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- ItemInfluence of Autapses on Synchronization in Neural Networks With Chemical Synapses(Lausanne : Frontiers Media, 2020) Protachevicz, Paulo R.; Iarosz, Kelly C.; Caldas, Iberê L.; Antonopoulos, Chris G.; Batista, Antonio M.; Kurths, JürgenA great deal of research has been devoted on the investigation of neural dynamics in various network topologies. However, only a few studies have focused on the influence of autapses, synapses from a neuron onto itself via closed loops, on neural synchronization. Here, we build a random network with adaptive exponential integrate-and-fire neurons coupled with chemical synapses, equipped with autapses, to study the effect of the latter on synchronous behavior. We consider time delay in the conductance of the pre-synaptic neuron for excitatory and inhibitory connections. Interestingly, in neural networks consisting of both excitatory and inhibitory neurons, we uncover that synchronous behavior depends on their synapse type. Our results provide evidence on the synchronous and desynchronous activities that emerge in random neural networks with chemical, inhibitory and excitatory synapses where neurons are equipped with autapses. © Copyright © 2020 Protachevicz, Iarosz, Caldas, Antonopoulos, Batista and Kurths.
- ItemInfluence of Delayed Conductance on Neuronal Synchronization(Lausanne : Frontiers Media, 2020) Protachevicz, Paulo R.; Borges, Fernando S.; Iarosz, Kelly C.; Baptista, Murilo S.; Lameu, Ewandson L.; Hansen, Matheus; Caldas, Iberê L.; Szezech Jr., José D.; Batista, Antonio M.; Kurths, JürgenIn the brain, the excitation-inhibition balance prevents abnormal synchronous behavior. However, known synaptic conductance intensity can be insufficient to account for the undesired synchronization. Due to this fact, we consider time delay in excitatory and inhibitory conductances and study its effect on the neuronal synchronization. In this work, we build a neuronal network composed of adaptive integrate-and-fire neurons coupled by means of delayed conductances. We observe that the time delay in the excitatory and inhibitory conductivities can alter both the state of the collective behavior (synchronous or desynchronous) and its type (spike or burst). For the weak coupling regime, we find that synchronization appears associated with neurons behaving with extremes highest and lowest mean firing frequency, in contrast to when desynchronization is present when neurons do not exhibit extreme values for the firing frequency. Synchronization can also be characterized by neurons presenting either the highest or the lowest levels in the mean synaptic current. For the strong coupling, synchronous burst activities can occur for delays in the inhibitory conductivity. For approximately equal-length delays in the excitatory and inhibitory conductances, desynchronous spikes activities are identified for both weak and strong coupling regimes. Therefore, our results show that not only the conductance intensity, but also short delays in the inhibitory conductance are relevant to avoid abnormal neuronal synchronization. © Copyright © 2020 Protachevicz, Borges, Iarosz, Baptista, Lameu, Hansen, Caldas, Szezech, Batista and Kurths.
- ItemInstantaneous Cardiac Baroreflex Sensitivity: xBRS Method Quantifies Heart Rate Blood Pressure Variability Ratio at Rest and During Slow Breathing(Lausanne : Frontiers Media, 2020) Wessel, Niels; Gapelyuk, Andrej; Weiß, Jonas; Kraemer, Jan F.; Schmidt, Martin; Berg, Karsten; Malberg, Hagen; Stepan, Holger; Kurths, JürgenSpontaneous baroreflex sensitivity (BRS) is a widely used tool for the quantification of the cardiovascular regulation. Numerous groups use the xBRS method, which calculates the cross-correlation between the systolic beat-to-beat blood pressure and the R-R interval (resampled at 1 Hz) in a 10 s sliding window, with 0–5 s delays for the interval. The delay with the highest correlation is selected and, if significant, the quotient of the standard deviations of the R-R intervals and the systolic blood pressures is recorded as the corresponding xBRS value. In this paper we test the hypothesis that the xBRS method quantifies the causal interactions of spontaneous BRS from non-invasive measurements at rest. We use the term spontaneous BRS in the sense of the sensitivity curve is calculated from non-interventional, i.e., spontaneous, baroreceptor activity. This study includes retrospective analysis of 1828 measurements containing ECG as well as continues blood pressure under resting conditions. Our results show a high correlation between the heart rate – systolic blood pressure variability (HRV/BPV) quotient and the xBRS (r = 0.94, p < 0.001). For a deeper understanding we conducted two surrogate analyses by substituting the systolic blood pressure by its reversed time series. These showed that the xBRS method was not able to quantify causal relationships between the two signals. It was not possible to distinguish between random and baroreflex controlled sequences. It appears xBRS rather determines the HRV/BPV quotient. We conclude that the xBRS method has a potentially large bias in characterizing the capacity of the arterial baroreflex under resting conditions. During slow breathing, estimates for xBRS are significantly increased, which clearly shows that measurements at rest only involve limited baroreflex activity, but does neither challenge, nor show the full range of the arterial baroreflex regulatory capacity. We show that xBRS is exclusively dominated by the heart rate to systolic blood pressure ratio (r = 0.965, p < 0.001). Further investigations should focus on additional autonomous testing procedures such as slow breathing or orthostatic testing to provide a basis for a non-invasive evaluation of baroreflex sensitivity. © Copyright © 2020 Wessel, Gapelyuk, Weiß, Schmidt, Kraemer, Berg, Malberg, Stepan and Kurths.
- ItemMusic improves the therapeutic effects of bevacizumab in rats with glioblastoma: Modulation of drug distribution to the brain(Lausanne : Frontiers Media, 2022) Semyachkina-Glushkovskaya, Oxana; Diduk, Sergey; Anna, Eroshova; Elina, Dosadina; Artem, Kruglov; Khorovodov, Alexander; Shirokov, Alexander; Fedosov, Ivan; Dubrovsky, Alexander; Blokhina, Inna; Terskov, Andrey; Navolokin, Nikita; Evsukova, Arina; Elovenko, Daria; Adushkina, Viktoria; Kurths, JürgenBackground: The development of new methods for modulation of drug distribution across to the brain is a crucial step in the effective therapies for glioblastoma (GBM). In our previous work, we discovered the phenomenon of music-induced opening of the blood-brain barrier (OBBB) in healthy rodents. In this pilot study on rats, we clearly demonstrate that music-induced BBB opening improves the therapeutic effects of bevacizumab (BZM) in rats with GBM via increasing BZM distribution to the brain along the cerebral vessels. Methods: The experiments were performed on Wistar male rats (200-250 g, n=161) using transfected C6-TagRFP cell line and the loud rock music for OBBB. The OBBB was assessed by spectrofluorometric assay of Evans Blue (EB) extravasation and confocal imaging of fluorescent BZM (fBZM) delivery into the brain. Additionally, distribution of fBZM and Omniscan in the brain was studied using fluorescent and magnetic resonance imaging (MRI), respectively. To analyze the therapeutic effects of BZM on the GBM growth in rats without and with OBBB, the GBM volume (MRI scans), as well as immunohistochemistry assay of proliferation (Ki67 marker) and apoptosis (Bax marker) in the GBM cells were studied. The Mann-Whitney-Wilcoxon test was used for all analysis, the significance level was p < 0.05, n=7 in each group. Results: Our finding clearly demonstrates that music-induced OBBB increases the delivery of EB into the brain tissues and the extravasation of BZM into the brain around the cerebral vessels of rats with GBM. Music significantly increases distribution of tracers (fBZM and Omniscan) in the rat brain through the pathways of brain drainage system (perivascular and lymphatic), which are an important route of drug delivery into the brain. The music-induced OBBB improves the suppressive effects of BZM on the GBM volume and the cellular mechanisms of tumor progression that was accompanied by higher survival among rats in the GBM+BZM+Music group vs. other groups. Conclusion: We hypothesized that music improves the therapeutic effects of BZM via OBBB in the normal cerebral vessels and lymphatic drainage of the brain tissues. This contributes better distribution of BZM in the brain fluids and among the normal cerebral vessels, which are used by GBM for invasion and co-opt existing vessels as a satellite tumor form. These results open the new perspectives for an improvement of therapeutic effects of BZM via the music-induced OBBB for BZM in the normal cerebral vessels, which are used by GBM for migration and progression.
- ItemCardiac Autonomic Dysfunction and Incidence of de novo Atrial Fibrillation: Heart Rate Variability vs. Heart Rate Complexity(Lausanne : Frontiers Media, 2020) Wessel, Niels; Berg, Karsten; Kraemer, Jan F.; Gapelyuk, Andrej; Rietsch, Katrin; Hauser, Tino; Kurths, Jürgen; Wenzel, Dave; Klein, Norbert; Kolb, Christof; Belke, Roberto; Schirdewan, Alexander; Kääb, StefanBackground: The REACT DX registry evaluates standard therapies to episodes of long-lasting atrial tachyarrhythmias and assesses the quality of sensing and stability of the lead and the implantable cardioverter-defibrillator (ICD) (BIOTRONIK Lumax VR-T DX and successors) over at least a 1-year follow-up period. Objective: To study the association between the risk of de novo device-detected atrial fibrillation (AF), the autonomic perturbations before the onset of paroxysmal AF and a 7-days heart rate variability (7dHRV) 1 month after ICD implantation. Methods: The registry consists of 234 patients implanted with an ICD, including 10 with de novo long-lasting atrial tachyarrhythmias with no prior history of AF. The patients were matched via the propensity-score methodology as well as for properties directly influencing the ECGs recorded using GE CardioMem CM 3000. Heart rate variability (HRV) analysis was performed using standard parameters from time- and frequency-domains, and from non-linear dynamics. Results: No linear HRV was associated with an increased risk of AF (p = n.s.). The only significant approach was derived from symbolic dynamics with the parameter “forbidden words” which distinguished both groups on all 7 days of measurements (p < 0.05), thereby quantifying the heart rate complexity (HRC) as drastically lower in the de novo AF group. Conclusion: Cardiac autonomic dysfunction denoted by low HRC may be associated with higher AF incidence. For patients with mild to moderate heart failure, standard HRV parameters are not appropriate to quantify cardiac autonomic perturbations before the onset of AF. Further studies are needed to determine the individual risk for AF that would enable interventions to restore autonomic balance in the general population. © Copyright © 2020 Wessel, Berg, Kraemer, Gapelyuk, Rietsch, Hauser, Kurths, Wenzel, Klein, Kolb, Belke, Schirdewan and Kääb.