An unsupervised method for realtime spike sorting

Overlapping is one of the serious problems in the spike sorting of multi-channel recordings. Although techniques to resolve this problem have been developed, there still remains much room for improvement. We present in this paper a new overlapping resolution method which is simple and can easily be incorporated in the existing spike sorting systems. The proposed method combines spike sorting algorithms with the linear projections, such that each projection eliminates single-neuronal activity. Simulations show that our method successfully resolves overlapping in real neural data

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.

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.

Microphone array post-filtering allows additional reduction of noise components at a beamformer output. Existing techniques are either restricted to classical delay-and-sum beamformers, or are based on single-channel speech enhancement algorithms that are inefficient at attenuating highly non-stationary noise components. In this paper, we introduce a microphone array post-filtering approach, applicable to adaptive beamformer, that differentiates non-stationary noise components from speech components. The ratio between the transient power at the beamformer primary output and the transient power at the reference noise signals is used for indicating whether such a transient is desired or interfering. Based on a Gaussian statistical model and combined with an appropriate spectral enhancement technique, a significantly reduced level of non-stationary noise is achieved without further distorting speech components. Experimental results demonstrate the effectiveness of the proposed method.

Spike sorting is a technique in the field of neuroscience applied to identify and classify the action potentials (spikes) of neurons in extracellular recordings. This method is important considering that the simultaneous activity of several neurons can be recorded through the use of electrodes, but the recorded signals are often mixed. Extracting the characteristics of individual spikes provides valuable information about the identity of neurons that generate them, the type of cells involved (inhibitory/excitatory), encoding of information in spike rates or spike times, and so on. Therefore, unmixing the spikes recorded on an electrode via spike sorting is crucial. Here, we apply a novel method to extract features of mixed spikes, namely the Superlet transform, which enables the computation of spectral characteristics with a higher resolution. We use machine learning to determine which features of the Superlet spectrum contain the most information about the shapes of individual spikes, thereby enabling their unmixing during spike sorting.

In spike sorting systems, front-end electronics is a crucial pre-processing step that not only has a direct impact on detection and sorting accuracy, but also on power and silicon area. In this work, a behavioural front-end model is proposed to assess the impact of the design parameters (including signal-to-noise ratio, filter type/order, bandwidth, converter resolution/rate) on subsequent spike processing. Initial validation of the model is provided by applying a test stimulus to a hardware platform and comparing the measured circuit response to the expected from the behavioural model. Our model is then used to demonstrate the effect of the Analogue Front-End (AFE) on subsequent spike processing by testing established spike detection and sorting methods on a selection of systems reported in the literature. It is revealed that although these designs have a wide variation in design parameters (and thus also circuit complexity), the ultimate impact on spike processing performance is relatively low (10-15%). This can be used to inform the design of future systems to have an efficient AFE whilst also maintaining good processing performance.

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.

Sensory information is represented in the brain through the activity of populations of neurons. How this information is encoded and how it is processed and read out are crucial questions in neuroscience. The work presented here examines these issues using an insect brain model system. Specifically, this work addresses how odor information is represented across a population of neurons in this relatively simple nervous system. It asks how the dynamics of a population of neurons contribute to the encoding of information. To address these questions, simultaneous multi-unit extracellular recordings were made in vivo in the locust brain. The first part of the dissertation describes several advances in spike-sorting methods that were necessary for analyzing such recordings. These advances include quantitative tests of sorting quality, and they allow for automated spike-sorting. Using these techniques, data sampled from tens of neurons over hours of recording can be analyzed with relative ease. The remainder of the dissertation examines the encoding of olfactory information by a population of neurons called projection neurons (PNs), located in the first olfactory relay of the brain. Odor information is shown to be represented by a subpopulation of responsive PNs. The composition of this population changes over time in an odor-specific manner, thus forming a distributed, dynamical representation. The statistics of this response and its dynamics are quantified. Furthermore, the mechanism by which odor information is extracted from the PN population response is examined. A second set of recordings were made from Kenyon cells (KCs), which receive direct excitatory synaptic input from PNs. The dynamic response of the PN population appears to be decoded by KCs through a mechanism based on several underlying components, including oscillatory dynamics, feed-forward inhibition, and intrinsic properties of the KCs. This decoding process is shown to drastically change the odor representations, from dense to sparse. Taken together, the results presented in this dissertation establish that the complex spatial and temporal dynamics of the PN population do encode odor information, and that this information is decoded by other neurons (KCs) in a very precise way, resulting in a drastic transformation of representation. The basic mechanisms underlying this transformation exist in many brain areas and across phyla, suggesting that many of the principles described here could be of general relevance.

Precise crop classification is an essential step towards effective agricultural management.Information about different crop types growing in a region helps in crop monitoring and estimating yield.Advanced remote sensing technologies allow us to map different crops growing in a region more accurately and frequently than traditional field surveys.Hyperspectral data's spectral and spatial richness has made it possible to use this data for more accurate classification of various crops compared to multispectral datasets.The present research focuses on effectively utilizing high-resolution hyperspectral data for agricultural crop classification.Combining hyperspectral data with advanced machine learning techniques, i.e., autoencoder (AE) and artificial Neural Networks (ANN), are used for generating a hybrid crop classification technique based on unsupervised feature extraction and supervised classification.Unsupervised AE techniques are used for feature extraction of high dimensional hyperspectral data and supervised ANN is used for final crop classification with the help of learned features.This research focuses on developing a hybrid AE-ANNbased model to achieve classification with better discrimination.The hyperspectral data acquired by the Airborne Visible Infrared Imaging Spectrometer-Next Generation (AVIRIS-NG) sensor from the Anand region of Gujarat, representing the study area, was used for crop classification.The developed model showed an overall accuracy (OA) of 97% using 20 extracted features.The proposed neural network model outperformed the popular SVM classifier, providing better classification accuracies and demonstrating the excellent discrimination of extracted features.

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.

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 a fundamental process for decoding neural activity, involving preprocessing, spike detection, feature extraction, clustering, and validation. However, conventional spike sorting methods are highly fragmented, labor-intensive, and heavily reliant on expert manual curation, limiting their scalability and reproducibility. This challenge has become more pressing with advances in neural recording technology, such as high-density Neuropixels for large-scale neural recording or flexible electrodes for long-term stable recording over months to years. The volume and complexity of these datasets make manual curation infeasible, requiring an automated and scalable solution. Here, we introduce SpikeAgent, a multimodal large language model (LLM)-based AI agent that automates and standardizes the entire spike sorting pipeline. Unlike traditional approaches, SpikeAgent integrates multiple LLM backends, coding functions, and established algorithms, autonomously performing spike sorting with reasoning-based decision-making and real-time interaction with intermediate results. It generates interpretable reports, providing transparent justifications for each sorting decision, enhancing transparency and reliability. We benchmarked SpikeAgent against human experts across various neural recording technology, demonstrating its versatility and ability to achieve curation consistency that are equal to, or even higher than human experts. It also drastically reduces the expertise barrier and accelerates the curation and validation time by orders of magnitude. Moreover, it enables automated interpretability of the neural spiking data, which cannot be achieved by any conventional methods. SpikeAgent presents a paradigm shift in processing signals for neuroscience and brain-computer interfaces, while laying the ground for AI agent-augmented science across various domains.

Neural spike sorting is used to classify neural spike signals based on neuron type and so is an essential step in decoding brain signals. Because of its computational complexity, spike sorting is generally carried out offline or, at least, using a transmitted signal. In contrast, in-brain spike sorting would reduce the data that needs to be transmitted by orders of magnitude with a corresponding reduction in transmission power. This would enable real-time wireless neural recordings. In this paper, we design and characterize a hardware prototype for in-brain spike sorting. Our design is able to reduce the wireless transmission power by a factor of over 200 over direct transmission. Also, compared with the current state-of-the-art, our design increases the sorting accuracy from 75% to 93% while remaining within hard constraints for power, power density, and real-time processing.

We present a method for automated spike sorting for recordings with high-density, large-scale multielectrode arrays. Exploiting the dense sampling of single neurons by multiple electrodes, an efficient, low-dimensional representation of detected spikes consisting of estimated spatial spike locations and dominant spike shape features is exploited for fast and reliable clustering into single units. Millions of events can be sorted in minutes, and the method is parallelized and scales better than quadratically with the number of detected spikes. Performance is demonstrated using recordings with a 4,096-channel array and validated using anatomical imaging, optogeneticstimulation, and model-based quality control. A comparison with semi-automated, shape-based spike sorting exposes significant limitations of conventional methods. Our approach demonstrates that it is feasible to reliably isolate the activity of up to thousands of neurons and that dense, multi-channel probes substantially aid reliable spike sorting.

Recent progress in multi-electrode spike sorting methods