Unsupervised spike sorting based on discriminative subspace learning.

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Spike sorting is a fundamental preprocessing step for many neuroscience studies which rely on the analysis of spike trains. In this paper, we present two unsupervised spike sorting algorithms based on discriminative subspace learning. The first algorithm simultaneously learns the discriminative feature subspace and performs clustering. It uses histogram of features in the most discriminative projection to detect the number of neurons. The second algorithm performs hierarchical divisive clustering that learns a discriminative 1-dimensional subspace for clustering in each level of the hierarchy until achieving almost unimodal distribution in the subspace. The algorithms are tested on synthetic and in-vivo data, and are compared against two widely used spike sorting methods. The comparative results demonstrate that our spike sorting methods can achieve substantially higher accuracy in lower dimensional feature space, and they are highly robust to noise. Moreover, they provide significantly better cluster separability in the learned subspace than in the subspace obtained by principal component analysis or wavelet transform.

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CitationsShowing 6 of 6 papers
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  • 10.1101/387142
Cortex-wide neural interfacing via transparent polymer skulls
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  • Leila Ghanbari + 14 more

ABSTRACTNeural computations occurring simultaneously in multiple cerebral cortical regions are critical for mediating cognition, perception and sensorimotor behaviors. Enormous progress has been made in understanding how neural activity in specific cortical regions contributes to behavior. However, there is a lack of tools that allow simultaneous monitoring and perturbing neural activity from multiple cortical regions. To fill this need, we have engineered “See-Shells” – digitally designed, morphologically realistic, transparent polymer skulls that allow long-term (>200 days) optical access to 45 mm2 of the dorsal cerebral cortex in the mouse. We demonstrate the ability to perform mesoscopic imaging, as well as cellular and subcellular resolution two-photon imaging of neural structures up to 600 µm through the See-Shells. See-Shells implanted on transgenic mice expressing genetically encoded calcium (Ca2+) indicators allow tracking of neural activities from multiple, non-contiguous regions spread across millimeters of the cortex. Further, neural probes can access the brain through perforated See-Shells, either for perturbing or recording neural activity from localized brain regions simultaneously with whole cortex imaging. As See-Shells can be constructed using readily available desktop fabrication tools and modified to fit a range of skull geometries, they provide a powerful tool for investigating brain structure and function.

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  • 10.3389/dyst.2023.10974
Altered brain state during episodic dystonia in tottering mice decouples primary motor cortex from limb kinematics.
  • Feb 2, 2023
  • Dystonia
  • Madelyn M Gray + 3 more

Episodic Ataxia Type 2 (EA2) is a rare neurological disorder caused by a mutation in the CACNA1A gene, encoding the P/Q-type voltage-gated Ca2+ channel important for neurotransmitter release. Patients with this channelopathy exhibit both cerebellar and cerebral pathologies, suggesting the condition affects both regions. The tottering (tg/tg) mouse is the most commonly used EA2 model due to an orthologous mutation in the cacna1a gene. The tg/tg mouse has three prominent behavioral phenotypes: a dramatic episodic dystonia; absence seizures with generalized spike and wave discharges (GSWDs); and mild ataxia. We previously observed a novel brain state, transient low-frequency oscillations (LFOs) in the cerebellum and cerebral cortex under anesthesia. In this study, we examine the relationships among the dystonic attack, GSWDs, and LFOs in the cerebral cortex. Previous studies characterized LFOs in the motor cortex of anesthetized tg/tg mice using flavoprotein autofluorescence imaging testing the hypothesis that LFOs provide a mechanism for the paroxysmal dystonia. We sought to obtain a more direct understanding of motor cortex (M1) activity during the dystonic episodes. Using two-photon Ca2+ imaging to investigate neuronal activity in M1 before, during, and after the dystonic attack, we show that there is not a significant change in the activity of M1 neurons from baseline through the attack. We also conducted simultaneous, multi-electrode recordings to further understand how M1 cellular activity and local field potentials change throughout the progression of the dystonic attack. Neither putative pyramidal nor inhibitory interneuron firing rate changed during the dystonic attack. However, we did observe a near complete loss of GSWDs during the dystonic attack in M1. Finally, using spike triggered averaging to align simultaneously recorded limb kinematics to the peak Ca2+ response, and vice versa, revealed a reduction in the spike triggered average during the dystonic episodes. Both the loss of GSWDs and the reduction in the coupling suggest that, during the dystonic attack, M1 is effectively decoupled from other structures. Overall, these results indicate that the attack is not initiated or controlled in M1, but elsewhere in the motor circuitry. The findings also highlight that LFOs, GSWDs, and dystonic attacks represent three brain states in tg/tg mice.

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  • 10.1109/tnsre.2021.3074162
A Unified Optimization Model of Feature Extraction and Clustering for Spike Sorting.
  • Jan 1, 2021
  • IEEE Transactions on Neural Systems and Rehabilitation Engineering
  • Libo Huang + 2 more

Spike sorting technologies support neuroscientists to access the neural activity with single-neuron or single-action-potential resolutions. However, conventional spike sorting technologies perform the feature extraction and the clustering separately after the spikes are well detected. It not only induces many redundant processes, but it also yields a lower accuracy and an unstable result especially when noises and/or overlapping spikes exist in the dataset. To address these issues, this paper proposes a unified optimization model integrating the feature extraction and the clustering for spike sorting. Unlike the widely used combination strategies, i.e., performing the principal component analysis (PCA) for spike feature extraction and the K-means (KM) for clustering in sequence, interestingly, this paper finds the solution of the proposed unified model by iteratively performing PCA and KM-like procedures. Subsequently, by embedding the K-means++ strategy in KM-like initializing and a comparison updating rule in the solving process, the proposed model can well handle the noises and overlapping interference as well as enjoy a high accuracy and a low computational complexity. Finally, an automatic spike sorting method is derived after taking the best of the clustering validity indices into the proposed model. The extensive numerical simulation results on both synthetic and real-world datasets confirm that our proposed method outperforms the related state-of-the-art approaches.

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  • Cite Count Icon 17
  • 10.1088/1741-2552/aab385
A review on cluster estimation methods and their application to neural spike data
  • Apr 16, 2018
  • Journal of Neural Engineering
  • James Zhang + 6 more

The extracellular action potentials recorded on an electrode result from the collective simultaneous electrophysiological activity of an unknown number of neurons. Identifying and assigning these action potentials to their firing neurons—‘spike sorting’—is an indispensable step in studying the function and the response of an individual or ensemble of neurons to certain stimuli. Given the task of neural spike sorting, the determination of the number of clusters (neurons) is arguably the most difficult and challenging issue, due to the existence of background noise and the overlap and interactions among neurons in neighbouring regions. It is not surprising that some researchers still rely on visual inspection by experts to estimate the number of clusters in neural spike sorting. Manual inspection, however, is not suitable to processing the vast, ever-growing amount of neural data. To address this pressing need, in this paper, thirty-three clustering validity indices have been comprehensively reviewed and implemented to determine the number of clusters in neural datasets. To gauge the suitability of the indices to neural spike data, and inform the selection process, we then calculated the indices by applying k-means clustering to twenty widely used synthetic neural datasets and one empirical dataset, and compared the performance of these indices against pre-existing ground truth labels. The results showed that the top five validity indices work consistently well across variations in noise level, both for the synthetic datasets and the real dataset. Using these top performing indices provides strong support for the determination of the number of neural clusters, which is essential in the spike sorting process.

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  • 10.1038/s41598-022-19771-8
A robust spike sorting method based on the joint optimization of linear discrimination analysis and density peaks
  • Sep 15, 2022
  • Scientific Reports
  • Yiwei Zhang + 5 more

Spike sorting is a fundamental step in extracting single-unit activity from neural ensemble recordings, which play an important role in basic neuroscience and neurotechnologies. A few algorithms have been applied in spike sorting. However, when noise level or waveform similarity becomes relatively high, their robustness still faces a big challenge. In this study, we propose a spike sorting method combining Linear Discriminant Analysis (LDA) and Density Peaks (DP) for feature extraction and clustering. Relying on the joint optimization of LDA and DP: DP provides more accurate classification labels for LDA, LDA extracts more discriminative features to cluster for DP, and the algorithm achieves high performance after iteration. We first compared the proposed LDA-DP algorithm with several algorithms on one publicly available simulated dataset and one real rodent neural dataset with different noise levels. We further demonstrated the performance of the LDA-DP method on a real neural dataset from non-human primates with more complex distribution characteristics. The results show that our LDA-DP algorithm extracts a more discriminative feature subspace and achieves better cluster quality than previously established methods in both simulated and real data. Especially in the neural recordings with high noise levels or waveform similarity, the LDA-DP still yields a robust performance with automatic detection of the number of clusters. The proposed LDA-DP algorithm achieved high sorting accuracy and robustness to noise, which offers a promising tool for spike sorting and facilitates the following analysis of neural population activity.

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  • 10.1101/2022.02.10.479846
A Robust Spike Sorting Method based on the Joint Optimization of Linear Discrimination Analysis and Density Peaks
  • Feb 10, 2022
  • Yiwei Zhang + 5 more

Abstract ObjectiveSpike sorting is a fundamental step in extracting single-unit activity from neural ensemble recordings, which play an important role in basic neuroscience and neurotechnologies. A few algorithms have been applied in spike sorting. However, when noise level or waveform similarity becomes relatively high, their robustness still faces a big challenge.ApproachIn this study, we propose a spike sorting method combining Linear Discriminant Analysis (LDA) and Density Peaks (DP) for feature extraction and clustering. Relying on the joint optimization of LDA and DP: DP provides more accurate classification labels for LDA, LDA extracts more discriminative features to cluster for DP, and the algorithm achieves high performance after iteration. We first compared the proposed LDA-DP algorithm with several algorithms on one publicly available simulated dataset and one real rodent neural dataset with different noise levels. We further demonstrated the performance of the LDA-DP method on a real neural dataset from non-human primates with more complex distribution characteristics.Main resultsThe results show that our LDA-DP algorithm extracts a more discriminative feature subspace and achieves better cluster quality than previously established methods in both simulated and real data. Especially in the neural recordings with high noise levels or waveform similarity, the LDA-DP still yields a robust performance with automatic detection of the number of clusters.SignificanceThe proposed LDA-DP algorithm achieved high sorting accuracy and robustness to noise, which offers a promising tool for spike sorting and facilitates the following analysis of neural population activity.

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Objective. Spike sorting is a fundamental preprocessing step for many neuroscience studies which rely on the analysis of spike trains. Most of the feature extraction and dimensionality reduction techniques that have been used for spike sorting give a projection subspace which is not necessarily the most discriminative one. Therefore, the clusters which appear inherently separable in some discriminative subspace may overlap if projected using conventional feature extraction approaches leading to a poor sorting accuracy especially when the noise level is high. In this paper, we propose a noise-robust and unsupervised spike sorting algorithm based on learning discriminative spike features for clustering. Approach. The proposed algorithm uses discriminative subspace learning to extract low dimensional and most discriminative features from the spike waveforms and perform clustering with automatic detection of the number of the clusters. The core part of the algorithm involves iterative subspace selection using linear discriminant analysis and clustering using Gaussian mixture model with outlier detection. A statistical test in the discriminative subspace is proposed to automatically detect the number of the clusters. Main results. Comparative results on publicly available simulated and real in vivo datasets demonstrate that our algorithm achieves substantially improved cluster distinction leading to higher sorting accuracy and more reliable detection of clusters which are highly overlapping and not detectable using conventional feature extraction techniques such as principal component analysis or wavelets. Significance. By providing more accurate information about the activity of more number of individual neurons with high robustness to neural noise and outliers, the proposed unsupervised spike sorting algorithm facilitates more detailed and accurate analysis of single- and multi-unit activities in neuroscience and brain machine interface studies.

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This study introduces a new spike sorting method that classifies spike waveforms from multiunit recordings into spike trains of individual neurons. In particular, we develop a method to sort a spike mixture generated by a heterogeneous neural population. Such a spike sorting has a significant practical value, but was previously difficult. The method combines a feature extraction method, which we may term “multimodality-weighted principal component analysis” (mPCA), and a clustering method by variational Bayes for Student's t mixture model (SVB). The performance of the proposed method was compared with that of other conventional methods for simulated and experimental data sets. We found that the mPCA efficiently extracts highly informative features as clusters clearly separable in a relatively low-dimensional feature space. The SVB was implemented explicitly without relying on Maximum-A-Posterior (MAP) inference for the “degree of freedom” parameters. The explicit SVB is faster than the conventional SVB derived with MAP inference and works more reliably over various data sets that include spiking patterns difficult to sort. For instance, spikes of a single bursting neuron may be separated incorrectly into multiple clusters, whereas those of a sparsely firing neuron tend to be merged into clusters for other neurons. Our method showed significantly improved performance in spike sorting of these “difficult” neurons. A parallelized implementation of the proposed algorithm (EToS version 3) is available as open-source code at http://etos.sourceforge.net/.

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