An online spike detection and spike classification algorithm capable of instantaneous resolution of overlapping spikes

For the analysis of neuronal cooperativity, simultaneously recorded extracellular signals from neighboring neurons need to be sorted reliably by a spike sorting method. Many algorithms have been developed to this end, however, to date, none of them manages to fulfill a set of demanding requirements. In particular, it is desirable to have an algorithm that operates online, detects and classifies overlapping spikes in real time, and that adapts to non-stationary data. Here, we present a combined spike detection and classification algorithm, which explicitly addresses these issues. Our approach makes use of linear filters to find a new representation of the data and to optimally enhance the signal-to-noise ratio. We introduce a method called “Deconfusion” which de-correlates the filter outputs and provides source separation. Finally, a set of well-defined thresholds is applied and leads to simultaneous spike detection and spike classification. By incorporating a direct feedback, the algorithm adapts to non-stationary data and is, therefore, well suited for acute recordings. We evaluate our method on simulated and experimental data, including simultaneous intra/extra-cellular recordings made in slices of a rat cortex and recordings from the prefrontal cortex of awake behaving macaques. We compare the results to existing spike detection as well as spike sorting methods. We conclude that our algorithm meets all of the mentioned requirements and outperforms other methods under realistic signal-to-noise ratios and in the presence of overlapping spikes

Online detection and sorting of extracellularly recorded action potentials in human medial temporal lobe recordings, in vivo

Understanding the function of complex cortical circuits requires the simultaneous recording of action potentials from many neurons in awake and behaving animals. Practically, this can be achieved by extracellularly recording from multiple brain sites using single wire electrodes. However, in densely packed neural structures such as the human hippocampus, a single electrode can record the activity of multiple neurons. Thus, analytic techniques that differentiate action potentials of different neurons are required. Offline spike sorting approaches are currently used to detect and sort action potentials after finishing the experiment. Because the opportunities to record from the human brain are relatively rare, it is desirable to analyze large numbers of simultaneous recordings quickly using online sorting and detection algorithms. In this way, the experiment can be optimized for the particular response properties of the recorded neurons. Here we present and evaluate a method that is capable of detecting and sorting extracellular single-wire recordings in realtime. We demonstrate the utility of the method by applying it to an extensive data set we acquired from chronically-implanted depth electrodes in the hippocampus of human epilepsy patients. This dataset is particularly challenging because it was recorded in a noisy clinical environment. This method will allow the development of closed-loop experiments, which immediately adapt the experimental stimuli and/or tasks to the neural response observed.Comment: 9 figures, 2 tables. Journal of Neuroscience Methods 2006 (in press). Journal of Neuroscience Methods, 2006 (in press

A Deep Neural Network-Based Spike Sorting with Improved Channel Selection and Artefact Removal

In order to implement highly efficient brain-machine interface (BMI) systems, high-channel count sensing is often used to record extracellular action potentials. However, the extracellular recordings are typically severely contaminated by artefacts and various noise sources, rendering the separation of multi-unit neural recordings an immensely challenging task. Removing artefact and noise from neural events can improve the spike sorting performance and classification accuracy. This paper presents a deep learning technique called deep spike detection (DSD) with a strong learning ability of high-dimensional vectors for neural channel selection and artefacts removal from the selected neural channel. The proposed method significantly improves spike detection compared to the conventional methods by sequentially diminishing the noise level and discarding the active artefacts in the recording channels. The simulated and experimental results show that there is considerably better performance when the extracellular raw recordings are cleaned prior to assigning individual spikes to the neurons that generated them. The DSD achieves an overall classification accuracy of 91.53% and outperformes Wave_clus by 3.38% on the simulated dataset with various noise levels and artefacts

Uber-Claws : unsupervised pattern classification for multi-unit extracellular neuronal burst extraction

To further an understanding of how a neuronal population generates patterns of rhythmic activity, the temporal dynamics of the group of neurons must be formalized. Essential to this pursuit, is the ability to reliably detect and separate the classes of single-unit neuronal activity from multi-unit extracellular signals recorded in a single channel. This study proposes a unified approach to automatically detect and classify single-unit bursts, and to observe the precise onset and offset of burst activity. Existing approaches to the problem fundamentally depend on the statistics of spike waveform variability, both extrinsic and intrinsic to the neuron. In contrast, the proposed approach depends on statistics that characterize the burst variability. An unsupervised learning procedure is implemented using hierarchical clustering to derive a complete and natural description of the variability in terms of clusters of bursts that possess strong internal similarities. Redundant solution vectors are used to parameterize each cluster, and a fuzzy classification approach assigns each burst to a class. Accuracy of the technique is demonstrated on in vivo and in vitro recordings of the triphasic pyloric rhythm in stomatogastric ganglion of crab Cancer borealis. The results, evaluated against a widely used manual classification approach, show that the technique performs detection and classification with comparable accuracy and quantifiable certainty, and is robust to background activity and noise

Resource efficient on-node spike sorting

Current implantable brain-machine interfaces are recording multi-neuron activity by utilising multi-channel, multi-electrode micro-electrodes. With the rapid increase in recording capability has come more stringent constraints on implantable system power consumption and size. This is even more so with the increasing demand for wireless systems to increase the number of channels being monitored whilst overcoming the communication bottleneck (in transmitting raw data) via transcutaneous bio-telemetries. For systems observing unit activity, real-time spike sorting within an implantable device offers a unique solution to this problem. However, achieving such data compression prior to transmission via an on-node spike sorting system has several challenges. The inherent complexity of the spike sorting problem arising from various factors (such as signal variability, local field potentials, background and multi-unit activity) have required computationally intensive algorithms (e.g. PCA, wavelet transform, superparamagnetic clustering). Hence spike sorting systems have traditionally been implemented off-line, usually run on work-stations. Owing to their complexity and not-so-well scalability, these algorithms cannot be simply transformed into a resource efficient hardware. On the contrary, although there have been several attempts in implantable hardware, an implementation to match comparable accuracy to off-line within the required power and area requirements for future BMIs have yet to be proposed. Within this context, this research aims to fill in the gaps in the design towards a resource efficient implantable real-time spike sorter which achieves performance comparable to off-line methods. The research covered in this thesis target: 1) Identifying and quantifying the trade-offs on subsequent signal processing performance and hardware resource utilisation of the parameters associated with analogue-front-end. Following the development of a behavioural model of the analogue-front-end and an optimisation tool, the sensitivity of the spike sorting accuracy to different front-end parameters are quantified. 2) Identifying and quantifying the trade-offs associated with a two-stage hybrid solution to realising real-time on-node spike sorting. Initial part of the work focuses from the perspective of template matching only, while the second part of the work considers these parameters from the point of whole system including detection, sorting, and off-line training (template building). A set of minimum requirements are established which ensure robust, accurate and resource efficient operation. 3) Developing new feature extraction and spike sorting algorithms towards highly scalable systems. Based on waveform dynamics of the observed action potentials, a derivative based feature extraction and a spike sorting algorithm are proposed. These are compared with most commonly used methods of spike sorting under varying noise levels using realistic datasets to confirm their merits. The latter is implemented and demonstrated in real-time through an MCU based platform.Open Acces

Low-frequency local field potentials in primate motor cortex and their application to neural interfaces

PhD ThesisFor patients with spinal cord injury and paralysis, there are currently very limited options for clinical therapy. Brain-machine interfaces (BMIs) are neuroprosthetic devices that are being developed to record from the motor cortex in such patients, bypass the spinal lesion, and use decoded signals to control an effector, such as a prosthetic limb. The ideal BMI would be durable, reliable, totally predictable, fully-implantable, and have generous battery life. Current, state-of-the-art BMIs are limited in all of these domains; partly because the typical signals used—neuronal action potentials, or ‘spikes’—are very susceptible to micro-movement of recording electrodes. Recording spikes from the same neurons over many months is therefore difficult, and decoder behaviour may be unpredictable from day-today. Spikes also need to be digitized at high frequencies (~104 Hz) and heavily processed. As a result, devices are energy-hungry and difficult to miniaturise. Low-frequency local field potentials (lf-LFPs; < 5 Hz) are an alternative cortical signal. They are more stable and can be captured and processed at much lower frequencies (~101 Hz). Here we investigate rhythmical lf-LFP activity, related to the firing of local cortical neurons, during isometric wrist movements in Rhesus macaques. Multichannel spike-related slow potentials (SRSPs) can be used to accurately decode the firing rates of individual motor cortical neurons, and subjects can control a BMI task using this synthetic signal, as if they were controlling the actual firing rate. Lf-LFP–based firing rate estimates are stable over time – even once actual spike recordings have been lost. Furthermore, the dynamics of lf-LFPs are distinctive enough, that an unsupervised approach can be used to train a decoder to extract movement-related features for use in biofeedback BMIs. Novel electrode designs may help us optimise the recording of these signals, and facilitate progress towards a new generation of robust, implantable BMIs for patients.Research Studentship from the MRC, and Andy Jackson’s laboratory (hence this work) is supported by the Wellcome Trust

Resolution of Spike Overlapping by Biogeography-Based Optimization

There are many cases in which the separation of different sources from single channel recordings is important, for example, in fluorescence spectral overlap compensation, electrical impedance signaling, intramuscular electromyogram decomposition or in the case of spike sorting of neuron potentials from microelectrode arrays (MEA). Focusing on the latter, the problem can be faced by identifying spikes emerging from the background and clustering into different groups, indicating the activity of different neurons. Problems are found when more spikes are superimposed in overlapped waveforms. We discuss the application of Biogeography-Based Optimization (BBO) to resolve this specific problem. Our algorithm is compared with three spike-sorting methods (SpyKING Circus, Common Basis Pursuit and Klusta), showing statistically better performance (in terms of F1 score, True Positive Rate—TPR and Positive Predictive Value—PPV) in resolving overlaps in realistic, simulated data. Specifically, BBO showed median F1, TPR and PPV of 100%, 100% and about 75%, respectively, considering a simulated noise with the same spectral density as the experimental one and a similar power with highly statistically significant improvements of at least two performance indexes over each of the other three tested algorithm

Improving data quality in neuronal population recordings

Understanding how the brain operates requires understanding how large sets of neurons function together. Modern recording technology makes it possible to simultaneously record the activity of hundreds of neurons, and technological developments will soon allow recording of thousands or tens of thousands. As with all experimental techniques, these methods are subject to confounds that complicate the interpretation of such recordings, and could lead to erroneous scientific conclusions. Here, we discuss methods for assessing and improving the quality of data from these techniques, and outline likely future directions in this field

The iso-response method

Throughout the nervous system, neurons integrate high-dimensional input streams and transform them into an output of their own. This integration of incoming signals involves filtering processes and complex non-linear operations. The shapes of these filters and non-linearities determine the computational features of single neurons and their functional roles within larger networks. A detailed characterization of signal integration is thus a central ingredient to understanding information processing in neural circuits. Conventional methods for measuring single-neuron response properties, such as reverse correlation, however, are often limited by the implicit assumption that stimulus integration occurs in a linear fashion. Here, we review a conceptual and experimental alternative that is based on exploring the space of those sensory stimuli that result in the same neural output. As demonstrated by recent results in the auditory and visual system, such iso-response stimuli can be used to identify the non-linearities relevant for stimulus integration, disentangle consecutive neural processing steps, and determine their characteristics with unprecedented precision. Automated closed-loop experiments are crucial for this advance, allowing rapid search strategies for identifying iso-response stimuli during experiments. Prime targets for the method are feed-forward neural signaling chains in sensory systems, but the method has also been successfully applied to feedback systems. Depending on the specific question, “iso-response” may refer to a predefined firing rate, single-spike probability, first-spike latency, or other output measures. Examples from different studies show that substantial progress in understanding neural dynamics and coding can be achieved once rapid online data analysis and stimulus generation, adaptive sampling, and computational modeling are tightly integrated into experiments