Semi-automated neuron boundary detection and nonbranching process segmentation in electron microscopy images.

Neuroscientists are developing new imaging techniques and generating large volumes of data in an effort to understand the complex structure of the nervous system. The complexity and size of this data makes human interpretation a labor-intensive task. To aid in the analysis, new segmentation techniques for identifying neurons in these feature rich datasets are required. This paper presents a method for neuron boundary detection and nonbranching process segmentation in electron microscopy images and visualizing them in three dimensions. It combines both automated segmentation techniques with a graphical user interface for correction of mistakes in the automated process. The automated process first uses machine learning and image processing techniques to identify neuron membranes that deliniate the cells in each two-dimensional section. To segment nonbranching processes, the cell regions in each two-dimensional section are connected in 3D using correlation of regions between sections. The combination of this method with a graphical user interface specially designed for this purpose, enables users to quickly segment cellular processes in large volumes.

Serial section registration of axonal confocal microscopy datasets for long-range neural circuit reconstruction.

In the context of long-range digital neural circuit reconstruction, this paper investigates an approach for registering axons across histological serial sections. Tracing distinctly labeled axons over large distances allows neuroscientists to study very explicit relationships between the brain's complex interconnects and, for example, diseases or aberrant development. Large scale histological analysis requires, however, that the tissue be cut into sections. In immunohistochemical studies thin sections are easily distorted due to the cutting, preparation, and slide mounting processes. In this work we target the registration of thin serial sections containing axons. Sections are first traced to extract axon centerlines, and these traces are used to define registration landmarks where they intersect section boundaries. The trace data also provides distinguishing information regarding an axon's size and orientation within a section. We propose the use of these features when pairing axons across sections in addition to utilizing the spatial relationships among the landmarks. The global rotation and translation of an unregistered section are accounted for using a random sample consensus (RANSAC) based technique. An iterative nonrigid refinement process using B-spline warping is then used to reconnect axons and produce the sought after connectivity information.

Detection of neuron membranes in electron microscopy images using a serial neural network architecture.

Study of nervous systems via the connectome, the map of connectivities of all neurons in that system, is a challenging problem in neuroscience. Towards this goal, neurobiologists are acquiring large electron microscopy datasets. However, the shear volume of these datasets renders manual analysis infeasible. Hence, automated image analysis methods are required for reconstructing the connectome from these very large image collections. Segmentation of neurons in these images, an essential step of the reconstruction pipeline, is challenging because of noise, anisotropic shapes and brightness, and the presence of confounding structures. The method described in this paper uses a series of artificial neural networks (ANNs) in a framework combined with a feature vector that is composed of image intensities sampled over a stencil neighborhood. Several ANNs are applied in series allowing each ANN to use the classification context provided by the previous network to improve detection accuracy. We develop the method of serial ANNs and show that the learned context does improve detection over traditional ANNs. We also demonstrate advantages over previous membrane detection methods. The results are a significant step towards an automated system for the reconstruction of the connectome.

Sequential Monte Carlo point-process estimation of kinematics from neural spiking activity for brain-machine interfaces.

Many decoding algorithms for brain machine interfaces' (BMIs) estimate hand movement from binned spike rates, which do not fully exploit the resolution contained in spike timing and may exclude rich neural dynamics from the modeling. More recently, an adaptive filtering method based on a Bayesian approach to reconstruct the neural state from the observed spike times has been proposed. However, it assumes and propagates a gaussian distributed state posterior density, which in general is too restrictive. We have also proposed a sequential Monte Carlo estimation methodology to reconstruct the kinematic states directly from the multichannel spike trains. This letter presents a systematic testing of this algorithm in a simulated neural spike train decoding experiment and then in BMI data. Compared to a point-process adaptive filtering algorithm with a linear observation model and a gaussian approximation (the counterpart for point processes of the Kalman filter), our sequential Monte Carlo estimation methodology exploits a detailed encoding model (tuning function) derived for each neuron from training data. However, this added complexity is translated into higher performance with real data. To deal with the intrinsic spike randomness in online modeling, several synthetic spike trains are generated from the intensity function estimated from the neurons and utilized as extra model inputs in an attempt to decrease the variance in the kinematic predictions. The performance of the sequential Monte Carlo estimation methodology augmented with this synthetic spike input provides improved reconstruction, which raises interesting questions and helps explain the overall modeling requirements better.

A reproducing kernel Hilbert space framework for spike train signal processing.

This letter presents a general framework based on reproducing kernel Hilbert spaces (RKHS) to mathematically describe and manipulate spike trains. The main idea is the definition of inner products to allow spike train signal processing from basic principles while incorporating their statistical description as point processes. Moreover, because many inner products can be formulated, a particular definition can be crafted to best fit an application. These ideas are illustrated by the definition of a number of spike train inner products. To further elicit the advantages of the RKHS framework, a family of these inner products, the cross-intensity (CI) kernels, is analyzed in detail. This inner product family encapsulates the statistical description from the conditional intensity functions of spike trains. The problem of their estimation is also addressed. The simplest of the spike train kernels in this family provide an interesting perspective to others' work, as will be demonstrated in terms of spike train distance measures. Finally, as an application example, the RKHS framework is used to derive a clustering algorithm for spike trains from simple principles.

Peri-event cross-correlation over time for analysis of interactions in neuronal firing.

Several methods have been described in the literature to verify the presence of couplings between neurons in the brain. In this paper we introduce the peri-event cross-correlation over time (PECCOT) to describe the interaction among the two neurons as a function of the event onset. Instead of averaging over time, the PECCOT averages the cross-correlation over instances of the event. As a consequence, the PECCOT is able to characterize with high temporal resolution the interactions over time among neurons. To illustrate the method, the PECCOT is applied to a simulated dataset and for analysis of synchrony in recordings of a rat performing a go/no go behavioral lever press task. We verify the presence of synchrony before the lever press time and its suppression afterwards.

An efficient algorithm for continuous time cross correlogram of spike trains.

We propose an efficient algorithm to compute the smoothed correlogram for the detection of temporal relationship between two spike trains. Unlike the conventional histogram-based correlogram estimations, the proposed algorithm operates on continuous time and does not bin either the spike train nor the correlogram. Hence it can be more precise in detecting the effective delay between two recording sites. Moreover, it can take advantage of the higher temporal resolution of the spike times provided by the current recording methods. The Laplacian kernel for smoothing enables efficient computation of the algorithm. We also provide the basic statistics of the estimator and a guideline for choosing the kernel size. This new technique is demonstrated by estimating the effective delays in a neuronal network from synthetic data and recordings of dissociated cortical tissue.

Self-organizing maps with dynamic learning for signal reconstruction.

Wireless Brain Machine Interface (BMI) communication protocols are faced with the challenge of transmitting the activity of hundreds of neurons which requires large bandwidth. Previously a data compression scheme for neural activity was introduced based on Self Organizing Maps (SOM). In this paper we propose a dynamic learning rule for improved training of the SOM on signals with sparse events which allows for more representative prototype vectors to be found, and consequently better signal reconstruction. This work was developed with BMI applications in mind and therefore our examples are geared towards this type of signals. The simulation results show that the proposed strategy outperforms conventional vector quantization methods for spike reconstruction.

On the use of standards for microarray lossless image compression.

The interest in methods that are able to efficiently compress microarray images is relatively new. This is not surprising, since the appearance and fast growth of the technology responsible for producing these images is also quite recent. In this paper, we present a set of compression results obtained with 49 publicly available images, using three image coding standards: lossless JPEG2000, JBIG, and JPEG-LS. We concluded that the compression technology behind JBIG seems to be the one that offers the best combination of compression efficiency and flexibility for microarray image compression.