Learning with Precise Spike Times: A New Decoding Algorithm for Liquid State Machines.

There is extensive evidence that biological neural networks encode information in the precise timing of the spikes generated and transmitted by neurons, which offers several advantages over rate-based codes. Here we adopt a vector space formulation of spike train sequences and introduce a new liquid state machine (LSM) network architecture and a new forward orthogonal regression algorithm to learn an input-output signal mapping or to decode the brain activity. The proposed algorithm uses precise spike timing to select the presynaptic neurons relevant to each learning task. We show that using precise spike timing to train the LSM and selecting the readout presynaptic neurons leads to a significant increase in performance on binary classification tasks, in decoding neural activity from multielectrode array recordings, as well as in a speech recognition task, compared with what is achieved using the standard architecture and training methods.

Analysing the performance of low-cost air quality sensors, their drivers, relative benefits and calibration in cities-a case study in Sheffield.

Traditional real-time air quality monitoring instruments are expensive to install and maintain; therefore, such existing air quality monitoring networks are sparsely deployed and lack the measurement density to develop high-resolution spatiotemporal air pollutant maps. More recently, low-cost sensors have been used to collect high-resolution spatial and temporal air pollution data in real-time. In this paper, for the first time, Envirowatch E-MOTEs are employed for air quality monitoring as a case study in Sheffield. Ten E-MOTEs were deployed for a year (October 2016 to September 2017) monitoring several air pollutants (NO, NO2, CO) and meteorological parameters. Their performance was compared to each other and to a reference instrument installed nearby. E-MOTEs were able to successfully capture the temporal variability such as diurnal, weekly and annual cycles in air pollutant concentrations and demonstrated significant similarity with reference instruments. NO2 concentrations showed very strong positive correlation between various sensors. Mostly, correlation coefficients (r values) were greater than 0.92. CO from different sensors also had r values mostly greater than 0.92; however, NO showed r value less than 0.5. Furthermore, several multiple linear regression models (MLRM) and generalised additive models (GAM) were developed to calibrate the E-MOTE data and reproduce NO and NO2 concentrations measured by the reference instruments. GAMs demonstrated significantly better performance than linear models by capturing the non-linear association between the response and explanatory variables. The best GAM developed for reproducing NO2 concentrations returned values of 0.95, 3.91, 0.81, 0.005 and 0.61 for factor of two (FAC2), root mean square error (RMSE), coefficient of determination (R2), normalised mean biased (NMB) and coefficient of efficiency (COE), respectively. The low-cost sensors offer a more affordable alternative for providing real-time high-resolution spatiotemporal air quality and meteorological parameter data with acceptable performance.

Identification of Linear and Nonlinear Sensory Processing Circuits from Spiking Neuron Data.

Inferring mathematical models of sensory processing systems directly from input-output observations, while making the fewest assumptions about the model equations and the types of measurements available, is still a major issue in computational neuroscience. This letter introduces two new approaches for identifying sensory circuit models consisting of linear and nonlinear filters in series with spiking neuron models, based only on the sampled analog input to the filter and the recorded spike train output of the spiking neuron. For an ideal integrate-and-fire neuron model, the first algorithm can identify the spiking neuron parameters as well as the structure and parameters of an arbitrary nonlinear filter connected to it. The second algorithm can identify the parameters of the more general leaky integrate-and-fire spiking neuron model, as well as the parameters of an arbitrary linear filter connected to it. Numerical studies involving simulated and real experimental recordings are used to demonstrate the applicability and evaluate the performance of the proposed algorithms.

A matrix-based approach to solving the inverse Frobenius-Perron problem using sequences of density functions of stochastically perturbed dynamical systems.

The paper introduces a matrix-based approach to estimate the unique one-dimensional discrete-time dynamical system that generated a given sequence of probability density functions whilst subjected to an additive stochastic perturbation with known density.

A Novel Reconstruction Framework for Time-Encoded Signals with Integrate-and-Fire Neurons.

Integrate-and-fire neurons are time encoding machines that convert the amplitude of an analog signal into a nonuniform, strictly increasing sequence of spike times. Under certain conditions, the encoded signals can be reconstructed from the nonuniform spike time sequences using a time decoding machine. Time encoding and time decoding methods have been studied using the nonuniform sampling theory for band-limited spaces, as well as for generic shift-invariant spaces. This letter proposes a new framework for studying IF time encoding and decoding by reformulating the IF time encoding problem as a uniform sampling problem. This framework forms the basis for two new algorithms for reconstructing signals from spike time sequences. We demonstrate that the proposed reconstruction algorithms are faster, and thus better suited for real-time processing, while providing a similar level of accuracy, compared to the standard reconstruction algorithm.

Aging-related defects in macrophage function are driven by MYC and USF1 transcriptional programs.

Macrophages are central innate immune cells whose function declines with age. The molecular mechanisms underlying age-related changes remain poorly understood, particularly in human macrophages. We report a substantial reduction in phagocytosis, migration, and chemotaxis in human monocyte-derived macrophages (MDMs) from older (>50 years old) compared with younger (18-30 years old) donors, alongside downregulation of transcription factors MYC and USF1. In MDMs from young donors, knockdown of MYC or USF1 decreases phagocytosis and chemotaxis and alters the expression of associated genes, alongside adhesion and extracellular matrix remodeling. A concordant dysregulation of MYC and USF1 target genes is also seen in MDMs from older donors. Furthermore, older age and loss of either MYC or USF1 in MDMs leads to an increased cell size, altered morphology, and reduced actin content. Together, these results define MYC and USF1 as key drivers of MDM age-related functional decline and identify downstream targets to improve macrophage function in aging.

A dynamic model of neurovascular coupling: implications for blood vessel dilation and constriction.

Neurovascular coupling in response to stimulation of the rat barrel cortex was investigated using concurrent multichannel electrophysiology and laser Doppler flowmetry. The data were used to build a linear dynamic model relating neural activity to blood flow. Local field potential time series were subject to current source density analysis, and the time series of a layer IV sink of the barrel cortex was used as the input to the model. The model output was the time series of the changes in regional cerebral blood flow (CBF). We show that this model can provide excellent fit of the CBF responses for stimulus durations of up to 16 s. The structure of the model consisted of two coupled components representing vascular dilation and constriction. The complex temporal characteristics of the CBF time series were reproduced by the relatively simple balance of these two components. We show that the impulse response obtained under the 16-s duration stimulation condition generalised to provide a good prediction to the data from the shorter duration stimulation conditions. Furthermore, by optimising three out of the total of nine model parameters, the variability in the data can be well accounted for over a wide range of stimulus conditions. By establishing linearity, classic system analysis methods can be used to generate and explore a range of equivalent model structures (e.g., feed-forward or feedback) to guide the experimental investigation of the control of vascular dilation and constriction following stimulation.

Modified variational Bayes EM estimation of hidden Markov tree model of cell lineages.

MOTIVATION: Human pluripotent stem cell lines persist in culture as a heterogeneous population of SSEA3 positive and SSEA3 negative cells. Tracking individual stem cells in real time can elucidate the kinetics of cells switching between the SSEA3 positive and negative substates. However, identifying a cell's substate at all time points within a cell lineage tree is technically difficult. RESULTS: A variational Bayesian Expectation Maximization (EM) with smoothed probabilities (VBEMS) algorithm for hidden Markov trees (HMT) is proposed for incomplete tree structured data. The full posterior of the HMT parameters is determined and the underflow problems associated with previous algorithms are eliminated. Example results for the prediction of the types of cells in synthetic and real stem cell lineage trees are presented. AVAILABILITY: The Matlab code for the VBEMS algorithm is freely available at http://www.acse.dept.shef.ac.uk/repository/vbems_lineage_tree/VBEMS.ZIP CONTACT: visakan@sheffield.ac.uk SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

High-performance hardware implementation of a parallel database search engine for real-time peptide mass fingerprinting.

MOTIVATION: Peptide mass fingerprinting (PMF) is a method for protein identification in which a protein is fragmented by a defined cleavage protocol (usually proteolysis with trypsin), and the masses of these products constitute a 'fingerprint' that can be searched against theoretical fingerprints of all known proteins. In the first stage of PMF, the raw mass spectrometric data are processed to generate a peptide mass list. In the second stage this protein fingerprint is used to search a database of known proteins for the best protein match. Although current software solutions can typically deliver a match in a relatively short time, a system that can find a match in real time could change the way in which PMF is deployed and presented. In a paper published earlier we presented a hardware design of a raw mass spectra processor that, when implemented in Field Programmable Gate Array (FPGA) hardware, achieves almost 170-fold speed gain relative to a conventional software implementation running on a dual processor server. In this article we present a complementary hardware realization of a parallel database search engine that, when running on a Xilinx Virtex 2 FPGA at 100 MHz, delivers 1800-fold speed-up compared with an equivalent C software routine, running on a 3.06 GHz Xeon workstation. The inherent scalability of the design means that processing speed can be multiplied by deploying the design on multiple FPGAs. The database search processor and the mass spectra processor, running on a reconfigurable computing platform, provide a complete real-time PMF protein identification solution.

Communication Sparsity in Distributed Spiking Neural Network Simulations to Improve Scalability.

In the last decade there has been a surge in the number of big science projects interested in achieving a comprehensive understanding of the functions of the brain, using Spiking Neuronal Network (SNN) simulations to aid discovery and experimentation. Such an approach increases the computational demands on SNN simulators: if natural scale brain-size simulations are to be realized, it is necessary to use parallel and distributed models of computing. Communication is recognized as the dominant part of distributed SNN simulations. As the number of computational nodes increases, the proportion of time the simulation spends in useful computing (computational efficiency) is reduced and therefore applies a limit to scalability. This work targets the three phases of communication to improve overall computational efficiency in distributed simulations: implicit synchronization, process handshake and data exchange. We introduce a connectivity-aware allocation of neurons to compute nodes by modeling the SNN as a hypergraph. Partitioning the hypergraph to reduce interprocess communication increases the sparsity of the communication graph. We propose dynamic sparse exchange as an improvement over simple point-to-point exchange on sparse communications. Results show a combined gain when using hypergraph-based allocation and dynamic sparse communication, increasing computational efficiency by up to 40.8 percentage points and reducing simulation time by up to 73%. The findings are applicable to other distributed complex system simulations in which communication is modeled as a graph network.

Hardware acceleration of processing of mass spectrometric data for proteomics.

MOTIVATION: High-resolution mass spectrometers generate large data files that are complex, noisy and require extensive processing to extract the optimal data from raw spectra. This processing is readily achieved in software and is often embedded in manufacturers' instrument control and data processing environments. However, the speed of this data processing is such that it is usually performed off-line, post data acquisition. We have been exploring strategies that would allow real-time advanced processing of mass spectrometric data, making use of the reconfigurable computing paradigm, which exploits the flexibility and versatility of Field Programmable Gate Arrays (FPGAs). This approach has emerged as a powerful solution for speeding up time-critical algorithms. We describe here a reconfigurable computing solution for processing raw mass spectrometric data generated by MALDI-ToF instruments. The hardware-implemented algorithms for de-noising, baseline correction, peak identification and deisotoping, running on a Xilinx Virtex 2 FPGA at 180 MHz, generate a mass fingerprint over 100 times faster than an equivalent algorithm written in C, running on a Dual 3 GHz Xeon workstation.

Identification of Stochastically Perturbed Autonomous Systems from Temporal Sequences of Probability Density Functions.

The paper introduces a method for reconstructing one-dimensional iterated maps that are driven by an external control input and subjected to an additive stochastic perturbation, from sequences of probability density functions that are generated by the stochastic dynamical systems and observed experimentally.

Identification and Single-Cell Functional Characterization of an Endodermally Biased Pluripotent Substate in Human Embryonic Stem Cells.

Human embryonic stem cells (hESCs) display substantial heterogeneity in gene expression, implying the existence of discrete substates within the stem cell compartment. To determine whether these substates impact fate decisions of hESCs we used a GFP reporter line to investigate the properties of fractions of putative undifferentiated cells defined by their differential expression of the endoderm transcription factor, GATA6, together with the hESC surface marker, SSEA3. By single-cell cloning, we confirmed that substates characterized by expression of GATA6 and SSEA3 include pluripotent stem cells capable of long-term self-renewal. When clonal stem cell colonies were formed from GATA6-positive and GATA6-negative cells, more of those derived from GATA6-positive cells contained spontaneously differentiated endoderm cells than similar colonies derived from the GATA6-negative cells. We characterized these discrete cellular states using single-cell transcriptomic analysis, identifying a potential role for SOX17 in the establishment of the endoderm-biased stem cell state.

Code Generation in Computational Neuroscience: A Review of Tools and Techniques.

Advances in experimental techniques and computational power allowing researchers to gather anatomical and electrophysiological data at unprecedented levels of detail have fostered the development of increasingly complex models in computational neuroscience. Large-scale, biophysically detailed cell models pose a particular set of computational challenges, and this has led to the development of a number of domain-specific simulators. At the other level of detail, the ever growing variety of point neuron models increases the implementation barrier even for those based on the relatively simple integrate-and-fire neuron model. Independently of the model complexity, all modeling methods crucially depend on an efficient and accurate transformation of mathematical model descriptions into efficiently executable code. Neuroscientists usually publish model descriptions in terms of the mathematical equations underlying them. However, actually simulating them requires they be translated into code. This can cause problems because errors may be introduced if this process is carried out by hand, and code written by neuroscientists may not be very computationally efficient. Furthermore, the translated code might be generated for different hardware platforms, operating system variants or even written in different languages and thus cannot easily be combined or even compared. Two main approaches to addressing this issues have been followed. The first is to limit users to a fixed set of optimized models, which limits flexibility. The second is to allow model definitions in a high level interpreted language, although this may limit performance. Recently, a third approach has become increasingly popular: using code generation to automatically translate high level descriptions into efficient low level code to combine the best of previous approaches. This approach also greatly enriches efforts to standardize simulator-independent model description languages. In the past few years, a number of code generation pipelines have been developed in the computational neuroscience community, which differ considerably in aim, scope and functionality. This article provides an overview of existing pipelines currently used within the community and contrasts their capabilities and the technologies and concepts behind them.

Reproducibility of parameters of postocclusive reactive hyperemia measured by diffuse optical tomography.

The application of near-infrared spectroscopy (NIRS) to assess microvascular function has shown promising results. An important limitation when using a single source-detector pair, however, is the lack of depth sensitivity. Diffuse optical tomography (DOT) overcomes this limitation using an array of sources and detectors that allow the reconstruction of volumetric hemodynamic changes. This study compares the key parameters of postocclusive reactive hyperemia measured in the forearm using standard NIRS and DOT. We show that while the mean parameter values are similar for the two techniques, DOT achieves much better reproducibility, as measured by the intraclass correlation coefficient (ICC). We show that DOT achieves high reproducibility for muscle oxygen consumption (ICC: 0.99), time to maximal HbO2 (ICC: 0.94), maximal HbO2 (ICC: 0.99), and time to maximal HbT (ICC: 0.99). Absolute reproducibility as measured by the standard error of measurement is consistently smaller and close to zero (ideal value) across all parameters measured by DOT compared to NIRS. We conclude that DOT provides a more robust characterization of the reactive hyperemic response and show how the availability of volumetric hemodynamic changes allows the identification of areas of temporal consistency, which could help characterize more precisely the microvasculature.

Fly Photoreceptors Encode Phase Congruency.

More than five decades ago it was postulated that sensory neurons detect and selectively enhance behaviourally relevant features of natural signals. Although we now know that sensory neurons are tuned to efficiently encode natural stimuli, until now it was not clear what statistical features of the stimuli they encode and how. Here we reverse-engineer the neural code of Drosophila photoreceptors and show for the first time that photoreceptors exploit nonlinear dynamics to selectively enhance and encode phase-related features of temporal stimuli, such as local phase congruency, which are invariant to changes in illumination and contrast. We demonstrate that to mitigate for the inherent sensitivity to noise of the local phase congruency measure, the nonlinear coding mechanisms of the fly photoreceptors are tuned to suppress random phase signals, which explains why photoreceptor responses to naturalistic stimuli are significantly different from their responses to white noise stimuli.

Time-lapse analysis of human embryonic stem cells reveals multiple bottlenecks restricting colony formation and their relief upon culture adaptation.

Using time-lapse imaging, we have identified a series of bottlenecks that restrict growth of early-passage human embryonic stem cells (hESCs) and that are relieved by karyotypically abnormal variants that are selected by prolonged culture. Only a minority of karyotypically normal cells divided after plating, and these were mainly cells in the later stages of cell cycle at the time of plating. Furthermore, the daughter cells showed a continued pattern of cell death after division, so that few formed long-term proliferating colonies. These colony-forming cells showed distinct patterns of cell movement. Increasing cell density enhanced cell movement facilitating cell:cell contact, which resulted in increased proportion of dividing cells and improved survival postplating of normal hESCs. In contrast, most of the karyotypically abnormal cells reentered the cell cycle on plating and gave rise to healthy progeny, without the need for cell:cell contacts and independent of their motility patterns.

Reduced-order modeling of light transport in tissue for real-time monitoring of brain hemodynamics using diffuse optical tomography.

This paper proposes a new reconstruction method for diffuse optical tomography using reduced-order models of light transport in tissue. The models, which directly map optical tissue parameters to optical flux measurements at the detector locations, are derived based on data generated by numerical simulation of a reference model. The reconstruction algorithm based on the reduced-order models is a few orders of magnitude faster than the one based on a finite element approximation on a fine mesh incorporating a priori anatomical information acquired by magnetic resonance imaging. We demonstrate the accuracy and speed of the approach using a phantom experiment and through numerical simulation of brain activation in a rat's head. The applicability of the approach for real-time monitoring of brain hemodynamics is demonstrated through a hypercapnic experiment. We show that our results agree with the expected physiological changes and with results of a similar experimental study. However, by using our approach, a three-dimensional tomographic reconstruction can be performed in ∼3 s per time point instead of the 1 to 2 h it takes when using the conventional finite element modeling approach.

Stochastic, adaptive sampling of information by microvilli in fly photoreceptors.

BACKGROUND: In fly photoreceptors, light is focused onto a photosensitive waveguide, the rhabdomere, consisting of tens of thousands of microvilli. Each microvillus is capable of generating elementary responses, quantum bumps, in response to single photons using a stochastically operating phototransduction cascade. Whereas much is known about the cascade reactions, less is known about how the concerted action of the microvilli population encodes light changes into neural information and how the ultrastructure and biochemical machinery of photoreceptors of flies and other insects evolved in relation to the information sampling and processing they perform. RESULTS: We generated biophysically realistic fly photoreceptor models, which accurately simulate the encoding of visual information. By comparing stochastic simulations with single cell recordings from Drosophila photoreceptors, we show how adaptive sampling by 30,000 microvilli captures the temporal structure of natural contrast changes. Following each bump, individual microvilli are rendered briefly (~100-200 ms) refractory, thereby reducing quantum efficiency with increasing intensity. The refractory period opposes saturation, dynamically and stochastically adjusting availability of microvilli (bump production rate: sample rate), whereas intracellular calcium and voltage adapt bump amplitude and waveform (sample size). These adapting sampling principles result in robust encoding of natural light changes, which both approximates perceptual contrast constancy and enhances novel events under different light conditions, and predict information processing across a range of species with different visual ecologies. CONCLUSIONS: These results clarify why fly photoreceptors are structured the way they are and function as they do, linking sensory information to sensory evolution and revealing benefits of stochasticity for neural information processing.