An automated method for characterization of evoked single-trial local field potentials recorded from rat barrel cortex under mechanical whisker stimulation

Rodents explore their surroundings through whisking by localizing objects and detecting textures very precisely. During such tactile exploration, whisker deflection is first mechanically transduced by receptors and then information encoded throughout the somatosensory pathway ending in the somatosensory ‘barrel’ cortex. In the barrel cortex, tactile information from a single whisker is segregated and processed in a cortical column corresponding to the deflected whisker. Local Field Potentials (LFPs) generated by whisker deflection in the barrel cortex present typical signatures in terms of shape and amplitude that are related to the activation of the local neuronal populations. Therefore, rigorous analysis of such responses may reveal important features about the function of underlying neuronal microcircuits. In this context, software methods for characterizing single-trial LFPs are needed that are also suitable for online extraction of LFP features and for brain–machine interfacing applications. In this work, we present an automated and efficient method to analyze evoked LFP responses in the rat barrel cortex through automatic removal of stimulation artifacts, detection of single events and characterization of their relevant parameters. Evoked single-trial LFPs recorded under two different anesthetics are examined to demonstrate the feasibility, accuracy and applicability of the method

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

Plasticity and Adaptation in Neuromorphic Biohybrid Systems

Neuromorphic systems take inspiration from the principles of biological information processing to form hardware platforms that enable the large-scale implementation of neural networks. The recent years have seen both advances in the theoretical aspects of spiking neural networks for their use in classification and control tasks and a progress in electrophysiological methods that is pushing the frontiers of intelligent neural interfacing and signal processing technologies. At the forefront of these new technologies, artificial and biological neural networks are tightly coupled, offering a novel \u201cbiohybrid\u201d experimental framework for engineers and neurophysiologists. Indeed, biohybrid systems can constitute a new class of neuroprostheses opening important perspectives in the treatment of neurological disorders. Moreover, the use of biologically plausible learning rules allows forming an overall fault-tolerant system of co-developing subsystems. To identify opportunities and challenges in neuromorphic biohybrid systems, we discuss the field from the perspectives of neurobiology, computational neuroscience, and neuromorphic engineering. \ua9 2020 The Author(s

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

New evidence reveals the earliest use of cinnabar in the western Mediterranean: The Neolithic settlement of La Marmotta (Lazio, Italy)

Numerous researchers point out the emergence of human symbolism is related to the evolution of the complexity of human cognition. Red mineral pigments have been used extensively, particularly with anatomically modern humans, for various purposes. However, the management and supply of these pigments during prehistoric periods remains poorly investigated. Still today, the limited application of physico-chemical analyses often leads to a simplistic attribution of these pigments as ochre. The studies of data from recent literature presented in our paper show a progressive introduction and exploitation of cinnabar ore, to achieve a red pigment, from the seventh millennium BC. In this panorama, the new data obtained from the analyses of samples of artefacts from La Marmotta (Italy) show a wide use of cinnabar in central Italy from the early Neolithic and attest to the earliest use of this ore in the western Mediterranean area

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

Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial

Aims The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). Methods and results ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P < 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P = 0.07 for interaction). Conclusion This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without D

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