Spike sorting using Superlets: Identifying feature importance through perturbation

Reliability and Representational Bandwidth in the Auditory Cortex

Objective. Spike sorting is a set of techniques used to analyze extracellular neural recordings, attributing individual spikes to individual neurons. This field has gained significant interest in neuroscience due to advances in implantable microelectrode arrays, capable of recording thousands of neurons simultaneously. High-density electrodes, combined with efficient and accurate spike sorting systems, are essential for various applications, including brain machine interfaces (BMIs), experimental neural prosthetics, real-time neurological disorder monitoring, and neuroscience research. However, given the resource constraints of modern applications, relying solely on algorithmic innovation is not enough. Instead, a co-optimization approach that combines hardware and spike sorting algorithms must be taken to develop neural recording systems suitable for resource-constrained environments, such as wearable devices and BMIs. This co-design requires careful consideration when selecting appropriate spike-sorting algorithms that match specific hardware and use cases. Approach. We investigated the recent literature on spike sorting, both in terms of hardware advancements and algorithms innovations. Moreover, we dedicated special attention to identifying suitable algorithm-hardware combinations, and their respective real-world applicabilities. Main results. In this review, we first examined the current progress in algorithms, and described the recent departure from the conventional ‘3-step’ algorithms in favor of more advanced template matching or machine-learning-based techniques. Next, we explored innovative hardware options, including application-specific integrated circuits, field-programmable gate arrays, and in-memory computing devices (IMCs). Additionally, the challenges and future opportunities for spike sorting are discussed. Significance. This comprehensive review systematically summarizes the latest spike sorting techniques and demonstrates how they enable researchers to overcome traditional obstacles and unlock novel applications. Our goal is for this work to serve as a roadmap for future researchers seeking to identify the most appropriate spike sorting implementations for various experimental settings. By doing so, we aim to facilitate the advancement of this exciting field and promote the development of innovative solutions that drive progress in neural engineering research.

Spiking Irregularity and Frequency Modulate the Behavioral Report of Single-Neuron Stimulation

A biologically plausible model of myelin plasticity demonstrates how oligodendrocytes can selectively adjust conduction delays in axon bundles to allow robust communication between brain regions through long-range synchronization.

Developing electrophysiological recordings of brain neuronal activity and their analysis provide a basis for exploring the structure of brain function and nervous system investigation. The recorded signals are typically a combination of spikes and noise. High amounts of background noise and possibility of electric signaling recording from several neurons adjacent to the recording site have led scientists to develop neuronal signal processing tools such as spike sorting to facilitate brain data analysis. Spike sorting plays a pivotal role in understanding the electrophysiological activity of neuronal networks. This process prepares recorded data for interpretations of neurons interactions and understanding the overall structure of brain functions. Spike sorting consists of three steps: spike detection, feature extraction, and spike clustering. There are several methods to implement each of spike sorting steps. This paper provides a systematic comparison of various spike sorting sub-techniques applied to real extracellularly recorded data from a rat brain basolateral amygdala. An efficient sorted data resulted from careful choice of spike sorting sub-methods leads to better interpretation of the brain structures connectivity under different conditions, which is a very sensitive concept in diagnosis and treatment of neurological disorders. Here, spike detection is performed by appropriate choice of threshold level via three different approaches. Feature extraction is done through PCA and Kernel PCA methods, which Kernel PCA outperforms. We have applied four different algorithms for spike clustering including K-means, Fuzzy C-means, Bayesian and Fuzzy maximum likelihood estimation. As one requirement of most clustering algorithms, optimal number of clusters is achieved through validity indices for each method. Finally, the sorting results are evaluated using inter-spike interval histograms.

Event Abstract Back to Event Optimizing Spike-Sorting Yield through Selection of Optimal Recording Sites in High-density Microelectrode Arrays Jan Müller1*, Felix Franke2, Michele Fiscella1, Urs Frey3, Douglas Bakkum1 and Andreas Hierlemann1 1 ETH Zurich, Department of Biosystems Science and Engineering, Switzerland 2 ETH Zürich, Department of Biosystems Science and Engineering, Switzerland 3 Riken, Quantitative Biology Center, Japan Motivation Recently, various high-density microelectrode arrays (HDMEA) were developed for in-vitro and in-vivo applications. Some of these arrays feature hundreds to thousands of electrodes, from which a subset can be selected for recording at one time [1-4]. Our goal here is to simultaneously extract the activity of a maximum number of identifiable neurons from such recordings. Careful choice of recording electrodes is required, when the number of recorded neurons exceeds the number of available recording channels. When analyzing data from networks of neurons, one is typically interested in the exact relative timing of the occurrence of action potentials in different neurons. Here, we consider the assignment of recorded action potentials to individual neurons a classification problem. Therefore, we propose a metric relying on linear discriminant analysis (LDA) to compute the expected classification error for a given electrode arrangement. Moreover, we propose an algorithm to automatically find optimal electrode configurations. Material and Methods HDMEA: To demonstrate the feasibility of our method, we used a recently developed HDMEA featuring 26,400 Pt microelectrodes, arranged in a grid-like configuration with a center-to-center pitch of 17.5 μm [3]. 1024 of these electrodes can be selected for simultaneous recording by means of low-noise amplifiers (2.4 μV rms in the action potential signal band 300 Hz–10 kHz). Algorithm: The extent to which action potentials from two neurons can be clearly distinguished depends on their multi-electrode waveforms. The best separation can be achieved if information from all electrodes is available. However, only a subset of all available electrodes can be used for recording at the same time. Our method starts out by successively recording through blocks of all 26,400 electrodes, spike sorting each of the recordings, and building templates for each neuron (Step 1). Using the templates from all neurons and linear discriminant analysis [5], we compute the expected spike sorting error (ESSE) using all electrodes. We then compute for each electrode the ESSE under the assumption that the corresponding electrode would not be used for recording (Step 2). Electrodes, the removal of which increases the ESSE by the least amount will then be discarded (Step 3). Step 2 and 3 are iterated until the desired number of electrodes, i.e., the number of available readout channels is reached. Results We recorded from a patch of hamster retina for ten minutes per electrode. Based on this data, action potential templates were computed, and the algorithm has been applied to identify the optimal recording electrodes. The classification error decays exponentially upon increasing the number of used electrodes. Discussion/Conclusion We have presented a framework to assess the quality of a particular recording scenario. The framework quantifies the error probability for discriminating between all a-priori known templates for all present neurons. The algorithm was applied to recordings from a retina performed with a recently developed HDMEA. Our approach is related to earlier work [6]. However, by relying on linear discriminant analysis, we make - in a Bayesian sense - optimal use of the available recording resources. [1] Lopez, Carolina M., et al. "A 966-electrode neural probe with 384 configurable channels in 0.13μm SOI CMOS", ISSCC (2016), 392-393. [2] Viswam, Vijay, et al. "Multi-Functional Microelectrode Array System featuring 59’760 Electrodes, 2048 Electrophysiology Channels, Impedance and Neurotransmitter Measurement Units", ISSCC (2016), 394-396. [3] Ballini, Marco, et al. "A 1024-Channel CMOS microelectrode array with 26,400 electrodes for recording and stimulation of electrogenic cells in vitro." Solid-State Circuits, IEEE Journal of 49.11 (2014): 2705-2719. [4] Seidl, Karsten, et al. "CMOS-based high-density silicon microprobe arrays for electronic depth control in intracortical neural recording" Microelectromechanical Systems, Journal of, 20(6):1439– 1448, 2011. [5] Franke, Felix, et al. "Bayes Optimal Template Matching for Spike Sorting – Combining Fisher Discriminant Analysis with Optimal Filtering, " J. Comput. Neurosci., vol. 38, no. 3, pp. 439–459, 2015. [6] Vysotska, Olga, "Automatic channel selection and neural signal estimation across channels of neural probes", International Conference on Intelligent Robots and Systems (2014), 1453–1459. Keywords: Retina, CMOS, Spike-sorting, high-density microelectrode array (HDMEA) Conference: MEA Meeting 2016 | 10th International Meeting on Substrate-Integrated Electrode Arrays, Reutlingen, Germany, 28 Jun - 1 Jul, 2016. Presentation Type: Poster Presentation Topic: MEA Meeting 2016 Citation: Müller J, Franke F, Fiscella M, Frey U, Bakkum D and Hierlemann A (2016). Optimizing Spike-Sorting Yield through Selection of Optimal Recording Sites in High-density Microelectrode Arrays. Front. Neurosci. Conference Abstract: MEA Meeting 2016 | 10th International Meeting on Substrate-Integrated Electrode Arrays. doi: 10.3389/conf.fnins.2016.93.00122 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 22 Jun 2016; Published Online: 24 Jun 2016. * Correspondence: Dr. Jan Müller, ETH Zurich, Department of Biosystems Science and Engineering, Basel, Switzerland, jan.mueller@bsse.ethz.ch Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Jan Müller Felix Franke Michele Fiscella Urs Frey Douglas Bakkum Andreas Hierlemann Google Jan Müller Felix Franke Michele Fiscella Urs Frey Douglas Bakkum Andreas Hierlemann Google Scholar Jan Müller Felix Franke Michele Fiscella Urs Frey Douglas Bakkum Andreas Hierlemann PubMed Jan Müller Felix Franke Michele Fiscella Urs Frey Douglas Bakkum Andreas Hierlemann Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Spike sorting, i.e., the separation of the firing activity of different neurons from extracellular measurements, is a crucial but often error-prone step in the analysis of neuronal responses. Usually, three different problems have to be solved: the detection of spikes in the extracellular recordings, the estimation of the number of neurons and their prototypical (template) spike waveforms, and the assignment of individual spikes to those putative neurons. If the template spike waveforms are known, template matching can be used to solve the detection and classification problem. Here, we show that for the colored Gaussian noise case the optimal template matching is given by a form of linear filtering, which can be derived via linear discriminant analysis. This provides a Bayesian interpretation for the well-known matched filter output. Moreover, with this approach it is possible to compute a spike detection threshold analytically. The method can be implemented by a linear filter bank derived from the templates, and can be used for online spike sorting of multielectrode recordings. It may also be applicable to detection and classification problems of transient signals in general. Its application significantly decreases the error rate on two publicly available spike-sorting benchmark data sets in comparison to state-of-the-art template matching procedures. Finally, we explore the possibility to resolve overlapping spikes using the template matching outputs and show that they can be resolved with high accuracy.

Neural decoding and its applications to brain computer interfaces (BCI) are essential for understanding the association between neural activity and behavior. A prerequisite for many decoding approaches is spike sorting, the assignment of action potentials (spikes) to individual neurons. Current spike sorting algorithms, however, can be inaccurate and do not properly model uncertainty of spike assignments, therefore discarding information that could potentially improve decoding performance. Recent advances in high-density probes (e.g., Neuropixels) and computational methods now allow for extracting a rich set of spike features from unsorted data; these features can in turn be used to directly decode behavioral correlates. To this end, we propose a spike sorting-free decoding method that directly models the distribution of extracted spike features using a mixture of Gaussians (MoG) encoding the uncertainty of spike assignments, without aiming to solve the spike clustering problem explicitly. We allow the mixing proportion of the MoG to change over time in response to the behavior and develop variational inference methods to fit the resulting model and to perform decoding. We benchmark our method with an extensive suite of recordings from different animals and probe geometries, demonstrating that our proposed decoder can consistently outperform current methods based on thresholding (i.e. multi-unit activity) and spike sorting. Open source code is available at https://github.com/yzhang511/density_decoding.

BackgroundPrincipal component analysis (PCA) has been widely employed for automatic neuronal spike sorting. Calculating principal components (PCs) is computationally expensive, and requires complex numerical operations and large memory resources. Substantial hardware resources are therefore needed for hardware implementations of PCA. General Hebbian algorithm (GHA) has been proposed for calculating PCs of neuronal spikes in our previous work, which eliminates the needs of computationally expensive covariance analysis and eigenvalue decomposition in conventional PCA algorithms. However, large memory resources are still inherently required for storing a large volume of aligned spikes for training PCs. The large size memory will consume large hardware resources and contribute significant power dissipation, which make GHA difficult to be implemented in portable or implantable multi-channel recording micro-systems.MethodIn this paper, we present a new algorithm for PCA-based spike sorting based on GHA, namely stream-based Hebbian eigenfilter, which eliminates the inherent memory requirements of GHA while keeping the accuracy of spike sorting by utilizing the pseudo-stationarity of neuronal spikes. Because of the reduction of large hardware storage requirements, the proposed algorithm can lead to ultra-low hardware resources and power consumption of hardware implementations, which is critical for the future multi-channel micro-systems. Both clinical and synthetic neural recording data sets were employed for evaluating the accuracy of the stream-based Hebbian eigenfilter. The performance of spike sorting using stream-based eigenfilter and the computational complexity of the eigenfilter were rigorously evaluated and compared with conventional PCA algorithms. Field programmable logic arrays (FPGAs) were employed to implement the proposed algorithm, evaluate the hardware implementations and demonstrate the reduction in both power consumption and hardware memories achieved by the streaming computingResults and discussionResults demonstrate that the stream-based eigenfilter can achieve the same accuracy and is 10 times more computationally efficient when compared with conventional PCA algorithms. Hardware evaluations show that 90.3% logic resources, 95.1% power consumption and 86.8% computing latency can be reduced by the stream-based eigenfilter when compared with PCA hardware. By utilizing the streaming method, 92% memory resources and 67% power consumption can be saved when compared with the direct implementation of GHA.ConclusionStream-based Hebbian eigenfilter presents a novel approach to enable real-time spike sorting with reduced computational complexity and hardware costs. This new design can be further utilized for multi-channel neuro-physiological experiments or chronic implants.

Spike sorting is one of the cornerstones of extracellular electrophysiology. By leveraging advanced signal processing and data analysis techniques, spike sorting makes it possible to detect, isolate, and map single neuron spiking activity from both in vivo and in vitro extracellular electrophysiological recordings. A crucial step of any spike sorting pipeline is to reduce the dimensionality of the recorded spike waveform data. Reducing the dimensionality of the processed data is a near-universal practice, fundamentally motivated by the use of clustering algorithms responsible to detect, isolate, and sort the recorded putative neurons. In this paper, we propose and illustrate on both synthetic and experimental data that employing the nonlinear dimensionality reduction technique Uniform Manifold Approximation and Projection (UMAP) can drastically improve the performance, efficiency, robustness, and scalability of spike sorting pipelines without increasing their computational cost. We show how replacing the linear or ad hoc, expert-defined, supervised nonlinear dimensionality reduction methods commonly used in spike sorting pipelines by the unsupervised, mathematically grounded, nonlinear dimensionality reduction method provided by UMAP drastically increases the number of correctly sorted neurons, makes the identification of quieter, seldom spiking neurons more reliable, enables deeper and more precise explorations and analysis of the neural code, and paves new ways toward more efficient and end-to-end automatable spike sorting pipelines of large-scale extracellular neural recording as those produced by high-density multielectrode arrays.

In this research, we study the effect of feature selection in the spike detection and sorting accuracy. We introduce a new feature representation for neural spikes from multichannel recordings. The features selection plays a significant role in analyzing the response of brain neurons. The more precise selection of features leads to a more accurate spike sorting, which can group spikes more precisely into clusters based on the similarity of spikes. Proper spike sorting will enable the association between spikes and neurons. Different with other threshold-based methods, the cepstrum of spike signals is employed in our method to select the candidates of spike features. To choose the best features among different candidates, the Kolmogorov-Smirnov (KS) test is utilized. Then, we rely on the super paramagnetic method to cluster the neural spikes based on KS features. Simulation results demonstrate that the proposed method not only achieve more accurate clustering results but also reduce computational burden, which implies that it can be applied into real-time spike analysis.

Unsupervised spike sorting, a vital processing step in real-time brain-implantable microsystems, is faced with the prominent challenge of managing nonstationarity in neural signals. In long-term recordings, spike waveforms gradually change and new source neurons are likely to become activated. Adaptive spike sorters combined with on-implant training units effectively process the nonstationary signals at the cost of high hardware resource utilization. On the other hand, static approaches, while being hardware-friendly, are subjected to decreased processing performance in such recordings where the neural signal characteristics gradually change. To strike a balance between the hardware cost and processing performance, this study proposes a hardware-efficient novelty-aware spike sorting approach that is capable of dealing with both variated spike waveforms and spike waveforms generated from new source neurons. Its improved hardware efficiency compared to adaptive ones and capability of dealing with nonstationary signals make it attractive for implantable applications. The proposed novelty-aware spike sorting especially would be a good fit for brain-computer interfaces where long-term, real-time interaction with the brain is required, and the available on-implant hardware resources are limited. Our unsupervised spike sorting benefits from a novelty detection process to deal with neural signal variations. It tracks the spike features so that in case of detecting an unexpected change (novelty detection) both on and off-implant parameters are updated to preserve the performance in new state. To make the proposed approach agile enough to be suitable for brain implants, the on-implant computations are reduced while the computational burden is realized off-implant. The performance of our proposed approach is evaluated using both synthetic and real datasets. The results demonstrate that, in the mean, it is capable of detecting 94.31% of novel spikes (wave-drifted or emerged spikes) with a classification accuracy (CA) of 96.31%. Moreover, an FPGA prototype of the on-implant circuit is implemented and tested. It is shown that in comparison to the OSORT algorithm, a pivotal spike sorting method, our spike sorting provides a higher CA at significantly lower hardware resources. The proposed circuit is also implemented in a 180-nm standard CMOS process, achieving a power consumption of 1.78[Formula: see text][Formula: see text] per channel and a chip area of 0.07[Formula: see text]mm2 per channel.

Spike sorting is the process of separating the extracellular recording of the brain signal into one unit activity. There are a number of proposed algorithms for this purpose, but there is still no acceptable solution. In this paper a spike sorting method has been proposed based on the Euclidean distance of the most effective features of spikes represented by principle components (PCs) of the detected and aligned spikes. The assessments of the method, based on signal-to-noise ratio (SNR) representing background noise, showed that the method performed spike sorting to a high level of accuracy.

A large amount of neurophysiological research is based on the study of biological neural populations. The data is gathered from extra-cellular recordings with multi-electrode arrays (MEAs). The signal is a stream containing an unknown number of neural sources superpositioned with non-stationary noise components. In order to analyze the recorded spike trains, a prior separation into its individual components is required. The increasing number of sensors on a MEA surface demand an automatic spike sorting procedure. In this article the proposed spike sorting method replaces the manual steps with artificial neural networks to enable an unsupervised separation of mixed signal components. Furthermore the artificial neural network based feature extraction allows realtime processing and ensures high flexbibility and adaptivity for unknown signals with non-stationary noise components.

Human brain neuron activities are incredibly significant nowadays. Neuronal behavior is assessed by analyzing signal data such as extracellular recording, which can offer scientists valuable information about diseases and neuron activities. One of the difficulties researchers confront while evaluating these signals is the existence of large volumes of spike data. Spikes are significant components of signal data that can happen as a consequence of vital biomarkers or physical issues such as electrode movements. Hence, distinguishing types of spikes is essential. From this spot, the spike classification concept commences. Previously, researchers classified spikes manually. The manual classification was not precise enough, as it involved extensive analysis. Consequently, Artificial Intelligence (AI) was introduced into neuroscience to assist clinicians in classifying spikes correctly. Recognizing noises from spikes produced by neural activity causes the spike classification task to bear a significant demand. Classifying spikes accurately and quickly reveals the role of AI in the scope of spike classification. This review provides an in‐depth discussion of the importance and use of AI in spike classification. This work organizes materials in the spike classification field for future studies and fully describes how spikes are recognized. Therefore, the existing datasets are described first. The topic of spike classification is then separated into three major components: preprocessing, classification, and evaluation. Each of these sections introduces existing methods and determines their importance. Having been summarized and compared, more efficient algorithms are highlighted. The primary goal of this work is to provide a perspective on spike classification for future research, as well as a thorough grasp of the methodologies and issues involved. In this work, numerous studies were extracted from various databases. The PRISMA‐related research guidelines were then used to choose papers. Then, research studies based on spike classification using machine learning and deep learning approaches with effective preprocessing were selected. Although there are research papers on spike sorting using the keyword spike, the primary focus of this study is on spike classification. Finally, 47 papers were selected for in‐depth review. First, useful information on the datasets for these papers is supplied. In addition, preprocessing approaches, classification methods, and ultimate performance are investigated in each of these studies. The material is then summarized. Furthermore, the fundamental concerns regarding spike classification raised in the opening of this paper are thoroughly addressed throughout the review. Our reviewing outcomes illustrate that support vector machine and clustering‐based algorithms drastically influence machine learning methods in terms of high accuracy and many uses. Moreover, convolutional neural networks, spiky neural networks, and attention‐based techniques can classify spikes with considerable functionality among deep learning methods. Various preprocessing and classification techniques have been used practically to classify extracted signal data from patients in medical institutions. Our review emphasizes the importance of classifying spikes in neuroscience applications with machine learning and deep learning models. This can provide precious insights and hands‐on solutions for using AI to classify real‐world medical data. This article is categorized under: Technologies > Artificial Intelligence Technologies > Machine Learning Algorithmic Development > Biological Data Mining