Enduring Medial Perforant Path Short-Term Synaptic Depression at High Pressure

The high pressure neurological syndrome develops during deep-diving (>1.1 MPa) involving impairment of cognitive functions, alteration of synaptic transmission and increased excitability in cortico-hippocampal areas. The medial perforant path (MPP), connecting entorhinal cortex with the hippocampal formation, displays synaptic frequency-dependent-depression (FDD) under normal conditions. Synaptic FDD is essential for specific functions of various neuronal networks. We used rat cortico-hippocampal slices and computer simulations for studying the effects of pressure and its interaction with extracellular Ca2+ ([Ca2+]o) on FDD at the MPP synapses. At atmospheric pressure, high [Ca2+]o (4–6 mM) saturated single MPP field EPSP (fEPSP) and increased FDD in response to short trains at 50 Hz. High pressure (HP; 10.1 MPa) depressed single fEPSPs by 50%. Increasing [Ca2+]o to 4 mM at HP saturated synaptic response at a subnormal level (only 20% recovery of single fEPSPs), but generated a FDD similar to atmospheric pressure. Mathematical model analysis of the fractions of synaptic resources used by each fEPSP during trains (normalized to their maximum) and the total fraction utilized within a train indicate that HP depresses synaptic activity also by reducing synaptic resources. This data suggest that MPP synapses may be modulated, in addition to depression of single events, by reduction of synaptic resources and then may have the ability to conserve their dynamic properties under different conditions

On the Firing Rate Dependency of the Phase Response Curve of Rat Purkinje Neurons In Vitro

Synchronous spiking during cerebellar tasks has been observed across Purkinje cells: however, little is known about the intrinsic cellular mechanisms responsible for its initiation, cessation and stability. The Phase Response Curve (PRC), a simple input-output characterization of single cells, can provide insights into individual and collective properties of neurons and networks, by quantifying the impact of an infinitesimal depolarizing current pulse on the time of occurrence of subsequent action potentials, while a neuron is firing tonically. Recently, the PRC theory applied to cerebellar Purkinje cells revealed that these behave as phase-independent integrators at low firing rates, and switch to a phase-dependent mode at high rates. Given the implications for computation and information processing in the cerebellum and the possible role of synchrony in the communication with its post-synaptic targets, we further explored the firing rate dependency of the PRC in Purkinje cells. We isolated key factors for the experimental estimation of the PRC and developed a closed-loop approach to reliably compute the PRC across diverse firing rates in the same cell. Our results show unambiguously that the PRC of individual Purkinje cells is firing rate dependent and that it smoothly transitions from phase independent integrator to a phase dependent mode. Using computational models we show that neither channel noise nor a realistic cell morphology are responsible for the rate dependent shift in the phase response curve

Highly Scalable Parallel Processing of Extracellular Recordings of Multielectrode Arrays

Technological advances of Multielectrode Arrays (MEAs) used for multi- site, parallel electrophysiological recordings, lead to an ever increasing amount of raw data being generated. Arrays with hundreds up to a few thousands of electrodes are slowly seeing widespread use and the expectation is that more sophisticated arrays will become available in the near future. In order to process the large data volumes resulting from MEA recordings there is a pressing need for new software tools able to process many data channels in parallel. Here we present a new tool for processing MEA data recordings that makes use of new programming paradigms and recent technology developments to unleash the power of modern highly parallel hardware, such as multi-core CPUs with vector instruction sets or GPGPUs. Our tool builds on and complements existing MEA data analysis packages. It shows high scalability and can be used to speed up some performance critical pre-processing steps such as data filtering and spike detection, helping to make the analysis of larger data sets tractable

Enhancement of SSVEPs Classification in BCI-based Wearable Instrumentation Through Machine Learning Techniques

This work addresses the adoption of Machine Learning classifiers and Convolutional Neural Networks to improve the performance of highly wearable, single-channel instrumentation for Brain-Computer Interfaces. The proposed measurement system is based on the classification of Steady-State Visually Evoked Potentials (SSVEPs). In particular, Head-Mounted Displays for Augmented Reality are used to generate and display the flickering stimuli for the SSVEPs elicitation. Four experiments were conducted by employing, in turn, a different Head-Mounted Display. For each experiment, two different algorithms were applied and compared with the state-of-the-art-techniques. Furthermore, the impact of different Augmented Reality technologies in the elicitation and classification of SSVEPs was also explored. The experimental metrological characterization demonstrates (i) that the proposed Machine Learning-based processing strategies provide a significant enhancement of the SSVEP classification accuracy with respect to the state of the art, and (ii) that choosing an adequate Head-Mounted Display is crucial to obtain acceptable performance. Finally, it is also shown that the adoption of inter-subjective validation strategies such as the Leave-One-Subject-Out Cross Validation successfully leads to an increase in the inter-individual 1-σ reproducibility: this, in turn, anticipates an easier development of ready-to-use systems

Ruptured Brain Arteriovenous Malformations: Surgical Timing and Outcomes-A Retrospective Study of 25 Cases

Background One important problem in treatment of ruptured brain arteriovenous malformations (bAVMs) is surgical timing. The aim of the study was to understand which parameters affect surgical timing and outcomes the most. Materials and Methods Between January 2010 and December 2018, 25patients underwent surgery for a ruptured bAVM at our institute. Intracerebral hemorrhage (ICH) score was used to evaluate hemorrhage severity, while Spetzler-Martin scale for AVM architecture. We divided patients in two groups: early surgery and delayed surgery. The modified Rankin Scale (mRS) evaluated the outcomes. Results Eleven patients were in the early surgery group: age 38 ± 18 years, Glasgow Coma Scale (GCS) 7.64 ± 2.86, ICH score 2.82 ± 0.71, hematoma volume 45.55 ± 23.21 mL. Infratentorial origin of hemorrhage was found in 27.3% cases; AVM grades were I to II in 82%, III in 9%, and IV in 9% cases. Outcome at 3 months was favorable in 36.4% cases and in 54.5% after 1 year. Fourteen patients were in the delayed surgery group: age 41 ± 16 years, GCS 13.21 ± 2.39, ICH score 1.14 ± 0.81, hematoma volume 29.89 ± 21.33 mL. Infratentorial origin of hemorrhage was found in 14.2% cases; AVM grades were I to II in 50% and III in 50%. Outcome at 3 months was favorable in 78.6% cases and in 92.8% after 1 year. Conclusions The early outcome is influenced more by the ICH score, while the delayed outcome by Spetzler-Martin grading. These results suggest that it is better to perform surgery after a rest period, away from the hemorrhage when possible. Moreover, this study suggests how in young patient with a high ICH score and a low AVM grade, early surgery seems to be a valid and feasible therapeutic strategy

A ML-based Approach to Enhance Metrological Performance of Wearable Brain-Computer Interfaces

In this paper, the adoption of Machine Learning (ML) classifiers is addressed to improve the performance of highly wearable, single-channel instrumentation for Brain-Computer Interfaces (BCIs). The proposed BCI is based on the classification of Steady-State Visually Evoked Potentials (SSVEPs). In this setup, Augmented Reality Smart Glasses are used to generate and display the flickering stimuli for the SSVEP elicitation. An experimental campaign was conducted on 20 adult volunteers. Successively, a Leave-One-Subject-Out Cross Validation was performed to validate the proposed algorithm. The obtained experimental results demonstrate that suitable ML-based processing strategies outperform the state-of-the-art techniques in terms of classification accuracy. Furthermore, it was also shown that the adoption of an inter-subjective model successfully led to a decrease in the 3-σ uncertainty: this can facilitate future developments of ready-to-use systems

Non-invasive vulnerable plaque imaging: how do we know that treatment works?

Atherosclerosis is an inflammatory disorder that can evolve into an acute clinical event by plaque development, rupture, and thrombosis. Plaque vulnerability represents the susceptibility of a plaque to rupture and to result in an acute cardiovascular event. Nevertheless, plaque vulnerability is not an established medical diagnosis, but rather an evolving concept that has gained attention to improve risk prediction. The availability of high-resolution imaging modalities has significantly facilitated the possibility of performing in vivo regression studies and documenting serial changes in plaque stability. This review summarizes the currently available non-invasive methods to identify vulnerable plaques and to evaluate the effects of the current cardiovascular treatments on plaque evolution

Edoxaban vs. warfarin in patients with atrial fibrillation on amiodarone: a subgroup analysis of the ENGAGE AF-TIMI 48 trial

Background In the ENGAGE AF-TIMI 48 trial, the higher-dose edoxaban (HDE) regimen had a similar incidence of ischaemic stroke compared with warfarin, whereas a higher incidence was observed with the lower-dose regimen (LDE). Amiodarone increases edoxaban plasma levels via P-glycoprotein inhibition. The current pre-specified exploratory analysis was performed to determine the effect of amiodarone on the relative efficacy and safety profile of edoxaban. Methods and results At randomization, 2492 patients (11.8%) were receiving amiodarone. The primary efficacy endpoint of stroke or systemic embolic event was significantly lower with LDE compared with warfarin in amiodarone treated patients vs. patients not on amiodarone (hazard ratio [HR] 0.60, 95% confidence intervals [CIs] 0.36-0.99 and HR 1.20, 95% CI 1.03-1.40, respectively; P interaction <0.01). In patients randomized to HDE, no such interaction for efficacy was observed (HR 0.73, 95% CI 0.46-1.17 vs. HR 0.89, 95% CI 0.75-1.05, P interaction = 0.446). Major bleeding was similar in patients on LDE (HR 0.35, 95% CI 0.21-0.59 vs. HR 0.53, 95% CI 0.46-0.61, P interaction = 0.131) and HDE (HR 0.94, 95% CI 0.65-1.38 vs. HR 0.79, 95% CI 0.69-0.90, P interaction = 0.392) when compared with warfarin, independent of amiodarone use. Conclusions Patients randomized to the LDE treated with amiodarone at the time of randomization demonstrated a significant reduction in ischaemic events vs. warfarin when compared with those not on amiodarone, while preserving a favourable bleeding profile. In contrast, amiodarone had no effect on the relative efficacy and safety of HD

Dissecting the Interactions between Chlorin e6 and Human Serum Albumin

Chlorin e6 (Ce6) is among the most used sensitizers in photodynamic (PDT) and sonodynamic (SDT) therapy; its low solubility in water, however, hampers its clinical exploitation. Ce6 has a strong tendency to aggregate in physiological environments, reducing its performance as a photo/sono-sensitizer, as well as yielding poor pharmacokinetic and pharmacodynamic properties. The interaction of Ce6 with human serum albumin (HSA) (i) governs its biodistribution and (ii) can be used to improve its water solubility by encapsulation. Here, using ensemble docking and microsecond molecular dynamics simulations, we identified the two Ce6 binding pockets in HSA, i.e., the Sudlow I site and the heme binding pocket, providing an atomistic description of the binding. Comparing the photophysical and photosensitizing properties of Ce6@HSA with respect to the same properties regarding the free Ce6, it was observed that (i) a red-shift occurred in both the absorption and emission spectra, (ii) a maintaining of the fluorescence quantum yield and an increase of the excited state lifetime was detected, and (iii) a switch from the type II to the type I mechanism in a reactive oxygen species (ROS) production, upon irradiation, took place