Comparison of Different Spike Sorting Subtechniques Based on Rat Brain Basolateral Amygdala Neuronal Activity

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.Comment: 8 pages, 12 figure

Increased GABAA Receptor ε-Subunit Expression on Ventral Respiratory Column Neurons Protects Breathing during Pregnancy

GABAergic signaling is essential for proper respiratory function. Potentiation of this signaling with allosteric modulators such as anesthetics, barbiturates, and neurosteroids can lead to respiratory arrest. Paradoxically, pregnant animals continue to breathe normally despite nearly 100-fold increases in circulating neurosteroids. ε subunit-containing GABAARs are insensitive to positive allosteric modulation, thus we hypothesized that pregnant rats increase ε subunit-containing GABAAR expression on brainstem neurons of the ventral respiratory column (VRC). In vivo, pregnancy rendered respiratory motor output insensitive to otherwise lethal doses of pentobarbital, a barbiturate previously used to categorize the ε subunit. Using electrode array recordings in vitro, we demonstrated that putative respiratory neurons of the preBötzinger Complex (preBötC) were also rendered insensitive to the effects of pentobarbital during pregnancy, but unit activity in the VRC was rapidly inhibited by the GABAAR agonist, muscimol. VRC unit activity from virgin and post-partum females was potently inhibited by both pentobarbital and muscimol. Brainstem ε subunit mRNA and protein levels were increased in pregnant rats, and GABAAR ε subunit expression co-localized with a marker of rhythm generating neurons (neurokinin 1 receptors) in the preBötC. These data support the hypothesis that pregnancy renders respiratory motor output and respiratory neuron activity insensitive to barbiturates, most likely via increased ε subunit-containing GABAAR expression on respiratory rhythm-generating neurons. Increased ε subunit expression may be critical to preserve respiratory function (and life) despite increased neurosteroid levels during pregnancy

Gershgorin circle theorem-based feature extraction for biomedical signal analysis

Recently, graph theory has become a promising tool for biomedical signal analysis, wherein the signals are transformed into a graph network and represented as either adjacency or Laplacian matrices. However, as the size of the time series increases, the dimensions of transformed matrices also expand, leading to a significant rise in computational demand for analysis. Therefore, there is a critical need for efficient feature extraction methods demanding low computational time. This paper introduces a new feature extraction technique based on the Gershgorin Circle theorem applied to biomedical signals, termed Gershgorin Circle Feature Extraction (GCFE). The study makes use of two publicly available datasets: one including synthetic neural recordings, and the other consisting of EEG seizure data. In addition, the efficacy of GCFE is compared with two distinct visibility graphs and tested against seven other feature extraction methods. In the GCFE method, the features are extracted from a special modified weighted Laplacian matrix from the visibility graphs. This method was applied to classify three different types of neural spikes from one dataset, and to distinguish between seizure and non-seizure events in another. The application of GCFE resulted in superior performance when compared to seven other algorithms, achieving a positive average accuracy difference of 2.67% across all experimental datasets. This indicates that GCFE consistently outperformed the other methods in terms of accuracy. Furthermore, the GCFE method was more computationally-efficient than the other feature extraction techniques. The GCFE method can also be employed in real-time biomedical signal classification where the visibility graphs are utilized such as EKG signal classification

SpikeDeep-classifier: a deep-learning based fully automatic offline spike sorting algorithm

Objective. Advancements in electrode design have resulted in micro-electrode arrays with hundreds of channels for single cell recordings. In the resulting electrophysiological recordings, each implanted electrode can record spike activity (SA) of one or more neurons along with background activity (BA). The aim of this study is to isolate SA of each neural source. This process is called spike sorting or spike classification. Advanced spike sorting algorithms are time consuming because of the human intervention at various stages of the pipeline. Current approaches lack generalization because the values of hyperparameters are not fixed, even for multiple recording sessions of the same subject. In this study, a fully automatic spike sorting algorithm called "SpikeDeep-Classifier" is proposed. The values of hyperparameters remain fixed for all the evaluation data. Approach. The proposed approach is based on our previous study (SpikeDeeptector) and a novel background activity rejector (BAR), which are both supervised learning algorithms and an unsupervised learning algorithm (K-means). SpikeDeeptector and BAR are used to extract meaningful channels and remove BA from the extracted meaningful channels, respectively. The process of clustering becomes straight-forward once the BA is completely removed from the data. Then, K-means with a predefined maximum number of clusters is applied on the remaining data originating from neural sources only. Lastly, a similarity-based criterion and a threshold are used to keep distinct clusters and merge similar looking clusters. The proposed approach is called cluster accept or merge (CAOM) and it has only two hyperparameters (maximum number of clusters and similarity threshold) which are kept fixed for all the evaluation data after tuning. Main Results. We compared the results of our algorithm with ground-truth labels. The algorithm is evaluated on data of human patients and publicly available labeled non-human primates (NHPs) datasets. The average accuracy of BAR on datasets of human patients is 92.3% which is further reduced to 88.03% after (K-means + CAOM). In addition, the average accuracy of BAR on a publicly available labeled dataset of NHPs is 95.40% which reduces to 86.95% after (K-mean + CAOM). Lastly, we compared the performance of the SpikeDeep-Classifier with two human experts, where SpikeDeep-Classifier has produced comparable results. Significance. The results demonstrate that "SpikeDeep-Classifier" possesses the ability to generalize well on a versatile dataset and henceforth provides a generalized well on a versatile dataset and henceforth provides a generalized and fully automated solution to offline spike sorting

ラット大脳新皮質における局所神経細胞群動特性の解明

Tohoku University川島隆太課

Automatic online spike sorting with singular value decomposition and fuzzy C-mean clustering

Background: Understanding how neurons contribute to perception, motor functions and cognition requires the reliable detection of spiking activity of individual neurons during a number of different experimental conditions. An important problem in computational neuroscience is thus to develop algorithms to automatically detect and sort the spiking activity of individual neurons from extracellular recordings. While many algorithms for spike sorting exist, the problem of accurate and fast online sorting still remains a challenging issue.Results: Here we present a novel software tool, called FSPS (Fuzzy SPike Sorting), which is designed to optimize: (i) fast and accurate detection, (ii) offline sorting and (iii) online classification of neuronal spikes with very limited or null human intervention. The method is based on a combination of Singular Value Decomposition for fast and highly accurate pre-processing of spike shapes, unsupervised Fuzzy C-mean, high-resolution alignment of extracted spike waveforms, optimal selection of the number of features to retain, automatic identification the number of clusters, and quantitative quality assessment of resulting clusters independent on their size. After being trained on a short testing data stream, the method can reliably perform supervised online classification and monitoring of single neuron activity. The generalized procedure has been implemented in our FSPS spike sorting software (available free for non-commercial academic applications at the address: http://www.spikesorting.com) using LabVIEW (National Instruments, USA). We evaluated the performance of our algorithm both on benchmark simulated datasets with different levels of background noise and on real extracellular recordings from premotor cortex of Macaque monkeys. The results of these tests showed an excellent accuracy in discriminating low-amplitude and overlapping spikes under strong background noise. The performance of our method is competitive with respect to other robust spike sorting algorithms.Conclusions: This new software provides neuroscience laboratories with a new tool for fast and robust online classification of single neuron activity. This feature could become crucial in situations when online spike detection from multiple electrodes is paramount, such as in human clinical recordings or in brain-computer interfaces.Instituto de Física La Plat