SigMate: a MATLAB-based automated tool for extracellular neuronal signal processing and analysis

Rapid advances in neuronal probe technology for multisite recording of brain activity have posed a significant challenge to neuroscientists for processing and analyzing the recorded signals. To be able to infer meaningful conclusions quickly and accurately from large datasets, automated and sophisticated signal processing and analysis tools are required. This paper presents a Matlab-based novel tool, “SigMate”, incorporating standard methods to analyze spikes and EEG signals, and in-house solutions for local field potentials (LFPs) analysis. Available modules at present are – 1. In-house developed algorithms for: data display (2D and 3D), file operations (file splitting, file concatenation, and file column rearranging), baseline correction, slow stimulus artifact removal, noise characterization and signal quality assessment, current source density (CSD) analysis, latency estimation from LFPs and CSDs, determination of cortical layer activation order using LFPs and CSDs, and single LFP clustering; 2. Existing modules: spike detection, sorting and spike train analysis, and EEG signal analysis. SigMate has the flexibility of analyzing multichannel signals as well as signals from multiple recording sources. The in-house developed tools for LFP analysis have been extensively tested with signals recorded using standard extracellular recording electrode, and planar and implantable multi transistor array (MTA) based neural probes. SigMate will be disseminated shortly to the neuroscience community under the open-source GNU-General Public License

An automated method for detection of layer activation order in information processing pathway of rat barrel cortex under mechanical whisker stimulation

Rodents perform object localization, texture and shape discrimination very precisely through whisking. During whisking, microcircuits in corresponding barrel columns get activated to segregate and integrate tactile information through the information processing pathway. Sensory signals are projected through the brainstem and thalamus to the corresponding ‘barrel columns’ where different cortical layers are activated during signal projection. Therefore, having precise information about the layer activation order is desirable to better understand this signal processing pathway. This work proposes an automated, computationally efficient and easy to implement method to determine the cortical layer activation from intracortically recorded local field potentials (LFPs) and derived current source density (CSD) profiles: 1. Barrel cortex LFPs are represented by a template of four subsequent events: small positive/negative (E1) → large negative (E2) → slow positive (E3)→ slow long negative (E4). The method exploits the layer specific characteristics of LFPs to obtain latencies of the individual events (E1–E4), then taking the latency of E2 for calculating the layer activation order. 2. The corresponding CSD profile is calculated from the LFPs and the first sink’s peak is considered as a reference point to calculate latencies and evaluate the layer activation order. Other reference points require manual calculation. Similar results of layer activation sequence are found using LFPs and CSDs. Extensive tests on LFPs recorded using standard borosilicate micropipettes demonstrated the method’s workability. An interpretation of layer activation order and CSD profiles on the basis of a simplified interacortical barrel column architecture is also provided

An automated classification method for single sweep local field potentials recorded from rat barrel cortex under mechanical whisker stimulation

Understanding brain signals as an outcome of brain’s information processing is a challenge for the neuroscience and neuroengineering community. Rodents sense and explore the environment through whisking. The local field potentials (LFPs) recorded from the barrel 28 columns of the rat somatosensory cortex (S1) during whisking provide information about the tactile information processing pathway. Particularly when using large-scale high-resolution neuronal probes, during each experiment many single LFPs are recorded as an outcome of underlying neuronal network activation and averaged to extract information. However, single LFP signals are frequently very different from each other and extracting information provided by their shape is a useful way to better decode information transmitted by the network. In this work, we propose an automated method capable of classifying these signals based on their shapes. We used template matching approach to recognize single LFPs and extracted the contour information from the recognized signal to generate a feature matrix, which is then classified using the intelligent K–means clustering. As an application example, shape specific information (e.g., latency, and amplitude) of LFPs evoked in the rat somatosensory barrel cortex and used in decoding the rat whiskers information processing pathway is provided by the method

Mechanical and Electrophysiological Properties of the Sarcolemma of Muscle Fibers in Two Murine Models of Muscle Dystrophy: Col6a1−/− and Mdx

This study aimed to analyse the sarcolemma of Col6a1−/− fibers in comparison with wild type and mdx fibers, taken as positive control in view of the known structural and functional alterations of their membranes. Structural and mechanical properties were studied in single muscle fibers prepared from FDB muscle using atomic force microscopy (AFM) and conventional electrophysiological techniques to measure ionic conductance and capacitance. While the sarcolemma topography was preserved in both types of dystrophic fibers, membrane elasticity was significantly reduced in Col6a1−/− and increased in mdx fibers. In the membrane of Col6a1−/− fibers ionic conductance was increased likely due to an increased leakage, whereas capacitance was reduced, and the action potential (ap) depolarization rate was reduced. The picture emerging from experiments on fibers in culture was consistent with that obtained on intact freshly dissected muscle. Mdx fibers in culture showed a reduction of both membrane conductance and capacitance. In contrast, in mdx intact FDB muscle resting conductance was increased while resting potential and ap depolarization rate were reduced, likely indicating the presence of a consistent population of severely altered fibers which disappear during the culture preparation

On the way to large-scale and high-resolution brain-chip interfacing

Brain-chip-interfaces (BCHIs) are hybrid entities where chips and nerve cells establish a close physical interaction allowing the transfer of information in one or both directions. Typical examples are represented by multi-site-recording chips interfaced to cultured neurons, cultured/acute brain slices, or implanted “in vivo”. This paper provides an overview on recent achievements in our laboratory in the field of BCHIs leading to enhancement of signals transmission from nerve cells to chip or from chip to nerve cells with an emphasis on in vivo interfacing, either in terms of signal-to-noise ratio or of spatiotemporal resolution. Oxide-insulated chips featuring large-scale and high-resolution arrays of stimulation and recording elements are presented as a promising technology for high spatiotemporal resolution interfacing, as recently demonstrated by recordings obtained from hippocampal slices and brain cortex in implanted animals. Finally, we report on an automated tool for processing and analysis of acquired signals by BCHIs

Influence of Myocardial Fibrosis on Left Ventricular Hypertrophy in Patients with Symptomatic Severe Aortic Stenosis.

Aim: It was the aim of our study to determine whether myocardial fibrosis influences physiologic or non-physiologic left ventricular (LV) hypertrophy in severe aortic stenosis. Methods: Myocardial fibrosis was evaluated using specimens taken from the ventricular septum in 79 patients submitted to aortic valve replacement because of symptomatic aortic stenosis. Patients were considered to have physiologic LV hypertrophy if end-systolic wall stress, evaluated by echocardiography, was 90 kdyn/cm(2) were considered to have non-physiologic hypertrophy. Results: Fibrosis tissue mass index was significantly inversely related with LV fractional shortening and directly related with LV diastolic and systolic diameter and LV mass index (LVMI). Patients with non-physiologic hypertrophy (n = 24) had a higher LVMI due to larger LV diastolic and systolic diameters with thinner wall, resulting in lower relative wall thickness. These patients had a higher fibrosis tissue mass index and impaired LV systolic and diastolic functions, as suggested by lower LV fractional shortening and higher mean wedge pressure. At follow-up of 7.4 \ub1 2.1 months, the LVMI and New York Heart Association class remained higher in patients with non-physiologic hypertrophy. Conclusions: Our study suggests a different quality of hypertrophies in patients with aortic stenosis, where myocardial fibrosis seems to be the critical abnormality that differentiates adaptive from maladaptive response to increased afterload

Prognostic Value of Indeterminable Anaerobic Threshold in Heart Failure.

Background In patients with heart failure (HF), during maximal cardiopulmonary exercise test, anaerobic threshold (AT) is not always identified. We evaluated whether this finding has a prognostic meaning. Methods and Results We recruited and prospectively followed up, in 14 dedicated HF units, 3058 patients with systolic (left ventricular ejection fraction <40%) HF in stable clinical conditions, New York Heart Association class I to III, who underwent clinical, laboratory, echocardiographic, and cardiopulmonary exercise test investigations at study enrollment. We excluded 921 patients who did not perform a maximal exercise, based on lack of achievement of anaerobic metabolism (peak respiratory quotient 1.05). Primary study end point was a composite of cardiovascular death and urgent cardiac transplant, and secondary end point was all-cause death. Median follow-up was 3.01 (1.39-4.98) years. AT was identified in 1935 out of 2137 patients (90.54%). At multivariable logistic analysis, failure in detecting AT resulted significantly in reduced peak oxygen uptake and higher metabolic exercise and cardiac and kidney index score value, a powerful prognostic composite HF index (P<0.001). At multivariable analysis, the following variables were significantly associated with primary study end point: peak oxygen uptake (% pred; P<0.001; hazard ratio [HR]=0.977; confidence interval [CI]=0.97-0.98), ventilatory efficiency slope (P=0.01; HR=1.02; CI=1.01-1.03), hemoglobin (P<0.05; HR=0.931; CI=0.87-1.00), left ventricular ejection fraction (P<0.001; HR=0.948; CI=0.94-0.96), renal function (modification of diet in renal disease; P<0.001; HR=0.990; CI=0.98-0.99), sodium (P<0.05; HR=0.967; CI=0.94-0.99), and AT nonidentification (P<0.05; HR=1.41; CI=1.06-1.89). Nonidentification of AT remained associated to prognosis also when compared with metabolic exercise and cardiac and kidney index score (P<0.01; HR=1.459; CI=1.09-1.10). Similar results were obtained for the secondary study end point. Conclusions The inability to identify AT most often occurs in patients with severe HF, and it has an independent prognostic role in HF

Transfusional approach in multi-ethnic Sickle Cell patients: real-world practice data from a Multicenter survey in Italy

Sickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder characterized by recurrent acute vaso-occlusive crises (VOCs and anemia). Gold standard treatments are hydroxycarbamide (HC) and/or different red blood cell (RBC) transfusion regimens to limit disease progression. Here, we report a retrospective study on 1,579 SCD patients (median age 23 years; 802 males/777 females), referring to 34 comprehensive Italian centers for hemoglobinopathies. Although we observed a similar proportion of Caucasian (47.9%) and African (48.7%) patients, Italian SCD patients clustered into two distinct overall groups: children of African descent and adults of Caucasian descent. We found a subset of SCD patients requiring more intensive therapy with a combination of HC plus chronic transfusion regimen, due to partial failure of HC treatment alone in preventing or reducing sickle cell-related acute manifestations. Notably, we observed a higher use of acute transfusion approaches for SCD patients of African descent when compared to Caucasian subjects. This might be related to (i) age of starting HC treatment; (ii) patients' low social status; (iii) patients' limited access to family practitioners; or (iv) discrimination. In our cohort, alloimmunization was documented in 135 patients (8.5%) and was more common in Caucasians (10.3%) than in Africans (6.6%). Alloimmunization was similar in male and female and more frequent in adults than in children. Our study reinforces the importance of donor-recipient exact matching for ABO, Rhesus, and Kell antigen systems for RBC compatibility as a winning strategy to avoid or limit alloimmunization events that negatively impact the clinical management of SCD-related severe complications

The additional value of patient-reported health status in predicting 1-year mortality after invasive coronary procedures: A report from the Euro Heart Survey on Coronary Revascularisation

Objective: Self-perceived health status may be helpful in identifying patients at high risk for adverse outcomes. The Euro Heart Survey on Coronary Revascularization (EHS-CR) provided an opportunity to explore whether impaired health status was a predictor of 1-year mortality in patients with coronary artery disease (CAD) undergoing angiographic procedures. Methods: Data from the EHS-CR that included 5619 patients from 31 member countries of the European Society of Cardiology were used. Inclusion criteria for the current study were completion of a self-report measure of health status, the EuroQol Questionnaire (EQ-5D) at discharge and information on 1-year follow-up, resulting in a study population of 3786 patients. Results: The 1-year mortality was 3.2% (n = 120). Survivors reported fewer problems on the five dimensions of the EQ-5D as compared with non-survivors. A broad range of potential confounders were adjusted for, which reached a p<0.10 in the unadjusted analyses. In the adjusted analyses, problems with self-care (OR 3.45; 95% CI 2.14 to 5.59) and a low rating (≤ 60) on health status (OR 2.41; 95% CI 1.47 to 3.94) were the most powerful independent predictors of mortality, among the 22 clinical variables included in the analysis. Furthermore, patients who reported no problems on all five dimensions had significantly lower 1-year mortality rates (OR 0.47; 95% CI 0.28 to 0.81). Conclusions: This analysis shows that impaired health status is associated with a 2-3-fold increased risk of all-cause mortality in patients with CAD, independent of other conventional risk factors. These results highlight the importance of including patients' subjective experience of their own health status in the evaluation strategy to optimise risk stratification and management in clinical practice

Sex- and age-related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long-Term Registry

Aims: This study aimed to assess age- and sex-related differences in management and 1-year risk for all-cause mortality and hospitalization in chronic heart failure (HF) patients. Methods and results: Of 16 354 patients included in the European Society of Cardiology Heart Failure Long-Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline-directed medical therapy (GDMT) were high (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P\ua0 64 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1-year follow-up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all-cause mortality were lower in women than in men (7.1% vs. 8.7%; P\ua0=\ua00.015), as were rates of all-cause hospitalization (21.9% vs. 27.3%; P\ua075 years. Conclusions: There was a decline in GDMT use with advanced age in both sexes. Sex was not an independent predictor of GDMT or adverse outcomes. However, age >75 years independently predicted lower GDMT use and higher all-cause mortality in patients with LVEF 6445%