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.

Several binless spike train measures which avoid the limitations of binning have been recently been proposed in the literature. This paper presents a systematic comparison of these measures in three simulated paradigms designed to address specific situations of interest in spike train analysis where the relevant feature may be in the form of firing rate, firing rate modulations, and/or synchrony. The measures are first disseminated and extended for ease of comparison. It also discusses how the measures can be used to measure dissimilarity in spike trains' firing rate despite their explicit formulation for synchrony.

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.

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.

Abstract-Over the last decade several positive definite kernels have been proposed to treat spike trains as objects in Hilbert space. However, for the most part, such attempts still remain a mere curiosity for both computational neuroscientists and signal processing experts. This tutorial illustrates why kernel methods can, and have already started to, change the way spike trains are analyzed and processed. The presentation incorporates simple mathematical analogies and convincing practical examples in an attempt to show the yet unexplored potential of positive definite functions to quantify point processes. It also provides a detailed overview of the current state of the art and future challenges with the hope of engaging the readers in active participation.