Automatic sorting for multi-neuronal activity recorded with tetrodes in the presence of overlapping spikes

Multi-neuronal recording is a powerful electrophysiological technique that has revealed much of what is known about the neuronal interactions in the brain. However, it is difficult to detect precise spike timings, especially synchronized simultaneous firings, among closely neighboring neurons recorded by one common electrode because spike waveforms overlap on the electrode when two or more neurons fire simultaneously. In addition, the non-Gaussian variability (nonstationarity) of spike waveforms, typically seen in the presence of so-called complex spikes, limits the ability to sort multi-neuronal activities into their single-neuron components. Because of these problems, the ordinary spike-sorting techniques often give inaccurate results. Our previous study has shown that independent component analysis (ICA) can solve these problems and separate single-neuron components from multi-neuronal recordings. The ICA has, however, one serious limitation that the number of separated neurons must be less than the number of electrodes. The present study combines the ICA and the efficiency of the ordinary spike-sorting technique (k-means clustering) to solve the spike-overlapping and the nonstationarity problems with no limitation on the number of single neurons to be separated. First, multi-neuronal activities are sorted into an overly large number of clusters by k-means clustering. Second, the sorted clusters are decomposed by ICA. Third, the decomposed clusters are progressively aggregated into a minimal set of putative single neurons based on similarities of basis vectors estimated by ICA. We applied the present procedure to multi-neuronal waveforms recorded with tetrodes composed of four microwires in the prefrontal cortex of awake behaving monkeys. The results demonstrate that there are functional connections among neighboring pyramidal neurons, some of which fire in a precise simultaneous manner and that precisely time-locked monosynaptic connections are working between neighboring pyramidal neurons and interneurons. Detection of these phenomena suggests that the present procedure can sort multi-neuronal activities, which include overlapping spikes and realistic non-Gaussian variability of spike waveforms, into their single-neuron components. We processed several types of synthesized data sets in this procedure and confirmed that the procedure was highly reliable and stable. The present method provides insights into the local circuit bases of excitatory and inhibitory interactions among neighboring neurons.     

CLEC5A expression can be triggered by spike glycoprotein and may be a potential target for COVID-19 therapy

The immune response is crucial for coronavirus disease 19 (COVID-19) progression, with the participation of proinflammatory cells and cytokines, inducing lung injury and loss of respiratory function. CLEC5A expression on monocytes can be triggered by viral and bacterial infections, leading to poor outcomes. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is able to induce neutrophil activation by CLEC5A and Toll-like receptor 2, leading to an aggressive inflammatory cascade, but little is known about the molecular interactions between CLEC5A and SARS-CoV-2 proteins. Here, we aimed to explore how CLEC5A expression could be affected by SARS-CoV-2 infection using immunological tools with in vitro, in vivo, and in silico assays. The findings revealed that high levels of CLEC5A expression were found in monocytes from severe COVID-19 patients in comparison with mild COVID-19 and unexposed subjects, but not in vaccinated subjects who developed mild COVID-19. In hamsters, we detected CLEC5A gene expression during 3–15 days of Omicron strain viral challenge. Our results also showed that CLEC5A can interact with SARS-CoV-2, promoting inflammatory cytokine production, probably through an interaction with the receptor-binding domain in the N-acetylglucosamine binding site (NAG-601). The high expression of CLEC5A and high levels of proinflammatory cytokine production were reduced in vitro by a human CLEC5A monoclonal antibody. Finally, CLEC5A was triggered by spike glycoprotein, suggesting its involvement in COVID-19 progression; therapy with a monoclonal antibody could be a good strategy for COVID-19 treatment, but vaccines are still the best option to avoid hospitalization/deaths.     

A new single sucrose-gap method allowing current to be injected and the resulting potential change to be recorded

A novel single sucrose-gap technique which allows the injection of current and the recording of the resulting changes in the gap potential has been developed. Current injection is achieved discontinuously at a chopping rate of between 500 Hz and 5 kHz and the gap potential is recorded during the off-period of current injection and held until the next sampling period. This approach eliminates the potential drop in the sucrose solution and makes the measurement of electrical properties possible with a single sucrose-gap technique. Membrane properties of the dorsal roots of the bullfrog were examined using this technique. An outward-going rectification was evident around the resting potential and an inward-going rectification appeared on hyperpolarization below –70 mV. This rectification gave rise to a sigmoidal relationship between voltage and current. Hyperpolarization in response to current injection revealed a very long charging time constant. These observed membrane characteristics were in general agreement with those intracellulary recorded from the thick myelinated fiber in the frog dorsal roots.Part of this study was presented at the 8th Annual Meeting of the Neuroscience Society of Japan (Hashiguchi 1985)     

Electromagnetic irradiation may be a new approach to therapy for peri-implantitis

Peri-implantitis can lead to bone destruction around a dental implant through inflammation and immune reactions caused by bacteria adhering to the surface of the implant abutment. Electromagnetic irradiation can inhibit bacterial growth, increase bone formation, decrease bone resorption and reduce the inflammatory response. Our hypothesis is that electromagnetic irradiation may be a new treatment approach for peri-implantitis and may simultaneously maintain bone mass around the dental implant. The results would be more significant when combined with other agents, because the effect of some antibiotics and anti-inflammatory drugs is strengthened by electromagnetic irradiation. This non-invasive therapy is expected to be conducted in a convenient manner, and even by patients at home, thereby facilitating the prevention and treatment of peri-implantitis.     

A practical approach to ichthyoses with systemic manifestations

Inherited ichthyoses are rare disorders in terms of patient numbers, but abundant in terms of clinical‐genetic subtypes. These disorders are often associated with severe systemic manifestations, in addition to significant medical, cosmetic and social problems. There are 17 subtypes of syndromic ichthyosis identified so far and most patients with these syndromes are living in countries with high consanguinity rates. Frequently, clinicians cannot make a definitive diagnosis and patients are not managed properly owing to the rarity and complexity of these disorders. These difficulties make this group of ichthyosis and the patients living with them ‘orphan’. After skin and skin appendages, nervous system is the most frequently involved system in ichthyosis syndromes. Thus, association of ichthyosis with neurological symptoms provides an important clue for diagnosis. In this article, we aim to increase clinicians' comprehension of ichthyosis syndromes by providing a symptomatology‐based approach based on this observation. Additionally, we provide a review of ichthyosis syndromes, with special emphasis on neurological symptoms, hoping to attract interest to this complicated field.     

A practical approach to managing patients with HCV infection

Hepatitis C virus (HCV) infection is a major worldwide public health concern. It is a common cause of chronic liver disease and hepatocellular carcinoma. HCV antibody and HCV RNA testing are available diagnostic studies that offer high degree of accuracy. Current standard therapy includes a combination of pegylated interferon and ribavirin. Response rate is approximately 40% for genotype 1 and 80% for genotypes 2 and 3, respectively. Successful treatment can stop the progression of chronic liver disease, reduce the need for liver transplantation, and possibly decrease the risk for Hepatocellular carcinoma (HCC). Evaluating for potential treatment candidacy is an important initial step in the management of chronic HCV infection as not all individuals may need or qualify for the treatment. Understanding the natural history, the different diagnostic modalities, the current therapeutic options and, the treatment response and adverse effect profiles can help the practitioners better manage chronic HCV infection.     

Leptin in sperm analysis can be a new indicator

Purpose Radiotherapy, chemotherapy, various tumors and invasive surgery can result in ejaculatory dysfunction and testicular insufficiency. Sperm cryopreservation is the only method which can provide a baby for couples. Cryopreservation freezes tissues and cells, allowing them to be stored for future use by stopping all biological activities. Cryopreservation can cause some harmful changes in the structure and function of the sperm. Leptin molecule plays many roles in most biological processes including the satiety and cell renewal, proliferation, angiogenesis, modulation of energy expenditure and regulation of the neuroendocrine system. Leptin was also reported to be associated with spermatogenesis in several studies. Methods This study aims to use leptin molecule as a parameter for sperm motility and DNA fragmentation before and after the cryopreservation. In this study, semen samples were taken from 30 normospermic male volunteers. Each semen sample was examined for the same parameters before and after the cryopreservation. Samples were analyzed before and after cryopreservation in terms of sperm motility by morphological sperm analysis with spermac stain dye, DNA fragmentation by TUNEL assay, ultrastructural analysis with transmission electron microscopy (TEM), seminal leptin levels by ELISA method and reactive oxygen species (ROS) levels by colorimetric method. Results Decreased sperm motility, distribution of sperm morphology and increased DNA fragmentation were determined after cryopreservation. Similarly, seminal ROS and leptin levels were also increased significantly. There was a negative correlation between seminal leptin and sperm motility. Additionally, there was a positive correlation between seminal leptin and DNA fragmentation. Conclusion According to these results, leptin molecule can be used as a marker for sperm motility and DNA fragmentation before and after cryopreservation. We think that the results of this study can contribute to further studies in the clinical aspect.     

一种多维生理信号分析的新方法及其应用

背景：脑电源之间的高度相关性会导致脑电相关矩阵的秩缺损,经典的时空源定位方法不能定位相干源。 目的：发展一种相干源成像的方法,用于脑电源头表成像。 方法：提出一种多变量相关系数分解法。通过分解相关系数矩阵,得到对应变量的相关指标,该指标可以用来衡量该变量与整个系统的相关程度。通过数字试验,验证这种解法的正确性。 结果与结论：这种多变量相关系数矩阵分解算法,把变量两两之间的关系转换为每个变量与产生变量的系统之间的关系,便于相关程度的直观表达和理解,除了在认知神经科学方面有应用前景外,这种方法对其他领域的多变量分析也有一定的参考价值。     

A practical approach to grossing breast specimens

The grossing of breast specimens has been evolving over the past few decades. As image-guided core-needle biopsy has gradually replaced surgical biopsy in the initial assessment of breast lesions, most patients have a definitive diagnosis at the time of excision. Breast conserving therapy is now well accepted as a definitive treatment. Neoadjuvant therapy is also selected by a large number of patients. In addition, since its introduction in the 1990s, sentinel lymph node biopsy has become a standard procedure performed at the time of excision, as clinically indicated. Based on our institutional experience, practical guidelines for grossing breast excision specimens, as well as sentinel lymph nodes, are provided in this article.     

A practical approach to prevent gantry-couch collision for linac-based radiosurgery

Gantry-couch collision is a serious concern for treatment planning of the linear accelerator (linac) based stereotactic radiosurgery (SRS). The ability to detect collision at the time of planning eliminates the need for backup plans and preserves the useful beam angles that would be deemed unsafe and discarded otherwise. Most collision-detection schemes embedded in commercial planning software guard only against the most apparent collisions. On the other hand, a fool-proof collision-map or lookup table often requires detailed measurement of machine geometry and complex graphic operations. In this study, we have developed a simple analytical method for collision detection with the use of quick machine-specific measurements. The collision detection is mathematically solved by determining whether two facets in three-dimensional space, representing gantry and couch surfaces, intersect with each other. A computer code was implemented and tested on a Varian Clinac 600C linac equipped with a BrainLab micromultileaf collimator (MLC) device. To measure machine-specific parameters, the lesion isocenter was set to the origin of the stereotactic coordinate system. The reference coordinates of couch bracket corners and micro-MLC to the linac isocenter were measured only once in the treatment room before they were incorporated into the computer program. Couch, gantry, and collimator were subsequently translated and rotated to study the clearance of various beam arrangements and lesion locations. Predicted results were verified at the machine. Our method correctly confirmed clearance for a retrospective study of 54 previously treated SRS plans (76 isocenters). It also accurately predicted the collisions for all ten artificially created cases. In conclusion, we have developed an analytical method for SRS collision detection that is accurate, easy to implement, and computationally inexpensive.     

颈内动脉床旁动脉瘤对侧入路的显微外科解剖研究

目的:为经对侧手术入路治疗颈内动脉(ICA)床旁动脉瘤提供解剖学依据。方法:15例成人尸头标本,在手术显微镜下经对侧额颞入路模拟进行ICA床旁动脉瘤手术。暴露对侧ICA眼段、床段及其分支,进行解剖学观察,测量参数A和B以评估视交叉前池的大小。结果:在所有15例标本(共30侧)上,对侧ICA眼段和床段及垂体上动脉均被满意暴露。在14例标本(共28侧)上暴露了对侧眼动脉(OA)起始点。参数A和B分别为(8.0±1.2)mm(5.2￣10.4mm)和(13.6±1.7)mm(10.4￣17.3mm)。视交叉前池的大小对ICA床段的暴露无影响;视交叉前池越小,ICA眼段内侧面暴露的面积越少。暴露过程中无需牵拉视神经和ICA,或仅需轻微牵拉视神经。结论:对侧入路适用于直径较小的起源于ICA眼段近端及床段内侧面并向内侧突出的床旁动脉瘤。