β-catenin activation drives overproduction of primarily glial-like Type I taste cells in both anterior fungiform (FF) and posterior circumvallate (CV) taste buds, with a small increase in Type II receptor cells for sweet, bitter and umami, but does not alter Type III sour detector cells. Beta-catenin activation in post-mitotic taste bud precursors likewise regulates cell differentiation; forced activation of β-catenin in these Shh+ cells promotes Type I cell fate in both FF and CV taste buds, but likely does so non-cell autonomously. Our data are consistent with a model where β-catenin signaling levels within lingual epithelial progenitors dictate cell fate prior to or during entry of new cells into taste buds; high signaling induces Type I cells, intermediate levels drive Type II cell differentiation, while low levels may drive differentiation of Type III cells. PMID:26020789

  5. A New Application of the Electrical Penetration Graph (EPG) for Acquiring and Measuring Electrical Signals in Phloem Sieve Elements.

    PubMed

    Salvador-Recatalà, Vicenta; Tjallingii, W Freddy

    2015-07-02

    Electrophysiological properties of cells are often studied in vitro, after dissociating them from their native environments. However, the study of electrical transmission between distant cells in an organism requires in vivo, artifact-free recordings of cells embedded within their native environment. The transmission of electrical signals from wounded to unwounded areas in a plant has since long piqued the interest of botanists. The phloem, the living part of the plant vasculature that is spread throughout the plant, has been postulated as a major tissue in electrical transmission in plants. The lack of suitable electrophysiological methods poses many challenges for the study of the electrical properties of the phloem cells in vivo. Here we present a novel approach for intracellular electrophysiology of sieve elements (SEs) that uses living aphids, or other phloem-feeding hemipteran insects, integrated in the electrical penetration graph (EPG) circuit. The versatility, robustness, and accuracy of this method made it possible to record and study in detail the wound-induced electrical signals in SEs of central veins of the model plant Arabidopsis thaliana(1). Here we show that EPG-electrodes can be easily implemented for intracellular electrophysiological recordings of SEs in marginal veins, as well as to study the capacity of SEs to respond with electrical signals to several external stimuli. The EPG approach applied to intracellular electrophysiology of SEs can be implemented to a wide variety of plant species, in a large number of plant/insect combinations, and for many research aims.

  6. Ectopic cross-talk between thyroid and retinoic acid signaling: A possible etiology for spinal neural tube defects.

    PubMed

    Li, Huili; Bai, Baoling; Zhang, Qin; Bao, Yihua; Guo, Jin; Chen, Shuyuan; Miao, Chunyue; Liu, Xiaozhen; Zhang, Ting

    2015-12-01

    Previous studies have highlighted the connections between neural tube defects (NTDs) and both thyroid hormones (TH) and vitamin A. However, whether the two hormonal signaling pathways interact in NTDs has remained unclear. We measured the expression levels of TH signaling genes in human fetuses with spinal NTDs associated with maternal hyperthyroidism as well as levels of retinoic acid (RA) signaling genes in mouse fetuses exposed to an overdose of RA using NanoString or real-time PCR on spinal cord tissues. Interactions between the two signaling pathways were detected by ChIP assays. The data revealed attenuated DIO2/DIO3 switching in fetuses with NTDs born to hyperthyroid mothers. The promoters of the RA signaling genes CRABP1 and RARB were ectopically occupied by increased RXRG and RXRB but displayed decreased levels of inhibitory histone modifications, suggesting that elevated TH signaling abnormally stimulates RA signaling genes. Conversely, in the mouse model, the observed decrease in Dio3 expression could be explained by increased levels of inhibitory histone modifications in the Dio3 promoter region, suggesting that overactive RA signaling may ectopically derepress TH signaling. This study thus raises in vivo a possible abnormal cross-promotion between two different hormonal signals through their common RXRs and the subsequent recruitment of histone modifications, prompting further investigation into their involvement in the etiology of spinal NTDs.

  7. Potential dynamics of the human striate cortex cerebrum realistic neural network under the influence of an external signal

    NASA Astrophysics Data System (ADS)

    Melnikov, Leonid A.; Novosselova, Anna V.; Blinova, Nadejda V.; Vinitsky, Sergey I.; Serov, Vladislav V.; Bakutkin, Valery V.; Camenskich, T. G.; Guileva, E. V.

    2000-03-01

    In this work the numerical investigations of a potential dynamics of a neural network as the non-linear system and dynamics of the visual nerve which connect the eye retina receptors with the striate cortex cerebrum as the answer to the through-skin excitement of the eye retina by the electrical signal were realized. The visual evoked potential is the answer and characterizes the human brain state over the structures retina state and the conduction of the visual nerve fibers. The results of these investigations were presented. Specific features of the neural network, such as the excitation and depression, we took into account too. The discussion about the model parameters, used at the time of the numerical investigation, was made. The comparative analysis of the retina potential data and the data of the external signal filing by the brain hemicerebrum visual centers was made too.

  8. Activin/Nodal Signaling Supports Retinal Progenitor Specification in a Narrow Time Window during Pluripotent Stem Cell Neuralization

    PubMed Central

    Bertacchi, Michele; Lupo, Giuseppe; Pandolfini, Luca; Casarosa, Simona; D’Onofrio, Mara; Pedersen, Roger A.; Harris, William A.; Cremisi, Federico

    2015-01-01

    Summary Retinal progenitors are initially found in the anterior neural plate region known as the eye field, whereas neighboring areas undertake telencephalic or hypothalamic development. Eye field cells become specified by switching on a network of eye field transcription factors, but the extracellular cues activating this network remain unclear. In this study, we used chemically defined media to induce in vitro differentiation of mouse embryonic stem cells (ESCs) toward eye field fates. Inhibition of Wnt/β-catenin signaling was sufficient to drive ESCs to telencephalic, but not retinal, fates. Instead, retinal progenitors could be generated from competent differentiating mouse ESCs by activation of Activin/Nodal signaling within a narrow temporal window corresponding to the emergence of primitive anterior neural progenitors. Activin also promoted eye field gene expression in differentiating human ESCs. Our results reveal insights into the mechanisms of eye field specification and open new avenues toward the generation of retinal progenitors for translational medicine. PMID:26388287

  9. Embedded neural recording with TinyOS-based wireless-enabled processor modules.

    PubMed

    Farshchi, Shahin; Pesterev, Aleksey; Nuyujukian, Paul; Guenterberg, Eric; Mody, Istvan; Judy, Jack W

    2010-04-01

    To create a wireless neural recording system that can benefit from the continuous advancements being made in embedded microcontroller and communications technologies, an embedded-system-based architecture for wireless neural recording has been designed, fabricated, and tested. The system consists of commercial-off-the-shelf wireless-enabled processor modules (motes) for communicating the neural signals, and a back-end database server and client application for archiving and browsing the neural signals. A neural-signal-acquisition application has been developed to enable the mote to either acquire neural signals at a rate of 4000 12-bit samples per second, or detect and transmit spike heights and widths sampled at a rate of 16670 12-bit samples per second on a single channel. The motes acquire neural signals via a custom low-noise neural-signal amplifier with adjustable gain and high-pass corner frequency that has been designed, and fabricated in a 1.5-microm CMOS process. In addition to browsing acquired neural data, the client application enables the user to remotely toggle modes of operation (real-time or spike-only), as well as amplifier gain and high-pass corner frequency.

  10. Curcumin mediates oxaliplatin-acquired resistance reversion in colorectal cancer cell lines through modulation of CXC-Chemokine/NF-κB signalling pathway

    PubMed Central

    Ruiz de Porras, Vicenç; Bystrup, Sara; Martínez-Cardús, Anna; Pluvinet, Raquel; Sumoy, Lauro; Howells, Lynne; James, Mark I.; Iwuji, Chinenye; Manzano, José Luis; Layos, Laura; Bugés, Cristina; Abad, Albert; Martínez-Balibrea, Eva

    2016-01-01

    Resistance to oxaliplatin (OXA) is a complex process affecting the outcomes of metastatic colorectal cancer (CRC) patients treated with this drug. De-regulation of the NF-κB signalling pathway has been proposed as an important mechanism involved in this phenomenon. Here, we show that NF-κB was hyperactivated in in vitro models of OXA-acquired resistance but was attenuated by the addition of Curcumin, a non-toxic NF-κB inhibitor. The concomitant combination of Curcumin + OXA was more effective and synergistic in cell lines with acquired resistance to OXA, leading to the reversion of their resistant phenotype, through the inhibition of the NF-κB signalling cascade. Transcriptomic profiling revealed the up-regulation of three NF-κB-regulated CXC-chemokines, CXCL8, CXCL1 and CXCL2, in the resistant cells that were more efficiently down-regulated after OXA + Curcumin treatment as compared to the sensitive cells. Moreover, CXCL8 and CXCL1 gene silencing made resistant cells more sensitive to OXA through the inhibition of the Akt/NF-κB pathway. High expression of CXCL1 in FFPE samples from explant cultures of CRC patients-derived liver metastases was associated with response to OXA + Curcumin. In conclusion, we suggest that combination of OXA + Curcumin could be an effective treatment, for which CXCL1 could be used as a predictive marker, in CRC patients. PMID:27091625

  11. Signal, Noise, and Variation in Neural and Sensory-Motor Latency.

    PubMed

    Lee, Joonyeol; Joshua, Mati; Medina, Javier F; Lisberger, Stephen G

    2016-04-06

    Analysis of the neural code for sensory-motor latency in smooth pursuit eye movements reveals general principles of neural variation and the specific origin of motor latency. The trial-by-trial variation in neural latency in MT comprises a shared component expressed as neuron-neuron latency correlations and an independent component that is local to each neuron. The independent component arises heavily from fluctuations in the underlying probability of spiking, with an unexpectedly small contribution from the stochastic nature of spiking itself. The shared component causes the latency of single-neuron responses in MT to be weakly predictive of the behavioral latency of pursuit. Neural latency deeper in the motor system is more strongly predictive of behavioral latency. A model reproduces both the variance of behavioral latency and the neuron-behavior latency correlations in MT if it includes realistic neural latency variation, neuron-neuron latency correlations in MT, and noisy gain control downstream of MT.

  12. Semi-real-time monitoring of cracking on couplings by neural network analysis of acoustic emission signals

    NASA Astrophysics Data System (ADS)

    Godinez-Azcuaga, Valery F.; Shu, Fong; Finlayson, Richard D.; O'Donnell, Bruce W.

    2004-07-01

    This paper presents the results obtained during the development of a semi-real-time monitoring methodology based on Neural Network Pattern Recognition of Acoustic Emission (AE) signals for early detection of cracks in couplings used in aircraft and engine drive systems. AE signals were collected in order to establish a baseline of a gear-testing fixture background noise and its variations due to rotational speed and torque. Also, simulated cracking signals immersed in background noise were collected. EDM notches were machined in the driving gear and the load on the gearbox was increased until damaged was induced. Using these data, a Neural Network Signal Classifier (NNSC) was implemented and tested. The testing showed that the NNSC was capable of correctly identifying six different classes of AE signals corresponding to different gearbox operation conditions. Also, a semi-real-time classification software was implemented. This software includes functions that allow the user to view and classify AE data from a dynamic process as they are recorded at programmable time intervals. The software is capable of monitoring periodic statistics of AE data, which can be used as an indicator of damage presence and severity in a dynamic system. The semi-real-time classification software was successfully tested in situations where a delay of 10 seconds between data acquisition and classification was achieved with a hit rate of 50 hits/second per channel on eight active AE channels.

  13. A Fully Integrated Wireless Compressed Sensing Neural Signal Acquisition System for Chronic Recording and Brain Machine Interface.

    PubMed

    Liu, Xilin; Zhang, Milin; Xiong, Tao; Richardson, Andrew G; Lucas, Timothy H; Chin, Peter S; Etienne-Cummings, Ralph; Tran, Trac D; Van der Spiegel, Jan

    2016-07-18

    Reliable, multi-channel neural recording is critical to the neuroscience research and clinical treatment. However, most hardware development of fully integrated, multi-channel wireless neural recorders to-date, is still in the proof-of-concept stage. To be ready for practical use, the trade-offs between performance, power consumption, device size, robustness, and compatibility need to be carefully taken into account. This paper presents an optimized wireless compressed sensing neural signal recording system. The system takes advantages of both custom integrated circuits and universal compatible wireless solutions. The proposed system includes an implantable wireless system-on-chip (SoC) and an external wireless relay. The SoC integrates 16-channel low-noise neural amplifiers, programmable filters and gain stages, a SAR ADC, a real-time compressed sensing module, and a near field wireless power and data transmission link. The external relay integrates a 32 bit low-power microcontroller with Bluetooth 4.0 wireless module, a programming interface, and an inductive charging unit. The SoC achieves high signal recording quality with minimized power consumption, while reducing the risk of infection from through-skin connectors. The external relay maximizes the compatibility and programmability. The proposed compressed sensing module is highly configurable, featuring a SNDR of 9.78 dB with a compression ratio of 8×. The SoC has been fabricated in a 180 nm standard CMOS technology, occupying 2.1 mm × 0.6 mm silicon area. A pre-implantable system has been assembled to demonstrate the proposed paradigm. The developed system has been successfully used for long-term wireless neural recording in freely behaving rhesus monkey.

  14. Investigations of Escherichia coli promoter sequences with artificial neural networks: New signals discovered upstream of the transcriptional startpoint

    SciTech Connect

    Pedersen, A.G.; Engelbrecht, J.

    1995-12-31

    In this paper we present a novel method for using the learning ability of a neural network as a measure of information in local regions of input data. Using the method to analyze Escherichia coli promoters, we discover all previously described signals, and furthermore find new signals that are regularly spaced along the promoter region. The spacing of all signals correspond to the helical periodicity of DNA, meaning that the signals are all present on the same face of the DNA helix in the promoter region. This is consistent with a model where the RNA polymerase contacts the promoter on one side of the DNA, and suggests that the regions important for promoter recognition may include more positions on the DNA than usually assumed. We furthermore analyze the E.coli promoters by calculating the Kullback Leibler distance, and by constructing sequence logos.

  15. Anharmonicity, neural-like lattices, and fast signal/electric transmission

    NASA Astrophysics Data System (ADS)

    Velarde, Manuel G.

    2007-02-01

    Anharmonic interactions in lattices may sustain robust oscillatory modes and (nonlinear) waves including solitons. This is illustrated here by using an exponentially repulsive interaction introduced by Toda. To cope with friction and dissipation -always present in real systems- and hence to make robust, e.g., solitons, following Lord Rayleigh, an appropriate input-output energy balance is added to the dynamics. Noise (and hence temperature) is also incorporated by embedding the system in a Gaussian, white noise environment (thermal bath). In the particular case of a lattice ring with six units it is shown how such a Toda-Rayleigh lattice can be used as a Central Pattern Generator of three different oscillatory modes. These three modes are shown to map three walking (metachronal/low speed, caterpillar/medium speed, and tripod/fast speed) gaits in insects (hexapods). An electronic implementation (diodes map easily exponential interactions) of the Toda-Rayleigh lattice ring is also discussed, including leg motor controls for an hexapod robot. Finally, the Toda-Rayleigh mechanical lattice is converted into an electromechanical wire-like, lattice electric conductor. This is done by considering the lattice units as positive ion cores and adding free electrons to the system. The coupling of Toda dynamics with Coulomb interactions yields remarkable current-field/voltage and current-temperature characteristics in the presence of an external electric field. An Ohmic-non Ohmic transition is possible in the lattice conductor. Such feature permits to consider it as a neural-like conveyor of subsonic (Ohmic) and fast supersonic (non-Ohmic) electric or other signals.

  16. Radiation-induced glioblastoma signaling cascade regulates viability, apoptosis and differentiation of neural stem cells (NSC).

    PubMed

    Ivanov, Vladimir N; Hei, Tom K

    2014-12-01

    Ionizing radiation alone or in combination with chemotherapy is the main treatment modality for brain tumors including glioblastoma. Adult neurons and astrocytes demonstrate substantial radioresistance; in contrast, human neural stem cells (NSC) are highly sensitive to radiation via induction of apoptosis. Irradiation of tumor cells has the potential risk of affecting the viability and function of NSC. In this study, we have evaluated the effects of irradiated glioblastoma cells on viability, proliferation and differentiation potential of non-irradiated (bystander) NSC through radiation-induced signaling cascades. Using media transfer experiments, we demonstrated significant effects of the U87MG glioblastoma secretome after gamma-irradiation on apoptosis in non-irradiated NSC. Addition of anti-TRAIL antibody to the transferred media partially suppressed apoptosis in NSC. Furthermore, we observed a dramatic increase in the production and secretion of IL8, TGFβ1 and IL6 by irradiated glioblastoma cells, which could promote glioblastoma cell survival and modify the effects of death factors in bystander NSC. While differentiation of NSC into neurons and astrocytes occurred efficiently with the corresponding differentiation media, pretreatment of NSC for 8 h with medium from irradiated glioblastoma cells selectively suppressed the differentiation of NSC into neurons, but not into astrocytes. Exogenous IL8 and TGFβ1 increased NSC/NPC survival, but also suppressed neuronal differentiation. On the other hand, IL6 was known to positively affect survival and differentiation of astrocyte progenitors. We established a U87MG neurosphere culture that was substantially enriched by SOX2(+) and CD133(+) glioma stem-like cells (GSC). Gamma-irradiation up-regulated apoptotic death in GSC via the FasL/Fas pathway. Media transfer experiments from irradiated GSC to non-targeted NSC again demonstrated induction of apoptosis and suppression of neuronal differentiation of NSC. In

  17. A system of recurrent neural networks for modularising, parameterising and dynamic analysis of cell signalling networks.

    PubMed

    Samarasinghe, S; Ling, H

    2017-02-04

    In this paper, we show how to extend our previously proposed novel continuous time Recurrent Neural Networks (RNN) approach that retains the advantage of continuous dynamics offered by Ordinary Differential Equations (ODE) while enabling parameter estimation through adaptation, to larger signalling networks using a modular approach. Specifically, the signalling network is decomposed into several sub-models based on important temporal events in the network. Each sub-model is represented by the proposed RNN and trained using data generated from the corresponding ODE model. Trained sub-models are assembled into a whole system RNN which is then subjected to systems dynamics and sensitivity analyses. The concept is illustrated by application to G1/S transition in cell cycle using Iwamoto et al. (2008) ODE model. We decomposed the G1/S network into 3 sub-models: (i) E2F transcription factor release; (ii) E2F and CycE positive feedback loop for elevating cyclin levels; and (iii) E2F and CycA negative feedback to degrade E2F. The trained sub-models accurately represented system dynamics and parameters were in good agreement with the ODE model. The whole system RNN however revealed couple of parameters contributing to compounding errors due to feedback and required refinement to sub-model 2. These related to the reversible reaction between CycE/CDK2 and p27, its inhibitor. The revised whole system RNN model very accurately matched dynamics of the ODE system. Local sensitivity analysis of the whole system model further revealed the most dominant influence of the above two parameters in perturbing G1/S transition, giving support to a recent hypothesis that the release of inhibitor p27 from Cyc/CDK complex triggers cell cycle stage transition. To make the model useful in a practical setting, we modified each RNN sub-model with a time relay switch to facilitate larger interval input data (≈20min) (original model used data for 30s or less) and retrained them that produced

  18. A negative modulatory role for rho and rho-associated kinase signaling in delamination of neural crest cells

    PubMed Central

    Groysman, Maya; Shoval, Irit; Kalcheim, Chaya

    2008-01-01

    Background Neural crest progenitors arise as epithelial cells and then undergo a process of epithelial to mesenchymal transition that precedes the generation of cellular motility and subsequent migration. We aim at understanding the underlying molecular network. Along this line, possible roles of Rho GTPases that act as molecular switches to control a variety of signal transduction pathways remain virtually unexplored, as are putative interactions between Rho proteins and additional known components of this cascade. Results We investigated the role of Rho/Rock signaling in neural crest delamination. Active RhoA and RhoB are expressed in the membrane of epithelial progenitors and are downregulated upon delamination. In vivo loss-of-function of RhoA or RhoB or of overall Rho signaling by C3 transferase enhanced and/or triggered premature crest delamination yet had no effect on cell specification. Consistently, treatment of explanted neural primordia with membrane-permeable C3 or with the Rock inhibitor Y27632 both accelerated and enhanced crest emigration without affecting cell proliferation. These treatments altered neural crest morphology by reducing stress fibers, focal adhesions and downregulating membrane-bound N-cadherin. Reciprocally, activation of endogenous Rho by lysophosphatidic acid inhibited emigration while enhancing the above. Since delamination is triggered by BMP and requires G1/S transition, we examined their relationship with Rho. Blocking Rho/Rock function rescued crest emigration upon treatment with noggin or with the G1/S inhibitor mimosine. In the latter condition, cells emigrated while arrested at G1. Conversely, BMP4 was unable to rescue cell emigration when endogenous Rho activity was enhanced by lysophosphatidic acid. Conclusion Rho-GTPases, through Rock, act downstream of BMP and of G1/S transition to negatively regulate crest delamination by modifying cytoskeleton assembly and intercellular adhesion. PMID:18945340

  19. Long-term stability of neural prosthetic control signals from silicon cortical arrays in rhesus macaque motor cortex

    NASA Astrophysics Data System (ADS)

    Chestek, Cynthia A.; Gilja, Vikash; Nuyujukian, Paul; Foster, Justin D.; Fan, Joline M.; Kaufman, Matthew T.; Churchland, Mark M.; Rivera-Alvidrez, Zuley; Cunningham, John P.; Ryu, Stephen I.; Shenoy, Krishna V.

    2011-08-01

    Cortically-controlled prosthetic systems aim to help disabled patients by translating neural signals from the brain into control signals for guiding prosthetic devices. Recent reports have demonstrated reasonably high levels of performance and control of computer cursors and prosthetic limbs, but to achieve true clinical viability, the long-term operation of these systems must be better understood. In particular, the quality and stability of the electrically-recorded neural signals require further characterization. Here, we quantify action potential changes and offline neural decoder performance over 382 days of recording from four intracortical arrays in three animals. Action potential amplitude decreased by 2.4% per month on average over the course of 9.4, 10.4, and 31.7 months in three animals. During most time periods, decoder performance was not well correlated with action potential amplitude (p > 0.05 for three of four arrays). In two arrays from one animal, action potential amplitude declined by an average of 37% over the first 2 months after implant. However, when using simple threshold-crossing events rather than well-isolated action potentials, no corresponding performance loss was observed during this time using an offline decoder. One of these arrays was effectively used for online prosthetic experiments over the following year. Substantial short-term variations in waveforms were quantified using a wireless system for contiguous recording in one animal, and compared within and between days for all three animals. Overall, this study suggests that action potential amplitude declines more slowly than previously supposed, and performance can be maintained over the course of multiple years when decoding from threshold-crossing events rather than isolated action potentials. This suggests that neural prosthetic systems may provide high performance over multiple years in human clinical trials.

  20. Gene Expression Profile of Adult Human Olfactory Bulb and Embryonic Neural Stem Cell Suggests Distinct Signaling Pathways and Epigenetic Control

    PubMed Central

    Marei, Hany E. S.; Ahmed, Abd-Elmaksoud; Michetti, Fabrizio; Pescatori, Mario; Pallini, Roberto; Casalbore, Patricia; Cenciarelli, Carlo; Elhadidy, Mohamed

    2012-01-01

    Global gene expression profiling was performed using RNA from human embryonic neural stem cells (hENSC), and adult human olfactory bulb-derived neural stem cells (OBNSCs), to define a gene expression pattern and signaling pathways that are specific for each cell lineage. We have demonstrated large differences in the gene expression profile of human embryonic NSC, and adult human OBNSCs, but less variability between parallel cultures. Transcripts of genes involved in neural tube development and patterning (ALDH1A2, FOXA2), progenitor marker genes (LMX1a, ALDH1A1, SOX10), proliferation of neural progenitors (WNT1 and WNT3a), neuroplastin (NPTN), POU3F1 (OCT6), neuroligin (NLGN4X), MEIS2, and NPAS1 were up-regulated in both cell populations. By Gene Ontology, 325 out of 3875 investigated gene sets were scientifically different. 41 out of the 307 investigated Cellular Component (CC) categories, 45 out of the 620 investigated Molecular Function (MF) categories, and 239 out of the 2948 investigated Biological Process (BP) categories were significant. KEGG Pathway Class Comparison had revealed that 75 out of 171 investigated gene sets passed the 0.005 significance threshold. Levels of gene expression were explored in three signaling pathways, Notch, Wnt, and mTOR that are known to be involved in NS cell fates determination. The transcriptional signature also deciphers the role of genes involved in epigenetic modifications. SWI/SNF DNA chromatin remodeling complex family, including SMARCC1 and SMARCE1, were found specifically up-regulated in our OBNSC but not in hENSC. Differences in gene expression profile of transcripts controlling epigenetic modifications, and signaling pathways might indicate differences in the therapeutic potential of our examined two cell populations in relation to in cell survival, proliferation, migration, and differentiation following engraftments in different CNS insults. PMID:22485144

  1. Neural mechanisms underlying the effects of face-based affective signals on memory for faces: a tentative model

    PubMed Central

    Tsukiura, Takashi

    2012-01-01

    In our daily lives, we form some impressions of other people. Although those impressions are affected by many factors, face-based affective signals such as facial expression, facial attractiveness, or trustworthiness are important. Previous psychological studies have demonstrated the impact of facial impressions on remembering other people, but little is known about the neural mechanisms underlying this psychological process. The purpose of this article is to review recent functional MRI (fMRI) studies to investigate the effects of face-based affective signals including facial expression, facial attractiveness, and trustworthiness on memory for faces, and to propose a tentative concept for understanding this affective-cognitive interaction. On the basis of the aforementioned research, three brain regions are potentially involved in the processing of face-based affective signals. The first candidate is the amygdala, where activity is generally modulated by both affectively positive and negative signals from faces. Activity in the orbitofrontal cortex (OFC), as the second candidate, increases as a function of perceived positive signals from faces; whereas activity in the insular cortex, as the third candidate, reflects a function of face-based negative signals. In addition, neuroscientific studies have reported that the three regions are functionally connected to the memory-related hippocampal regions. These findings suggest that the effects of face-based affective signals on memory for faces could be modulated by interactions between the regions associated with the processing of face-based affective signals and the hippocampus as a memory-related region. PMID:22837740

  2. Identification of an Intracranial Pressure (ICP) Response Function from Continuously Acquired Electroencephalographic and ICP Signals in Burst-Suppressed Patients.

    PubMed

    Connolly, Mark; Liou, Raymond; Vespa, Paul; Hu, Xiao

    2016-01-01

    Continuous intracranial pressure (ICP) and electroencephalographic (EEG) monitoring are used in the management of patients with brain injury. It is possible that these two signals could be related through neurovascular coupling. To explore this mechanism, we modeled the ICP response to brain activity by treating spontaneous burst activity in burst-suppressed patients as an impulse, and identified the ICP response function (ICPRF) as the subsequent change in ICP.Segments of ICP were filtered, classified as elevating or stable, and suitable ICPRFs were identified. After calibration, each ICPRF was convolved with the EEG to produce the estimated ICP. The mean error (ME) versus distance from the selected ICPRF was calculated and the elevating and stable ICP segments compared.Eighty-four ICPRFs were identified from 15 data segments. The ME of the elevating segments increased at an average rate of 57 mmHg/min, whereas the average ME of the stable segments increased at a rate of 0.05 mmHg/min.These findings demonstrate that deriving an ICPRF from a burst-suppressed patient is a suitable approach for stable segments. To completely model the ICP response to EEG activity, a more robust model should be developed.

  3. Modulation of Cell Metabolic Pathways and Oxidative Stress Signaling Contribute to Acquired Melphalan Resistance in Multiple Myeloma Cells

    PubMed Central

    Zub, Kamila Anna; de Sousa, Mirta Mittelstedt Leal; Sarno, Antonio; Sharma, Animesh; Demirovic, Aida; Rao, Shalini; Young, Clifford; Aas, Per Arne; Ericsson, Ida; Sundan, Anders; Jensen, Ole Nørregaard; Slupphaug, Geir

    2015-01-01

    Alkylating agents are widely used chemotherapeutics in the treatment of many cancers, including leukemia, lymphoma, multiple myeloma, sarcoma, lung, breast and ovarian cancer. Melphalan is the most commonly used chemotherapeutic agent against multiple myeloma. However, despite a 70–80% initial response rate, virtually all patients eventually relapse due to the emergence of drug-resistant tumour cells. By using global proteomic and transcriptomic profiling on melphalan sensitive and resistant RPMI8226 cell lines followed by functional assays, we discovered changes in cellular processes and pathways not previously associated with melphalan resistance in multiple myeloma cells, including a metabolic switch conforming to the Warburg effect (aerobic glycolysis), and an elevated oxidative stress response mediated by VEGF/IL8-signaling. In addition, up-regulated aldo-keto reductase levels of the AKR1C family involved in prostaglandin synthesis contribute to the resistant phenotype. Finally, selected metabolic and oxidative stress response enzymes were targeted by inhibitors, several of which displayed a selective cytotoxicity against the melphalan-resistant cells and should be further explored to elucidate their potential to overcome melphalan resistance. PMID:25769101

  4. Modulation of cell metabolic pathways and oxidative stress signaling contribute to acquired melphalan resistance in multiple myeloma cells.

    PubMed

    Zub, Kamila Anna; Sousa, Mirta Mittelstedt Leal de; Sarno, Antonio; Sharma, Animesh; Demirovic, Aida; Rao, Shalini; Young, Clifford; Aas, Per Arne; Ericsson, Ida; Sundan, Anders; Jensen, Ole Nørregaard; Slupphaug, Geir

    2015-01-01

    Alkylating agents are widely used chemotherapeutics in the treatment of many cancers, including leukemia, lymphoma, multiple myeloma, sarcoma, lung, breast and ovarian cancer. Melphalan is the most commonly used chemotherapeutic agent against multiple myeloma. However, despite a 70-80% initial response rate, virtually all patients eventually relapse due to the emergence of drug-resistant tumour cells. By using global proteomic and transcriptomic profiling on melphalan sensitive and resistant RPMI8226 cell lines followed by functional assays, we discovered changes in cellular processes and pathways not previously associated with melphalan resistance in multiple myeloma cells, including a metabolic switch conforming to the Warburg effect (aerobic glycolysis), and an elevated oxidative stress response mediated by VEGF/IL8-signaling. In addition, up-regulated aldo-keto reductase levels of the AKR1C family involved in prostaglandin synthesis contribute to the resistant phenotype. Finally, selected metabolic and oxidative stress response enzymes were targeted by inhibitors, several of which displayed a selective cytotoxicity against the melphalan-resistant cells and should be further explored to elucidate their potential to overcome melphalan resistance.

  5. Gallic acid inhibition of Src-Stat3 signaling overcomes acquired resistance to EGF receptor tyrosine kinase inhibitors in advanced non-small cell lung cancer

    PubMed Central

    Phan, Ai N.H.; Hua, Tuyen N.M.; Kim, Min-Kyu; Vo, Vu T.A.; Choi, Jong-Whan; Kim, Hyun-Won; Rho, Jin Kyung; Kim, Ki Woo; Jeong, Yangsik

    2016-01-01

    Tyrosine kinase inhibitors (TKIs) targeting epidermal growth factor receptor (EGFR) have clinically benefited to lung cancer patients harboring a subset of activating EGFR mutations. However, even with the remarkable therapeutic response at the initial TKI treatment, most lung cancer patients eventually have relapsed aggressive tumors due to acquired resistance to the TKIs. Here, we report that 3, 4, 5-trihydroxybenzoic acid or gallic acid (GA), a natural polyphenolic compound, shows anti-tumorigenic effects in TKI-resistant non-small cell lung cancer (NSCLC). Using both in vitro growth assay and in vivo xenograft animal model, we demonstrated tumor suppressive effect of GA was more selective for the TKI-resistant cancer compared to the TKI-sensitive one. Mechanistically, GA treatment inhibited Src-Stat3-mediated signaling and decreased the expression of Stat3-regulated tumor promoting genes, subsequently inducing apoptosis and cell cycle arrest in the TKI-resistant lung cancer but not in the TKI-sensitive one. Consistent with the in vitro results, in vivo xenograft experiments showed the TKI-resistant tumor-selective growth inhibition and suppression of Src-Stat3-dependent signaling in the GA-treated tumors isolated from the xenograft model. This finding identified an importance of Src-Stat3 signaling cascade in GA-mediated tumor-suppression activity and, more importantly, provides a novel therapeutic insight of GA for advanced TKI-resistant lung cancer. PMID:27419630

  6. Bacillus cereus AR156 activates PAMP-triggered immunity and induces a systemic acquired resistance through a NPR1-and SA-dependent signaling pathway.

    PubMed

    Niu, Dongdong; Wang, Xiujuan; Wang, Yanru; Song, Xiaoou; Wang, Jiansheng; Guo, Jianhua; Zhao, Hongwei

    2016-01-01

    Induced resistance responses play a potent role in plant defense system against pathogen attack. Bacillus cereus AR156 is a plant growth promoting rhizobacterium (PGPR) that installs induced systemic resistance (ISR) to Pseudomonas syringae pv. tomato (Pst) in Arabidopsis. Here, we show that AR156 leaf infiltration enhances disease resistance in Arabidopsis through the activation of a systemic acquired resistance (SAR). PR1 protein expression and reactive oxygen species (ROS) burst are strongly induced in plants treated with AR156 and inoculated with Pst than that in plants inoculated with Pst only. Moreover, AR156 can trigger SAR in jar1 or ein2 mutants, but not in the NahG transgenic and NPR1 mutant plants. Our results indicate that AR156-induced SAR depends on SA-signaling pathway and NPR1, but not JA and ET. Also, AR156-treated plants are able to rapidly activate MAPK signaling and FRK1 gene expression, which are involved in pathogen associated molecular pattern (PAMP)-triggered immunity (PTI). Altogether, our results indicate that AR156 can induce SAR by the SA-signaling pathways in an NPR1-dependent manner and involves multiple PTI components.

  7. An evaluation of neural networks for identification of system parameters in reactor noise signals

    SciTech Connect

    Miller, L.F.

    1991-12-31

    Several backpropagation neural networks for identifying fundamental mode eigenvalues were evaluated. The networks were trained and tested on analytical data and on results from other numerical methods. They were then used to predict first mode break frequencies for noise data from several sources. These predictions were, in turn, compared with analytical values and with results from alternative methods. Comparisons of results for some data sets suggest that the accuracy of predictions from neural networks are essentially equivalent to results from conventional methods while other evaluations indicate that either method may be superior. Experience gained from these numerical experiments provide insight for improving the performance of neural networks relative to other methods for identifying parameters associated with experimental data. Neural networks may also be used in support of conventional algorithms by providing starting points for nonlinear minimization algorithms.

  8. Perturbation of Hoxb5 signaling in vagal and trunk neural crest cells causes apoptosis and neurocristopathies in mice.

    PubMed

    Kam, M K M; Cheung, M C H; Zhu, J J; Cheng, W W C; Sat, E W Y; Tam, P K H; Lui, V C H

    2014-02-01

    Neural crest cells (NCCs) migrate from different regions along the anterior-posterior axis of the neural tube (NT) to form different structures. Defective NCC development causes congenital neurocristopathies affecting multiple NCC-derived tissues in human. Perturbed Hoxb5 signaling in vagal NCC causes enteric nervous system (ENS) defects. This study aims to further investigate if perturbed Hoxb5 signaling in trunk NCC contributes to defects of other NCC-derived tissues besides the ENS. We perturbed Hoxb5 signaling in NCC from the entire NT, and investigated its impact in the development of tissues derived from these cells in mice. Perturbation of Hoxb5 signaling in these NCC resulted in Sox9 downregulation, NCC apoptosis, hypoplastic sympathetic and dorsal root ganglia, hypopigmentation and ENS defects. Mutant mice with NCC-specific Sox9 deletion also displayed some of these phenotypes. In vitro and in vivo assays indicated that the Sox9 promoter was bound and trans-activated by Hoxb5. In ovo studies further revealed that Sox9 alleviated apoptosis induced by perturbed Hoxb5 signaling, and Hoxb5 induced ectopic Sox9 expression in chick NT. This study demonstrates that Hoxb5 regulates Sox9 expression in NCC and disruption of this signaling causes Sox9 downregulation, NCC apoptosis and multiple NCC-developmental defects. Phenotypes such as ENS deficiency, hypopigmentation and some of the neurological defects are reported in patients with Hirschsprung disease (HSCR). Whether dysregulation of Hoxb5 signaling and early depletion of NCC contribute to ENS defect and other neurocristopathies in HSCR patients deserves further investigation.

  9. How and when the fMRI BOLD signal relates to underlying neural activity: The danger in dissociation

    PubMed Central

    Ekstrom, Arne

    2013-01-01

    Functional magnetic resonance imaging (fMRI) has become the dominant means of measuring behavior-related neural activity in the human brain. Yet the relation between the blood oxygen-level dependent (BOLD) signal and underlying neural activity remains an open and actively researched question. A widely accepted model, established for sensory neo-cortex, suggests that the BOLD signal reflects peri-synaptic activity in the form of the local field potential rather than the spiking rate of individual neurons. Several recent experimental results, however, suggest situations in which BOLD, spiking, and the local field potential dissociate. Two different models are discussed, based on the literature reviewed to account for this dissociation, a circuitry-based and vascular-based explanation. Both models are found to account for existing data under some testing situations and in certain brain regions. Because both the vascular and local circuitry-based explanations challenge the BOLD-LFP coupling model, these models provide guidance in predicting when BOLD can be expected to reflect neural processing and when the underlying relation with BOLD may be more complex than a direct correspondence. PMID:20026191

  10. Fatty acid-induced gut-brain signaling attenuates neural and behavioral effects of sad emotion in humans.

    PubMed

    Van Oudenhove, Lukas; McKie, Shane; Lassman, Daniel; Uddin, Bilal; Paine, Peter; Coen, Steven; Gregory, Lloyd; Tack, Jan; Aziz, Qasim

    2011-08-01

    Although a relationship between emotional state and feeding behavior is known to exist, the interactions between signaling initiated by stimuli in the gut and exteroceptively generated emotions remain incompletely understood. Here, we investigated the interaction between nutrient-induced gut-brain signaling and sad emotion induced by musical and visual cues at the behavioral and neural level in healthy nonobese subjects undergoing functional magnetic resonance imaging. Subjects received an intragastric infusion of fatty acid solution or saline during neutral or sad emotion induction and rated sensations of hunger, fullness, and mood. We found an interaction between fatty acid infusion and emotion induction both in the behavioral readouts (hunger, mood) and at the level of neural activity in multiple pre-hypothesized regions of interest. Specifically, the behavioral and neural responses to sad emotion induction were attenuated by fatty acid infusion. These findings increase our understanding of the interplay among emotions, hunger, food intake, and meal-induced sensations in health, which may have important implications for a wide range of disorders, including obesity, eating disorders, and depression.

  11. Assessing the user experience of older adults using a neural network trained to recognize emotions from brain signals.

    PubMed

    Meza-Kubo, Victoria; Morán, Alberto L; Carrillo, Ivan; Galindo, Gilberto; García-Canseco, Eloisa

    2016-08-01

    The use of Ambient Assisted Living (AAL) technologies as a means to cope with problems that arise due to an increasing and aging population is becoming usual. AAL technologies are used to prevent, cure and improve the wellness and health conditions of the elderly. However, their adoption and use by older adults is still a major challenge. User Experience (UX) evaluations aim at aiding on this task, by identifying the experience that a user has while interacting with an AAL technology under particular conditions. This may help designing better products and improve user engagement and adoption of AAL solutions. However, evaluating the UX of AAL technologies is a difficult task, due to the inherent limitations of their subjects and of the evaluation methods. In this study, we validated the feasibility of assessing the UX of older adults while they use a cognitive stimulation application using a neural network trained to recognize pleasant and unpleasant emotions from electroencephalography (EEG) signals by contrasting our results with those of additional self-report and qualitative analysis UX evaluations. Our study results provide evidence about the feasibility of assessing the UX of older adults using a neural network that take as input the EEG signals; the classification accuracy of our neural network ranges from 60.87% to 82.61%. As future work we will conduct additional UX evaluation studies using the three different methods, in order to appropriately validate these results.

  12. Mechanism of the differentiation of neural responses to excitatory input signals

    NASA Astrophysics Data System (ADS)

    Zakharov, D. G.; Kuznetsov, A. S.

    2012-08-01

    A dynamical mechanism of the generation of qualitatively different neural responses to typical excitatory stimuli such as an applied current or AMPA and NMDA synaptic currents has been presented. The mechanism is based on a nonlinearity simulating the calcium-dependent potassium current. It has been shown with the FitzHugh-Nagumo equation that, in the presence of such a nonlinearity, only the NMDA synaptic current can strongly increase the frequency of self-sustained oscillations, whereas other stimuli suppress neural activity.

  13. Neural network based on the input organization of an identified neuron signaling impending collision.

    PubMed

    Rind, F C; Bramwell, D I

    1996-03-01

    1. We describe a four-layered neural network (Fig. 1), based on the input organization of a collision signaling neuron in the visual system of the locust, the lobula giant movement detector (LGMD). The 250 photoreceptors ("P" units) in layer 1 are excited by any change in illumination, generated when an image edge passes over them. Layers 2 and 3 incorporate both excitatory and inhibitory interactions, and layer 4 consists of a single output element, equivalent to the locust LGMD. 2. The output element of the neural network, the "LGMD", responds directionally when challenged with approaching versus receding objects, preferring approaching objects (Figs. 2-4). The time course and shape of the "LGMD" response matches that of the LGMD (Fig. 4). Directionality is maintained with objects of various sizes and approach velocities. The network is tuned to direct approach (Fig. 5). The "LGMD" shows no directional selectivity for translatory motion at a constant velocity across the "eye", but its response increases with edge velocity (Figs. 6 and 9). 3. The critical image cues for a selective response to object approach by the "LGMD" are edges that change in extent or in velocity as they move (Fig. 7). Lateral inhibition is crucial to the selectivity of the "LGMD" and the selective response is abolished or else much reduced if lateral inhibition is taken out of the network (Fig. 7). We conclude that lateral inhibition in the neuronal network for the locust LGMD also underlies the experimentally observed critical image cues for its directional response. 4. Lateral inhibition shapes the velocity tuning of the network for objects moving in the X and Y directions without approaching the eye (see Fig. 1). As an edge moves over the eye at a constant velocity, a race occurs between the excitation that is caused by edge movement and which passes down the network and the inhibition that passes laterally. Excitation must win this race for units in layer 3 to reach threshold (Fig. 8

  14. Combining genetic algorithm and Levenberg-Marquardt algorithm in training neural network for hypoglycemia detection using EEG signals.

    PubMed

    Nguyen, Lien B; Nguyen, Anh V; Ling, Sai Ho; Nguyen, Hung T

    2013-01-01

    Hypoglycemia is the most common but highly feared complication induced by the intensive insulin therapy in patients with type 1 diabetes mellitus (T1DM). Nocturnal hypoglycemia is dangerous because sleep obscures early symptoms and potentially leads to severe episodes which can cause seizure, coma, or even death. It is shown that the hypoglycemia onset induces early changes in electroencephalography (EEG) signals which can be detected non-invasively. In our research, EEG signals from five T1DM patients during an overnight clamp study were measured and analyzed. By applying a method of feature extraction using Fast Fourier Transform (FFT) and classification using neural networks, we establish that hypoglycemia can be detected efficiently using EEG signals from only two channels. This paper demonstrates that by implementing a training process of combining genetic algorithm and Levenberg-Marquardt algorithm, the classification results are improved markedly up to 75% sensitivity and 60% specificity on a separate testing set.

  15. Transcriptional Profiling of Hypoxic Neural Stem Cells Identifies Calcineurin-NFATc4 Signaling as a Major Regulator of Neural Stem Cell Biology.

    PubMed

    Moreno, Marta; Fernández, Virginia; Monllau, Josep M; Borrell, Víctor; Lerin, Carles; de la Iglesia, Núria

    2015-08-11

    Neural stem cells (NSCs) reside in a hypoxic microenvironment within the brain. However, the crucial transcription factors (TFs) that regulate NSC biology under physiologic hypoxia are poorly understood. Here we have performed gene set enrichment analysis (GSEA) of microarray datasets from hypoxic versus normoxic NSCs with the aim of identifying pathways and TFs that are activated under oxygen concentrations mimicking normal brain tissue microenvironment. Integration of TF target (TFT) and pathway enrichment analysis identified the calcium-regulated TF NFATc4 as a major candidate to regulate hypoxic NSC functions. Nfatc4 expression was coordinately upregulated by top hypoxia-activated TFs, while NFATc4 target genes were enriched in hypoxic NSCs. Loss-of-function analyses further revealed that the calcineurin-NFATc4 signaling axis acts as a major regulator of NSC self-renewal and proliferation in vitro and in vivo by promoting the expression of TFs, including Id2, that contribute to the maintenance of the NSC state.

  16. Neural correlates of post-error slowing during a stop signal task: a functional magnetic resonance imaging study.

    PubMed

    Li, Chiang-shan Ray; Huang, Cong; Yan, Peisi; Paliwal, Prashni; Constable, Robert Todd; Sinha, Rajita

    2008-06-01

    The ability to detect errors and adjust behavior accordingly is essential for maneuvering in an uncertain environment. Errors are particularly prone to occur when multiple, conflicting responses are registered in a situation that requires flexible behavioral outputs; for instance, when a go signal requires a response and a stop signal requires inhibition of the response during a stop signal task (SST). Previous studies employing the SST have provided ample evidence indicating the importance of the medial cortical brain regions in conflict/error processing. Other studies have also related these regional activations to postconflict/error behavioral adjustment. However, very few studies have directly explored the neural correlates of postconflict/error behavioral adjustment. Here we employed an SST to elicit errors in approximately half of the stop trials despite constant behavioral adjustment of the observers. Using functional magnetic resonance imaging, we showed that prefrontal loci including the ventrolateral prefrontal cortex are involved in post-error slowing in reaction time. These results delineate the neural circuitry specifically involved in error-associated behavioral modifications.

  17. Fgf-signaling-dependent Sox9a and Atoh1a regulate otic neural development in zebrafish.

    PubMed

    Wang, Jialiang; Wu, Ying; Zhao, Feng; Wu, Yuting; Dong, Wei; Zhao, Jue; Zhu, Zuoyan; Liu, Dong

    2015-01-07

    Fibroblast growth factors (Fgfs) play important roles in developmental processes of the inner ear, including the ontogeny of the statoacoustic ganglia (SAG) and hair cells. However, the detailed genetic mechanism(s) underlying Fgf/Fgfr-dependent otic neural development remains elusive. Using conditional genetic approaches and inhibitory small molecules, we have revealed that Fgfr-PI3K/Akt signaling is mainly responsible for zebrafish SAG development and have determined that Sox9a and Atoh1a act downstream of Fgfr-Akt signaling to specify and/or maintain the otic neuron fate during the early segmentation stage. Sox9a and Atoh1a coregulate numerous downstream factors identified through our ChIP-seq analyses, including Tlx2 and Eya2. Fgfr-Erk1/2 signaling contributes to ultricular hair cell development during a critical period between 9 and 15 hours postfertilization. Our work reveals that a genetic network of the previously known sensory determinant Atoh1 and the neural crest determinant Sox9 plays critical roles in SAG development. These newly uncovered roles for Atoh1and Sox9 in zebrafish otic development may be relevant to study in other species.

  18. A High-Performance Lossless Compression Scheme for EEG Signals Using Wavelet Transform and Neural Network Predictors

    PubMed Central

    Sriraam, N.

    2012-01-01

    Developments of new classes of efficient compression algorithms, software systems, and hardware for data intensive applications in today's digital health care systems provide timely and meaningful solutions in response to exponentially growing patient information data complexity and associated analysis requirements. Of the different 1D medical signals, electroencephalography (EEG) data is of great importance to the neurologist for detecting brain-related disorders. The volume of digitized EEG data generated and preserved for future reference exceeds the capacity of recent developments in digital storage and communication media and hence there is a need for an efficient compression system. This paper presents a new and efficient high performance lossless EEG compression using wavelet transform and neural network predictors. The coefficients generated from the EEG signal by integer wavelet transform are used to train the neural network predictors. The error residues are further encoded using a combinational entropy encoder, Lempel-Ziv-arithmetic encoder. Also a new context-based error modeling is also investigated to improve the compression efficiency. A compression ratio of 2.99 (with compression efficiency of 67%) is achieved with the proposed scheme with less encoding time thereby providing diagnostic reliability for lossless transmission as well as recovery of EEG signals for telemedicine applications. PMID:22489238

  19. Stem cells and neural signalling: the case of neoblast recruitment and plasticity in low dose X-ray treated planarians.

    PubMed

    Rossi, Leonardo; Iacopetti, Paola; Salvetti, Alessandra

    2012-01-01

    Planarians (Platyhelminthes) possess an abundant population of adult stem cells, the neoblasts, capable to give rise to both somatic and germ cells. Although neoblasts share similar morphological features, several pieces of evidence suggest that they constitute a heterogeneous population of cells with distinct ultrastructural and molecular features. We found that in planarians treated with low X-ray doses (5 Gy), only a few neoblasts survive. Among these cells, those located close to the nervous system activate an intense proliferation program and migrate to reconstitute the whole complex neoblast population. This phenomenon is inhibited by the substance P receptor antagonist spantide, and accompanied by the up-regulation of a number of genes implicated in neuronal signalling and plasticity, suggesting that signals of neural origin modulate neoblast proliferation and/or migration. Here, we review these findings and the literature available on the influence of the nervous system on stem cell activity, both in planarians and vertebrates, and we propose 5 Gy-treated planarians as a unique model system to study the influence of neural signalling on stem cell biology.

  20. Electronic bypass of spinal lesions: activation of lower motor neurons directly driven by cortical neural signals

    PubMed Central

    2014-01-01

    Background Lower motor neurons in the spinal cord lose supraspinal inputs after complete spinal cord injury, leading to a loss of volitional control below the injury site. Extensive locomotor training with spinal cord stimulation can restore locomotion function after spinal cord injury in humans and animals. However, this locomotion is non-voluntary, meaning that subjects cannot control stimulation via their natural “intent”. A recent study demonstrated an advanced system that triggers a stimulator using forelimb stepping electromyographic patterns to restore quadrupedal walking in rats with spinal cord transection. However, this indirect source of “intent” may mean that other non-stepping forelimb activities may false-trigger the spinal stimulator and thus produce unwanted hindlimb movements. Methods We hypothesized that there are distinguishable neural activities in the primary motor cortex during treadmill walking, even after low-thoracic spinal transection in adult guinea pigs. We developed an electronic spinal bridge, called “Motolink”, which detects these neural patterns and triggers a “spinal” stimulator for hindlimb movement. This hardware can be head-mounted or carried in a backpack. Neural data were processed in real-time and transmitted to a computer for analysis by an embedded processor. Off-line neural spike analysis was conducted to calculate and preset the spike threshold for “Motolink” hardware. Results We identified correlated activities of primary motor cortex neurons during treadmill walking of guinea pigs with spinal cord transection. These neural activities were used to predict the kinematic states of the animals. The appropriate selection of spike threshold value enabled the “Motolink” system to detect the neural “intent” of walking, which triggered electrical stimulation of the spinal cord and induced stepping-like hindlimb movements. Conclusion We present a direct cortical “intent”-driven electronic spinal

  1. A power-efficient analog integrated circuit for amplification and detection of neural signals.

    PubMed

    Borghi, T; Bonfanti, A; Gusmeroli, R; Zambra, G; Spinelli, A S

    2008-01-01

    We present a neural amplifier that optimizes the trade-off between power consumption and noise performance down to the best so far reported. In the perspective of realizing a fully autonomous implantable system we also address the problem of spike detection by using a new simple algorithm and we discuss the implementation with analog integrated circuits. Implemented in 0.35-microm CMOS technology and with total current consumption of about 20 microA, the whole circuit occupies an area of 0.18 mm(2). Reduced power consumption and small area make it suited to be used in chronic multichannel recording systems for neural prosthetics and neuroscience experiments.

  2. Sonic hedgehog signaling coordinates the proliferation and differentiation of neural stem/progenitor cells by regulating cell cycle kinetics during development of the neocortex.

    PubMed

    Komada, Munekazu

    2012-06-01

    Sonic hedgehog (Shh) acts as a morphogen in normal development of various vertebrate tissues and organs. Shh signaling is essential for patterning and cell-fate specification, particularly in the central nervous system. Shh signaling plays different roles depending on its concentration, area, and timing of exposure. During the development of the neocortex, a low level of Shh is expressed in the neural stem/progenitor cells as well as in mature neurons in the dorsal telencephalon. Shh signaling in neocortex development has been shown to regulate cell cycle kinetics of radial glial cells and intermediate progenitor cells, thereby maintaining the proliferation, survival and differentiation of neurons in the neocortex. During the development of the telencephalon, endogenous Shh signaling is involved in the transition of slow-cycling neural stem cells to fast-cycling neural progenitor cells. It seems that high-level Shh signaling in the ventral telencephalon is essential for ventral specification, while low-level Shh signaling in the dorsal telencephalon plays important roles in the fine-tuning of cell cycle kinetics. The Shh levels and multiple functions of Shh signaling are important for proper corticogenesis in the developing brain. The present paper discusses the roles of Shh signaling in the proliferation and differentiation of neural stem/progenitor cells.

  3. Poly-L-ornithine promotes preferred differentiation of neural stem/progenitor cells via ERK signalling pathway

    NASA Astrophysics Data System (ADS)

    Ge, Hongfei; Tan, Liang; Wu, Pengfei; Yin, Yi; Liu, Xin; Meng, Hui; Cui, Gaoyu; Wu, Nan; Lin, Jiangkai; Hu, Rong; Feng, Hua

    2015-10-01

    Neural stem/progenitor cells (NSPCs) replacement therapies are the most attractive strategies to restore an injured brain. Key challenges of such therapies are enriching NSPCs and directing them differentiation into specific neural cell types. Here, three biomaterial substrates Poly-L-ornithine (PO), Poly-L-lysine (PLL) and fibronectin (FN) were investigated for their effects on proliferation and differentiation of rat NSPCs, and the underlying mechanisms were also explored. The results showed PO significantly increased NSPCs proliferation and induced preferred differentiation, compared with PLL and FN. Checking protein markers of several neural cell subtypes, it is showed PO significantly induced NSPCs expressing Doublecortin (DCX) and Olig2, one for neuroblasts and young neurons and the other for young oligodendrocytes. It is suggested the ERK signaling pathway was involving in this process because an ERK antagonist U0126 could inhibit PO’s effects mentioned above, as well as an ERK pathway agonist Ceramide C6 could enhance them. Given that both neurons and oligodendrocytes are the most vulnerable cells in many neurological diseases, PO-induced preferred differentiation into neurons and oligodendrocytes is a potential paradigm for NSPCs-based therapies.

  4. Regulation of proliferation and histone acetylation in embryonic neural precursors by CREB/CREM signaling

    PubMed Central

    Parlato, Rosanna; Mandl, Claudia; Hölzl-Wenig, Gabriele; Liss, Birgit; Tucker, Kerry L; Ciccolini, Francesca

    2014-01-01

    The transcription factor CREB (cAMP-response element binding protein) regulates differentiation, migration, survival and activity-dependent gene expression in the developing and mature nervous system. However, its specific role in the proliferation of embryonic neural progenitors is still not completely understood. Here we investigated how CREB regulates proliferation of mouse embryonic neural progenitors by a conditional mutant lacking Creb gene in neural progenitors. In parallel, we explored possible compensatory effects by the genetic ablation of another member of the same gene family, the cAMP-responsive element modulator (Crem). We show that CREB loss differentially impaired the proliferation, clonogenic potential and self-renewal of precursors derived from the ganglionic eminence (GE), in comparison to those derived from the cortex. This phenotype was associated with a specific reduction of histone acetylation in the GE of CREB mutant mice, and this reduction was rescued in vivo by inhibition of histone deacetylation. These observations indicate that the impaired proliferation could be caused by a reduced acetyltransferase activity in Creb conditional knock-out mice. These findings support a crucial role of CREB in controlling embryonic neurogenesis and propose a novel mechanism by which CREB regulates embryonic neural development. PMID:27504469

  5. The Sustained Effect of Emotional Signals on Neural Processing in 12-Month-Olds

    ERIC Educational Resources Information Center

    Leventon, Jacqueline S.; Bauer, Patricia J.

    2013-01-01

    Around the end of the first year of life, infants develop a social referencing ability -- using emotional information from others to guide their own behavior. Much research on social referencing has focused on changes in behavior in response to emotional information. The present study was an investigation of the changes in neural responses that…

  6. Development of extraocular muscles require early signals from periocular neural crest and the developing eye

    PubMed Central

    Bohnsack, Brenda L.; Gallina, Donika; Thompson, Hannah; Kasprick, Daniel; Lucarelli, Mark J.; Dootz, Gregory; Nelson, Christine; McGonnell, Imelda M.; Kahana, Alon

    2011-01-01

    Purpose Identify and explain morphologic changes of the extraocular muscles (EOMs) in anophthalmic patients. Methods Retrospective chart review of patients with congenital anophthalmia, using MRI and intraoperative findings to characterize EOM morphology. We then employ molecular biology techniques in zebrafish and chick embryos to determine the relationships among the developing eye, periocular neural crest, and EOMs. Results In three human patients with bilateral congenital anophthalmia and preoperative orbital imaging, we observed a spectrum of EOM morphologies ranging from indiscernible muscle tissue to well-formed, organized EOMs. Timing of eye loss in zebrafish and chick embryos correlated with the morphology of EOM organization in the orbit (“eye socket”). In congenitally eyeless Rx3 zebrafish mutants, or following genetic ablation of the cranial neural crest cells, EOMs failed to organize, which was independent of other craniofacial muscle development. Conclusions Orbital development is dependent on interactions between the eye, neural crest, and developing EOMs. Timing of the ocular insult, in relation to neural crest migration and EOM development, is a key determinant of aberrant EOM organization. Additional research will be required to study patients with unilateral and syndromic anophthalmia, and assess for possible differences in clinical outcomes among patients with varied EOM morphology. Clinical relevance The presence and organization of EOMs in anophthalmic sockets may serve as a marker for the timing of genetic or teratogenic insults, improving genetic counseling, and assisting with surgical reconstruction and family counseling efforts. PMID:21482859

  7. The Systemic Acquired Resistance Regulator OsNPR1 Attenuates Growth by Repressing Auxin Signaling through Promoting IAA-Amido Synthase Expression1[OPEN

    PubMed Central

    2016-01-01

    Systemic acquired resistance is a long-lasting and broad-spectrum disease resistance to pathogens. Our previous study demonstrated that overexpression of NONEXPRESSOR OF PATHOGENESIS-RELATED GENES1 (OsNPR1), a master gene for systemic acquired resistance in rice (Oryza sativa), greatly enhanced resistance to bacterial blight caused by Xanthomonas oryzae pv oryzae. However, the growth and development of the OsNPR1 overexpression (OsNPR1-OX) plants were restrained, and the mechanism remained elusive. In this study, we dissected the OsNPR1-induced growth inhibition. We found that the OsNPR1-OX lines displayed phenotypes mimicking auxin-defective mutants, with decreases in root system, seed number and weight, internode elongation, and tiller number. Whole-genome expression analysis revealed that genes related to the auxin metabolism and signaling pathway were differentially expressed between the OsNPR1-OX and wild-type plants. Consistently, the indole-3-acetic acid (IAA) content was decreased and the auxin distribution pattern was altered in OsNPR1-OX plants. Importantly, we found that some GH3 family members, in particular OsGH3.8 coding IAA-amido synthetase, were constitutively up-regulated in OsNPR1-OX plants. Decreased OsGH3.8 expression by RNA interference could partially restore IAA level and largely rescue the restrained growth and development phenotypes but did not affect the disease resistance of OsNPR1-OX plants. Taken together, we revealed that OsNPR1 affects rice growth and development by disrupting the auxin pathway at least partially through indirectly up-regulating OsGH3.8 expression. PMID:27378815

  8. The Systemic Acquired Resistance Regulator OsNPR1 Attenuates Growth by Repressing Auxin Signaling through Promoting IAA-Amido Synthase Expression.

    PubMed

    Li, Xiaozun; Yang, Dong-Lei; Sun, Li; Li, Qun; Mao, Bizeng; He, Zuhua

    2016-09-01

    Systemic acquired resistance is a long-lasting and broad-spectrum disease resistance to pathogens. Our previous study demonstrated that overexpression of NONEXPRESSOR OF PATHOGENESIS-RELATED GENES1 (OsNPR1), a master gene for systemic acquired resistance in rice (Oryza sativa), greatly enhanced resistance to bacterial blight caused by Xanthomonas oryzae pv oryzae However, the growth and development of the OsNPR1 overexpression (OsNPR1-OX) plants were restrained, and the mechanism remained elusive. In this study, we dissected the OsNPR1-induced growth inhibition. We found that the OsNPR1-OX lines displayed phenotypes mimicking auxin-defective mutants, with decreases in root system, seed number and weight, internode elongation, and tiller number. Whole-genome expression analysis revealed that genes related to the auxin metabolism and signaling pathway were differentially expressed between the OsNPR1-OX and wild-type plants. Consistently, the indole-3-acetic acid (IAA) content was decreased and the auxin distribution pattern was altered in OsNPR1-OX plants. Importantly, we found that some GH3 family members, in particular OsGH3.8 coding IAA-amido synthetase, were constitutively up-regulated in OsNPR1-OX plants. Decreased OsGH3.8 expression by RNA interference could partially restore IAA level and largely rescue the restrained growth and development phenotypes but did not affect the disease resistance of OsNPR1-OX plants. Taken together, we revealed that OsNPR1 affects rice growth and development by disrupting the auxin pathway at least partially through indirectly up-regulating OsGH3.8 expression.

  9. Tcf3 Represses Wnt–β-Catenin Signaling and Maintains Neural Stem Cell Population during Neocortical Development

    PubMed Central

    Itoh, Yasuhiro; Hirabayashi, Yusuke; Gotoh, Yukiko

    2014-01-01

    During mouse neocortical development, the Wnt–β-catenin signaling pathway plays essential roles in various phenomena including neuronal differentiation and proliferation of neural precursor cells (NPCs). Production of the appropriate number of neurons without depletion of the NPC population requires precise regulation of the balance between differentiation and maintenance of NPCs. However, the mechanism that suppresses Wnt signaling to prevent premature neuronal differentiation of NPCs is poorly understood. We now show that the HMG box transcription factor Tcf3 (also known as Tcf7l1) contributes to this mechanism. Tcf3 is highly expressed in undifferentiated NPCs in the mouse neocortex, and its expression is reduced in intermediate neuronal progenitors (INPs) committed to the neuronal fate. We found Tcf3 to be a repressor of Wnt signaling in neocortical NPCs in a reporter gene assay. Tcf3 bound to the promoter of the proneural bHLH gene Neurogenin1 (Neurog1) and repressed its expression. Consistent with this, Tcf3 repressed neuronal differentiation and increased the self-renewal activity of NPCs. We also found that Wnt signal stimulation reduces the level of Tcf3, and increases those of Tcf1 (also known as Tcf7) and Lef1, positive mediators of Wnt signaling, in NPCs. Together, these results suggest that Tcf3 antagonizes Wnt signaling in NPCs, thereby maintaining their undifferentiated state in the neocortex and that Wnt signaling promotes the transition from Tcf3-mediated repression to Tcf1/Lef1-mediated enhancement of Wnt signaling, constituting a positive feedback loop that facilitates neuronal differentiation. PMID:24832538

  10. Deletion of Rictor in neural progenitor cells reveals contributions of mTORC2 signaling to tuberous sclerosis complex.

    PubMed

    Carson, Robert P; Fu, Cary; Winzenburger, Peggy; Ess, Kevin C

    2013-01-01

    Tuberous sclerosis complex (TSC) is a multisystem genetic disorder with severe neurologic manifestations, including epilepsy, autism, anxiety and attention deficit hyperactivity disorder. TSC is caused by the loss of either the TSC1 or TSC2 genes that normally regulate the mammalian target of rapamycin (mTOR) kinase. mTOR exists within two distinct complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). Loss of either TSC gene leads to increased mTORC1 but decreased mTORC2 signaling. As the contribution of decreased mTORC2 signaling to neural development and homeostasis has not been well studied, we generated a conditional knockout (CKO) of Rictor, a key component of mTORC2. mTORC2 signaling is impaired in the brain, whereas mTORC1 signaling is unchanged. Rictor CKO mice have small brains and bodies, normal lifespan and are fertile. Cortical layering is normal, but neurons are smaller than those in control brains. Seizures were not observed, although excessive slow activity was seen on electroencephalography. Rictor CKO mice are hyperactive and have reduced anxiety-like behavior. Finally, there is decreased white matter and increased levels of monoamine neurotransmitters in the cerebral cortex. Loss of mTORC2 signaling in the cortex independent of mTORC1 can disrupt normal brain development and function and may contribute to some of the neurologic manifestations seen in TSC.

  11. Albumin induces excitatory synaptogenesis through astrocytic TGF-β/ALK5 signaling in a model of acquired epilepsy following blood-brain barrier dysfunction

    PubMed Central

    Weissberg, Itai; Wood, Lydia; Kamintsky, Lyn; Vazquez, Oscar; Milikovsky, Dan Z.; Alexander, Allyson; Oppenheim, Hannah; Ardizzone, Carolyn; Becker, Albert; Frigerio, Federica; Vezzani, Annamaria; Buckwalter, Marion S.; Huguenard, John; Friedman, Alon; Kaufer, Daniela

    2015-01-01

    Post injury epilepsy (PIE) is a common complication following brain insults, including ischemic and traumatic brain injuries. At present there are no means to identify the patients at-risk to develop PIE or to prevent its development. Seizures can occur months or years after the insult, do not respond to anti-seizure medications in over third of the patients, and are often associated with significant neuropsychiatric morbidities. We have previously established the critical role of blood-brain barrier dysfunction in PIE, demonstrating that exposure of brain tissue to extravasated serum albumin induces activation of inflammatory transforming growth factor beta (TGF-β) signaling in astrocytes and eventually seizures. However, the link between the acute astrocytic inflammatory responses and reorganization of neural networks that underlie recurrent spontaneous seizures, remains unknown. Here we demonstrate in-vitro and in-vivo that activation of the astrocytic ALK5/TGF-β-pathway induces excitatory, but not inhibitory, synaptogenesis that precedes the appearance of seizures. Moreover, we show that treatment with SJN2511, a specific ALK5/TGF-β inhibitor, prevents synaptogenesis and epilepsy. Our findings point to astrocyte-mediated synaptogenesis as a key epileptogenic process, and highlight manipulation of the TGF-β-pathway as a potential strategy for the prevention of PIE. PMID:25836421

  12. Albumin induces excitatory synaptogenesis through astrocytic TGF-β/ALK5 signaling in a model of acquired epilepsy following blood-brain barrier dysfunction.

    PubMed

    Weissberg, Itai; Wood, Lydia; Kamintsky, Lyn; Vazquez, Oscar; Milikovsky, Dan Z; Alexander, Allyson; Oppenheim, Hannah; Ardizzone, Carolyn; Becker, Albert; Frigerio, Federica; Vezzani, Annamaria; Buckwalter, Marion S; Huguenard, John R; Friedman, Alon; Kaufer, Daniela

    2015-06-01

    Post-injury epilepsy (PIE) is a common complication following brain insults, including ischemic, and traumatic brain injuries. At present, there are no means to identify the patients at risk to develop PIE or to prevent its development. Seizures can occur months or years after the insult, do not respond to anti-seizure medications in over third of the patients, and are often associated with significant neuropsychiatric morbidities. We have previously established the critical role of blood-brain barrier dysfunction in PIE, demonstrating that exposure of brain tissue to extravasated serum albumin induces activation of inflammatory transforming growth factor beta (TGF-β) signaling in astrocytes and eventually seizures. However, the link between the acute astrocytic inflammatory responses and reorganization of neural networks that underlie recurrent spontaneous seizures remains unknown. Here we demonstrate in vitro and in vivo that activation of the astrocytic ALK5/TGF-β-pathway induces excitatory, but not inhibitory, synaptogenesis that precedes the appearance of seizures. Moreover, we show that treatment with SJN2511, a specific ALK5/TGF-β inhibitor, prevents synaptogenesis and epilepsy. Our findings point to astrocyte-mediated synaptogenesis as a key epileptogenic process and highlight the manipulation of the TGF-β-pathway as a potential strategy for the prevention of PIE.

  13. Notch signaling acts before cell division to promote asymmetric cleavage and cell fate of neural precursor cells.

    PubMed

    Bhat, Krishna Moorthi

    2014-10-21

    Asymmetric cell divisions in the central nervous system generate neurons of diverse fates. In Drosophila melanogaster, the protein Numb localizes asymmetrically to dividing neural precursor cells such that only one daughter cell inherits Numb. Numb inhibits Notch signaling in this daughter cell, resulting in a different cell fate from the Notch-induced fate in the other-Numb-negative-daughter cell. Precursor cells undergo asymmetric cytokinesis generating daughter cells of different sizes. I found that inactivation of Notch in fly embryonic neural precursor cells disrupted the asymmetric positioning of the cleavage furrow and produced daughter cells of the same size and fate. Moreover, inactivation of Notch at different times altered the degree of asymmetric Numb localization, such that earlier inactivation of Notch caused symmetric distribution of Numb and later inactivation produced incomplete asymmetric localization of Numb. The extent of asymmetrically localized Numb positively correlated with the degree of asymmetric cytokinesis and the size disparity in daughter cells. Loss of Numb or expression of constitutively active Notch led to premature specification of the precursor cells into the fate of one of the daughter cells. Thus, in addition to its role in the specification of daughter cell fate after division, Notch controls Numb localization in the precursor cells to determine the size and fate of daughter cells. Numb also inhibits Notch signaling in precursor cells to prevent Notch-induced differentiation of the precursor cell, forming an autoregulatory loop.

  14. Calcium-mediated repression of β-catenin and its transcriptional signaling mediates neural crest cell death in an avian model of fetal alcohol syndrome.

    PubMed

    Flentke, George R; Garic, Ana; Amberger, Ed; Hernandez, Marcos; Smith, Susan M

    2011-07-01

    Fetal alcohol syndrome (FAS) is a common birth defect in many societies. Affected individuals have neurodevelopmental disabilities and a distinctive craniofacial dysmorphology. These latter deficits originate during early development from the ethanol-mediated apoptotic depletion of cranial facial progenitors, a population known as the neural crest. We showed previously that this apoptosis is caused because acute ethanol exposure activates G-protein-dependent intracellular calcium within cranial neural crest progenitors, and this calcium transient initiates the cell death. The dysregulated signals that reside downstream of ethanol's calcium transient and effect neural crest death are unknown. Here we show that ethanol's repression of the transcriptional effector β-catenin causes the neural crest losses. Clinically relevant ethanol concentrations (22-78 mM) rapidly deplete nuclear β-catenin from neural crest progenitors, with accompanying losses of β-catenin transcriptional activity and downstream genes that govern neural crest induction, expansion, and survival. Using forced expression studies, we show that β-catenin loss of function (via dominant-negative T cell transcription factor [TCF]) recapitulates ethanol's effects on neural crest apoptosis, whereas β-catenin gain-of-function in ethanol's presence preserves neural crest survival. Blockade of ethanol's calcium transient using Bapta-AM normalizes β-catenin activity and prevents the neural crest losses, whereas ionomycin treatment is sufficient to destabilize β-catenin. We propose that ethanol's repression of β-catenin causes the neural crest losses in this model of FAS. β-Catenin is a novel target for ethanol's teratogenicity. β-Catenin/Wnt signals participate in many developmental events and its rapid and persistent dysregulation by ethanol may explain why the latter is such a potent teratogen.

  15. Acquired hyperpigmentations*

    PubMed Central

    Cestari, Tania Ferreira; Dantas, Lia Pinheiro; Boza, Juliana Catucci

    2014-01-01

    Cutaneous hyperpigmentations are frequent complaints, motivating around 8.5% of all dermatological consultations in our country. They can be congenital, with different patterns of inheritance, or acquired in consequence of skin problems, systemic diseases or secondary to environmental factors. The vast majority of them are linked to alterations on the pigment melanin, induced by different mechanisms. This review will focus on the major acquired hyperpigmentations associated with increased melanin, reviewing their mechanisms of action and possible preventive measures. Particularly prominent aspects of diagnosis and therapy will be emphasized, with focus on melasma, post-inflammatory hyperpigmentation, periorbital pigmentation, dermatosis papulosa nigra, phytophotodermatoses, flagellate dermatosis, erythema dyschromicum perstans, cervical poikiloderma (Poikiloderma of Civatte), acanthosis nigricans, cutaneous amyloidosis and reticulated confluent dermatitis PMID:24626644

  16. The Cellular Prion Protein Controls Notch Signaling in Neural Stem/Progenitor Cells.

    PubMed

    Martin-Lannerée, Séverine; Halliez, Sophie; Hirsch, Théo Z; Hernandez-Rapp, Julia; Passet, Bruno; Tomkiewicz, Céline; Villa-Diaz, Ana; Torres, Juan-Maria; Launay, Jean-Marie; Béringue, Vincent; Vilotte, Jean-Luc; Mouillet-Richard, Sophie

    2017-03-01

    The prion protein is infamous for its involvement in a group of neurodegenerative diseases known as Transmissible Spongiform Encephalopathies. In the longstanding quest to decipher the physiological function of its cellular isoform, PrP(C) , the discovery of its participation to the self-renewal of hematopoietic and neural stem cells has cast a new spotlight on its potential role in stem cell biology. However, still little is known on the cellular and molecular mechanisms at play. Here, by combining in vitro and in vivo murine models of PrP(C) depletion, we establish that PrP(C) deficiency severely affects the Notch pathway, which plays a major role in neural stem cell maintenance. We document that the absence of PrP(C) in a neuroepithelial cell line or in primary neurospheres is associated with drastically reduced expression of Notch ligands and receptors, resulting in decreased levels of Notch target genes. Similar alterations of the Notch pathway are recovered in the neuroepithelium of Prnp(-/-) embryos during a developmental window encompassing neural tube closure. In addition, in line with Notch defects, our data show that the absence of PrP(C) results in altered expression of Nestin and Olig2 as well as N-cadherin distribution. We further provide evidence that PrP(C) controls the expression of the epidermal growth factor receptor (EGFR) downstream from Notch. Finally, we unveil a negative feedback action of EGFR on both Notch and PrP(C) . As a whole, our study delineates a molecular scenario through which PrP(C) takes part to the self-renewal of neural stem and progenitor cells. Stem Cells 2017;35:754-765.

  17. Achieving supercomputer performance for neural net simulation with an array of digital signal processors

    SciTech Connect

    Muller, U.A.; Baumle, B.; Kohler, P.; Gunzinger, A.; Guggenbuhl, W.

    1992-10-01

    Music, a DSP-based system with a parallel distributed-memory architecture, provides enormous computing power yet retains the flexibility of a general-purpose computer. Reaching a peak performance of 2.7 Gflops at a significantly lower cost, power consumption, and space requirement than conventional supercomputers, Music is well suited to computationally intensive applications such as neural network simulation. 12 refs., 9 figs., 2 tabs.

  18. Improved exponential convergence result for generalized neural networks including interval time-varying delayed signals.

    PubMed

    Rajchakit, G; Saravanakumar, R; Ahn, Choon Ki; Karimi, Hamid Reza

    2017-02-01

    This article examines the exponential stability analysis problem of generalized neural networks (GNNs) including interval time-varying delayed states. A new improved exponential stability criterion is presented by establishing a proper Lyapunov-Krasovskii functional (LKF) and employing new analysis theory. The improved reciprocally convex combination (RCC) and weighted integral inequality (WII) techniques are utilized to obtain new sufficient conditions to ascertain the exponential stability result of such delayed GNNs. The superiority of the obtained results is clearly demonstrated by numerical examples.

  19. C5a receptor signaling prevents folate deficiency-induced neural tube defects in mice.

    PubMed

    Denny, Kerina J; Coulthard, Liam G; Jeanes, Angela; Lisgo, Steven; Simmons, David G; Callaway, Leonie K; Wlodarczyk, Bogdan; Finnell, Richard H; Woodruff, Trent M; Taylor, Stephen M

    2013-04-01

    The complement system is involved in a range of diverse developmental processes, including cell survival, growth, differentiation, and regeneration. However, little is known about the role of complement in embryogenesis. In this study, we demonstrate a novel role for the canonical complement 5a receptor (C5aR) in the development of the mammalian neural tube under conditions of maternal dietary folic acid deficiency. Specifically, we found C5aR and C5 to be expressed throughout the period of neurulation in wild-type mice and localized the expression to the cephalic regions of the developing neural tube. C5aR was also found to be expressed in the neuroepithelium of early human embryos. Ablation of the C5ar1 gene or the administration of a specific C5aR peptide antagonist to folic acid-deficient pregnant mice resulted in a high prevalence of severe anterior neural tube defect-associated congenital malformations. These findings provide a new and compelling insight into the role of the complement system during mammalian embryonic development.

  20. Shared developmental and evolutionary origins for neural basis of vocal–acoustic and pectoral–gestural signaling

    PubMed Central

    Bass, Andrew H.; Chagnaud, Boris P.

    2012-01-01

    Acoustic signaling behaviors are widespread among bony vertebrates, which include the majority of living fishes and tetrapods. Developmental studies in sound-producing fishes and tetrapods indicate that central pattern generating networks dedicated to vocalization originate from the same caudal hindbrain rhombomere (rh) 8-spinal compartment. Together, the evidence suggests that vocalization and its morphophysiological basis, including mechanisms of vocal–respiratory coupling that are widespread among tetrapods, are ancestral characters for bony vertebrates. Premotor-motor circuitry for pectoral appendages that function in locomotion and acoustic signaling develops in the same rh8-spinal compartment. Hence, vocal and pectoral phenotypes in fishes share both developmental origins and roles in acoustic communication. These findings lead to the proposal that the coupling of more highly derived vocal and pectoral mechanisms among tetrapods, including those adapted for nonvocal acoustic and gestural signaling, originated in fishes. Comparative studies further show that rh8 premotor populations have distinct neurophysiological properties coding for equally distinct behavioral attributes such as call duration. We conclude that neural network innovations in the spatiotemporal patterning of vocal and pectoral mechanisms of social communication, including forelimb gestural signaling, have their evolutionary origins in the caudal hindbrain of fishes. PMID:22723366

  1. Shared developmental and evolutionary origins for neural basis of vocal-acoustic and pectoral-gestural signaling.

    PubMed

    Bass, Andrew H; Chagnaud, Boris P

    2012-06-26

    Acoustic signaling behaviors are widespread among bony vertebrates, which include the majority of living fishes and tetrapods. Developmental studies in sound-producing fishes and tetrapods indicate that central pattern generating networks dedicated to vocalization originate from the same caudal hindbrain rhombomere (rh) 8-spinal compartment. Together, the evidence suggests that vocalization and its morphophysiological basis, including mechanisms of vocal-respiratory coupling that are widespread among tetrapods, are ancestral characters for bony vertebrates. Premotor-motor circuitry for pectoral appendages that function in locomotion and acoustic signaling develops in the same rh8-spinal compartment. Hence, vocal and pectoral phenotypes in fishes share both developmental origins and roles in acoustic communication. These findings lead to the proposal that the coupling of more highly derived vocal and pectoral mechanisms among tetrapods, including those adapted for nonvocal acoustic and gestural signaling, originated in fishes. Comparative studies further show that rh8 premotor populations have distinct neurophysiological properties coding for equally distinct behavioral attributes such as call duration. We conclude that neural network innovations in the spatiotemporal patterning of vocal and pectoral mechanisms of social communication, including forelimb gestural signaling, have their evolutionary origins in the caudal hindbrain of fishes.

  2. The neural inductive signal is transferred to ectoblast in 1-2 h but a continued contact with mesoblast for 2-3 h is essential for neuralization in the chick area pellucida.

    PubMed

    Joshi-Banka, D; Deshmukh, S; Modak, S P

    2001-09-01

    In the area pellucida of the chick gastrula, the Hensen's node (HN) graft must contact the competent ectoblast for at least 4 h to promote neural induction. When we removed the grafted HN after 1 to 3 h and replaced it by a non-inducing post nodal (PN) fragment, a 1-2 h contact with HN was found to be sufficient to promote neural induction. When HN graft was removed after 3 or 4 h and replaced by PN, the neural inductive response was substantially improved towards formation of archencephalic structures. Thus, our results indicate that neural induction takes place in two steps. In the first step, a contact with HN for 1-2 h is sufficient to transferthe inductive signal which is stabilized through a second step involving continued cell-cell contact with even non-inducing PN mesoblast.

  3. Ras-dva1 small GTPase regulates telencephalon development in Xenopus laevis embryos by controlling Fgf8 and Agr signaling at the anterior border of the neural plate.

    PubMed

    Tereshina, Maria B; Ermakova, Galina V; Ivanova, Anastasiya S; Zaraisky, Andrey G

    2014-03-15

    We previously found that the small GTPase Ras-dva1 is essential for the telencephalic development in Xenopus laevis because Ras-dva1 controls the Fgf8-mediated induction of FoxG1 expression, a key telencephalic regulator. In this report, we show, however, that Ras-dva1 and FoxG1 are expressed in different groups of cells; whereas Ras-dva1 is expressed in the outer layer of the anterior neural fold, FoxG1 and Fgf8 are activated in the inner layer from which the telencephalon is derived. We resolve this paradox by demonstrating that Ras-dva1 is involved in the transduction of Fgf8 signal received by cells in the outer layer, which in turn send a feedback signal that stimulates FoxG1 expression in the inner layer. We show that this feedback signal is transmitted by secreted Agr proteins, the expression of which is activated in the outer layer by mediation of Ras-dva1 and the homeodomain transcription factor Otx2. In turn, Agrs are essential for maintaining Fgf8 and FoxG1 expression in cells at the anterior neural plate border. Our finding reveals a novel feedback loop mechanism based on the exchange of Fgf8 and Agr signaling between neural and non-neural compartments at the anterior margin of the neural plate and demonstrates a key role of Ras-dva1 in this mechanism.

  4. Signal processing with neural networks: throwing off the yoke of linearity

    NASA Astrophysics Data System (ADS)

    Hecht-Nielsen, Robert

    1991-11-01

    During the 1930s and 1940s Norbert Wiener and others invented the core concepts of linear signal processing. These ideas quickly became popular and played a significant role in the Allies' victory in World War II. During and after the war, linear signal processing theory was greatly expanded and began to take on the character of an imposing monolith. By the mid- 1940s, Wiener (and others, such as Dennis Gabor) came to recognize that linear signal processing theory, while interesting and very useful, was only a piece of a much larger picture. In 1946 and 1958 Gabor and Wiener, respectively, attempted to address the whole picture. While they were not completely successful, they did implicitly set an agenda for a more general approach to signal processing. Although a few others have, from time to time, addressed this agenda; in terms of the signal processing community as a whole it still remains lost in the shadow of the ever-growing monolith of linear signal processing theory. The thesis of this paper is that it is now time to get on with the Wiener and Gabor agenda. It is time to make general signal processing the mainstream focus of the subject. It is argued here that the best way to do this is to abandon the transfer function/Fourier analysis/z-transform approach of the current linear signal processing regime and replace it with a much more natural intellectual framework for general signal processing--the framework offered by neurocomputing. A potential benefit of this refocusing of the field is that the detailed engineering might soon be left to machines, while human technologists will be able to concentrate on the art of signal sculpting.

  5. Transcriptional Profiling of Hypoxic Neural Stem Cells Identifies Calcineurin-NFATc4 Signaling as a Major Regulator of Neural Stem Cell Biology

    PubMed Central

    Moreno, Marta; Fernández, Virginia; Monllau, Josep M.; Borrell, Víctor; Lerin, Carles; de la Iglesia, Núria

    2015-01-01

    Summary Neural stem cells (NSCs) reside in a hypoxic microenvironment within the brain. However, the crucial transcription factors (TFs) that regulate NSC biology under physiologic hypoxia are poorly understood. Here we have performed gene set enrichment analysis (GSEA) of microarray datasets from hypoxic versus normoxic NSCs with the aim of identifying pathways and TFs that are activated under oxygen concentrations mimicking normal brain tissue microenvironment. Integration of TF target (TFT) and pathway enrichment analysis identified the calcium-regulated TF NFATc4 as a major candidate to regulate hypoxic NSC functions. Nfatc4 expression was coordinately upregulated by top hypoxia-activated TFs, while NFATc4 target genes were enriched in hypoxic NSCs. Loss-of-function analyses further revealed that the calcineurin-NFATc4 signaling axis acts as a major regulator of NSC self-renewal and proliferation in vitro and in vivo by promoting the expression of TFs, including Id2, that contribute to the maintenance of the NSC state. PMID:26235896

  6. Neural correlates of spatial and nonspatial attention determined using intracranial electroencephalographic signals in humans

    PubMed Central

    Park, Ga Young; Kim, Taekyung; Park, Jinsick; Lee, Eun Mi; Ryu, Han Uk; Kim, Sun I.; Kim, In Young; Husain, Masud

    2016-01-01

    Abstract Few studies have directly compared the neural correlates of spatial attention (i.e., attention to a particular location) and nonspatial attention (i.e., attention to a feature in the visual scene) using well‐controlled tasks. Here, we investigated the neural correlates of spatial and nonspatial attention in humans using intracranial electroencephalography. The topography and number of electrodes showing significant event‐related desynchronization (ERD) or event‐related synchronization (ERS) in different frequency bands were studied in 13 epileptic patients. Performance was not significantly different between the two conditions. In both conditions, ERD in the low‐frequency bands and ERS in the high‐frequency bands were present bilaterally in the parietal cortex (prominently on the right hemisphere) and frontal regions. In addition to these common changes, spatial attention involved right‐lateralized activity that was maximal in the right superior parietal lobule (SPL), whereas nonspatial attention involved wider brain networks including the bilateral parietal, frontal, and temporal regions, but still had maximal activity in the right parietal lobe. Within the parietal lobe, spatial attention involved ERD or ERS in the right SPL, whereas nonspatial attention involved ERD or ERS in the right inferior parietal lobule. These findings reveal that common as well as different brain networks are engaged in spatial and nonspatial attention. Hum Brain Mapp 37:3041–3054, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:27125904

  7. Neural signal during immediate reward anticipation in schizophrenia: Relationship to real-world motivation and function

    PubMed Central

    Subramaniam, Karuna; Hooker, Christine I.; Biagianti, Bruno; Fisher, Melissa; Nagarajan, Srikantan; Vinogradov, Sophia

    2015-01-01

    Amotivation in schizophrenia is a central predictor of poor functioning, and is thought to occur due to deficits in anticipating future rewards, suggesting that impairments in anticipating pleasure can contribute to functional disability in schizophrenia. In healthy comparison (HC) participants, reward anticipation is associated with activity in frontal–striatal networks. By contrast, schizophrenia (SZ) participants show hypoactivation within these frontal–striatal networks during this motivated anticipatory brain state. Here, we examined neural activation in SZ and HC participants during the anticipatory phase of stimuli that predicted immediate upcoming reward and punishment, and during the feedback/outcome phase, in relation to trait measures of hedonic pleasure and real-world functional capacity. SZ patients showed hypoactivation in ventral striatum during reward anticipation. Additionally, we found distinct differences between HC and SZ groups in their association between reward-related immediate anticipatory neural activity and their reported experience of pleasure. HC participants recruited reward-related regions in striatum that significantly correlated with subjective consummatory pleasure, while SZ patients revealed activation in attention-related regions, such as the IPL, which correlated with consummatory pleasure and functional capacity. These findings may suggest that SZ patients activate compensatory attention processes during anticipation of immediate upcoming rewards, which likely contribute to their functional capacity in daily life. PMID:26413478

  8. Traumatic Brain Injury Stimulates Neural Stem Cell Proliferation via Mammalian Target of Rapamycin Signaling Pathway Activation

    PubMed Central

    Seekaew, Pich

    2016-01-01

    Abstract Neural stem cells in the adult brain possess the ability to remain quiescent until needed in tissue homeostasis or repair. It was previously shown that traumatic brain injury (TBI) stimulated neural stem cell (NSC) proliferation in the adult hippocampus, indicating an innate repair mechanism, but it is unknown how TBI promotes NSC proliferation. In the present study, we observed dramatic activation of mammalian target of rapamycin complex 1 (mTORC1) in the hippocampus of mice with TBI from controlled cortical impact (CCI). The peak of mTORC1 activation in the hippocampal subgranular zone, where NSCs reside, is 24–48 h after trauma, correlating with the peak of TBI-enhanced NSC proliferation. By use of a Nestin-GFP transgenic mouse, in which GFP is ectopically expressed in the NSCs, we found that TBI activated mTORC1 in NSCs. With 5-bromo-2′-deoxyuridine labeling, we observed that TBI increased mTORC1 activation in proliferating NSCs. Furthermore, administration of rapamycin abolished TBI-promoted NSC proliferation. Taken together, these data indicate that mTORC1 activation is required for NSC proliferation postinjury, and thus might serve as a therapeutic target for interventions to augment neurogenesis for brain repair after TBI. PMID:27822507

  9. Neural stem cells in the adult ciliary epithelium express GFAP and are regulated by Wnt signaling

    SciTech Connect

    Das, Ani V.; Zhao Xing; James, Jackson; Kim, Min; Cowan, Kenneth H.; Ahmad, Iqbal . E-mail: iahmad@unmc.edu

    2006-01-13

    The identification of neural stem cells with retinal potential in the ciliary epithelium (CE) of the adult mammals is of considerable interest because of their potential for replacing or rescuing degenerating retinal neurons in disease or injury. The evaluation of such a potential requires characterization of these cells with regard to their phenotypic properties, potential, and regulatory mechanisms. Here, we demonstrate that rat CE stem cells/progenitors in neurosphere culture display astrocytic nature in terms of expressing glial intermediate neurofilament protein, GFAP. The GFAP-expressing CE stem cells/progenitors form neurospheres in proliferating conditions and generate neurons when shifted to differentiating conditions. These cells express components of the canonical Wnt pathway and its activation promotes their proliferation. Furthermore, we demonstrate that the activation of the canonical Wnt pathway influences neuronal differentiation of CE stem cells/progenitors in a context dependent manner. Our observations suggest that CE stem cells/progenitors share phenotypic properties and regulatory mechanism(s) with neural stem cells elsewhere in the adult CNS.

  10. Neural signal during immediate reward anticipation in schizophrenia: Relationship to real-world motivation and function.

    PubMed

    Subramaniam, Karuna; Hooker, Christine I; Biagianti, Bruno; Fisher, Melissa; Nagarajan, Srikantan; Vinogradov, Sophia

    2015-01-01

    Amotivation in schizophrenia is a central predictor of poor functioning, and is thought to occur due to deficits in anticipating future rewards, suggesting that impairments in anticipating pleasure can contribute to functional disability in schizophrenia. In healthy comparison (HC) participants, reward anticipation is associated with activity in frontal-striatal networks. By contrast, schizophrenia (SZ) participants show hypoactivation within these frontal-striatal networks during this motivated anticipatory brain state. Here, we examined neural activation in SZ and HC participants during the anticipatory phase of stimuli that predicted immediate upcoming reward and punishment, and during the feedback/outcome phase, in relation to trait measures of hedonic pleasure and real-world functional capacity. SZ patients showed hypoactivation in ventral striatum during reward anticipation. Additionally, we found distinct differences between HC and SZ groups in their association between reward-related immediate anticipatory neural activity and their reported experience of pleasure. HC participants recruited reward-related regions in striatum that significantly correlated with subjective consummatory pleasure, while SZ patients revealed activation in attention-related regions, such as the IPL, which correlated with consummatory pleasure and functional capacity. These findings may suggest that SZ patients activate compensatory attention processes during anticipation of immediate upcoming rewards, which likely contribute to their functional capacity in daily life.

  11. Mature neurons modulate neurogenesis through chemical signals acting on neural stem cells.

    PubMed

    Pardal, Ricardo; López Barneo, José

    2016-06-01

    The discovery of neural stem cells has revealed a much higher structural and functional plasticity in the adult nervous system than previously anticipated. Progenitor cells are able to give rise to new neurons and glial cells when needed, thanks to their surveillance of the environment from the germinal niches. Multiple different factors define neural stem cell niches, including cellular and non-cellular components. Innervation of neurogenic centers is crucial, as it allows the functional connection between stem cell behavior and surrounding neuronal activity. Although the association between organismal behavior and neurogenesis is well documented, much less is known about the cellular and molecular mechanisms by which neurons control stem cell activity. In this review we discuss the existing data on this type of regulation from the three best characterized germinal niches in the adult nervous system: the subventricular zone, the hippocampal subgranular zone, and the carotid body. In all cases, neuronal activity modulates stem cell behavior either by neurotransmitter spillover or by synaptic-like contacts. Currently, the molecular mechanisms underlying mature neuron-stem cell interaction are being clarified. Functional consequences and potential clinical relevance of these phenomena are also discussed.

  12. R-Peak Detection using Daubechies Wavelet and ECG Signal Classification using Radial Basis Function Neural Network

    NASA Astrophysics Data System (ADS)

    Rai, H. M.; Trivedi, A.; Chatterjee, K.; Shukla, S.

    2014-01-01

    This paper employed the Daubechies wavelet transform (WT) for R-peak detection and radial basis function neural network (RBFNN) to classify the electrocardiogram (ECG) signals. Five types of ECG beats: normal beat, paced beat, left bundle branch block (LBBB) beat, right bundle branch block (RBBB) beat and premature ventricular contraction (PVC) were classified. 500 QRS complexes were arbitrarily extracted from 26 records in Massachusetts Institute of Technology-Beth Israel Hospital (MIT-BIH) arrhythmia database, which are available on Physionet website. Each and every QRS complex was represented by 21 points from p1 to p21 and these QRS complexes of each record were categorized according to types of beats. The system performance was computed using four types of parameter evaluation metrics: sensitivity, positive predictivity, specificity and classification error rate. The experimental result shows that the average values of sensitivity, positive predictivity, specificity and classification error rate are 99.8%, 99.60%, 99.90% and 0.12%, respectively with RBFNN classifier. The overall accuracy achieved for back propagation neural network (BPNN), multilayered perceptron (MLP), support vector machine (SVM) and RBFNN classifiers are 97.2%, 98.8%, 99% and 99.6%, respectively. The accuracy levels and processing time of RBFNN is higher than or comparable with BPNN, MLP and SVM classifiers.

  13. Massively parallel classification of single-trial EEG signals using a min-max modular neural network.

    PubMed

    Lu, Bao-Liang; Shin, Jonghan; Ichikawa, Michinori

    2004-03-01

    This paper presents a method for classifying single-trial electroencephalogram (EEG) signals using min-max modular neural networks implemented in a massively parallel way. The method has three main steps. First, a large-scale, complex EEG classification problem is simply divided into a reasonable number of two-class subproblems, as small as needed. Second, the two-class subproblems are simply learned by individual smaller network modules in parallel. Finally, all the individual trained network modules are integrated into a hierarchical, parallel, and modular classifier according to two module combination laws. To demonstrate the effectiveness of the method, we perform simulations on fifteen different four-class EEG classification tasks, each of which consists of 1491 training and 636 test data. These EEG classification tasks were created using a set of non-averaged, single-trial hippocampal EEG signals recorded from rats; the features of the EEG signals are extracted using wavelet transform techniques. The experimental results indicate that the proposed method has several attractive features. 1) The method is appreciably faster than the existing approach that is based on conventional multilayer perceptrons. 2) Complete learning of complex EEG classification problems can be easily realized, and better generalization performance can be achieved. 3) The method scales up to large-scale, complex EEG classification problems.

  14. xCyp26c Induced by Inhibition of BMP Signaling Is Involved in Anterior-Posterior Neural Patterning of Xenopus laevis

    PubMed Central

    Yu, Saet-Byeol; Umair, Zobia; Kumar, Shiv; Lee, Unjoo; Lee, Seung-Hwan; Kim, Jong-Il; Kim, SungChan; Park, Jae-Bong; Lee, Jae-Yong; Kim, Jaebong

    2016-01-01

    Vertebrate neurogenesis requires inhibition of endogenous bone morphogenetic protein (BMP) signals in the ectoderm. Blocking of BMPs in animal cap explants causes the formation of anterior neural tissues as a default fate. To identify genes involved in the anterior neural specification, we analyzed gene expression profiles using a Xenopus Affymetrix Gene Chip after BMP-4 inhibition in animal cap explants. We found that the xCyp26c gene, encoding a retinoic acid (RA) degradation enzyme, was upregulated following inhibition of BMP signaling in early neuroectodermal cells. Whole-mount in situ hybridization analysis showed that xCyp26c expression started in the anterior region during the early neurula stage. Overexpression of xCyp26c weakly induced neural genes in animal cap explants. xCyp26c abolished the expression of all trans-/cis-RA-induced posterior genes, but not basic FGF-induced posterior genes. Depletion of xCyp26c by morpholino-oligonucleotides suppressed the normal formation of the axis and head, indicating that xCyp26c plays a critical role in the specification of anterior neural tissue in whole embryos. In animal cap explants, however, xCyp26c morpholinos did not alter anterior-to-posterior neural tissue formation. Together, these results suggest that xCyp26c plays a specific role in anterior-posterior (A-P) neural patterning of Xenopus embryos. PMID:26923193

  15. xCyp26c Induced by Inhibition of BMP Signaling Is Involved in Anterior-Posterior Neural Patterning of Xenopus laevis.

    PubMed

    Yu, Saet-Byeol; Umair, Zobia; Kumar, Shiv; Lee, Unjoo; Lee, Seung-Hwan; Kim, Jong-Il; Kim, SungChan; Park, Jae-Bong; Lee, Jae-Yong; Kim, Jaebong

    2016-04-30

    Vertebrate neurogenesis requires inhibition of endogenous bone morphogenetic protein (BMP) signals in the ectoderm. Blocking of BMPs in animal cap explants causes the formation of anterior neural tissues as a default fate. To identify genes involved in the anterior neural specification, we analyzed gene expression profiles using a Xenopus Affymetrix Gene Chip after BMP-4 inhibition in animal cap explants. We found that the xCyp26c gene, encoding a retinoic acid (RA) degradation enzyme, was upregulated following inhibition of BMP signaling in early neuroectodermal cells. Whole-mount in situ hybridization analysis showed that xCyp26c expression started in the anterior region during the early neurula stage. Overexpression of xCyp26c weakly induced neural genes in animal cap explants. xCyp26c abolished the expression of all trans-/cis-RA-induced posterior genes, but not basic FGF-induced posterior genes. Depletion of xCyp26c by morpholino-oligonucleotides suppressed the normal formation of the axis and head, indicating that xCyp26c plays a critical role in the specification of anterior neural tissue in whole embryos. In animal cap explants, however, xCyp26c morpholinos did not alter anterior-to-posterior neural tissue formation. Together, these results suggest that xCyp26c plays a specific role in anterior-posterior (A-P) neural patterning of Xenopus embryos.

  16. The Hippo pathway member YAP enhances human neural crest cell fate and migration.

    PubMed

    Hindley, Christopher J; Condurat, Alexandra Larisa; Menon, Vishal; Thomas, Ria; Azmitia, Luis M; Davis, Jason A; Pruszak, Jan

    2016-03-16

    The Hippo/YAP pathway serves as a major integrator of cell surface-mediated signals and regulates key processes during development and tumorigenesis. The neural crest is an embryonic tissue known to respond to multiple environmental cues in order to acquire appropriate cell fate and migration properties. Using multiple in vitro models of human neural development (pluripotent stem cell-derived neural stem cells; LUHMES, NTERA2 and SH-SY5Y cell lines), we investigated the role of Hippo/YAP signaling in neural differentiation and neural crest development. We report that the activity of YAP promotes an early neural crest phenotype and migration, and provide the first evidence for an interaction between Hippo/YAP and retinoic acid signaling in this system.

  17. DNA damage in mammalian neural stem cells leads to astrocytic differentiation mediated by BMP2 signaling through JAK-STAT.

    PubMed

    Schneider, Leonid; Pellegatta, Serena; Favaro, Rebecca; Pisati, Federica; Roncaglia, Paola; Testa, Giuseppe; Nicolis, Silvia K; Finocchiaro, Gaetano; d'Adda di Fagagna, Fabrizio

    2013-01-01

    The consequences of DNA damage generation in mammalian somatic stem cells, including neural stem cells (NSCs), are poorly understood despite their potential relevance for tissue homeostasis. Here, we show that, following ionizing radiation-induced DNA damage, NSCs enter irreversible proliferative arrest with features of cellular senescence. This is characterized by increased cytokine secretion, loss of stem cell markers, and astrocytic differentiation. We demonstrate that BMP2 is necessary to induce expression of the astrocyte marker GFAP in irradiated NSCs via a noncanonical signaling pathway engaging JAK-STAT. This is promoted by ATM and antagonized by p53. Using a SOX2-Cre reporter mouse model for cell-lineage tracing, we demonstrate irradiation-induced NSC differentiation in vivo. Furthermore, glioblastoma assays reveal that irradiation therapy affects the tumorigenic potential of cancer stem cells by ablating self-renewal and inducing astroglial differentiation.

  18. States versus Rewards: Dissociable neural prediction error signals underlying model-based and model-free reinforcement learning

    PubMed Central

    Gläscher, Jan; Daw, Nathaniel; Dayan, Peter; O’Doherty, John P.

    2010-01-01

    Reinforcement learning (RL) uses sequential experience with situations (“states”) and outcomes to assess actions. Whereas model-free RL uses this experience directly, in the form of a reward prediction error (RPE), model-based RL uses it indirectly, building a model of the state transition and outcome structure of the environment, and evaluating actions by searching this model. A state prediction error (SPE) plays a central role, reporting discrepancies between the current model and the observed state transitions. Using functional magnetic resonance imaging in humans solving a probabilistic Markov decision task we found the neural signature of an SPE in the intraparietal sulcus and lateral prefrontal cortex, in addition to the previously well-characterized RPE in the ventral striatum. This finding supports the existence of two unique forms of learning signal in humans, which may form the basis of distinct computational strategies for guiding behavior. PMID:20510862

  19. Thirst driving and suppressing signals encoded by distinct neural populations in the brain.

    PubMed

    Oka, Yuki; Ye, Mingyu; Zuker, Charles S

    2015-04-16

    Thirst is the basic instinct to drink water. Previously, it was shown that neurons in several circumventricular organs of the hypothalamus are activated by thirst-inducing conditions. Here we identify two distinct, genetically separable neural populations in the subfornical organ that trigger or suppress thirst. We show that optogenetic activation of subfornical organ excitatory neurons, marked by the expression of the transcription factor ETV-1, evokes intense drinking behaviour, and does so even in fully water-satiated animals. The light-induced response is highly specific for water, immediate and strictly locked to the laser stimulus. In contrast, activation of a second population of subfornical organ neurons, marked by expression of the vesicular GABA transporter VGAT, drastically suppresses drinking, even in water-craving thirsty animals. These results reveal an innate brain circuit that can turn an animal's water-drinking behaviour on and off, and probably functions as a centre for thirst control in the mammalian brain.

  20. Neural signaling in the spleen controls B-cell responses to blood-borne antigen.

    PubMed

    Mina-Osorio, Paola; Rosas-Ballina, Mauricio; Valdes-Ferrer, Sergio I; Al-Abed, Yousef; Tracey, Kevin J; Diamond, Betty

    2012-05-09

    Entry of blood-borne pathogens into the spleen elicits a series of changes in cellular architecture that culminates in the systemic release of protective antibodies. Despite an abundance of work that has characterized these processes, the regulatory mechanisms that coordinate cell trafficking and antibody production are still poorly understood. Here, marginal zone (MZ) B cells responding to streptococcus in the blood were observed to migrate along splenic nerves, arriving at the red pulp venous sinuses where they become antibody-secreting cells. Electrical stimulation of the vagus nerve, which in turn regulates the splenic nerve, arrested B-cell migration and decreased antibody secretion. Thus, neural circuits regulate the first wave of antibody production following B-cell exposure to blood-borne antigen.

  1. Nitric oxide signaling pathways at neural level in invertebrates: functional implications in cnidarians.

    PubMed

    Cristino, Luigia; Guglielmotti, Vittorio; Cotugno, Antonio; Musio, Carlo; Santillo, Silvia

    2008-08-15

    Nitric oxide (NO) is a small molecule with unconventional properties. It is found in organisms throughout the phylogenetic scale, from fungi to mammals, in which it acts as an intercellular messenger of main physiological events, or even as an intracellular messenger in invertebrates. In both vertebrates and invertebrates, NO is involved in many processes, regulated in part by cyclic guanosine monophosphate (cGMP), and reacts with different oxygen molecular species. The presence of NO in the early-diverging metazoan phylum of Cnidaria, of which Hydra represents the first known species having a nervous system, supports a role of this molecule as an ancestral neural messenger with physiological roles that remain to be largely elucidated. Therefore, our novel findings on the presence of NO in Hydra are here integrated in such a comparative frame.

  2. Self-organized neural network for the quality control of 12-lead ECG signals.

    PubMed

    Chen, Yun; Yang, Hui

    2012-09-01

    Telemedicine is very important for the timely delivery of health care to cardiovascular patients, especially those who live in the rural areas of developing countries. However, there are a number of uncertainty factors inherent to the mobile-phone-based recording of electrocardiogram (ECG) signals such as personnel with minimal training and other extraneous noises. PhysioNet organized a challenge in 2011 to develop efficient algorithms that can assess the ECG signal quality in telemedicine settings. This paper presents our efforts in this challenge to integrate multiscale recurrence analysis with a self-organizing map for controlling the ECG signal quality. As opposed to directly evaluating the 12-lead ECG, we utilize an information-preserving transform, i.e. Dower transform, to derive the 3-lead vectorcardiogram (VCG) from the 12-lead ECG in the first place. Secondly, we delineate the nonlinear and nonstationary characteristics underlying the 3-lead VCG signals into multiple time-frequency scales. Furthermore, a self-organizing map is trained, in both supervised and unsupervised ways, to identify the correlations between signal quality and multiscale recurrence features. The efficacy and robustness of this approach are validated using real-world ECG recordings available from PhysioNet. The average performance was demonstrated to be 95.25% for the training dataset and 90.0% for the independent test dataset with unknown labels.

  3. Striatal Activity and Reward Relativity: Neural Signals Encoding Dynamic Outcome Valuation

    PubMed Central

    Webber, Emily S.; Mankin, David E.

    2016-01-01

    Abstract The striatum is a key brain region involved in reward processing. Striatal activity has been linked to encoding reward magnitude and integrating diverse reward outcome information. Recent work has supported the involvement of striatum in the valuation of outcomes. The present work extends this idea by examining striatal activity during dynamic shifts in value that include different levels and directions of magnitude disparity. A novel task was used to produce diverse relative reward effects on a chain of instrumental action. Rats (Rattus norvegicus) were trained to respond to cues associated with specific outcomes varying by food pellet magnitude. Animals were exposed to single-outcome sessions followed by mixed-outcome sessions, and neural activity was compared among identical outcome trials from the different behavioral contexts. Results recording striatal activity show that neural responses to different task elements reflect incentive contrast as well as other relative effects that involve generalization between outcomes or possible influences of outcome variety. The activity that was most prevalent was linked to food consumption and post-food consumption periods. Relative encoding was sensitive to magnitude disparity. A within-session analysis showed strong contrast effects that were dependent upon the outcome received in the immediately preceding trial. Significantly higher numbers of responses were found in ventral striatum linked to relative outcome effects. Our results support the idea that relative value can incorporate diverse relationships, including comparisons from specific individual outcomes to general behavioral contexts. The striatum contains these diverse relative processes, possibly enabling both a higher information yield concerning value shifts and a greater behavioral flexibility. PMID:27822506

  4. Estimating complicated baselines in analytical signals using the iterative training of Bayesian regularized artificial neural networks.

    PubMed

    Mani-Varnosfaderani, Ahmad; Kanginejad, Atefeh; Gilany, Kambiz; Valadkhani, Abolfazl

    2016-10-12

    The present work deals with the development of a new baseline correction method based on the comparative learning capabilities of artificial neural networks. The developed method uses the Bayes probability theorem for prevention of the occurrence of the over-fitting and finding a generalized baseline. The developed method has been applied on simulated and real metabolomic gas-chromatography (GC) and Raman data sets. The results revealed that the proposed method can be used to handle different types of baselines with cave, convex, curvelinear, triangular and sinusoidal patterns. For further evaluation of the performances of this method, it has been compared with benchmarking baseline correction methods such as corner-cutting (CC), morphological weighted penalized least squares (MPLS), adaptive iteratively-reweighted penalized least squares (airPLS) and iterative polynomial fitting (iPF). In order to compare the methods, the projected difference resolution (PDR) criterion has been calculated for the data before and after the baseline correction procedure. The calculated values of PDR after the baseline correction using iBRANN, airPLS, MPLS, iPF and CC algorithms for the GC metabolomic data were 4.18, 3.64, 3.88, 1.88 and 3.08, respectively. The obtained results in this work demonstrated that the developed iterative Bayesian regularized neural network (iBRANN) method in this work thoroughly detects the baselines and is superior over the CC, MPLS, airPLS and iPF techniques. A graphical user interface has been developed for the suggested algorithm and can be used for easy implementation of the iBRANN algorithm for the correction of different chromatography, NMR and Raman data sets.

  5. Striatal Activity and Reward Relativity: Neural Signals Encoding Dynamic Outcome Valuation.

    PubMed

    Webber, Emily S; Mankin, David E; Cromwell, Howard C

    2016-01-01

    The striatum is a key brain region involved in reward processing. Striatal activity has been linked to encoding reward magnitude and integrating diverse reward outcome information. Recent work has supported the involvement of striatum in the valuation of outcomes. The present work extends this idea by examining striatal activity during dynamic shifts in value that include different levels and directions of magnitude disparity. A novel task was used to produce diverse relative reward effects on a chain of instrumental action. Rats (Rattus norvegicus) were trained to respond to cues associated with specific outcomes varying by food pellet magnitude. Animals were exposed to single-outcome sessions followed by mixed-outcome sessions, and neural activity was compared among identical outcome trials from the different behavioral contexts. Results recording striatal activity show that neural responses to different task elements reflect incentive contrast as well as other relative effects that involve generalization between outcomes or possible influences of outcome variety. The activity that was most prevalent was linked to food consumption and post-food consumption periods. Relative encoding was sensitive to magnitude disparity. A within-session analysis showed strong contrast effects that were dependent upon the outcome received in the immediately preceding trial. Significantly higher numbers of responses were found in ventral striatum linked to relative outcome effects. Our results support the idea that relative value can incorporate diverse relationships, including comparisons from specific individual outcomes to general behavioral contexts. The striatum contains these diverse relative processes, possibly enabling both a higher information yield concerning value shifts and a greater behavioral flexibility.

  6. Performance sustaining intracortical neural prostheses

    NASA Astrophysics Data System (ADS)

    Nuyujukian, Paul; Kao, Jonathan C.; Fan, Joline M.; Stavisky, Sergey D.; Ryu, Stephen I.; Shenoy, Krishna V.

    2014-12-01

    Objective. Neural prostheses, or brain-machine interfaces, aim to restore efficient communication and movement ability to those suffering from paralysis. A major challenge these systems face is robust performance, particularly with aging signal sources. The aim in this study was to develop a neural prosthesis that could sustain high performance in spite of signal instability while still minimizing retraining time. Approach. We trained two rhesus macaques implanted with intracortical microelectrode arrays 1-4 years prior to this study to acquire targets with a neurally-controlled cursor. We measured their performance via achieved bitrate (bits per second, bps). This task was repeated over contiguous days to evaluate the sustained performance across time. Main results. We found that in the monkey with a younger (i.e., two year old) implant and better signal quality, a fixed decoder could sustain performance for a month at a rate of 4 bps, the highest achieved communication rate reported to date. This fixed decoder was evaluated across 22 months and experienced a performance decline at a rate of 0.24 bps yr-1. In the monkey with the older (i.e., 3.5 year old) implant and poorer signal quality, a fixed decoder could not sustain performance for more than a few days. Nevertheless, performance in this monkey was maintained for two weeks without requiring additional online retraining time by utilizing prior days’ experimental data. Upon analysis of the changes in channel tuning, we found that this stability appeared partially attributable to the cancelling-out of neural tuning fluctuations when projected to two-dimensional cursor movements. Significance. The findings in this study (1) document the highest-performing communication neural prosthesis in monkeys, (2) confirm and extend prior reports of the stability of fixed decoders, and (3) demonstrate a protocol for system stability under conditions where fixed decoders would otherwise fail. These improvements to decoder

  7. NEUSORT2.0: a multiple-channel neural signal processor with systolic array buffer and channel-interleaving processing schedule.

    PubMed

    Chen, Tung-Chien; Yang, Zhi; Liu, Wentai; Chen, Liang-Gee

    2008-01-01

    An emerging class of neuroprosthetic devices aims to provide aggressive performance by integrating more complicated signal processing hardware into the neural recording system with a large amount of electrodes. However, the traditional parallel structure duplicating one neural signal processor (NSP) multiple times for multiple channels takes a heavy burden on chip area. The serial structure sequentially switching the processing task between channels requires a bulky memory to store neural data and may has a long processing delay. In this paper, a memory hierarchy of systolic array buffer is proposed to support signal processing interleavingly channel by channel in cycle basis to match up with the data flow of the optimized multiple-channel frontend interface circuitry. The NSP can thus be tightly coupled to the analog frontend interface circuitry and perform signal processing for multiple channels in real time without any bulky memory. Based on our previous one-channel NSP of NEUSORT1.0 [1], the proposed memory hierarchy is realized on NEUSORT2.0 for a 16-channel neural recording system. Compared to 16 of NEUSORT1.0, NEUSORT2.0 demonstrates a 81.50% saving in terms of areaxpower factor.

  8. A hardware model of the auditory periphery to transduce acoustic signals into neural activity

    PubMed Central

    Tateno, Takashi; Nishikawa, Jun; Tsuchioka, Nobuyoshi; Shintaku, Hirofumi; Kawano, Satoyuki

    2013-01-01

    To improve the performance of cochlear implants, we have integrated a microdevice into a model of the auditory periphery with the goal of creating a microprocessor. We constructed an artificial peripheral auditory system using a hybrid model in which polyvinylidene difluoride was used as a piezoelectric sensor to convert mechanical stimuli into electric signals. To produce frequency selectivity, the slit on a stainless steel base plate was designed such that the local resonance frequency of the membrane over the slit reflected the transfer function. In the acoustic sensor, electric signals were generated based on the piezoelectric effect from local stress in the membrane. The electrodes on the resonating plate produced relatively large electric output signals. The signals were fed into a computer model that mimicked some functions of inner hair cells, inner hair cell–auditory nerve synapses, and auditory nerve fibers. In general, the responses of the model to pure-tone burst and complex stimuli accurately represented the discharge rates of high-spontaneous-rate auditory nerve fibers across a range of frequencies greater than 1 kHz and middle to high sound pressure levels. Thus, the model provides a tool to understand information processing in the peripheral auditory system and a basic design for connecting artificial acoustic sensors to the peripheral auditory nervous system. Finally, we discuss the need for stimulus control with an appropriate model of the auditory periphery based on auditory brainstem responses that were electrically evoked by different temporal pulse patterns with the same pulse number. PMID:24324432

  9. Gender Signalling in Russian: A Contrastive Analysis of Native Speakers and Artificial Neural Networks.

    ERIC Educational Resources Information Center

    Andrews, Edna; And Others

    1993-01-01

    Two surveys conducted in the Soviet Union are reported that demonstrate the complicated interrelationship between linguistic form and meaning. They support Jakobson and Gorbacevic on gender signalling, particularly when the speaker is not certain of the noun in question. (Contains 44 references.) (LB)

  10. Separate Perceptual and Neural Processing of Velocity- and Disparity-Based 3D Motion Signals.

    PubMed

    Joo, Sung Jun; Czuba, Thaddeus B; Cormack, Lawrence K; Huk, Alexander C

    2016-10-19

    Although the visual system uses both velocity- and disparity-based binocular information for computing 3D motion, it is unknown whether (and how) these two signals interact. We found that these two binocular signals are processed distinctly at the levels of both cortical activity in human MT and perception. In human MT, adaptation to both velocity-based and disparity-based 3D motions demonstrated direction-selective neuroimaging responses. However, when adaptation to one cue was probed using the other cue, there was no evidence of interaction between them (i.e., there was no "cross-cue" adaptation). Analogous psychophysical measurements yielded correspondingly weak cross-cue motion aftereffects (MAEs) in the face of very strong within-cue adaptation. In a direct test of perceptual independence, adapting to opposite 3D directions generated by different binocular cues resulted in simultaneous, superimposed, opposite-direction MAEs. These findings suggest that velocity- and disparity-based 3D motion signals may both flow through area MT but constitute distinct signals and pathways.

  11. Static frequency tuning accounts for changes in neural synchrony evoked by transient communication signals.

    PubMed

    Walz, Henriette; Grewe, Jan; Benda, Jan

    2014-08-15

    Although communication signals often vary continuously on the underlying signal parameter, they are perceived as distinct categories. We here report the opposite case where an electrocommunication signal is encoded in four distinct regimes, although the behavior described to date does not show distinct categories. In particular, we studied the encoding of chirps by P-unit afferents in the weakly electric fish Apteronotus leptorhynchus. These fish generate an electric organ discharge that oscillates at a certain individual-specific frequency. The interaction of two fish in communication contexts leads to the emergence of a beating amplitude modulation (AM) at the frequency difference between the two individual signals. This frequency difference represents the social context of the encounter. Chirps are transient increases of the fish's frequency leading to transient changes in the frequency of the AM. We stimulated the cells with the same chirp on different, naturally occurring backgrounds beats. The P-units responded either by synchronization or desynchronization depending on the background. Although the duration of a chirp is often shorter than a full cycle of the AM it elicits, the distinct responses of the P-units to the chirp can be predicted solely from the frequency of the AM based on the static frequency tuning of the cells.

  12. Associative, Bidirectional Changes in Neural Signaling Utilizing NMDA Receptor- and Endocannabinoid-Dependent Mechanisms

    ERIC Educational Resources Information Center

    Li, Qin; Burrell, Brian D.

    2011-01-01

    Persistent, bidirectional changes in synaptic signaling (that is, potentiation and depression of the synapse) can be induced by the precise timing of individual pre- and postsynaptic action potentials. However, far less attention has been paid to the ability of paired trains of action potentials to elicit persistent potentiation or depression. We…

  13. An SVM-Based Classifier for Estimating the State of Various Rotating Components in Agro-Industrial Machinery with a Vibration Signal Acquired from a Single Point on the Machine Chassis

    PubMed Central

    Ruiz-Gonzalez, Ruben; Gomez-Gil, Jaime; Gomez-Gil, Francisco Javier; Martínez-Martínez, Víctor

    2014-01-01

    The goal of this article is to assess the feasibility of estimating the state of various rotating components in agro-industrial machinery by employing just one vibration signal acquired from a single point on the machine chassis. To do so, a Support Vector Machine (SVM)-based system is employed. Experimental tests evaluated this system by acquiring vibration data from a single point of an agricultural harvester, while varying several of its working conditions. The whole process included two major steps. Initially, the vibration data were preprocessed through twelve feature extraction algorithms, after which the Exhaustive Search method selected the most suitable features. Secondly, the SVM-based system accuracy was evaluated by using Leave-One-Out cross-validation, with the selected features as the input data. The results of this study provide evidence that (i) accurate estimation of the status of various rotating components in agro-industrial machinery is possible by processing the vibration signal acquired from a single point on the machine structure; (ii) the vibration signal can be acquired with a uniaxial accelerometer, the orientation of which does not significantly affect the classification accuracy; and, (iii) when using an SVM classifier, an 85% mean cross-validation accuracy can be reached, which only requires a maximum of seven features as its input, and no significant improvements are noted between the use of either nonlinear or linear kernels. PMID:25372618

  14. EEG Signals Analysis Using Multiscale Entropy for Depth of Anesthesia Monitoring during Surgery through Artificial Neural Networks.

    PubMed

    Liu, Quan; Chen, Yi-Feng; Fan, Shou-Zen; Abbod, Maysam F; Shieh, Jiann-Shing

    2015-01-01

    In order to build a reliable index to monitor the depth of anesthesia (DOA), many algorithms have been proposed in recent years, one of which is sample entropy (SampEn), a commonly used and important tool to measure the regularity of data series. However, SampEn only estimates the complexity of signals on one time scale. In this study, a new approach is introduced using multiscale entropy (MSE) considering the structure information over different time scales. The entropy values over different time scales calculated through MSE are applied as the input data to train an artificial neural network (ANN) model using bispectral index (BIS) or expert assessment of conscious level (EACL) as the target. To test the performance of the new index's sensitivity to artifacts, we compared the results before and after filtration by multivariate empirical mode decomposition (MEMD). The new approach via ANN is utilized in real EEG signals collected from 26 patients before and after filtering by MEMD, respectively; the results show that is a higher correlation between index from the proposed approach and the gold standard compared with SampEn. Moreover, the proposed approach is more structurally robust to noise and artifacts which indicates that it can be used for monitoring the DOA more accurately.

  15. EEG Signals Analysis Using Multiscale Entropy for Depth of Anesthesia Monitoring during Surgery through Artificial Neural Networks

    PubMed Central

    Liu, Quan; Chen, Yi-Feng; Fan, Shou-Zen; Abbod, Maysam F.; Shieh, Jiann-Shing

    2015-01-01

    In order to build a reliable index to monitor the depth of anesthesia (DOA), many algorithms have been proposed in recent years, one of which is sample entropy (SampEn), a commonly used and important tool to measure the regularity of data series. However, SampEn only estimates the complexity of signals on one time scale. In this study, a new approach is introduced using multiscale entropy (MSE) considering the structure information over different time scales. The entropy values over different time scales calculated through MSE are applied as the input data to train an artificial neural network (ANN) model using bispectral index (BIS) or expert assessment of conscious level (EACL) as the target. To test the performance of the new index's sensitivity to artifacts, we compared the results before and after filtration by multivariate empirical mode decomposition (MEMD). The new approach via ANN is utilized in real EEG signals collected from 26 patients before and after filtering by MEMD, respectively; the results show that is a higher correlation between index from the proposed approach and the gold standard compared with SampEn. Moreover, the proposed approach is more structurally robust to noise and artifacts which indicates that it can be used for monitoring the DOA more accurately. PMID:26491464

  16. Noncanonical transforming growth factor β (TGFβ) signaling in cranial neural crest cells causes tongue muscle developmental defects.

    PubMed

    Iwata, Jun-ichi; Suzuki, Akiko; Pelikan, Richard C; Ho, Thach-Vu; Chai, Yang

    2013-10-11

    Microglossia is a congenital birth defect in humans and adversely impacts quality of life. In vertebrates, tongue muscle derives from the cranial mesoderm, whereas tendons and connective tissues in the craniofacial region originate from cranial neural crest (CNC) cells. Loss of transforming growth factor β (TGFβ) type II receptor in CNC cells in mice (Tgfbr2(fl/fl);Wnt1-Cre) causes microglossia due to a failure of cell-cell communication between cranial mesoderm and CNC cells during tongue development. However, it is still unclear how TGFβ signaling in CNC cells regulates the fate of mesoderm-derived myoblasts during tongue development. Here we show that activation of the cytoplasmic and nuclear tyrosine kinase 1 (ABL1) cascade in Tgfbr2(fl/fl);Wnt1-Cre mice results in a failure of CNC-derived cell differentiation followed by a disruption of TGFβ-mediated induction of growth factors and reduction of myogenic cell proliferation and differentiation activities. Among the affected growth factors, the addition of fibroblast growth factor 4 (FGF4) and neutralizing antibody for follistatin (FST; an antagonist of bone morphogenetic protein (BMP)) could most efficiently restore cell proliferation, differentiation, and organization of muscle cells in the tongue of Tgfbr2(fl/fl);Wnt1-Cre mice. Thus, our data indicate that CNC-derived fibroblasts regulate the fate of mesoderm-derived myoblasts through TGFβ-mediated regulation of FGF and BMP signaling during tongue development.

  17. A systems biology approach to identify the signalling network regulated by Rho-GDI-γ during neural stem cell differentiation.

    PubMed

    Wang, Jiao; Hu, Fuyan; Cheng, Hua; Zhao, Xing-Ming; Wen, Tieqiao

    2012-11-01

    Understanding the molecular mechanism that underlies the differentiation of neural stem cells (NSCs) is vital to develop regenerative medicines for neurological disorders. In our previous work, Rho-GDI-γ was found to be able to prompt neuronal differentiation when it was down regulated. However, it is unclear how Rho-GDI-γ regulates this differentiation process. Therefore, a novel systems biology approach is presented here to identify putative signalling pathways regulated by Rho-GDI-γ during NSC differentiation, and these pathways can provide insights into the NSC differentiation mechanisms. In particular, our proposed approach combines the predictive power of computational biology and molecular experiments. With different biological experiments, the genes in the computationally identified signalling network were validated to be indeed regulated by Rho-GDI-γ during the differentiation of NSCs. In particular, one randomly selected pathway involving Vcp, Mapk8, Ywhae and Ywhah was experimentally verified to be regulated by Rho-GDI-γ. These promising results demonstrate the effectiveness of our proposed systems biology approach, indicating the potential predictive power of integrating computational and experimental approaches.

  18. Disruption of CXCR4 signaling in pharyngeal neural crest cells causes DiGeorge syndrome-like malformations.

    PubMed

    Escot, Sophie; Blavet, Cédrine; Faure, Emilie; Zaffran, Stéphane; Duband, Jean-Loup; Fournier-Thibault, Claire

    2016-02-15

    DiGeorge syndrome (DGS) is a congenital disease causing cardiac outflow tract anomalies, craniofacial dysmorphogenesis, thymus hypoplasia, and mental disorders. It results from defective development of neural crest cells (NCs) that colonize the pharyngeal arches and contribute to lower jaw, neck and heart tissues. Although TBX1 has been identified as the main gene accounting for the defects observed in human patients and mouse models, the molecular mechanisms underlying DGS etiology are poorly identified. The recent demonstrations that the SDF1/CXCR4 axis is implicated in NC chemotactic guidance and impaired in cortical interneurons of mouse DGS models prompted us to search for genetic interactions between Tbx1, Sdf1 (Cxcl12) and Cxcr4 in pharyngeal NCs and to investigate the effect of altering CXCR4 signaling on the ontogeny of their derivatives, which are affected in DGS. Here, we provide evidence that Cxcr4 and Sdf1 are genetically downstream of Tbx1 during pharyngeal NC development and that reduction of CXCR4 signaling causes misrouting of pharyngeal NCs in chick and dramatic morphological alterations in the mandibular skeleton, thymus and cranial sensory ganglia. Our results therefore support the possibility of a pivotal role for the SDF1/CXCR4 axis in DGS etiology.

  19. Lipid mediators in the neural cell nucleus: their metabolism, signaling, and association with neurological disorders.

    PubMed

    Farooqui, Akhlaq A

    2009-08-01

    Lipid mediators are important endogenous regulators of neural cell proliferation, differentiation, oxidative stress, inflammation, and apoptosis. They originate from enzymic degradation of glycerophospholipids, sphingolipids, and cholesterol by phospholipases, sphingomyelinases, and cytochrome P450 hydroxylases, respectively. Arachidonic acid-derived lipid mediators are called eicosanoids. Eicosanoids have emerged as key regulators of cell proliferation, differentiation, oxidative stress, and neuroinflammation. Another arachidonic acid-derived lipid mediator is lipoxin. Eicosanoids have proinflammatory effects, whereas lipoxins produce antiinflammatory effects. The crossponding lipid mediators of docosahexaenoic acid metabolism are named docosanoids. They include resolvins, protectins, and neuroprotectins. Docosanoids produce antioxidant, anti-inflammatory, and antiapoptotic effects in the brain tissue. Other glycerophospholipid-derived lipid mediators are platelet-activating factor, lysophosphatidic acid, and endocannabinoids. Degradation of sphingolipids also results in the generation of sphingolipid-derived lipid mediators. Sphingolipid-derived lipid mediators are ceramide, ceramide 1-phosphate, sphingosine, and sphingosine 1-phosphate. They mediate cellular differentiation, cell growth, and apoptosis. Similarly, cholesterol-derived lipid mediators hydroxycholesterol and oxycholesterol produce apoptosis. Most of these mediators originate from the plasma membrane. The nucleus has its own set of enzymes and lipid mediators that originate from the nuclear envelope and matrix. The purpose of this commentary is to describe basic and clinical information on lipid mediators in the nucleus.

  20. Feature Selection and Classification of Electroencephalographic Signals: An Artificial Neural Network and Genetic Algorithm Based Approach.

    PubMed

    Erguzel, Turker Tekin; Ozekes, Serhat; Tan, Oguz; Gultekin, Selahattin

    2015-10-01

    Feature selection is an important step in many pattern recognition systems aiming to overcome the so-called curse of dimensionality. In this study, an optimized classification method was tested in 147 patients with major depressive disorder (MDD) treated with repetitive transcranial magnetic stimulation (rTMS). The performance of the combination of a genetic algorithm (GA) and a back-propagation (BP) neural network (BPNN) was evaluated using 6-channel pre-rTMS electroencephalographic (EEG) patterns of theta and delta frequency bands. The GA was first used to eliminate the redundant and less discriminant features to maximize classification performance. The BPNN was then applied to test the performance of the feature subset. Finally, classification performance using the subset was evaluated using 6-fold cross-validation. Although the slow bands of the frontal electrodes are widely used to collect EEG data for patients with MDD and provide quite satisfactory classification results, the outcomes of the proposed approach indicate noticeably increased overall accuracy of 89.12% and an area under the receiver operating characteristic (ROC) curve (AUC) of 0.904 using the reduced feature set.

  1. Measurement of neural signals from inexpensive, wireless and dry EEG systems.

    PubMed

    Grummett, T S; Leibbrandt, R E; Lewis, T W; DeLosAngeles, D; Powers, D M W; Willoughby, J O; Pope, K J; Fitzgibbon, S P

    2015-07-01

    Electroencephalography (EEG) is challenged by high cost, immobility of equipment and the use of inconvenient conductive gels. We compared EEG recordings obtained from three systems that are inexpensive, wireless, and/or dry (no gel), against recordings made with a traditional, research-grade EEG system, in order to investigate the ability of these 'non-traditional' systems to produce recordings of comparable quality to a research-grade system. The systems compared were: Emotiv EPOC (inexpensive and wireless), B-Alert (wireless), g.Sahara (dry) and g.HIamp (research-grade). We compared the ability of the systems to demonstrate five well-studied neural phenomena: (1) enhanced alpha activity with eyes closed versus open; (2) visual steady-state response (VSSR); (3) mismatch negativity; (4) P300; and (5) event-related desynchronization/synchronization. All systems measured significant alpha augmentation with eye closure, and were able to measure VSSRs (although these were smaller with g.Sahara). The B-Alert and g.Sahara were able to measure the three time-locked phenomena equivalently to the g.HIamp. The Emotiv EPOC did not have suitably located electrodes for two of the tasks and synchronization considerations meant that data from the time-locked tasks were not assessed. The results show that inexpensive, wireless, or dry systems may be suitable for experimental studies using EEG, depending on the research paradigm, and within the constraints imposed by their limited electrode placement and number.

  2. Experimental and Computational Studies of Cortical Neural Network Properties Through Signal Processing

    NASA Astrophysics Data System (ADS)

    Clawson, Wesley Patrick

    Previous studies, both theoretical and experimental, of network level dynamics in the cerebral cortex show evidence for a statistical phenomenon called criticality; a phenomenon originally studied in the context of phase transitions in physical systems and that is associated with favorable information processing in the context of the brain. The focus of this thesis is to expand upon past results with new experimentation and modeling to show a relationship between criticality and the ability to detect and discriminate sensory input. A line of theoretical work predicts maximal sensory discrimination as a functional benefit of criticality, which can then be characterized using mutual information between sensory input, visual stimulus, and neural response,. The primary finding of our experiments in the visual cortex in turtles and neuronal network modeling confirms this theoretical prediction. We show that sensory discrimination is maximized when visual cortex operates near criticality. In addition to presenting this primary finding in detail, this thesis will also address our preliminary results on change-point-detection in experimentally measured cortical dynamics.

  3. A Diffusive Homeostatic Signal Maintains Neural Heterogeneity and Responsiveness in Cortical Networks

    PubMed Central

    Sweeney, Yann; Hellgren Kotaleski, Jeanette; Hennig, Matthias H.

    2015-01-01

    Gaseous neurotransmitters such as nitric oxide (NO) provide a unique and often overlooked mechanism for neurons to communicate through diffusion within a network, independent of synaptic connectivity. NO provides homeostatic control of intrinsic excitability. Here we conduct a theoretical investigation of the distinguishing roles of NO-mediated diffusive homeostasis in comparison with canonical non-diffusive homeostasis in cortical networks. We find that both forms of homeostasis provide a robust mechanism for maintaining stable activity following perturbations. However, the resulting networks differ, with diffusive homeostasis maintaining substantial heterogeneity in activity levels of individual neurons, a feature disrupted in networks with non-diffusive homeostasis. This results in networks capable of representing input heterogeneity, and linearly responding over a broader range of inputs than those undergoing non-diffusive homeostasis. We further show that these properties are preserved when homeostatic and Hebbian plasticity are combined. These results suggest a mechanism for dynamically maintaining neural heterogeneity, and expose computational advantages of non-local homeostatic processes. PMID:26158556

  4. The splicing factor PQBP1 regulates mesodermal and neural development through FGF signaling

    PubMed Central

    Iwasaki, Yasuno; Thomsen, Gerald H.

    2014-01-01

    Alternative splicing of pre-mRNAs is an important means of regulating developmental processes, yet the molecular mechanisms governing alternative splicing in embryonic contexts are just beginning to emerge. Polyglutamine-binding protein 1 (PQBP1) is an RNA-splicing factor that, when mutated, in humans causes Renpenning syndrome, an X-linked intellectual disability disease characterized by severe cognitive impairment, but also by physical defects that suggest PQBP1 has broader functions in embryonic development. Here, we reveal essential roles for PQBP1 and a binding partner, WBP11, in early development of Xenopus embryos. Both genes are expressed in the nascent mesoderm and neurectoderm, and morpholino knockdown of either causes defects in differentiation and morphogenesis of the mesoderm and neural plate. At the molecular level, knockdown of PQBP1 in Xenopus animal cap explants inhibits target gene induction by FGF but not by BMP, Nodal or Wnt ligands, and knockdown of either PQBP1 or WBP11 in embryos inhibits expression of fgf4 and FGF4-responsive cdx4 genes. Furthermore, PQBP1 knockdown changes the alternative splicing of FGF receptor-2 (FGFR2) transcripts, altering the incorporation of cassette exons that generate receptor variants (FGFR2 IIIb or IIIc) with different ligand specificities. Our findings may inform studies into the mechanisms underlying Renpenning syndrome. PMID:25209246

  5. Continuous neural identifier for uncertain nonlinear systems with time delays in the input signal.

    PubMed

    Alfaro-Ponce, M; Argüelles, A; Chairez, I

    2014-12-01

    Time-delay systems have been successfully used to represent the complexity of some dynamic systems. Time-delay is often used for modeling many real systems. Among others, biological and chemical plants have been described using time-delay terms with better results than those models that have not consider them. However, getting those models represented a challenge and sometimes the results were not so satisfactory. Non-parametric modeling offered an alternative to obtain suitable and usable models. Continuous neural networks (CNN) have been considered as a real alternative to provide models over uncertain non-parametric systems. This article introduces the design of a specific class of non-parametric model for uncertain time-delay system based on CNN considering the so-called delayed learning laws analysis. The convergence analysis as well as the learning laws were produced by means of a Lyapunov-Krasovskii functional. Three examples were developed to demonstrate the effectiveness of the modeling process forced by the identifier proposed in this study. The first example was a simple nonlinear model used as benchmark example. The second example regarded the human immunodeficiency virus dynamic behavior is used to show the performance of the suggested non-parametric identifier based on CNN for no fictitious neither academic models. Finally, a third example describing the evolution of hepatitis B virus served to test the identifier presented in this study and was also useful to provide evidence of its superior performance against a non-delayed identifier based on CNN.

  6. SEMICONDUCTOR INTEGRATED CIRCUITS: A four-channel microelectronic system for neural signal regeneration

    NASA Astrophysics Data System (ADS)

    Shushan, Xie; Zhigong, Wang; Xiaoying, Lü; Wenyuan, Li; Haixian, Pan

    2009-12-01

    This paper presents a microelectronic system which is capable of making a signal record and functional electric stimulation of an injured spinal cord. As a requirement of implantable engineering for the regeneration microelectronic system, the system is of low noise, low power, small size and high performance. A front-end circuit and two high performance OPAs (operational amplifiers) have been designed for the system with different functions, and the two OPAs are a low-noise low-power two-stage OPA and a constant-gm RTR input and output OPA. The system has been realized in CSMC 0.5-μm CMOS technology. The test results show that the system satisfies the demands of neuron signal regeneration.

  7. Simplest relationship between local field potential and intracellular signals in layered neural tissue.

    PubMed

    Chizhov, Anton V; Sanchez-Aguilera, Alberto; Rodrigues, Serafim; de la Prida, Liset Menendez

    2015-12-01

    The relationship between the extracellularly measured electric field potential resulting from synaptic activity in an ensemble of neurons and intracellular signals in these neurons is an important but still open question. Based on a model neuron with a cylindrical dendrite and lumped soma, we derive a formula that substantiates a proportionality between the local field potential and the total somatic transmembrane current that emerges from the difference between the somatic and dendritic membrane potentials. The formula is tested by intra- and extracellular recordings of evoked synaptic responses in hippocampal slices. Additionally, the contribution of different membrane currents to the field potential is demonstrated in a two-population mean-field model. Our formalism, which allows for a simple estimation of unknown dendritic currents directly from somatic measurements, provides an interpretation of the local field potential in terms of intracellularly measurable synaptic signals. It is also applicable to the study of cortical activity using two-compartment neuronal population models.

  8. Simplest relationship between local field potential and intracellular signals in layered neural tissue

    NASA Astrophysics Data System (ADS)

    Chizhov, Anton V.; Sanchez-Aguilera, Alberto; Rodrigues, Serafim; de la Prida, Liset Menendez

    2015-12-01

    The relationship between the extracellularly measured electric field potential resulting from synaptic activity in an ensemble of neurons and intracellular signals in these neurons is an important but still open question. Based on a model neuron with a cylindrical dendrite and lumped soma, we derive a formula that substantiates a proportionality between the local field potential and the total somatic transmembrane current that emerges from the difference between the somatic and dendritic membrane potentials. The formula is tested by intra- and extracellular recordings of evoked synaptic responses in hippocampal slices. Additionally, the contribution of different membrane currents to the field potential is demonstrated in a two-population mean-field model. Our formalism, which allows for a simple estimation of unknown dendritic currents directly from somatic measurements, provides an interpretation of the local field potential in terms of intracellularly measurable synaptic signals. It is also applicable to the study of cortical activity using two-compartment neuronal population models.

  9. Cloning of zebrafish nkx6.2 and a comprehensive analysis of the conserved transcriptional response to Hedgehog/Gli signaling in the zebrafish neural tube

    PubMed Central

    Guner, Burcu; Karlstrom, Rolf O.

    2007-01-01

    Sonic Hedgehog (Shh) signaling helps pattern the vertebrate neural tube, in part by regulating the dorsal/ventral expression of a number of homeodomain containing transcription factors. These Hh responsive genes have been divided into two classes, with Class II genes being activated by Hh signaling and Class I genes being repressed by Hh signaling. While the transcriptional response to varying Hh levels is well defined in chick and mouse, it is only partially described in zebrafish, despite the fact that zebrafish has emerged as a powerful genetic system for the study of neural patterning. To better characterize the Hh response in the zebrafish neural tube, we cloned the zebrafish Class II Hh target genes nkx2.9 and nkx6.2. We then analyzed the expression of a number of Class I and Class II Hh responsive genes in wild type, Hh mutant, and Hh over-expressing zebrafish embryos. We show that expression of Class I and Class II genes is highly conserved in the vertebrate neural tube. Further, ventral-most Class II gene expression was completely lost in all Hh pathway mutants analyzed, indicating high levels of Hh signaling are blocked in all of these mutants. In contrast, more dorsally expressed genes were variably affected in different Hh pathway mutants, indicating mid-levels of Hh signaling are differentially affected. This comprehensive expression study provides an important tool for the characterization of Hh signaling in zebrafish and provides a sensitive assay for determining the degree to which newly identified zebrafish mutants affect Hh signaling. PMID:17307034

  10. Intrinsic excitability state of local neuronal population modulates signal propagation in feed-forward neural networks

    NASA Astrophysics Data System (ADS)

    Han, Ruixue; Wang, Jiang; Yu, Haitao; Deng, Bin; Wei, Xilei; Qin, Yingmei; Wang, Haixu

    2015-04-01

    Reliable signal propagation across distributed brain areas is an essential requirement for cognitive function, and it has been investigated extensively in computational studies where feed-forward network (FFN) is taken as a generic model. But it is still unclear how distinct local network states, which are intrinsically generated by synaptic interactions within each layer, would affect the ability of FFN to transmit information. Here we investigate the impact of such network states on propagating transient synchrony (synfire) and firing rate by a combination of numerical simulations and analytical approach. Specifically, local network dynamics is attributed to the competition between excitatory and inhibitory neurons within each layer. Our results show that concomitant with different local network states, the performance of signal propagation differs dramatically. For both synfire propagation and firing rate propagation, there exists an optimal local excitability state, respectively, that optimizes the performance of signal propagation. Furthermore, we find that long-range connections strongly change the dependence of spiking activity propagation on local network state and propose that these two factors work jointly to determine information transmission across distributed networks. Finally, a simple mean field approach that bridges response properties of long-range connectivity and local subnetworks is utilized to reveal the underlying mechanism.

  11. A new aspect of the TrkB signaling pathway in neural plasticity.

    PubMed

    Ohira, K; Hayashi, M

    2009-12-01

    In the central nervous system (CNS), the expression of molecules is strictly regulated during development. Control of the spatiotemporal expression of molecules is a mechanism not only to construct the functional neuronal network but also to adjust the network in response to new information from outside of the individual, i.e., through learning and memory. Among the functional molecules in the CNS, one of the best-studied groups is the neurotrophins, which are nerve growth factor (NGF)-related gene family molecules. Neurotrophins include NGF, brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and NT-4/5 in the mammal. Among neurotrophins and their receptors, BDNF and tropomyosin-related kinases B (TrkB) are enriched in the CNS. In the CNS, the BDNF-TrkB signaling pathway fulfills a wide variety of functions throughout life, such as cell survival, migration, outgrowth of axons and dendrites, synaptogenesis, synaptic transmission, and remodeling of synapses. Although the same ligand and receptor, BDNF and TrkB, act in these various developmental events, we do not yet understand what kind of mechanism provokes the functional multiplicity of the BDNF-TrkB signaling pathway. In this review, we discuss the mechanism that elicits the variety of functions performed by the BDNF-TrkB signaling pathway in the CNS as a tool of pharmacological therapy.

  12. A New Aspect of the TrkB Signaling Pathway in Neural Plasticity

    PubMed Central

    Ohira, K; Hayashi, M

    2009-01-01

    In the central nervous system (CNS), the expression of molecules is strictly regulated during development. Control of the spatiotemporal expression of molecules is a mechanism not only to construct the functional neuronal network but also to adjust the network in response to new information from outside of the individual, i.e., through learning and memory. Among the functional molecules in the CNS, one of the best-studied groups is the neurotrophins, which are nerve growth factor (NGF)-related gene family molecules. Neurotrophins include NGF, brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and NT-4/5 in the mammal. Among neurotrophins and their receptors, BDNF and tropomyosin-related kinases B (TrkB) are enriched in the CNS. In the CNS, the BDNF-TrkB signaling pathway fulfills a wide variety of functions throughout life, such as cell survival, migration, outgrowth of axons and dendrites, synaptogenesis, synaptic transmission, and remodeling of synapses. Although the same ligand and receptor, BDNF and TrkB, act in these various developmental events, we do not yet understand what kind of mechanism provokes the functional multiplicity of the BDNF-TrkB signaling pathway. In this review, we discuss the mechanism that elicits the variety of functions performed by the BDNF-TrkB signaling pathway in the CNS as a tool of pharmacological therapy. PMID:20514207

  13. Intrinsic excitability state of local neuronal population modulates signal propagation in feed-forward neural networks.

    PubMed

    Han, Ruixue; Wang, Jiang; Yu, Haitao; Deng, Bin; Wei, Xilei; Qin, Yingmei; Wang, Haixu

    2015-04-01

    Reliable signal propagation across distributed brain areas is an essential requirement for cognitive function, and it has been investigated extensively in computational studies where feed-forward network (FFN) is taken as a generic model. But it is still unclear how distinct local network states, which are intrinsically generated by synaptic interactions within each layer, would affect the ability of FFN to transmit information. Here we investigate the impact of such network states on propagating transient synchrony (synfire) and firing rate by a combination of numerical simulations and analytical approach. Specifically, local network dynamics is attributed to the competition between excitatory and inhibitory neurons within each layer. Our results show that concomitant with different local network states, the performance of signal propagation differs dramatically. For both synfire propagation and firing rate propagation, there exists an optimal local excitability state, respectively, that optimizes the performance of signal propagation. Furthermore, we find that long-range connections strongly change the dependence of spiking activity propagation on local network state and propose that these two factors work jointly to determine information transmission across distributed networks. Finally, a simple mean field approach that bridges response properties of long-range connectivity and local subnetworks is utilized to reveal the underlying mechanism.

  14. The Multivariate Temporal Response Function (mTRF) Toolbox: A MATLAB Toolbox for Relating Neural Signals to Continuous Stimuli.

    PubMed

    Crosse, Michael J; Di Liberto, Giovanni M; Bednar, Adam; Lalor, Edmund C

    2016-01-01

    Understanding how brains process sensory signals in natural environments is one of the key goals of twenty-first century neuroscience. While brain imaging and invasive electrophysiology will play key roles in this endeavor, there is also an important role to be played by noninvasive, macroscopic techniques with high temporal resolution such as electro- and magnetoencephalography. But challenges exist in determining how best to analyze such complex, time-varying neural responses to complex, time-varying and multivariate natural sensory stimuli. There has been a long history of applying system identification techniques to relate the firing activity of neurons to complex sensory stimuli and such techniques are now seeing increased application to EEG and MEG data. One particular example involves fitting a filter-often referred to as a temporal response function-that describes a mapping between some feature(s) of a sensory stimulus and the neural response. Here, we first briefly review the history of these system identification approaches and describe a specific technique for deriving temporal response functions known as regularized linear regression. We then introduce a new open-source toolbox for performing this analysis. We describe how it can be used to derive (multivariate) temporal response functions describing a mapping between stimulus and response in both directions. We also explain the importance of regularizing the analysis and how this regularization can be optimized for a particular dataset. We then outline specifically how the toolbox implements these analyses and provide several examples of the types of results that the toolbox can produce. Finally, we consider some of the limitations of the toolbox and opportunities for future development and application.

  15. The Multivariate Temporal Response Function (mTRF) Toolbox: A MATLAB Toolbox for Relating Neural Signals to Continuous Stimuli

    PubMed Central

    Crosse, Michael J.; Di Liberto, Giovanni M.; Bednar, Adam; Lalor, Edmund C.

    2016-01-01

    Understanding how brains process sensory signals in natural environments is one of the key goals of twenty-first century neuroscience. While brain imaging and invasive electrophysiology will play key roles in this endeavor, there is also an important role to be played by noninvasive, macroscopic techniques with high temporal resolution such as electro- and magnetoencephalography. But challenges exist in determining how best to analyze such complex, time-varying neural responses to complex, time-varying and multivariate natural sensory stimuli. There has been a long history of applying system identification techniques to relate the firing activity of neurons to complex sensory stimuli and such techniques are now seeing increased application to EEG and MEG data. One particular example involves fitting a filter—often referred to as a temporal response function—that describes a mapping between some feature(s) of a sensory stimulus and the neural response. Here, we first briefly review the history of these system identification approaches and describe a specific technique for deriving temporal response functions known as regularized linear regression. We then introduce a new open-source toolbox for performing this analysis. We describe how it can be used to derive (multivariate) temporal response functions describing a mapping between stimulus and response in both directions. We also explain the importance of regularizing the analysis and how this regularization can be optimized for a particular dataset. We then outline specifically how the toolbox implements these analyses and provide several examples of the types of results that the toolbox can produce. Finally, we consider some of the limitations of the toolbox and opportunities for future development and application. PMID:27965557

  16. Subcutaneous Transplantation of Neural Precursor Cells in Experimental Autoimmune Encephalomyelitis Reduces Chemotactic Signals in the Central Nervous System

    PubMed Central

    Ravanidis, Stylianos; Poulatsidou, Kyriaki Nepheli; Lagoudaki, Roza; Touloumi, Olga; Polyzoidou, Elena; Lourbopoulos, Athanasios; Nousiopoulou, Evangelia; Theotokis, Paschalis; Kesidou, Evangelia; Tsalikakis, Dimitrios; Karacostas, Dimitrios; Grigoriou, Maria; Chlichlia, Katerina

    2015-01-01

    experimental autoimmune encephalomyelitis, the animal model of multiple sclerosis, may have a beneficial effect on the disease process. Several mechanisms have been proposed—among them, the potentiation of endogenous precursor cell differentiation of the central nervous system and the modulation of demyelinating and neurodegenerative immune-mediated processes. This article provides evidence of interference in immune signaling within the central nervous system as a potential mechanism underlying the immunomodulatory properties of transplanted neural precursor cells. PMID:26511651

  17. Distinct Steps of Neural Induction Revealed by Asterix, Obelix and TrkC, Genes Induced by Different Signals from the Organizer

    PubMed Central

    Pinho, Sonia; Simonsson, Pamela R.; Trevers, Katherine E.; Stower, Matthew J.; Sherlock, William T.; Khan, Mohsin; Streit, Andrea; Sheng, Guojun; Stern, Claudio D.

    2011-01-01

    The amniote organizer (Hensen's node) can induce a complete nervous system when grafted into a peripheral region of a host embryo. Although BMP inhibition has been implicated in neural induction, non-neural cells cannot respond to BMP antagonists unless previously exposed to a node graft for at least 5 hours before BMP inhibitors. To define signals and responses during the first 5 hours of node signals, a differential screen was conducted. Here we describe three early response genes: two of them, Asterix and Obelix, encode previously undescribed proteins of unknown function but Obelix appears to be a nuclear RNA-binding protein. The third is TrkC, a neurotrophin receptor. All three genes are induced by a node graft within 4–5 hours but they differ in the extent to which they are inducible by FGF: FGF is both necessary and sufficient to induce Asterix, sufficient but not necessary to induce Obelix and neither sufficient nor necessary for induction of TrkC. These genes are also not induced by retinoic acid, Noggin, Chordin, Dkk1, Cerberus, HGF/SF, Somatostatin or ionomycin-mediated Calcium entry. Comparison of the expression and regulation of these genes with other early neural markers reveals three distinct “epochs”, or temporal waves, of gene expression accompanying neural induction by a grafted organizer, which are mirrored by specific stages of normal neural plate development. The results are consistent with neural induction being a cascade of responses elicited by different signals, culminating in the formation of a patterned nervous system. PMID:21559472

  18. SOX1 links the function of neural patterning and Notch signalling in the ventral spinal cord during the neuron-glial fate switch

    SciTech Connect

    Genethliou, Nicholas; Panayiotou, Elena; Panayi, Helen; Orford, Michael; Mean, Richard; Lapathitis, George; Gill, Herman; Raoof, Sahir; Gasperi, Rita De; Elder, Gregory; Kessaris, Nicoletta; Richardson, William D.; Malas, Stavros

    2009-12-25

    During neural development the transition from neurogenesis to gliogenesis, known as the neuron-glial ({Nu}/G) fate switch, requires the coordinated function of patterning factors, pro-glial factors and Notch signalling. How this process is coordinated in the embryonic spinal cord is poorly understood. Here, we demonstrate that during the N/G fate switch in the ventral spinal cord (vSC) SOX1 links the function of neural patterning and Notch signalling. We show that, SOX1 expression in the vSC is regulated by PAX6, NKX2.2 and Notch signalling in a domain-specific manner. We further show that SOX1 regulates the expression of Hes1 and that loss of Sox1 leads to enhanced production of oligodendrocyte precursors from the pMN. Finally, we show that Notch signalling functions upstream of SOX1 during this fate switch and is independently required for the acquisition of the glial fate perse by regulating Nuclear Factor I A expression in a PAX6/SOX1/HES1/HES5-independent manner. These data integrate functional roles of neural patterning factors, Notch signalling and SOX1 during gliogenesis.

  19. Neural coding merges sex and habitat chemosensory signals in an insect herbivore

    PubMed Central

    Trona, Federica; Anfora, Gianfranco; Balkenius, Anna; Bengtsson, Marie; Tasin, Marco; Knight, Alan; Janz, Niklas; Witzgall, Peter; Ignell, Rickard

    2013-01-01

    Understanding the processing of odour mixtures is a focus in olfaction research. Through a neuroethological approach, we demonstrate that different odour types, sex and habitat cues are coded together in an insect herbivore. Stronger flight attraction of codling moth males, Cydia pomonella, to blends of female sex pheromone and plant odour, compared with single compounds, was corroborated by functional imaging of the olfactory centres in the insect brain, the antennal lobes (ALs). The macroglomerular complex (MGC) in the AL, which is dedicated to pheromone perception, showed an enhanced response to blends of pheromone and plant signals, whereas the response in glomeruli surrounding the MGC was suppressed. Intracellular recordings from AL projection neurons that transmit odour information to higher brain centres, confirmed this synergistic interaction in the MGC. These findings underscore that, in nature, sex pheromone and plant odours are perceived as an ensemble. That mating and habitat cues are coded as blends in the MGC of the AL highlights the dual role of plant signals in habitat selection and in premating sexual communication. It suggests that the MGC is a common target for sexual and natural selection in moths, facilitating ecological speciation. PMID:23595270

  20. Neuregulin 1 Type II-ErbB Signaling Promotes Cell Divisions Generating Neurons from Neural Progenitor Cells in the Developing Zebrafish Brain.

    PubMed

    Sato, Tomomi; Sato, Fuminori; Kamezaki, Aosa; Sakaguchi, Kazuya; Tanigome, Ryoma; Kawakami, Koichi; Sehara-Fujisawa, Atsuko

    2015-01-01

    Post-mitotic neurons are generated from neural progenitor cells (NPCs) at the expense of their proliferation. Molecular and cellular mechanisms that regulate neuron production temporally and spatially should impact on the size and shape of the brain. While transcription factors such as neurogenin1 (neurog1) and neurod govern progression of neurogenesis as cell-intrinsic mechanisms, recent studies show regulatory roles of several cell-extrinsic or intercellular signaling molecules including Notch, FGF and Wnt in production of neurons/neural progenitor cells from neural stem cells/radial glial cells (NSCs/RGCs) in the ventricular zone (VZ). However, it remains elusive how production of post-mitotic neurons from neural progenitor cells is regulated in the sub-ventricular zone (SVZ). Here we show that newborn neurons accumulate in the basal-to-apical direction in the optic tectum (OT) of zebrafish embryos. While neural progenitor cells are amplified by mitoses in the apical ventricular zone, neurons are exclusively produced through mitoses of neural progenitor cells in the sub-basal zone, later in the sub-ventricular zone, and accumulate apically onto older neurons. This neurogenesis depends on Neuregulin 1 type II (NRG1-II)-ErbB signaling. Treatment with an ErbB inhibitor, AG1478 impairs mitoses in the sub-ventricular zone of the optic tectum. Removal of AG1478 resumes sub-ventricular mitoses without precedent mitoses in the apical ventricular zone prior to basal-to-apical accumulation of neurons, suggesting critical roles of ErbB signaling in mitoses for post-mitotic neuron production. Knockdown of NRG1-II impairs both mitoses in the sub-basal/sub-ventricular zone and the ventricular zone. Injection of soluble human NRG1 into the developing brain ameliorates neurogenesis of NRG1-II-knockdown embryos, suggesting a conserved role of NRG1 as a cell-extrinsic signal. From these results, we propose that NRG1-ErbB signaling stimulates cell divisions generating neurons from

  1. Emergence of Coordinated Neural Dynamics Underlies Neuroprosthetic Learning and Skillful Control.

    PubMed

    Athalye, Vivek R; Ganguly, Karunesh; Costa, Rui M; Carmena, Jose M

    2017-02-22

    During motor learning, movements and underlying neural activity initially exhibit large trial-to-trial variability that decreases over learning. However, it is unclear how task-relevant neural populations coordinate to explore and consolidate activity patterns. Exploration and consolidation could happen for each neuron independently, across the population jointly, or both. We disambiguated among these possibilities by investigating how subjects learned de novo to control a brain-machine interface using neurons from motor cortex. We decomposed population activity into the sum of private and shared signals, which produce uncorrelated and correlated neural variance, respectively, and examined how these signals' evolution causally shapes behavior. We found that initially large trial-to-trial movement and private neural variability reduce over learning. Concomitantly, task-relevant shared variance increases, consolidating a manifold containing consistent neural trajectories that generate refined control. These results suggest that motor cortex acquires skillful control by leveraging both independent and coordinated variance to explore and consolidate neural patterns.

  2. Attention enhances synaptic efficacy and the signal-to-noise ratio in neural circuits.

    PubMed

    Briggs, Farran; Mangun, George R; Usrey, W Martin

    2013-07-25

    Attention is a critical component of perception. However, the mechanisms by which attention modulates neuronal communication to guide behaviour are poorly understood. To elucidate the synaptic mechanisms of attention, we developed a sensitive assay of attentional modulation of neuronal communication. In alert monkeys performing a visual spatial attention task, we probed thalamocortical communication by electrically stimulating neurons in the lateral geniculate nucleus of the thalamus while simultaneously recording shock-evoked responses from monosynaptically connected neurons in primary visual cortex. We found that attention enhances neuronal communication by increasing the efficacy of presynaptic input in driving postsynaptic responses, by increasing synchronous responses among ensembles of postsynaptic neurons receiving independent input, and by decreasing redundant signals between postsynaptic neurons receiving common input. The results demonstrate that attention finely tunes neuronal communication at the synaptic level by selectively altering synaptic weights, enabling enhanced detection of salient events in the noisy sensory environment.

  3. Neural mechanisms for filtering self-generated sensory signals in cerebellum-like circuits.

    PubMed

    Requarth, Tim; Sawtell, Nathaniel B

    2011-08-01

    This review focuses on recent progress in understanding mechanisms for filtering self-generated sensory signals in cerebellum-like circuits in fish and mammals. Recent in vitro studies in weakly electric gymnotid fish have explored the interplay among anti-Hebbian plasticity, synaptic dynamics, and feedforward inhibition in canceling self-generated electrosensory inputs. Studies of the mammalian dorsal cochlear nucleus have revealed multimodal integration and anti-Hebbian plasticity, suggesting that this circuit may adaptively filter incoming auditory information. In vivo studies in weakly electric mormryid fish suggest a key role for granule cell coding in sensory filtering. The clear links between synaptic plasticity and systems level sensory filtering in cerebellum-like circuits may provide insights into hypothesized adaptive filtering functions of the cerebellum itself.

  4. Sexual and seasonal plasticity in the emission of social electric signals. Behavioral approach and neural bases.

    PubMed

    Silva, Ana; Quintana, Laura; Perrone, Rossana; Sierra, Felipe

    2008-01-01

    Behavior in electric fish includes modulations of a stereotyped electric organ discharge (EOD) in addition to locomotor displays. Gymnotiformes can modulate the EOD rate to produce signals that participate in different behaviors. We studied the reproductive behavior of Brachyhypopomus pinnicaudatus both in the wild and laboratory settings. During the breeding season, fish produce sexually dimorphic social electric signals (SES): males emit three types of chirps (distinguished by their duration and internal structure), and accelerations, whereas females interrupt their EOD. Since these SES imply EOD frequency modulations, the pacemaker nucleus (PN) is involved in their generation and constitutes the main target organ to explore seasonal and sexual plasticity of the CNS. The PN has two types of neurons, pacemakers and relays, which receive modulatory inputs from pre-pacemaker structures. These neurons show an anisotropic rostro-caudal and dorso-ventral distribution that is paralleled by different field potential waveforms in distinct portions of the PN. In vivo glutamate injections in different areas of the PN provoke different kinds of EOD rate modulations. Ventral injections produce chirp-like responses in breeding males and EOD interruptions in breeding females, whereas dorsal injections provoke EOD frequency rises in both sexes. In the non-breeding season, males and females respond with interruptions when stimulated ventrally and frequency rises when injected dorsally. Our results show that changes of glutamate effects in the PN could explain the seasonal and sexual differences in the generation of SES. By means of behavioral recordings both in the wild and in laboratory settings, and by electrophysiological and pharmacological experiments, we have identified sexual and seasonal plasticity of the CNS and explored its underlying mechanisms.

  5. Decision support system for ultrasound inspection of fiber metal laminates using statistical signal processing and neural networks.

    PubMed

    Simas Filho, Eduardo F; Souza, Yure N; Lopes, Juliana L S; Farias, Cláudia T T; Albuquerque, Maria C S

    2013-08-01

    The growth of the aerospace industry has motivated the development of alternative materials. The fiber-metal laminate composites (FML) may replace the monolithic aluminum alloys in aircrafts structure as they present some advantages, such as higher stiffness, lower density and longer lifetime. However, a great variety of deformation modes can lead to failures in these composites and the degradation mechanisms are hard to detect in early stages through regular ultrasonic inspection. This paper aims at the automatic detection of defects (such as fiber fracture and delamination) in fiber-metal laminates composites through ultrasonic testing in the immersion pulse-echo configuration. For this, a neural network based decision support system was designed. The preprocessing stage (feature extraction) comprises Fourier transform and statistical signal processing techniques (Principal Component Analysis and Independent Component Analysis) aiming at extracting discriminant information and reduce redundancy in the set of features. Through the proposed system, classification efficiencies of ~99% were achieved and the misclassification of signatures corresponding to defects was almost eliminated.

  6. A neural network-based analysis of acoustic courtship signals and female responses in Chorthippus biguttulus grasshoppers.

    PubMed

    Wittmann, Jan P; Kolss, Munjong; Reinhold, Klaus

    2011-08-01

    In many animal species, male acoustic courtship signals are evaluated by females for mate choice. At the behavioural level, this phenomenon has been well studied. However, although several song characteristics have been determined to affect the attractiveness of a given song, the mechanisms of the evaluation process remain largely unclear. Here, we present a simple neural network model for analysing and evaluating courtship songs of Chorthippus biguttulus males in real-time. The model achieves a high predictive power of the attractiveness of artificial songs as assigned by real Chorthippus biguttulus females: about 87% of the variance can be explained. It also allows us to determine the relative contribution of different song characteristics to overall attractiveness and how each of the song components influences female responsiveness. In general, the obtained results closely match those of empirical studies. Therefore, our model may be used to obtain a first estimate of male song attractiveness and may thus complement actual testing of female responsiveness in the laboratory. In addition, the model allows including and testing novel song parameters to generate new hypotheses for further experimental studies. The supplemental material of this article contains the article's data in an active, re-usable format.

  7. Multiphasic on/off pheromone signalling in moths as neural correlates of a search strategy.

    PubMed

    Martinez, Dominique; Chaffiol, Antoine; Voges, Nicole; Gu, Yuqiao; Anton, Sylvia; Rospars, Jean-Pierre; Lucas, Philippe

    2013-01-01

    Insects and robots searching for odour sources in turbulent plumes face the same problem: the random nature of mixing causes fluctuations and intermittency in perception. Pheromone-tracking male moths appear to deal with discontinuous flows of information by surging upwind, upon sensing a pheromone patch, and casting crosswind, upon losing the plume. Using a combination of neurophysiological recordings, computational modelling and experiments with a cyborg, we propose a neuronal mechanism that promotes a behavioural switch between surge and casting. We show how multiphasic On/Off pheromone-sensitive neurons may guide action selection based on signalling presence or loss of the pheromone. A Hodgkin-Huxley-type neuron model with a small-conductance calcium-activated potassium (SK) channel reproduces physiological On/Off responses. Using this model as a command neuron and the antennae of tethered moths as pheromone sensors, we demonstrate the efficiency of multiphasic patterning in driving a robotic searcher toward the source. Taken together, our results suggest that multiphasic On/Off responses may mediate olfactory navigation and that SK channels may account for these responses.

  8. BMP, Wnt and FGF signals are integrated through evolutionarily conserved enhancers to achieve robust expression of Pax3 and Zic genes at the zebrafish neural plate border.

    PubMed

    Garnett, Aaron T; Square, Tyler A; Medeiros, Daniel M

    2012-11-01

    Neural crest cells generate a range of cells and tissues in the vertebrate head and trunk, including peripheral neurons, pigment cells, and cartilage. Neural crest cells arise from the edges of the nascent central nervous system, a domain called the neural plate border (NPB). NPB induction is known to involve the BMP, Wnt and FGF signaling pathways. However, little is known about how these signals are integrated to achieve temporally and spatially specific expression of genes in NPB cells. Furthermore, the timing and relative importance of these signals in NPB formation appears to differ between vertebrate species. Here, we use heat-shock overexpression and chemical inhibitors to determine whether, and when, BMP, Wnt and FGF signaling are needed for expression of the NPB specifiers pax3a and zic3 in zebrafish. We then identify four evolutionarily conserved enhancers from the pax3a and zic3 loci and test their response to BMP, Wnt and FGF perturbations. We find that all three signaling pathways are required during gastrulation for the proper expression of pax3a and zic3 in the zebrafish NPB. We also find that, although the expression patterns driven by the pax3a and zic3 enhancers largely overlap, they respond to different combinations of BMP, Wnt and FGF signals. Finally, we show that the combination of the two pax3a enhancers is less susceptible to signaling perturbations than either enhancer alone. Taken together, our results reveal how BMPs, FGFs and Wnts act cooperatively and redundantly through partially redundant enhancers to achieve robust, specific gene expression in the zebrafish NPB.

  9. Spatio-temporal Model of Endogenous ROS and Raft-Dependent WNT/Beta-Catenin Signaling Driving Cell Fate Commitment in Human Neural Progenitor Cells

    PubMed Central

    Haack, Fiete; Lemcke, Heiko; Ewald, Roland; Rharass, Tareck; Uhrmacher, Adelinde M.

    2015-01-01

    Canonical WNT/β-catenin signaling is a central pathway in embryonic development, but it is also connected to a number of cancers and developmental disorders. Here we apply a combined in-vitro and in-silico approach to investigate the spatio-temporal regulation of WNT/β-catenin signaling during the early neural differentiation process of human neural progenitors cells (hNPCs), which form a new prospect for replacement therapies in the context of neurodegenerative diseases. Experimental measurements indicate a second signal mechanism, in addition to canonical WNT signaling, being involved in the regulation of nuclear β-catenin levels during the cell fate commitment phase of neural differentiation. We find that the biphasic activation of β-catenin signaling observed experimentally can only be explained through a model that combines Reactive Oxygen Species (ROS) and raft dependent WNT/β-catenin signaling. Accordingly after initiation of differentiation endogenous ROS activates DVL in a redox-dependent manner leading to a transient activation of down-stream β-catenin signaling, followed by continuous auto/paracrine WNT signaling, which crucially depends on lipid rafts. Our simulation studies further illustrate the elaborate spatio-temporal regulation of DVL, which, depending on its concentration and localization, may either act as direct inducer of the transient ROS/β-catenin signal or as amplifier during continuous auto-/parcrine WNT/β-catenin signaling. In addition we provide the first stochastic computational model of WNT/β-catenin signaling that combines membrane-related and intracellular processes, including lipid rafts/receptor dynamics as well as WNT- and ROS-dependent β-catenin activation. The model’s predictive ability is demonstrated under a wide range of varying conditions for in-vitro and in-silico reference data sets. Our in-silico approach is realized in a multi-level rule-based language, that facilitates the extension and modification of the

  10. Thyroid hormone signaling: Contribution to neural function, cognition, and relationship to nicotine

    PubMed Central

    Leach, Prescott T.; Gould, Thomas J.

    2015-01-01

    Cigarette smoking is common despite its adverse effects on health, such as cardiovascular disease and stroke. Understanding the mechanisms that contribute to the addictive properties of nicotine makes it possible to target them to prevent the initiation of smoking behavior and/or increase the chance of successful quit attempts. While highly addictive, nicotine is not generally considered to be as reinforcing as other drugs of abuse. There are likely other mechanisms at work that contribute to the addictive liability of nicotine. Nicotine modulates aspects of the endocrine system, including the thyroid, which is critical for normal cognitive functioning. It is possible that nicotine’s effects on thyroid function may alter learning and memory, and this may underlie some of its addictive potential. Here, we review the literature on thyroid function and cognition, with a focus on how nicotine alters thyroid hormone signaling and the potential impact on cognition. Changes in cognition are a major symptom of nicotine addiction. Current anti-smoking therapies have modest success at best. If some of the cognitive effects of nicotine are mediated through the thyroid hormone system, then thyroid hormone agonists may be novel treatments for smoking cessation therapies. The content of this review is important because it clarifies the relationship between smoking and thyroid function, which has been ill-defined in the past. This review is timely because the reduction in smoking rates we have seen in recent decades, due to public awareness campaigns and public smoking bans, has leveled off in recent years. Therefore, novel treatment approaches are needed to help reduce smoking rates further. PMID:26344666

  11. Activation of mTor Signaling by Gene Transduction to Induce Axon Regeneration in the Central Nervous System Following Neural Injury

    DTIC Science & Technology

    2014-03-01

    Transduction to Induce Axon Regeneration in the Central Nervous System Following Neural Injury PRINCIPAL INVESTIGATOR: Robert E. Burke, MD...SUBTITLE 5a. CONTRACT NUMBER Activation of mTor Signaling by Gene Transduction to Induce Axon Regeneration in the Central Nervous System...has been that the mature mammalian central nervous system (CNS), unlike the peripheral nervous system (PNS), is incapable of axon regeneration. There

  12. Involvement of PKCα and ERK1/2 signaling pathways in EGCG's protection against stress-induced neural injuries in Wistar rats.

    PubMed

    Zhao, Xiaoling; Liu, Fengqin; Jin, Haimin; Li, Renjia; Wang, Yonghui; Zhang, Wanqi; Wang, Haichao; Chen, Weiqiang

    2017-03-27

    Stress-induced neural injuries are closely linked to the pathogenesis of various neuropsychiatric disorders and psychosomatic diseases. We and others have previously demonstrated certain protective effects of epigallocatechin-3-gallate (EGCG) in stress-induced cerebral impairments, but the underlying protective mechanisms still remain poorly elucidated. Here we provide evidence to support the possible involvement of PKCα and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathways in EGCG-mediated protection against restraint stress-induced neural injuries in rats. In both open-field and step-through behavioral tests, the restraint stress-induced neuronal impairments were significantly ameliorated by administration of EGCG or green tea polyphenols (GTPs), which was associated with a partial restoration of normal plasma glucocorticoid, dopamine and serotonin levels. Furthermore, the stress-induced decrease of PKCα and ERK1/2 expression and phosphorylation was significantly attenuated by EGCG and to a less extent by GTP administration. Additionally, EGCG supplementation restored the production of adenosine triphosphate (ATP) and the expression of a key regulator of cellular energy metabolism, the peroxisome proliferators-activated receptor-γ coactivator-1α (PGC-1α), in stressed animals. In conclusion, PKCα and ERK1/2 signaling pathways as well as PGC-1α-mediated ATP production might be involved in EGCG-mediated protection against stress-induced neural injuries.

  13. Development of exoskeletal robotic limbs for a rat controlled by neural signals based on a vehicular neuro-robotic platform RatCar.

    PubMed

    Fukayama, Osamu; Otsuka, Hiroshi; Hashimoto, Ryuta; Suzuki, Takafumi; Mabuchi, Kunihiko

    2012-01-01

    A pair of exoskeletal limbs for a rat has been developed based on a vehicular Brain-Machine Interface "Rat-Car". The "RatCar" is a whole-body motor prosthesis system for a rat developed by the authors, estimating locomotion velocity according to neural signals pattern to move the rat body by the vehicle instead of its original limbs. In this paper, exoskeletal limbs have displaced the wheels for more natural modality of body control. The system was tested by applying peripheral nerve signals from a behaving rat.

  14. Phenotypic Changes, Signaling Pathway, and Functional Correlates of GPR17-expressing Neural Precursor Cells during Oligodendrocyte Differentiation*

    PubMed Central

    Fumagalli, Marta; Daniele, Simona; Lecca, Davide; Lee, Philip R.; Parravicini, Chiara; Fields, R. Douglas; Rosa, Patrizia; Antonucci, Flavia; Verderio, Claudia; Trincavelli, M. Letizia; Bramanti, Placido; Martini, Claudia; Abbracchio, Maria P.

    2011-01-01

    The developing and mature central nervous system contains neural precursor cells expressing the proteoglycan NG2. Some of these cells continuously differentiate to myelin-forming oligodendrocytes; knowledge of the destiny of NG2+ precursors would benefit from the characterization of new key functional players. In this respect, the G protein-coupled membrane receptor GPR17 has recently emerged as a new timer of oligodendrogliogenesis. Here, we used purified oligodendrocyte precursor cells (OPCs) to fully define the immunophenotype of the GPR17-expressing cells during OPC differentiation, unveil its native signaling pathway, and assess the functional consequences of GPR17 activation by its putative endogenous ligands, uracil nucleotides and cysteinyl leukotrienes (cysLTs). GPR17 presence was restricted to very early differentiation stages and completely segregated from that of mature myelin. Specifically, GPR17 decorated two subsets of slowly proliferating NG2+ OPCs: (i) morphologically immature cells expressing other early proteins like Olig2 and PDGF receptor-α, and (ii) ramified preoligodendrocytes already expressing more mature factors, like O4 and O1. Thus, GPR17 is a new marker of these transition stages. In OPCs, GPR17 activation by either uracil nucleotides or cysLTs resulted in potent inhibition of intracellular cAMP formation. This effect was counteracted by GPR17 antagonists and receptor silencing with siRNAs. Finally, uracil nucleotides promoted and GPR17 inhibition, by either antagonists or siRNAs, impaired the normal program of OPC differentiation. These data have implications for the in vivo behavior of NG2+ OPCs and point to uracil nucleotides and cysLTs as main extrinsic local regulators of these cells under physiological conditions and during myelin repair. PMID:21209081

  15. Multiple roles of Activin/Nodal, bone morphogenetic protein, fibroblast growth factor and Wnt/β-catenin signalling in the anterior neural patterning of adherent human embryonic stem cell cultures

    PubMed Central

    Lupo, Giuseppe; Novorol, Claire; Smith, Joseph R.; Vallier, Ludovic; Miranda, Elena; Alexander, Morgan; Biagioni, Stefano; Pedersen, Roger A.; Harris, William A.

    2013-01-01

    Several studies have successfully produced a variety of neural cell types from human embryonic stem cells (hESCs), but there has been limited systematic analysis of how different regional identities are established using well-defined differentiation conditions. We have used adherent, chemically defined cultures to analyse the roles of Activin/Nodal, bone morphogenetic protein (BMP), fibroblast growth factor (FGF) and Wnt/β-catenin signalling in neural induction, anteroposterior patterning and eye field specification in hESCs. We show that either BMP inhibition or activation of FGF signalling is required for effective neural induction, but these two pathways have distinct outcomes on rostrocaudal patterning. While BMP inhibition leads to specification of forebrain/midbrain positional identities, FGF-dependent neural induction is associated with strong posteriorization towards hindbrain/spinal cord fates. We also demonstrate that Wnt/β-catenin signalling is activated during neural induction and promotes acquisition of neural fates posterior to forebrain. Therefore, inhibition of this pathway is needed for efficient forebrain specification. Finally, we provide evidence that the levels of Activin/Nodal and BMP signalling have a marked influence on further forebrain patterning and that constitutive inhibition of these pathways represses expression of eye field genes. These results show that the key mechanisms controlling neural patterning in model vertebrate species are preserved in adherent, chemically defined hESC cultures and reveal new insights into the signals regulating eye field specification. PMID:23576785

  16. Acquired Cystic Kidney Disease

    MedlinePlus

    ... They Work Kidney Disease A-Z Acquired Cystic Kidney Disease What is acquired cystic kidney disease? Acquired cystic kidney disease happens when a ... cysts. What are the differences between acquired cystic kidney disease and polycystic kidney disease? Acquired cystic kidney ...

  17. Review of Brain-Machine Interfaces Used in Neural Prosthetics with New Perspective on Somatosensory Feedback through Method of Signal Breakdown.

    PubMed

    Vidal, Gabriel W Vattendahl; Rynes, Mathew L; Kelliher, Zachary; Goodwin, Shikha Jain

    2016-01-01

    The brain-machine interface (BMI) used in neural prosthetics involves recording signals from neuron populations, decoding those signals using mathematical modeling algorithms, and translating the intended action into physical limb movement. Recently, somatosensory feedback has become the focus of many research groups given its ability in increased neural control by the patient and to provide a more natural sensation for the prosthetics. This process involves recording data from force sensitive locations on the prosthetics and encoding these signals to be sent to the brain in the form of electrical stimulation. Tactile sensation has been achieved through peripheral nerve stimulation and direct stimulation of the somatosensory cortex using intracortical microstimulation (ICMS). The initial focus of this paper is to review these principles and link them to modern day applications such as restoring limb use to those who lack such control. With regard to how far the research has come, a new perspective for the signal breakdown concludes the paper, offering ideas for more real somatosensory feedback using ICMS to stimulate particular sensations by differentiating touch sensors and filtering data based on unique frequencies.

  18. Review of Brain-Machine Interfaces Used in Neural Prosthetics with New Perspective on Somatosensory Feedback through Method of Signal Breakdown

    PubMed Central

    Vidal, Gabriel W. Vattendahl; Rynes, Mathew L.; Kelliher, Zachary; Goodwin, Shikha Jain

    2016-01-01

    The brain-machine interface (BMI) used in neural prosthetics involves recording signals from neuron populations, decoding those signals using mathematical modeling algorithms, and translating the intended action into physical limb movement. Recently, somatosensory feedback has become the focus of many research groups given its ability in increased neural control by the patient and to provide a more natural sensation for the prosthetics. This process involves recording data from force sensitive locations on the prosthetics and encoding these signals to be sent to the brain in the form of electrical stimulation. Tactile sensation has been achieved through peripheral nerve stimulation and direct stimulation of the somatosensory cortex using intracortical microstimulation (ICMS). The initial focus of this paper is to review these principles and link them to modern day applications such as restoring limb use to those who lack such control. With regard to how far the research has come, a new perspective for the signal breakdown concludes the paper, offering ideas for more real somatosensory feedback using ICMS to stimulate particular sensations by differentiating touch sensors and filtering data based on unique frequencies. PMID:27313959

  19. Application of Self Adaptive Unsupervised Neural Networks for Processing of VLF-LF signals to detect Seismic-Ionospheric Precursor Phenomena.

    NASA Astrophysics Data System (ADS)

    Skeberis, C.; Xenos, T. D.; Hadjileontiadis, L.; Contadakis, M. E.; Arabelos, D.

    2012-04-01

    This paper investigates the development and application of artificial neural networks (ANN) based on Predictive Modular Neural Networks (PREMONNs) to provide a self adaptive unsupervised method for detecting disturbances that can be attributed to seismic-ionospheric precursor phenomena using VLF radio signals. As such, the neural network is applied to bring forth and adaptively discriminate different characteristics in the received signals, in real time, in order to provide data segments of interest that can be correlated to subsequent seismic phenomena. PREMONNs have been developed for time series prediction and through that for source switching detection in a time series; they are constituted by two modules. The first tier is a module consisting of a dynamic array of neural networks following the data stream in order to predict the next value of a time series whereas the second is a decision one utilizing a Bayes probability equation to decide on source switching. That module is responsible for electing and appropriately training the closest fitting NN or switching to a new NN if a source switch is apparent. For the purpose of this paper, VLF signals transmitted by a number of European VLF transmitters are monitored for over a year in Thessaloniki (40.69N 22.78E) and the data from December 2010 to December 2011 are used. The received signals are sampled and stored for off line processing. The receiver was developed by Elettronika Srl, and is part of the International Network for Frontier Research on Earthquake Precursors (INFREP). Signals received from the 20.27KHz ICV station in Tavolara, Italy (Lat 40.923,Lon. 9.731) were used. The received VLF signal was normalized and then processed using the Empirical Mode Decomposition Method (EMD). The resulting data are used to train the unsupervised ANN and the performance of the developed network is then evaluated. The efficacy of different layouts of the PREMONN is evaluated and the application of a self

  20. A multi-channel low-power system-on-chip for single-unit recording and narrowband wireless transmission of neural signal.

    PubMed

    Bonfanti, A; Ceravolo, M; Zambra, G; Gusmeroli, R; Spinelli, A S; Lacaita, A L; Angotzi, G N; Baranauskas, G; Fadiga, L

    2010-01-01

    This paper reports a multi-channel neural recording system-on-chip (SoC) with digital data compression and wireless telemetry. The circuit consists of a 16 amplifiers, an analog time division multiplexer, an 8-bit SAR AD converter, a digital signal processor (DSP) and a wireless narrowband 400-MHz binary FSK transmitter. Even though only 16 amplifiers are present in our current die version, the whole system is designed to work with 64 channels demonstrating the feasibility of a digital processing and narrowband wireless transmission of 64 neural recording channels. A digital data compression, based on the detection of action potentials and storage of correspondent waveforms, allows the use of a 1.25-Mbit/s binary FSK wireless transmission. This moderate bit-rate and a low frequency deviation, Manchester-coded modulation are crucial for exploiting a narrowband wireless link and an efficient embeddable antenna. The chip is realized in a 0.35- εm CMOS process with a power consumption of 105 εW per channel (269 εW per channel with an extended transmission range of 4 m) and an area of 3.1 × 2.7 mm(2). The transmitted signal is captured by a digital TV tuner and demodulated by a wideband phase-locked loop (PLL), and then sent to a PC via an FPGA module. The system has been tested for electrical specifications and its functionality verified in in-vivo neural recording experiments.

  1. Physical methods for generating and decoding neural activity in Hirudo verbana

    NASA Astrophysics Data System (ADS)

    Migliori, Benjamin John

    neural transmission fibers. These signals control and coordinate sophisticated behavioral motions allowing the animal to combine several stereotypical behaviors to performs actions such as hunting. I developed a blind source separation technique to isolate individual axon activity patterns from noisy, highly overlapping local voltage measurements of the intact bundle. These axon activity patterns correspond to single neural sources. My unsupervised algorithm can extract candidate signal patterns that are undetectable by established techniques. Using a propagation-sensitive electrode I developed, I am able to acquire neural signal velocity and direction information. With this set of information, I successfully identify rhythmically active multifunctional neurons that participate in interganglionic signaling during swimming, crawling, and whole-body shortening. I also demonstrate tracking of single neural sources across distant measurement sites. These results demonstrate a new way to search for behaviorally important biological signals, and help locate and identify signals involved in specific behaviors in Hirudo.

  2. c-Met Overexpression Contributes to the Acquired Apoptotic Resistance of Nonadherent Ovarian Cancer Cells through a Cross Talk Mediated by Phosphatidylinositol 3-Kinase and Extracellular Signal-Regulated Kinase 1/212

    PubMed Central

    Tang, Maggie K S; Zhou, Hong Y; Yam, Judy W P; Wong, Alice S T

    2010-01-01

    Ovarian cancer is the most lethal gynecologic cancer mainly because of widespread peritoneal dissemination and malignant ascites. Key to this is the capacity of tumor cells to escape suspension-induced apoptosis (anoikis), which also underlies their resistance to chemotherapy. Here, we used a nonadherent cell culture model to investigate the molecular mechanisms of apoptotic resistance of ovarian cancer cells that may mimic the chemoresistance found in solid tumors. We found that ovarian cancer cells acquired a remarkable resistance to anoikis and apoptosis induced by exposure to clinically relevant doses of two front-line chemotherapeutic drugs cisplatin and paclitaxel when grown in three-dimensional than monolayer cultures. Inhibition of the hepatocyte growth factor (HGF) receptor c-Met, which is frequently overexpressed in ovarian cancer, by a specific inhibitor or small interfering RNA blocked the acquired anoikis resistance and restored chemosensitivity in three-dimensional not in two-dimensional cultures. These effects were found to be dependent on both phosphatidylinositol 3-kinase (PI3K)/Akt and extracellular signal-regulated kinase (ERK) 1/2 signaling pathways. Inhibitors of PI3K/Akt abrogated ERK1/2 activation and its associated anoikis resistance in response to HGF, suggesting a signaling relay between these two pathways. Furthermore, we identified a central role of Ras as a mechanism of this cross talk. Interestingly, Ras did not lie upstream of PI3K/Akt, whereas PI3K/Akt signaling to ERK1/2 involved Ras. These findings shed new light on the apoptotic resistance mechanism of nonadherent ovarian cancer ascites cells and may have important clinical implications. PMID:20126471

  3. Adults with high social anhedonia have altered neural connectivity with ventral lateral prefrontal cortex when processing positive social signals

    PubMed Central

    Yin, Hong; Tully, Laura M.; Lincoln, Sarah Hope; Hooker, Christine I.

    2015-01-01

    Social anhedonia (SA) is a debilitating characteristic of schizophrenia, a common feature in individuals at psychosis-risk, and a vulnerability for developing schizophrenia-spectrum disorders. Prior work (Hooker et al., 2014) revealed neural deficits in the ventral lateral prefrontal cortex (VLPFC) when processing positive social cues in a community sample of people with high SA. Lower VLPFC neural activity was related to more severe self-reported schizophrenia-spectrum symptoms as well as the exacerbation of symptoms after social stress. In the current study, psycho-physiological interaction (PPI) analysis was applied to further investigate the neural mechanisms mediated by the VLPFC during emotion processing. PPI analysis revealed that, compared to low SA controls, participants with high SA exhibited reduced connectivity between the VLPFC and the motor cortex, the inferior parietal and the posterior temporal regions when viewing socially positive (relative to neutral) emotions. Across all participants, VLPFC connectivity correlated with behavioral and self-reported measures of attentional control, emotion management, and reward processing. Our results suggest that impairments to the VLPFC mediated neural circuitry underlie the cognitive and emotional deficits associated with social anhedonia, and may serve as neural targets for prevention and treatment of schizophrenia-spectrum disorders. PMID:26379532

  4. CD99 regulates neural differentiation of Ewing sarcoma cells through miR-34a-Notch-mediated control of NF-kB signaling

    PubMed Central

    Ventura, Selena; Aryee, Dave NT; Felicetti, Federica; De Feo, Alessandra; Mancarella, Caterina; Manara, Maria Cristina; Picci, Piero; Colombo, Mario Paolo; Kovar, Heinrich; Carè, Alessandra; Scotlandi, Katia

    2016-01-01

    Sarcomas are mesenchymal tumors characterized by blocked differentiation process. In Ewing sarcoma (EWS) both CD99 and EWS-FLI1 concur to oncogenesis and inhibition of differentiation. Here we demonstrate that uncoupling CD99 from EWS-FLI1 by silencing the former, NF-kB signaling is inhibited and the neural differentiation program is re-established. NF-kB inhibition passes through miR-34a-mediated repression of Notch pathway. CD99 counteracts EWS-FLI1 in controlling NF-kB signaling through the miR-34a, which is increased and secreted into exosomes released by CD99-silenced EWS cells. Delivery of exosomes from CD99-silenced cells was sufficient to induce neural differentiation in recipient EWS cells through miR-34a inhibition of Notch-NF-kB signaling. Notably, even the partial delivery of CD99 siRNA may have a broad effect on the entire tumor cell population thanks to the spread operated by their miR-34a-enriched exosomes, a feature opening to a new therapeutic option. PMID:26616853

  5. OCT detection of neural activity in American cockroach nervous system

    NASA Astrophysics Data System (ADS)

    Gorczyńska, Iwona; Wyszkowska, Joanna; Bukowska, Danuta; Ruminski, Daniel; Karnowski, Karol; Stankiewicz, Maria; Wojtkowski, Maciej

    2013-03-01

    We show results of a project which focuses on detection of activity in neural tissue with Optical Coherence Tomography (OCT) methods. Experiments were performed in neural cords dissected from the American cockroach (Periplaneta americana L.). Functional OCT imaging was performed with ultrahigh resolution spectral / Fourier domain OCT system (axial resolution 2.5 μm). Electrical stimulation (voltage pulses) was applied to the sensory cercal nerve of the neural cord. Optical detection of functional activation of the sample was performed in the connective between the terminal abdominal ganglion and the fifth abdominal ganglion. Functional OCT data were collected over time with the OCT beam illuminating selected single point in the connectives (i.e. OCT M-scans were acquired). Phase changes of the OCT signal were analyzed to visualize occurrence of activation in the neural cord. Electrophysiology recordings (microelectrode method) were also performed as a reference method to demonstrate electrical response of the sample to stimulation.

  6. Neural Networks

    SciTech Connect

    Smith, Patrick I.

    2003-09-23

    Physicists use large detectors to measure particles created in high-energy collisions at particle accelerators. These detectors typically produce signals indicating either where ionization occurs along the path of the particle, or where energy is deposited by the particle. The data produced by these signals is fed into pattern recognition programs to try to identify what particles were produced, and to measure the energy and direction of these particles. Ideally, there are many techniques used in this pattern recognition software. One technique, neural networks, is particularly suitable for identifying what type of particle caused by a set of energy deposits. Neural networks can derive meaning from complicated or imprecise data, extract patterns, and detect trends that are too complex to be noticed by either humans or other computer related processes. To assist in the advancement of this technology, Physicists use a tool kit to experiment with several neural network techniques. The goal of this research is interface a neural network tool kit into Java Analysis Studio (JAS3), an application that allows data to be analyzed from any experiment. As the final result, a physicist will have the ability to train, test, and implement a neural network with the desired output while using JAS3 to analyze the results or output. Before an implementation of a neural network can take place, a firm understanding of what a neural network is and how it works is beneficial. A neural network is an artificial representation of the human brain that tries to simulate the learning process [5]. It is also important to think of the word artificial in that definition as computer programs that use calculations during the learning process. In short, a neural network learns by representative examples. Perhaps the easiest way to describe the way neural networks learn is to explain how the human brain functions. The human brain contains billions of neural cells that are responsible for processing

  7. Acquired resistance to oestrogen deprivation: role for growth factor signalling kinases/oestrogen receptor cross-talk revealed in new MCF-7X model.

    PubMed

    Staka, Cindy M; Nicholson, Robert I; Gee, Julia M W

    2005-07-01

    In vitro models of long-term oestrogen deprivation utilise increased oestrogen receptor (ER) and are oestrogen hypersensitive, with emerging evidence that growth factor signalling contributes and interacts with ER. However, such models are commonly derived in the presence of serum growth factors that may force the resistance mechanism. Our new in vitro model, MCF-7X, has thus been developed under conditions of both oestrogen and growth factor depletion. ER expression, serine 118 phosphorylation on this receptor and its transcriptional activity were modestly increased compared to the parental MCF-7 cells, although MCF-7X cells were not oestrogen hypersensitive. Faslodex (0.1 microM) partially decreased ER and its transcriptional activity, with associated decreases in serine 118 phosphorylation. Faslodex inhibited MCF-7X growth by 50% for 10 weeks. Classical growth factor receptors did not impact on MCF-7X growth and only a modest contribution for MAP kinase was revealed using PD98059 (25 microM; 35% inhibition for 3 weeks). However, the phosphatidylinositol-3-OH (PI3)-kinase inhibitor LY294002 (5 microM) inhibited MCF-7X growth by 65% for 10 weeks. In contrast to PD98059, LY294002 also partially-inhibited ER transcriptional activity and decreased serine 167 ER phosphorylation. Co-treatment with faslodex plus LY294002 to decrease activity of both serine 118 and 167 proved superior vs the single agents in decreasing ER transcriptional activity and MCF-7X growth (90% inhibition for 25 weeks). However, triple treatment including PD98059 was required to prevent resistance in MCF-7X, an event dependent on maximal depletion of serine 118 phosphorylation and ER transcriptional activity. Kinases clearly contribute in resistance to oestrogen deprivation, cross-talking with ER signalling via AF-1 phosphorylation. While inhibiting each pathway has potential to treat this state, combined therapy targeting all regulators of ER phosphorylation may be required to block subsequent

  8. Using an achiasmic human visual system to quantify the relationship between the fMRI BOLD signal and neural response

    PubMed Central

    Bao, Pinglei; Purington, Christopher J; Tjan, Bosco S

    2015-01-01

    Achiasma in humans causes gross mis-wiring of the retinal-fugal projection, resulting in overlapped cortical representations of left and right visual hemifields. We show that in areas V1-V3 this overlap is due to two co-located but non-interacting populations of neurons, each with a receptive field serving only one hemifield. Importantly, the two populations share the same local vascular control, resulting in a unique organization useful for quantifying the relationship between neural and fMRI BOLD responses without direct measurement of neural activity. Specifically, we can non-invasively double local neural responses by stimulating both neuronal populations with identical stimuli presented symmetrically across the vertical meridian to both visual hemifields, versus one population by stimulating in one hemifield. Measurements from a series of such doubling experiments show that the amplitude of BOLD response is proportional to approximately 0.5 power of the underlying neural response. Reanalyzing published data shows that this inferred relationship is general. DOI: http://dx.doi.org/10.7554/eLife.09600.001 PMID:26613411

  9. Implementing spiking neural networks for real-time signal-processing and control applications: a model-validated FPGA approach.

    PubMed

    Pearson, Martin J; Pipe, A G; Mitchinson, B; Gurney, K; Melhuish, C; Gilhespy, I; Nibouche, M

    2007-09-01

    In this paper, we present two versions of a hardware processing architecture for modeling large networks of leaky-integrate-and-fire (LIF) neurons; the second version provides performance enhancing features relative to the first. Both versions of the architecture use fixed-point arithmetic and have been implemented using a single field-programmable gate array (FPGA). They have successfully simulated networks of over 1000 neurons configured using biologically plausible models of mammalian neural systems. The neuroprocessor has been designed to be employed primarily for use on mobile robotic vehicles, allowing bio-inspired neural processing models to be integrated directly into real-world control environments. When a neuroprocessor has been designed to act as part of the closed-loop system of a feedback controller, it is imperative to maintain strict real-time performance at all times, in order to maintain integrity of the control system. This resulted in the reevaluation of some of the architectural features of existing hardware for biologically plausible neural networks (NNs). In addition, we describe a development system for rapidly porting an underlying model (based on floating-point arithmetic) to the fixed-point representation of the FPGA-based neuroprocessor, thereby allowing validation of the hardware architecture. The developmental system environment facilitates the cooperation of computational neuroscientists and engineers working on embodied (robotic) systems with neural controllers, as demonstrated by our own experience on the Whiskerbot project, in which we developed models of the rodent whisker sensory system.

  10. Neural Signals Evoked by Stimuli of Increasing Social Scene Complexity Are Detectable at the Single-Trial Level and Right Lateralized

    PubMed Central

    Amaral, Carlos P.; Simões, Marco A.; Castelo-Branco, Miguel S.

    2015-01-01

    Classification of neural signals at the single-trial level and the study of their relevance in affective and cognitive neuroscience are still in their infancy. Here we investigated the neurophysiological correlates of conditions of increasing social scene complexity using 3D human models as targets of attention, which may also be important in autism research. Challenging single-trial statistical classification of EEG neural signals was attempted for detection of oddball stimuli with increasing social scene complexity. Stimuli had an oddball structure and were as follows: 1) flashed schematic eyes, 2) simple 3D faces flashed between averted and non-averted gaze (only eye position changing), 3) simple 3D faces flashed between averted and non-averted gaze (head and eye position changing), 4) animated avatar alternated its gaze direction to the left and to the right (head and eye position), 5) environment with 4 animated avatars all of which change gaze and one of which is the target of attention. We found a late (> 300 ms) neurophysiological oddball correlate for all conditions irrespective of their complexity as assessed by repeated measures ANOVA. We attempted single-trial detection of this signal with automatic classifiers and obtained a significant balanced accuracy classification of around 79%, which is noteworthy given the amount of scene complexity. Lateralization analysis showed a specific right lateralization only for more complex realistic social scenes. In sum, complex ecological animations with social content elicit neurophysiological events which can be characterized even at the single-trial level. These signals are right lateralized. These finding paves the way for neuroscientific studies in affective neuroscience based on complex social scenes, and given the detectability at the single trial level this suggests the feasibility of brain computer interfaces that can be applied to social cognition disorders such as autism. PMID:25807525

  11. Neural signals evoked by stimuli of increasing social scene complexity are detectable at the single-trial level and right lateralized.

    PubMed

    Amaral, Carlos P; Simões, Marco A; Castelo-Branco, Miguel S

    2015-01-01

    Classification of neural signals at the single-trial level and the study of their relevance in affective and cognitive neuroscience are still in their infancy. Here we investigated the neurophysiological correlates of conditions of increasing social scene complexity using 3D human models as targets of attention, which may also be important in autism research. Challenging single-trial statistical classification of EEG neural signals was attempted for detection of oddball stimuli with increasing social scene complexity. Stimuli had an oddball structure and were as follows: 1) flashed schematic eyes, 2) simple 3D faces flashed between averted and non-averted gaze (only eye position changing), 3) simple 3D faces flashed between averted and non-averted gaze (head and eye position changing), 4) animated avatar alternated its gaze direction to the left and to the right (head and eye position), 5) environment with 4 animated avatars all of which change gaze and one of which is the target of attention. We found a late (> 300 ms) neurophysiological oddball correlate for all conditions irrespective of their complexity as assessed by repeated measures ANOVA. We attempted single-trial detection of this signal with automatic classifiers and obtained a significant balanced accuracy classification of around 79%, which is noteworthy given the amount of scene complexity. Lateralization analysis showed a specific right lateralization only for more complex realistic social scenes. In sum, complex ecological animations with social content elicit neurophysiological events which can be characterized even at the single-trial level. These signals are right lateralized. These finding paves the way for neuroscientific studies in affective neuroscience based on complex social scenes, and given the detectability at the single trial level this suggests the feasibility of brain computer interfaces that can be applied to social cognition disorders such as autism.

  12. The effect of pulsed electric fields on the electrotactic migration of human neural progenitor cells through the involvement of intracellular calcium signaling.

    PubMed

    Hayashi, Hisamitsu; Edin, Fredrik; Li, Hao; Liu, Wei; Rask-Andersen, Helge

    2016-12-01

    Endogenous electric fields (EFs) are required for the physiological control of the central nervous system development. Application of the direct current EFs to neural stem cells has been studied for the possibility of stem cell transplantation as one of the therapies for brain injury. EFs generated within the nervous system are often associated with action potentials and synaptic activity, apparently resulting in a pulsed current in nature. The aim of this study is to investigate the effect of pulsed EF, which can reduce the cytotoxicity, on the migration of human neural progenitor cells (hNPCs). We applied the mono-directional pulsed EF with a strength of 250mV/mm to hNPCs for 6h. The migration distance of the hNPCs exposed to pulsed EF was significantly greater compared with the control not exposed to the EF. Pulsed EFs, however, had less of an effect on the migration of the differentiated hNPCs. There was no significant change in the survival of hNPCs after exposure to the pulsed EF. To investigate the role of Ca(2+) signaling in electrotactic migration of hNPCs, pharmacological inhibition of Ca(2+) channels in the EF-exposed cells revealed that the electrotactic migration of hNPCs exposed to Ca(2+) channel blockers was significantly lower compared to the control group. The findings suggest that the pulsed EF induced migration of hNPCs is partly influenced by intracellular Ca(2+) signaling.

  13. Differential roles of AVP and VIP signaling in the postnatal changes of neural networks for coherent circadian rhythms in the SCN

    PubMed Central

    Ono, Daisuke; Honma, Sato; Honma, Ken-ichi

    2016-01-01

    The suprachiasmatic nucleus (SCN) is the site of the master circadian clock in mammals. The SCN neural network plays a critical role in expressing the tissue-level circadian rhythm. Previously, we demonstrated postnatal changes in the SCN network in mice, in which the clock gene products CRYPTOCHROMES (CRYs) are involved. Here, we show that vasoactive intestinal polypeptide (VIP) signaling is essential for the tissue-level circadian PER2::LUC rhythm in the neonatal SCN of CRY double-deficient mice (Cry1,2−/−). VIP and arginine vasopressin (AVP) signaling showed redundancy in expressing the tissue-level circadian rhythm in the SCN. AVP synthesis was significantly attenuated in the Cry1,2−/− SCN, which contributes to aperiodicity in the adult mice together with an attenuation of VIP signaling as a natural process of ontogeny. The SCN network consists of multiple clusters of cellular circadian rhythms that are differentially integrated by AVP and VIP signaling, depending on the postnatal period. PMID:27626074

  14. Species, sex and individual differences in the vasotocin/vasopressin system: relationship to neurochemical signaling in the social behavior neural network.

    PubMed

    Albers, H Elliott

    2015-01-01

    Arginine-vasotocin (AVT)/arginine vasopressin (AVP) are members of the AVP/oxytocin (OT) superfamily of peptides that are involved in the regulation of social behavior, social cognition and emotion. Comparative studies have revealed that AVT/AVP and their receptors are found throughout the "social behavior neural network (SBNN)" and display the properties expected from a signaling system that controls social behavior (i.e., species, sex and individual differences and modulation by gonadal hormones and social factors). Neurochemical signaling within the SBNN likely involves a complex combination of synaptic mechanisms that co-release multiple chemical signals (e.g., classical neurotransmitters and AVT/AVP as well as other peptides) and non-synaptic mechanisms (i.e., volume transmission). Crosstalk between AVP/OT peptides and receptors within the SBNN is likely. A better understanding of the functional properties of neurochemical signaling in the SBNN will allow for a more refined examination of the relationships between this peptide system and species, sex and individual differences in sociality.

  15. Differential distribution of competence for panplacodal and neural crest induction to non-neural and neural ectoderm.

    PubMed

    Pieper, Mareike; Ahrens, Katja; Rink, Elke; Peter, Annette; Schlosser, Gerhard

    2012-03-01

    It is still controversial whether cranial placodes and neural crest cells arise from a common precursor at the neural plate border or whether placodes arise from non-neural ectoderm and neural crest from neural ectoderm. Using tissue grafting in embryos of Xenopus laevis, we show here that the competence for induction of neural plate, neural plate border and neural crest markers is confined to neural ectoderm, whereas competence for induction of panplacodal markers is confined to non-neural ectoderm. This differential distribution of competence is established during gastrulation paralleling the dorsal restriction of neural competence. We further show that Dlx3 and GATA2 are required cell-autonomously for panplacodal and epidermal marker expression in the non-neural ectoderm, while ectopic expression of Dlx3 or GATA2 in the neural plate suppresses neural plate, border and crest markers. Overexpression of Dlx3 (but not GATA2) in the neural plate is sufficient to induce different non-neural markers in a signaling-dependent manner, with epidermal markers being induced in the presence, and panplacodal markers in the absence, of BMP signaling. Taken together, these findings demonstrate a non-neural versus neural origin of placodes and neural crest, respectively, strongly implicate Dlx3 in the regulation of non-neural competence, and show that GATA2 contributes to non-neural competence but is not sufficient to promote it ectopically.

  16. Tauroursodeoxycholic acid increases neural stem cell pool and neuronal conversion by regulating mitochondria-cell cycle retrograde signaling.

    PubMed

    Xavier, Joana M; Morgado, Ana L; Rodrigues, Cecília Mp; Solá, Susana

    2014-01-01

    The low survival and differentiation rates of stem cells after either transplantation or neural injury have been a major concern of stem cell-based therapy. Thus, further understanding long-term survival and differentiation of stem cells may uncover new targets for discovery and development of novel therapeutic approaches. We have previously described the impact of mitochondrial apoptosis-related events in modulating neural stem cell (NSC) fate. In addition, the endogenous bile acid, tauroursodeoxycholic acid (TUDCA) was shown to be neuroprotective in several animal models of neurodegenerative disorders by acting as an anti-apoptotic and anti-oxidant molecule at the mitochondrial level. Here, we hypothesize that TUDCA might also play a role on NSC fate decision. We found that TUDCA prevents mitochondrial apoptotic events typical of early-stage mouse NSC differentiation, preserves mitochondrial integrity and function, while enhancing self-renewal potential and accelerating cell cycle exit of NSCs. Interestingly, TUDCA prevention of mitochondrial alterations interfered with NSC differentiation potential by favoring neuronal rather than astroglial conversion. Finally, inhibition of mitochondrial reactive oxygen species (mtROS) scavenger and adenosine triphosphate (ATP) synthase revealed that the effect of TUDCA is dependent on mtROS and ATP regulation levels. Collectively, these data underline the importance of mitochondrial stress control of NSC fate decision and support a new role for TUDCA in this process.

  17. Single-trial analysis of neuroimaging data: inferring neural networks underlying perceptual decision-making in the human brain.

    PubMed

    Sajda, Paul; Philiastides, Marios G; Parra, Lucas C

    2009-01-01

    Advances in neural signal and image acquisition as well as in multivariate signal processing and machine learning are enabling a richer and more rigorous understanding of the neural basis of human decision-making. Decision-making is essentially characterized behaviorally by the variability of the decision across individual trials--e.g., error and response time distributions. To infer the neural processes that govern decision-making requires identifying neural correlates of such trial-to-trial behavioral variability. In this paper, we review efforts that utilize signal processing and machine learning to enable single-trial analysis of neural signals acquired while subjects perform simple decision-making tasks. Our focus is on neuroimaging data collected noninvasively via electroencephalograpy (EEG) and functional magnetic resonance imaging (fMRI). We review the specific framework for extracting decision-relevant neural components from the neuroimaging data, the goal being to analyze the trial-to-trial variability of the neural signal along these component directions and to relate them to elements of the decision-making process. We review results for perceptual decision-making and discrimination tasks, including paradigms in which EEG variability is used to inform an fMRI analysis. We discuss how single-trial analysis reveals aspects of the underlying decision-making networks that are unobservable using traditional trial-averaging methods.

  18. Single-Trial Analysis of Neuroimaging Data: Inferring Neural Networks Underlying Perceptual Decision-Making in the Human Brain

    PubMed Central

    Sajda, Paul; Philiastides, Marios G.; Parra, Lucas C.

    2012-01-01

    Advances in neural signal and image acquisition as well as in multivariate signal processing and machine learning are enabling a richer and more rigorous understanding of the neural basis of human decision-making. Decision-making is essentially characterized behaviorally by the variability of the decision across individual trials—e.g., error and response time distributions. To infer the neural processes that govern decision-making requires identifying neural correlates of such trial-to-trial behavioral variability. In this paper, we review efforts that utilize signal processing and machine learning to enable single-trial analysis of neural signals acquired while subjects perform simple decision-making tasks. Our focus is on neuroimaging data collected noninvasively via electroencephalograpy (EEG) and functional magnetic resonance imaging (fMRI). We review the specific frame-work for extracting decision-relevant neural components from the neuroimaging data, the goal being to analyze the trial-to-trial variability of the neural signal along these component directions and to relate them to elements of the decision-making process. We review results for perceptual decision-making and discrimination tasks, including paradigms in which EEG variability is used to inform an fMRI analysis. We discuss how single-trial analysis reveals aspects of the underlying decision-making networks that are unobservable using traditional trial-averaging methods. PMID:22275042

  19. IGF-1 Signaling Plays an Important Role in the Formation of Three-Dimensional Laminated Neural Retina and Other Ocular Structures From Human Embryonic Stem Cells.

    PubMed

    Mellough, Carla B; Collin, Joseph; Khazim, Mahmoud; White, Kathryn; Sernagor, Evelyne; Steel, David H W; Lako, Majlinda

    2015-08-01

    We and others have previously demonstrated that retinal cells can be derived from human embryonic stem cells (hESCs) and induced pluripotent stem cells under defined culture conditions. While both cell types can give rise to retinal derivatives in the absence of inductive cues, this requires extended culture periods and gives lower overall yield. Further understanding of this innate differentiation ability, the identification of key factors that drive the differentiation process, and the development of clinically compatible culture conditions to reproducibly generate functional neural retina is an important goal for clinical cell based therapies. We now report that insulin-like growth factor 1 (IGF-1) can orchestrate the formation of three-dimensional ocular-like structures from hESCs which, in addition to retinal pigmented epithelium and neural retina, also contain primitive lens and corneal-like structures. Inhibition of IGF-1 receptor signaling significantly reduces the formation of optic vesicle and optic cups, while exogenous IGF-1 treatment enhances the formation of correctly laminated retinal tissue composed of multiple retinal phenotypes that is reminiscent of the developing vertebrate retina. Most importantly, hESC-derived photoreceptors exhibit advanced maturation features such as the presence of primitive rod- and cone-like photoreceptor inner and outer segments and phototransduction-related functional responses as early as 6.5 weeks of differentiation, making these derivatives promising candidates for cell replacement studies and in vitro disease modeling.

  20. IGF‐1 Signaling Plays an Important Role in the Formation of Three‐Dimensional Laminated Neural Retina and Other Ocular Structures From Human Embryonic Stem Cells

    PubMed Central

    Mellough, Carla B.; Collin, Joseph; Khazim, Mahmoud; White, Kathryn; Sernagor, Evelyne; Steel, David H. W.

    2015-01-01

    Abstract We and others have previously demonstrated that retinal cells can be derived from human embryonic stem cells (hESCs) and induced pluripotent stem cells under defined culture conditions. While both cell types can give rise to retinal derivatives in the absence of inductive cues, this requires extended culture periods and gives lower overall yield. Further understanding of this innate differentiation ability, the identification of key factors that drive the differentiation process, and the development of clinically compatible culture conditions to reproducibly generate functional neural retina is an important goal for clinical cell based therapies. We now report that insulin‐like growth factor 1 (IGF‐1) can orchestrate the formation of three‐dimensional ocular‐like structures from hESCs which, in addition to retinal pigmented epithelium and neural retina, also contain primitive lens and corneal‐like structures. Inhibition of IGF‐1 receptor signaling significantly reduces the formation of optic vesicle and optic cups, while exogenous IGF‐1 treatment enhances the formation of correctly laminated retinal tissue composed of multiple retinal phenotypes that is reminiscent of the developing vertebrate retina. Most importantly, hESC‐derived photoreceptors exhibit advanced maturation features such as the presence of primitive rod‐ and cone‐like photoreceptor inner and outer segments and phototransduction‐related functional responses as early as 6.5 weeks of differentiation, making these derivatives promising candidates for cell replacement studies and in vitro disease modeling. Stem Cells 2015;33:2416–2430 PMID:25827910

  1. A 400 MHz Wireless Neural Signal Processing IC With 625 × On-Chip Data Reduction and Reconfigurable BFSK/QPSK Transmitter Based on Sequential Injection Locking.

    PubMed

    Teng, Kok-Hin; Wu, Tong; Liu, Xiayun; Yang, Zhi; Heng, Chun-Huat

    2017-03-03

    An 8-channel wireless neural signal processing IC, which can perform real-time spike detection, alignment, and feature extraction, and wireless data transmission is proposed. A reconfigurable BFSK/QPSK transmitter (TX) at MICS/MedRadio band is incorporated to support different data rate requirement. By using an Exponential Component-Polynomial Component (EC-PC) spike processing unit with an incremental principal component analysis (IPCA) engine, the detection of neural spikes with poor SNR is possible while achieving 625× data reduction. For the TX, a dual-channel at 401 MHz and 403.8 MHz are supported by applying sequential injection locked techniques while attaining phase noise of -102 dBc/Hz at 100 kHz offset. From the measurement, error vector magnitude (EVM) of 4.60%/9.55% with power amplifier (PA) output power of -15 dBm is achieved for the QPSK at 8 Mbps and the BFSK at 12.5 kbps. Fabricated in 65 nm CMOS with an active area of 1 mm (2), the design consumes a total current of 5  ∼ 5.6 mA with a maximum energy efficiency of 0.7 nJ/b.

  2. Non-Sinusoidal Activity Can Produce Cross-Frequency Coupling in Cortical Signals in the Absence of Functional Interaction between Neural Sources

    PubMed Central

    Ward, Andrew; Knight, Robert T.; Deouell, Leon Y.

    2016-01-01

    The analysis of cross-frequency coupling (CFC) has become popular in studies involving intracranial and scalp EEG recordings in humans. It has been argued that some cases where CFC is mathematically present may not reflect an interaction of two distinct yet functionally coupled neural sources with different frequencies. Here we provide two empirical examples from intracranial recordings where CFC can be shown to be driven by the shape of a periodic waveform rather than by a functional interaction between distinct sources. Using simulations, we also present a generalized and realistic scenario where such coupling may arise. This scenario, which we term waveform-dependent CFC, arises when sharp waveforms (e.g., cortical potentials) occur throughout parts of the data, in particular if they occur rhythmically. Since the waveforms contain both low- and high-frequency components, these components can be inherently phase-aligned as long as the waveforms are spaced with appropriate intervals. We submit that such behavior of the data, which seems to be present in various cortical signals, cannot be interpreted as reflecting functional modulation between distinct neural sources without additional evidence. In addition, we show that even low amplitude periodic potentials that cannot be readily observed or controlled for, are sufficient for significant CFC to occur. PMID:27941990

  3. Notch signaling induces retinal stem-like properties in perinatal neural retina progenitors and promotes symmetric divisions in adult retinal stem cells.

    PubMed

    Balenci, Laurent; van der Kooy, Derek

    2014-02-01

    Understanding the mechanisms regulating retinal stem cell (RSC) activity is fundamental for future stem cell-based therapeutic purposes. By combining gain and loss of function approaches, we addressed whether Notch signaling may play a selective role in retinal stem versus retinal progenitor cells in both developing and adult eyes. Inhibition of either Notch or fibroblast growth factor signaling reduced proliferation of retinal stem and retinal progenitor cells, and inhibited RSC self-renewal. Conversely, exogenous Delta-like 3 and direct intrinsic Notch activation stimulated expansionary symmetric divisions in adult RSCs with the concomitant upregulation of Hes5. Knocking down Hes5 expression specifically decreased the numbers, but not the diameters, of adult RSC primary spheres, indicating that HES5 is the downstream effector of Notch receptor in controlling adult RSC proliferation. In addition, constitutive Notch activation induced retinal stem-like asymmetric self-renewal properties, with no expansion (no symmetrical division) in perinatal neural retina progenitor cells. These findings highlight central roles of Notch signaling activity in regulating the modes of division of retinal stem and retinal progenitor cells.

  4. Involvement of serotonin and oxytocin in neural mechanism regulating amicable social signal in male mice: Implication for impaired recognition of amicable cues in BALB/c strain.

    PubMed

    Arakawa, Hiroyuki

    2017-04-01

    Social signals play a primary role in regulating social relationships among male mice. The present series of experiments investigated the neural mechanisms underlying an induction of amicable cues that facilitate social approach in male mice of the C57BL/6 (B6) and BALB/c (BALB) strains. Male mice exhibit approach behavior and suppression of territorial scent marking toward amicable counterparts. Exposure of a group-housed mouse that maintains an amicable relationship induced social approach in B6 recipient mice, as expressed by increased preference of stay in proximity and decreased scent marks relevant to those of a single-housed mouse. Nasal administration of oxytocin (OT) to stimulus mice appeared to enhance social approach in B6 recipient mice. Systemic administration of buspirone (5-HT1A agonist) to stimulus mice also increased approach in B6 recipient mice, whereas a nasal OT antagonist infusion followed by systemic buspirone injection of stimulus mice blocked this buspirone-induced approach in B6 recipient mice. BALB mice likely possess an intact signaling system as shown in B6 mice, in which the 5-HT → OT pathway is a primary modulator for social amicable signals. However, BALB mice could not exhibit signal-dependent change in approach behavior. No impairment in olfactory discrimination or approach behavior toward social stimuli was found in BALB mice. It is concluded that social cues for facilitating social approach are eliminated via the 5-HT → OT pathway, and BALB mice as a low social strain have a deficit in recognition of specific signals associated with amicability. (PsycINFO Database Record

  5. Neural Mechanisms of Extinction Learning and Retrieval

    PubMed Central

    Quirk, Gregory J.; Mueller, Devin

    2009-01-01

    Emotional learning is necessary for individuals to survive and prosper. Once acquired, however, emotional associations are not always expressed. Indeed, the regulation of emotional expression under varying environmental conditions is essential for mental health. The simplest form of emotional regulation is extinction, in which conditioned responding to a stimulus decreases when the reinforcer is omitted. Two decades of research on the neural mechanisms of fear conditioning have laid the groundwork for understanding extinction. In this review, we summarize recent work on the neural mechanisms of extinction learning. Like other forms of learning, extinction occurs in three phases: acquisition, consolidation, and retrieval, each of which depends on specific structures (amygdala, prefrontal cortex, hippocampus), and molecular mechanisms (receptors and signaling pathways). Pharmacological methods to facilitate consolidation and retrieval of extinction, for both aversive and appetitive conditioning, are setting the stage for novel treatments for anxiety disorders and addictions. PMID:17882236

  6. Dysregulation of Wnt-Signaling and a Candidate Set of miRNAs Underlie the Effect of Metformin on Neural Crest Cell Development.

    PubMed

    Banerjee, Poulomi; Dutta, Sunit; Pal, Rajarshi

    2016-02-01

    Neural crest cells (NCC) are a population of epithelial cells that arise from the dorsal tube and undergo epithelial-mesenchymal transition (EMT) eventually generating tissues from peripheral nervous system, melanocytes, craniofacial cartilage, and bone. The antidiabetic drug metformin reportedly inhibits EMT in physiological conditions like cancer and fibrosis. We hypothesize that perturbation of EMT may also contribute to developmental disabilities associated with neural crest (NC) development. To understand the molecular network underlying metformin action during NC formation, we first differentiated murine embryonic stem (ES) cells into NCC and characterized them by demonstrating spatiotemporal regulation of key markers. Metformin treatment prompted a delay in delamination of NCC by inhibiting key markers like Sox-1, Sox-9, HNK-1, and p-75. We then revealed that metformin impedes Wnt axis, a major signaling pathway active during NC formation via DVL-3 inhibition and impairment in nuclear translocation of β-catenin. Concomitantly we identified and tested a candidate set of miRNAs that play a crucial role in NC cell fate determination. Further studies involving loss and gain of function confirmed that NCC specifiers like Sox-1 and Sox-9 are direct targets of miR-200 and miR-145, respectively and that they are essentially modulated by metformin. Our in vitro findings were strongly supported by in vivo studies in zebrafish. Given that metformin is a widely used drug, for the first time we demonstrate that it can induce a delayed onset of developmental EMT during NC formation by interfering with canonical Wnt signaling and mysregulation of miR-145 and miR-200.

  7. A Grey Box Neural Network Model of Basal Ganglia for Gait Signal of Patients with Huntington Disease

    PubMed Central

    Pourhedayat, Abbas; Sarbaz, Yashar

    2016-01-01

    Introduction: Huntington disease (HD) is a progressive neurodegenerative disease which affects movement control system of the brain. HD symptoms lead to patient’s gait change and influence stride time intervals. In this study, we present a grey box mathematical model to simulate HD disorders. This model contains main physiological findings about BG. Methods: We used artificial neural networks (ANN) and predetermined data to model healthy state behavior, and then we trained patients with HD with this model. All blocks and relations between them were designed based on physiological findings. Results: According to the physiological findings, increasing or decreasing model connection weights are indicative of change in secretion of respective neurotransmitters. Our results show the simulating ability of the model in normal condition and different disease stages. Conclusion: Fine similarity between the presented model and BG physiological structure with its high ability in simulating HD disorders, introduces this model as a powerful tool to analyze HD behavior. PMID:27303605

  8. Prediction of the Nighttime VLF Subionospheric Signal Amplitude by Using Nonlinear Autoregressive with Exogenous Input Neural Network Model

    NASA Astrophysics Data System (ADS)

    Santosa, H.; Hobara, Y.; Balikhin, M. A.

    2015-12-01

    Very Low Frequency (VLF) waves have been proposed as an approach to study and monitor the lower ionospheric conditions. The ionospheric perturbations are identified in relation with thunderstorm activity, geomagnetic storm and other factors. The temporal dependence of VLF amplitude has a complicated and large daily variabilities in general due to combinations of both effects from above (space weather effect) and below (atmospheric and crustal processes) of the ionosphere. Quantitative contributions from different external sources are not known well yet. Thus the modelling and prediction of VLF wave amplitude are important issues to study the lower ionospheric responses from various external parameters and to also detect the anomalies of the ionosphere. The purpose of the study is to model and predict nighttime average amplitude of VLF wave propagation from the VLF transmitter in Hawaii (NPM) to receiver in Chofu (CHO) Tokyo, Japan path using NARX neural network. The constructed model was trained for the target parameter of nighttime average amplitude of NPM-CHO path. The NARX model, which was built based on daily input variables of various physical parameters such as stratosphere temperature, cosmic rays and total column ozone, possessed good accuracies. As a result, the constructed models are capable of performing accurate multistep ahead predictions, while maintaining acceptable one step ahead prediction accuracy. The results of the predicted daily VLF amplitude are in good agreement with observed (true) value for one step ahead prediction (r = 0.92, RMSE = 1.99), multi-step ahead 5 days prediction (r = 0.91, RMSE = 1.14) and multi-step ahead 10 days prediction (r = 0.75, RMSE = 1.74). The developed model indicates the feasibility and reliability of predicting lower ionospheric properties by the NARX neural network approach, and provides physical insights on the responses of lower ionosphere due to various external forcing.

  9. Light-induced Notch activity controls neurogenic and gliogenic potential of neural progenitors.

    PubMed

    Kim, Kyung-Tai; Song, Mi-Ryoung

    2016-10-28

    Oscillations in Notch signaling are essential for reserving neural progenitors for cellular diversity in developing brains. Thus, steady and prolonged overactivation of Notch signaling is not suitable for generating neurons. To acquire greater temporal control of Notch activity and mimic endogenous oscillating signals, here we adopted a light-inducible transgene system to induce active form of Notch NICD in neural progenitors. Alternating Notch activity saved more progenitors that are prone to produce neurons creating larger number of mixed clones with neurons and progenitors in vitro, compared to groups with no light or continuous light stimulus. Furthermore, more upper layer neurons and astrocytes arose upon intermittent Notch activity, indicating that dynamic Notch activity maintains neural progeny and fine-tune neuron-glia diversity.

  10. EphrinB-EphB receptor signaling contributes to neuropathic pain by regulating neural excitability and spinal synaptic plasticity in rats.

    PubMed

    Song, Xue-Jun; Zheng, Ji-Hong; Cao, Jun-Li; Liu, Wen-Tao; Song, Xue-Song; Huang, Zhi-Jiang

    2008-09-30

    Bidirectional signaling between ephrins and Eph receptor tyrosine kinases was first found to play important roles during development, but recently has been implicated in synaptic plasticity and pain processing in the matured nervous system. We show that ephrinB-EphB receptor signaling plays a critical role is induction and maintenance of neuropathic pain by regulating neural excitability and synaptic plasticity in the dorsal root ganglion (DRG) and the spinal dorsal horn (DH). Intrathecal application of blocking reagents for EphB-receptors, EphB1-Fc and EphB2-Fc chimeras inhibits the induction and maintenance of nerve injury-induced thermal hyperalgesia and mechanical allodynia. These blockers also prevent and suppress the nerve injury-induced hyperexcitability of nociceptive small DRG neurons, sensitization of DH neurons and long-term potentiation (LTP) of synapses between C fibers and DH neurons. In naïve, uninjured animals intrathecal administration of EphB-receptor activators ephrinB1-Fc and ephrinB2-Fc, respectively, induces thermal hypersensitivity and lowers the threshold for LTP, while EphB1-Fc prevents induction of the LTP. Western Blot analysis shows that nerve injury triggers an upregulation of the ephrinB1 and EphB1 receptor proteins in DRG and the spinal cord. These results indicate that, by regulating excitability of nociceptive-related neurons in DRG and DH and the synaptic plasticity at the spinal level, ephrinB-EphB receptor signaling contributes to neuropathic pain. This novel role for ephrinB-EphB receptor signaling suggests that these molecules may be useful therapeutic targets for treating pain after nerve injury.

  11. Acquired Idiopathic Generalized Anhidrosis.

    PubMed

    Gangadharan, Geethu; Criton, Sebastian; Surendran, Divya

    2015-01-01

    Acquired idiopathic generalized anhidrosis is a rare condition, where the exact pathomechanism is unknown. We report a case of acquired idiopathic generalized anhidrosis in a patient who later developed lichen planus. Here an autoimmune-mediated destruction of sweat glands may be the probable pathomechanism.

  12. LABORATORY-ACQUIRED MYCOSES

    DTIC Science & Technology

    laboratory- acquired mycoses . Insofar as possible, the etiological fungus, type of laboratory, classification of personnel, type of work conducted, and other...pertinent data have been listed in this study. More than 288 laboratory- acquired mycoses are described here, including 108 cases of

  13. Effects of Nerve Injury and Segmental Regeneration on the Cellular Correlates of Neural Morphallaxis

    PubMed Central

    Martinez, Veronica G.; Manson, Josiah M.B.; Zoran, Mark J.

    2009-01-01

    Functional recovery of neural networks after injury requires a series of signaling events similar to the embryonic processes that governed initial network construction. Neural morphallaxis, a form of nervous system regeneration, involves reorganization of adult neural connectivity patterns. Neural morphallaxis in the worm, Lumbriculus variegatus, occurs during asexual reproduction and segmental regeneration, as body fragments acquire new positional identities along the anterior–posterior axis. Ectopic head (EH) formation, induced by ventral nerve cord lesion, generated morphallactic plasticity including the reorganization of interneuronal sensory fields and the induction of a molecular marker of neural morphallaxis. Morphallactic changes occurred only in segments posterior to an EH. Neither EH formation, nor neural morphallaxis was observed after dorsal body lesions, indicating a role for nerve cord injury in morphallaxis induction. Furthermore, a hierarchical system of neurobehavioral control was observed, where anterior heads were dominant and an EH controlled body movements only in the absence of the anterior head. Both suppression of segmental regeneration and blockade of asexual fission, after treatment with boric acid, disrupted the maintenance of neural morphallaxis, but did not block its induction. Therefore, segmental regeneration (i.e., epimorphosis) may not be required for the induction of morphallactic remodeling of neural networks. However, on-going epimorphosis appears necessary for the long-term consolidation of cellular and molecular mechanisms underlying the morphallaxis of neural circuitry. PMID:18561185

  14. Correlation of neural responses in the cochlear nucleus with low-frequency noise amplitude modulation of a tonal signal

    NASA Astrophysics Data System (ADS)

    Bibikov, N. G.

    2014-09-01

    The responses of single neurons of the cochlear nucleus of a grass frog to long tonal signals amplitude-modulated by repeat intervals of low-frequency noise have been studied. The carrier frequency always corresponded to the characteristic frequency of the studied cell (a range of 0.2 kHz-2 kHz); the modulated signal was noise in the ranges 0-15 Hz, 0-50 Hz, or 0-150 Hz. We obtained the correlation functions of the cyclic histogram reflecting the change in probability of a neuron pulse discharge (spike) during the modulation period with the shape of the signal envelope in the same period. The form of the obtained correlation functions usually does not change qualitatively with a change in carrier level or modulation depth; however, this could essentially depend of the frequency component of the modulating function. In the majority of cases, comparison of the cyclic histogram of the reaction with only the current amplitude value does not adequately reveal the signal's time features that determine the reaction of a neuron. The response is also determined by the other sound features, primarily by the rate of the change in amplitude. The studied neurons differed among themselves, both in preference toward a certain range of modulated frequencies and in the features of the envelope that caused the cell's response.

  15. Reproductive neuropeptides: prevalence of GnRH and KNDy neural signalling components in a model avian, gallus gallus.

    PubMed

    Joseph, Nerine T; Tello, Javier A; Bedecarrats, Gregoy Y; Millar, Robert P

    2013-09-01

    Diverse external and internal environmental factors are integrated in the hypothalamus to regulate the reproductive system. This is mediated through the pulsatile secretion of GnRH into the portal system to stimulate pituitary gonadotrophin secretion, which in turn regulates gonadal function. A single subpopulation of neurones termed 'KNDy neurones' located in the hypothalamic arcuate nucleus co-localise kisspeptin (Kiss), neurokinin B (NKB) and dynorphin (Dyn) and are responsive to negative feedback effects of sex steroids. The co-ordinated secretion from KNDy neurones appears to modulate the pulsatile release of GnRH, acting as a proximate pacemaker. This review briefly describes the neuropeptidergic control of reproduction in the avian class, highlighting the status of reproductive neuropeptide signalling systems homologous to those found in mammalian genomes. Genes encoding the GnRH system are complete in the chicken with similar roles to the mammalian counterparts, whereas genes encoding Kiss signalling components appear missing in the avian lineage, indicating a differing set of hypothalamic signals controlling avian reproduction. Gene sequences encoding both NKB and Dyn signalling components are present in the chicken genome, but expression analysis and functional studies remain to be completed. The focus of this article is to describe the avian complement of neuropeptidergic reproductive hormones and provide insights into the putative mechanisms that regulate reproduction in birds. These postulations highlight differences in reproductive strategies of birds in terms of gonadal steroid feedback systems, integration of metabolic signals and seasonality. Also included are propositions of KNDy neuropeptide gene silencing and plasticity in utilisation of these neuropeptides during avian evolution.

  16. Simultaneous measurement of neural spike recordings and multi-photon calcium imaging in neuroblastoma cells.

    PubMed

    Kim, Suhwan; Jung, Unsang; Baek, Juyeong; Kang, Shinwon; Kim, Jeehyun

    2012-11-08

    This paper proposes the design and implementation of a micro-electrode array (MEA) for neuroblastoma cell culturing. It also explains the implementation of a multi-photon microscope (MPM) customized for neuroblastoma cell excitation and imaging under ambient light. Electrical signal and fluorescence images were simultaneously acquired from the neuroblastoma cells on the MEA. MPM calcium images of the cultured neuroblastoma cell on the MEA are presented and also the neural activity was acquired through the MEA recording. A calcium green-1 (CG-1) dextran conjugate of 10,000 D molecular weight was used in this experiment for calcium imaging. This study also evaluated the calcium oscillations and neural spike recording of neuroblastoma cells in an epileptic condition. Based on our observation of neural spikes in neuroblastoma cells with our proposed imaging modality, we report that neuroblastoma cells can be an important model for epileptic activity studies.

  17. Regulated segregation of kinase Dyrk1A during asymmetric neural stem cell division is critical for EGFR-mediated biased signaling.

    PubMed

    Ferron, Sacri R; Pozo, Natividad; Laguna, Ariadna; Aranda, Sergi; Porlan, Eva; Moreno, Mireia; Fillat, Cristina; de la Luna, Susana; Sánchez, Pilar; Arbonés, María L; Fariñas, Isabel

    2010-09-03

    Stem cell division can result in two sibling cells exhibiting differential mitogenic and self-renewing potential. Here, we present evidence that the dual-specificity kinase Dyrk1A is part of a molecular pathway involved in the regulation of biased epidermal growth factor receptor (EGFR) signaling in the progeny of dividing neural stem cells (NSC) of the adult subependymal zone (SEZ). We show that EGFR asymmetry requires regulated sorting and that a normal Dyrk1a dosage is required to sustain EGFR in the two daughters of a symmetrically dividing progenitor. Dyrk1A is symmetrically or asymmetrically distributed during mitosis, and biochemical analyses indicate that it prevents endocytosis-mediated degradation of EGFR by a mechanism that requires phosphorylation of the EGFR signaling modulator Sprouty2. Finally, Dyrk1a heterozygous NSCs exhibit defects in self-renewal, EGF-dependent cell-fate decisions, and long-term persistence in vivo, suggesting that symmetrical divisions play a role in the maintenance of the SEZ reservoir.

  18. Analysis of Abnormal Intra-QRS Potentials in Signal-Averaged Electrocardiograms Using a Radial Basis Function Neural Network.

    PubMed

    Lin, Chun-Cheng

    2016-09-27

    Abnormal intra-QRS potentials (AIQPs) are commonly observed in patients at high risk for ventricular tachycardia. We present a method for approximating a measured QRS complex using a non-linear neural network with all radial basis functions having the same smoothness. We extracted the high frequency, but low amplitude intra-QRS potentials using the approximation error to identify possible ventricular tachycardia. With a specified number of neurons, we performed an orthogonal least squares algorithm to determine the center of each Gaussian radial basis function. We found that the AIQP estimation error arising from part of the normal QRS complex could cause clinicians to misjudge patients with ventricular tachycardia. Our results also show that it is possible to correct this misjudgment by combining multiple AIQP parameters estimated using various spread parameters and numbers of neurons. Clinical trials demonstrate that higher AIQP-to-QRS ratios in the X, Y and Z leads are visible in patients with ventricular tachycardia than in normal subjects. A linear combination of 60 AIQP-to-QRS ratios can achieve 100% specificity, 90% sensitivity, and 95.8% total prediction accuracy for diagnosing ventricular tachycardia.

  19. Different types of signal coupling in the visual cortex related to neural mechanisms of associative processing and perception.

    PubMed

    Eckhorn, Reinhard; Gail, Alexander M; Bruns, Andreas; Gabriel, Andreas; Al-Shaikhli, Basim; Saam, Mirko

    2004-09-01

    The hypothesis of object representation by synchronization in the visual cortex has been supported by our recent experiments in monkeys. They demonstrated local synchrony among gamma activities (30-90 Hz) and their perceptual modulation, according to the rules of figure-ground segregation. However, gamma-synchrony in primary visual cortex is restricted to few mm, challenging the synchronization hypothesis for larger cortical object representations. The restriction is due to randomly changing phase relations among locally synchronized patches which, however, form continuous waves of gamma-activity, traveling across object representations. The phase continuity of these waves may support coding of object continuity. Interactions across still larger distances, measured among cortical areas in human data, involve amplitude envelopes of gamma signals. Based on models with spiking neurons we discuss potentially underlying mechanisms. Most important for gamma synchronization are local facilitatory connections with distance-dependent delays. They also explain the occurrence of gamma waves and the restriction of gamma-synchrony. Fast local feedback inhibition generates gamma oscillations and supports local synchrony, while slow shunting inhibitory feedback supports figure-ground segregation. Finally, dispersion in inter-areal far projections destroys coherence of gamma signals, but preserves their amplitude modulations. In conclusion, we propose that the hypothesis of associative processing by gamma synchronization be extended to more general forms of signal coupling.

  20. Control of Neural Daughter Cell Proliferation by Multi-level Notch/Su(H)/E(spl)-HLH Signaling

    PubMed Central

    Bivik, Caroline; MacDonald, Ryan B.; Gunnar, Erika; Mazouni, Khalil; Schweisguth, Francois; Thor, Stefan

    2016-01-01

    The Notch pathway controls proliferation during development and in adulthood, and is frequently affected in many disorders. However, the genetic sensitivity and multi-layered transcriptional properties of the Notch pathway has made its molecular decoding challenging. Here, we address the complexity of Notch signaling with respect to proliferation, using the developing Drosophila CNS as model. We find that a Notch/Su(H)/E(spl)-HLH cascade specifically controls daughter, but not progenitor proliferation. Additionally, we find that different E(spl)-HLH genes are required in different neuroblast lineages. The Notch/Su(H)/E(spl)-HLH cascade alters daughter proliferation by regulating four key cell cycle factors: Cyclin E, String/Cdc25, E2f and Dacapo (mammalian p21CIP1/p27KIP1/p57Kip2). ChIP and DamID analysis of Su(H) and E(spl)-HLH indicates direct transcriptional regulation of the cell cycle genes, and of the Notch pathway itself. These results point to a multi-level signaling model and may help shed light on the dichotomous proliferative role of Notch signaling in many other systems. PMID:27070787

  1. Regulation of self-renewing neural progenitors by FGF/ERK signaling controls formation of the inferior colliculus.

    PubMed

    Dee, Alexander; Li, Kairong; Heng, Xin; Guo, Qiuxia; Li, James Y H

    2016-10-15

    The embryonic tectum displays an anteroposterior gradient in development and produces the superior colliculus and inferior colliculus. Studies suggest that partition of the tectum is controlled by different strengths and durations of FGF signals originated from the so-called isthmic organizer at the mid/hindbrain junction; however, the underlying mechanism is unclear. We show that deleting Ptpn11, which links FGF with the ERK pathway, prevents inferior colliculus formation by depleting a previously uncharacterized stem cell zone. The stem-zone loss is attributed to shortening of S phase and acceleration of cell cycle exit and neurogenesis. Expression of a constitutively active Mek1 (Mek1(DD)), the known ERK activator, restores the tectal stem zone and the inferior colliculus without Ptpn11. By contrast, Mek1(DD) expression fails to rescue the tectal stem zone and the inferior colliculus in the absence of Fgf8 and the isthmic organizer, indicating that FGF and Mek1(DD) initiate qualitatively and/or quantitatively distinctive signaling. Together, our data show that the formation of the inferior colliculus relies on the provision of new cells from the tectal stem zone. Furthermore, distinctive ERK signaling mediates Fgf8 in the control of cell survival, tissue polarity and cytogenetic gradient during the development of the tectum.

  2. Acquired inflammatory demyelinating neuropathies.

    PubMed

    Ensrud, E R; Krivickas, L S

    2001-05-01

    The acquired demyelinating neuropathies can be divided into those with an acute onset and course and those with a more chronic course. The acute neuropathies present as Guillain-Barré syndrome and include acute inflammatory demyelinating polyradiculoneuropathy (AIDP), Miller Fisher syndrome, acute motor axonal neuropathy (AMAN), acute motor and sensory axonal neuropathy (AMSAN), and acute pandysautonomia. The chronic neuropathies are collectively known as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and include MADSAM (multifocal acquired demyelinating sensory and motor neuropathy, also know as Lewis-Sumner syndrome) and DADS (distal acquired demyelinating symmetric neuropathy) as variants. The clinical features, pathology, pathogenesis, diagnosis, treatment, rehabilitation, and prognosis of these neuropathies are discussed.

  3. Neural Cell Adhesion Molecule-Associated Polysialic Acid Regulates Synaptic Plasticity and Learning by Restraining the Signaling through GluN2B-Containing NMDA Receptors

    PubMed Central

    Kochlamazashvili, Gaga; Senkov, Oleg; Grebenyuk, Sergei; Robinson, Catrina; Xiao, Mei-Fang; Stummeyer, Katharina; Gerardy-Schahn, Rita; Engel, Andreas K.; Feig, Larry; Semyanov, Alexey; Suppiramaniam, Vishnu; Schachner, Melitta; Dityatev, Alexander

    2017-01-01

    The neural cell adhesion molecule (NCAM) is the predominant carrier of α2,8 polysialic acid (PSA) in the mammalian brain. Abnormalities in PSA and NCAM expression are associated with schizophrenia in humans and cause deficits in hippocampal synaptic plasticity and contextual fear conditioning in mice. Here, we show that PSA inhibits opening of recombinant NMDA receptors composed of GluN1/2B (NR1/NR2B) or GluN1/2A/2B (NR1/NR2A/NR2B) but not of GluN1/2A (NR1/NR2A) subunits. Deficits in NCAM/PSA increase GluN2B-mediated transmission and Ca2+ transients in the CA1 region of the hippocampus. In line with elevation of GluN2B-mediated transmission, defects in long-term potentiation in the CA1 region and contextual fear memory in NCAM/PSA-deficient mice are abrogated by application of a GluN2B-selective antagonist. Furthermore, treatment with the glutamate scavenger glutamic-pyruvic transaminase, ablation of Ras-GRF1 (a mediator of GluN2B signaling to p38 MAPK), or direct inhibition of hyperactive p38 MAPK can restore impaired synaptic plasticity in brain slices lacking PSA/NCAM. Thus, PSA carried by NCAM regulates plasticity and learning by inhibition of the GluN2B-Ras-GRF1-p38 MAPK signaling pathway. These findings implicate carbohydrates carried by adhesion molecules in modulating NMDA receptor signaling in the brain and demonstrate reversibility of cognitive deficits associated with ablation of a schizophrenia-related adhesion molecule. PMID:20237287

  4. Persistent Wnt/β-catenin signaling determines dorsalization of the postnatal subventricular zone and neural stem cell specification into oligodendrocytes and glutamatergic neurons.

    PubMed

    Azim, Kasum; Fischer, Bruno; Hurtado-Chong, Anahi; Draganova, Kalina; Cantù, Claudio; Zemke, Martina; Sommer, Lukas; Butt, Arthur; Raineteau, Olivier

    2014-05-01

    In the postnatal and adult central nervous system (CNS), the subventricular zone (SVZ) of the forebrain is the main source of neural stem cells (NSCs) that generate olfactory neurons and oligodendrocytes (OLs), the myelinating cells of the CNS. Here, we provide evidence of a primary role for canonical Wnt/β-catenin signaling in regulating NSC fate along neuronal and oligodendroglial lineages in the postnatal SVZ. Our findings demonstrate that glutamatergic neuronal precursors (NPs) and oligodendrocyte precursors (OPs) are derived strictly from the dorsal SVZ (dSVZ) microdomain under the control of Wnt/β-catenin, whereas GABAergic NPs are derived mainly from the lateral SVZ (lSVZ) microdomain independent of Wnt/β-catenin. Transcript analysis of microdissected SVZ microdomains revealed that canonical Wnt/β-catenin signaling was more pronounced in the dSVZ microdomain. This was confirmed using the β-catenin-activated Wnt-reporter mouse and by pharmacological stimulation of Wnt/β-catenin by infusion of the specific glycogen synthase kinase 3β inhibitor, AR-A014418, which profoundly increased the generation of cycling cells. In vivo genetic/pharmacological stimulation or inhibition of Wnt/β-catenin, respectively, increased and decreased the differentiation of dSVZ-NSCs into glutamatergic NPs, and had a converse effect on GABAergic NPs. Activation of Wnt/β-catenin dramatically stimulated the generation of OPs, but its inhibition had no effect, indicating other factors act in concert with Wnt/β-catenin to fine tune oligodendrogliogenesis in the postnatal dSVZ. These results demonstrate a role for Wnt/β-catenin signaling within the dorsal microdomain of the postnatal SVZ, in regulating the genesis of glutamatergic neurons and OLs.

  5. Large-scale multielectrode recording and stimulation of neural activity

    NASA Astrophysics Data System (ADS)

    Sher, A.; Chichilnisky, E. J.; Dabrowski, W.; Grillo, A. A.; Grivich, M.; Gunning, D.; Hottowy, P.; Kachiguine, S.; Litke, A. M.; Mathieson, K.; Petrusca, D.

    2007-09-01

    Large circuits of neurons are employed by the brain to encode and process information. How this encoding and processing is carried out is one of the central questions in neuroscience. Since individual neurons communicate with each other through electrical signals (action potentials), the recording of neural activity with arrays of extracellular electrodes is uniquely suited for the investigation of this question. Such recordings provide the combination of the best spatial (individual neurons) and temporal (individual action-potentials) resolutions compared to other large-scale imaging methods. Electrical stimulation of neural activity in turn has two very important applications: it enhances our understanding of neural circuits by allowing active interactions with them, and it is a basis for a large variety of neural prosthetic devices. Until recently, the state-of-the-art in neural activity recording systems consisted of several dozen electrodes with inter-electrode spacing ranging from tens to hundreds of microns. Using silicon microstrip detector expertise acquired in the field of high-energy physics, we created a unique neural activity readout and stimulation framework that consists of high-density electrode arrays, multi-channel custom-designed integrated circuits, a data acquisition system, and data-processing software. Using this framework we developed a number of neural readout and stimulation systems: (1) a 512-electrode system for recording the simultaneous activity of as many as hundreds of neurons, (2) a 61-electrode system for electrical stimulation and readout of neural activity in retinas and brain-tissue slices, and (3) a system with telemetry capabilities for recording neural activity in the intact brain of awake, naturally behaving animals. We will report on these systems, their various applications to the field of neurobiology, and novel scientific results obtained with some of them. We will also outline future directions.

  6. Acquired color vision deficiency.

    PubMed

    Simunovic, Matthew P

    2016-01-01

    Acquired color vision deficiency occurs as the result of ocular, neurologic, or systemic disease. A wide array of conditions may affect color vision, ranging from diseases of the ocular media through to pathology of the visual cortex. Traditionally, acquired color vision deficiency is considered a separate entity from congenital color vision deficiency, although emerging clinical and molecular genetic data would suggest a degree of overlap. We review the pathophysiology of acquired color vision deficiency, the data on its prevalence, theories for the preponderance of acquired S-mechanism (or tritan) deficiency, and discuss tests of color vision. We also briefly review the types of color vision deficiencies encountered in ocular disease, with an emphasis placed on larger or more detailed clinical investigations.

  7. Altered neural signaling and immune pathways in peripheral blood mononuclear cells of schizophrenia patients with cognitive impairment: A transcriptome analysis.

    PubMed

    Wu, Jing Qin; Green, Melissa J; Gardiner, Erin J; Tooney, Paul A; Scott, Rodney J; Carr, Vaughan J; Cairns, Murray J

    2016-03-01

    Cognitive deficits are a core feature of schizophrenia and contribute significantly to functional disability. We investigated the molecular pathways associated with schizophrenia (SZ; n=47) cases representing both 'cognitive deficit' (CD; n=22) and 'cognitively spared' (CS; n=25) subtypes of schizophrenia (based on latent class analysis of 9 cognitive performance indicators), compared with 49 healthy controls displaying 'normal' cognition. This was accomplished using gene-set analysis of transcriptome data derived from peripheral blood mononuclear cells (PBMCs). We detected 27 significantly altered pathways (19 pathways up-regulated and 8 down-regulated) in the combined SZ group and a further 6 pathways up-regulated in the CS group and 5 altered pathways (4 down-regulated and 1 up-regulated) in the CD group. The transcriptome profiling in SZ and cognitive subtypes were characterized by the up-regulated pathways involved in immune dysfunction (e.g., antigen presentation in SZ), energy metabolism (e.g., oxidative phosphorylation), and down-regulation of the pathways involved in neuronal signaling (e.g., WNT in SZ/CD and ERBB in SZ). When we looked for pathways that differentiated the two cognitive subtypes we found that the WNT signaling was significantly down-regulated (FDR<0.05) in the CD group in accordance with the combined SZ cohort, whereas it was unaffected in the CS group. This suggested suppression of WNT signaling was a defining feature of cognitive decline in schizophrenia. The WNT pathway plays a role in both the development/function of the central nervous system and peripheral tissues, therefore its alteration in PBMCs may be indicative of an important genomic axis relevant to cognition in the neuropathology of schizophrenia.

  8. Phase Detection Using Neural Networks.

    DTIC Science & Technology

    1997-03-10

    A likelihood of detecting a reflected signal characterized by phase discontinuities and background noise is enhanced by utilizing neural networks to...identify coherency intervals. The received signal is processed into a predetermined format such as a digital time series. Neural networks perform

  9. Visual threshold is set by linear and nonlinear mechanisms in the retina that mitigate noise: how neural circuits in the retina improve the signal-to-noise ratio of the single-photon response.

    PubMed

    Pahlberg, Johan; Sampath, Alapakkam P

    2011-06-01

    In sensory biology, a major outstanding question is how sensory receptor cells minimize noise while maximizing signal to set the detection threshold. This optimization could be problematic because the origin of both the signals and the limiting noise in most sensory systems is believed to lie in stimulus transduction. Signal processing in receptor cells can improve the signal-to-noise ratio. However, neural circuits can further optimize the detection threshold by pooling signals from sensory receptor cells and processing them using a combination of linear and nonlinear filtering mechanisms. In the visual system, noise limiting light detection has been assumed to arise from stimulus transduction in rod photoreceptors. In this context, the evolutionary optimization of the signal-to-noise ratio in the retina has proven critical in allowing visual sensitivity to approach the limits set by the quantal nature of light. Here, we discuss how noise in the mammalian retina is mitigated to allow for highly sensitive night vision.

  10. The retinoic acid signaling pathway regulates anterior/posterior patterning in the nerve cord and pharynx of amphioxus, a chordate lacking neural crest

    NASA Technical Reports Server (NTRS)

    Escriva, Hector; Holland, Nicholas D.; Gronemeyer, Hinrich; Laudet, Vincent; Holland, Linda Z.

    2002-01-01

    Amphioxus, the closest living invertebrate relative of the vertebrates, has a notochord, segmental axial musculature, pharyngeal gill slits and dorsal hollow nerve cord, but lacks neural crest. In amphioxus, as in vertebrates, exogenous retinoic acid (RA) posteriorizes the embryo. The mouth and gill slits never form, AmphiPax1, which is normally downregulated where gill slits form, remains upregulated and AmphiHox1 expression shifts anteriorly in the nerve cord. To dissect the role of RA signaling in patterning chordate embryos, we have cloned the single retinoic acid receptor (AmphiRAR), retinoid X receptor (AmphiRXR) and an orphan receptor (AmphiTR2/4) from amphioxus. AmphiTR2/4 inhibits AmphiRAR-AmphiRXR-mediated transactivation in the presence of RA by competing for DR5 or IR7 retinoic acid response elements (RAREs). The 5' untranslated region of AmphiTR2/4 contains an IR7 element, suggesting possible auto- and RA-regulation. The patterns of AmphiTR2/4 and AmphiRAR expression during embryogenesis are largely complementary: AmphiTR2/4 is strongly expressed in the cerebral vesicle (homologous to the diencephalon plus anterior midbrain), while AmphiRAR expression is high in the equivalent of the hindbrain and spinal cord. Similarly, while AmphiTR2/4 is expressed most strongly in the anterior and posterior thirds of the endoderm, the highest AmphiRAR expression is in the middle third. Expression of AmphiRAR is upregulated by exogenous RA and completely downregulated by the RA antagonist BMS009. Moreover, BMS009 expands the pharynx posteriorly; the first three gill slit primordia are elongated and shifted posteriorly, but do not penetrate, and additional, non-penetrating gill slit primordia are induced. Thus, in an organism without neural crest, initiation and penetration of gill slits appear to be separate events mediated by distinct levels of RA signaling in the pharyngeal endoderm. Although these compounds have little effect on levels of AmphiTR2/4 expression, RA

  11. The impact of command signal power distribution, processing delays, and speed scaling on neurally-controlled devices

    NASA Astrophysics Data System (ADS)

    Marathe, A. R.; Taylor, D. M.

    2015-08-01

    Objective. Decoding algorithms for brain-machine interfacing (BMI) are typically only optimized to reduce the magnitude of decoding errors. Our goal was to systematically quantify how four characteristics of BMI command signals impact closed-loop performance: (1) error magnitude, (2) distribution of different frequency components in the decoding errors, (3) processing delays, and (4) command gain. Approach. To systematically evaluate these different command features and their interactions, we used a closed-loop BMI simulator where human subjects used their own wrist movements to command the motion of a cursor to targets on a computer screen. Random noise with three different power distributions and four different relative magnitudes was added to the ongoing cursor motion in real time to simulate imperfect decoding. These error characteristics were tested with four different visual feedback delays and two velocity gains. Main results. Participants had significantly more trouble correcting for errors with a larger proportion of low-frequency, slow-time-varying components than they did with jittery, higher-frequency errors, even when the error magnitudes were equivalent. When errors were present, a movement delay often increased the time needed to complete the movement by an order of magnitude more than the delay itself. Scaling down the overall speed of the velocity command can actually speed up target acquisition time when low-frequency errors and delays are present. Significance. This study is the first to systematically evaluate how the combination of these four key command signal features (including the relatively-unexplored error power distribution) and their interactions impact closed-loop performance independent of any specific decoding method. The equations we derive relating closed-loop movement performance to these command characteristics can provide guidance on how best to balance these different factors when designing BMI systems. The equations reported

  12. Radio frequency interference mitigation using deep convolutional neural networks

    NASA Astrophysics Data System (ADS)

    Akeret, J.; Chang, C.; Lucchi, A.; Refregier, A.

    2017-01-01

    We propose a novel approach for mitigating radio frequency interference (RFI) signals in radio data using the latest advances in deep learning. We employ a special type of Convolutional Neural Network, the U-Net, that enables the classification of clean signal and RFI signatures in 2D time-ordered data acquired from a radio telescope. We train and assess the performance of this network using the HIDE &SEEK radio data simulation and processing packages, as well as early Science Verification data acquired with the 7m single-dish telescope at the Bleien Observatory. We find that our U-Net implementation is showing competitive accuracy to classical RFI mitigation algorithms such as SEEK's SUMTHRESHOLD implementation. We publish our U-Net software package on GitHub under GPLv3 license.

  13. Automatic welding quality classification for the spot welding based on the Hopfield associative memory neural network and Chernoff face description of the electrode displacement signal features

    NASA Astrophysics Data System (ADS)

    Zhang, Hongjie; Hou, Yanyan; Zhao, Jian; Wang, Lijing; Xi, Tao; Li, Yafeng

    2017-02-01

    To develop an automatic welding quality classification method for the spot welding based on the Chernoff face image created by the electrode displacement signal features, an effective pattern feature extraction method was proposed by which the Chernoff face images were converted to binary ones, and each binary image could be characterized by a binary matrix. According to expression categories on the Chernoff face images, welding quality was classified into five levels and each level just corresponded to a kind of expression. The Hopfield associative memory neural network was used to build a welding quality classifier in which the pattern feature matrices of some weld samples with different welding quality levels were remembered as the stable states. When the pattern feature matrix of a test weld is input into the classifier, it can be converged to the most similar stable state through associative memory, thus, welding quality corresponding to this finally locked stable state can represent the welding quality of the test weld. The classification performance test results show that the proposed method significantly improves the applicability and efficiency of the Chernoff faces technique for spot welding quality evaluation and it is feasible, effective and reliable.

  14. Intracellular signaling is changed after clustering of the neural cell adhesion molecules axonin-1 and NgCAM during neurite fasciculation

    PubMed Central

    1996-01-01

    Neural cell adhesion molecules of the immunoglobulin/fibronectin type III family on axons have been implicated in promotion of neurite outgrowth, fasciculation, and the mediation of specific cell adhesion. The present study demonstrates that two of these molecules on dorsal root ganglion neurons are associated with distinct protein kinases, axonin-1 with the src-related nonreceptor tyrosine kinase fyn and NgCAM with a casein kinase II-related activity and a serine/ threonine kinase related to S6 kinase. When neurites grew without contacts involving axonin-1 and NgCAM, strong fyn kinase activity was associated with axonin-1, whereas the NgCAM-associated kinase activities were low. Clustering of axonin-1 with NgCAM induced by the formation of cell-cell contacts correlated with a reduction of the axonin-1-associated fyn activity and an increased phosphorylation of NgCAM by the associated casein kinase II-related activity. Thus, axonin-1 and NgCAM trigger distinctive intracellular signals during in vitro differentiation depending on their state of association. PMID:8858178

  15. TGF-β mediated FGF10 signaling in cranial neural crest cells controls development of myogenic progenitor cells through tissue-tissue interactions during tongue morphogenesis

    PubMed Central

    Hosokawa, Ryoichi; Oka, Kyoko; Yamaza, Takayoshi; Iwata, Junichi; Urata, Mark; Xu, Xun; Bringas, Pablo; Nonaka, Kazuaki; Chai, Yang

    2012-01-01

    Skeletal muscles are formed from two cell lineages, myogenic and fibroblastic. Mesoderm-derived myogenic progenitors form muscle cells whereas fibroblastic cells give rise to the supportive connective tissue of skeletal muscles, such as the tendons and perimysium. It remains unknown how myogenic and fibroblastic cell-cell interactions affect cell fate determination and the organization of skeletal muscle. In the present study, we investigated the functional significance of cell-cell interactions in regulating skeletal muscle development. Our study shows that cranial neural crest (CNC) cells give rise to the fibroblastic cells of the tongue skeletal muscle in mice. Loss of Tgfbr2 in CNC cells (Wnt1-Cre;Tgfbr2flox/flox) results in microglossia with reduced Scleraxis and Fgf10 expression as well as decreased myogenic cell proliferation, reduced cell number and disorganized tongue muscles. Furthermore, TGF-β2 beads induced the expression of Scleraxis in tongue explant cultures. The addition of FGF10 rescued the muscle cell number in Wnt1-Cre;Tgfbr2flox/flox mice. Thus, TGF-β induced FGF10 signaling has a critical function in regulating tissue-tissue interaction during tongue skeletal muscle development. PMID:20193675

  16. Neural encoding of psychomotor activation in the nucleus accumbens core, but not the shell, requires cannabinoid receptor signaling

    PubMed Central

    Morra, Joshua T.; Glick, Stanley D.; Cheer, Joseph F.

    2010-01-01

    The current study aimed to further elucidate the role of endocannabinoid signaling in methamphetamine-induced psychomotor activation. Rats were treated with bilateral, intracranial microinjections of the cannabinoid CB1 receptor antagonists rimonabant (1 μg; 1 μl) or AM251 (1 μg; 1 μl), or vehicle (1 μl), followed by intravenous methamphetamine (3 mg/kg). Antagonist pretreatment in the nucleus accumbens core, but not shell, attenuated methamphetamine-induced stereotypy, while treatment in either brain region had no effect on drug-induced locomotion. In a parallel experiment, we recorded multiple single-units in the nucleus accumbens of behaving rats treated with intravenous rimonabant (0.3 mg/kg) or vehicle, followed by methamphetamine (0.01, 0.1, 1, 3 mg/kg; cumulative dosing). We observed robust, phasic changes in neuronal firing time-locked to the onset of methamphetamine-induced locomotion and stereotypy. Stereotypy encoding was observed in the core and was attenuated by CB1 receptor antagonism, while locomotor correlates were observed uniformly across the accumbens and were not affected by rimonabant. Psychomotor activation encoding was expressed predominantly by putative fast-spiking interneurons. We therefore propose that endocannabinoid modulation of psychomotor activation is preferentially driven by CB1 receptor-dependent interneuron activity in the nucleus accumbens core. PMID:20371830

  17. Dopamine-Signaled Reward Predictions Generated by Competitive Excitation and Inhibition in a Spiking Neural Network Model

    PubMed Central

    Chorley, Paul; Seth, Anil K.

    2011-01-01

    Dopaminergic neurons in the mammalian substantia nigra display characteristic phasic responses to stimuli which reliably predict the receipt of primary rewards. These responses have been suggested to encode reward prediction-errors similar to those used in reinforcement learning. Here, we propose a model of dopaminergic activity in which prediction-error signals are generated by the joint action of short-latency excitation and long-latency inhibition, in a network undergoing dopaminergic neuromodulation of both spike-timing dependent synaptic plasticity and neuronal excitability. In contrast to previous models, sensitivity to recent events is maintained by the selective modification of specific striatal synapses, efferent to cortical neurons exhibiting stimulus-specific, temporally extended activity patterns. Our model shows, in the presence of significant background activity, (i) a shift in dopaminergic response from reward to reward-predicting stimuli, (ii) preservation of a response to unexpected rewards, and (iii) a precisely timed below-baseline dip in activity observed when expected rewards are omitted. PMID:21629770

  18. Acquired hypofibrinogenemia: current perspectives