From Squid to Mammals with the HH Model through the Nav Channels’ Half-Activation-Voltage Parameter

The model family analyzed in this work stems from the classical Hodgkin-Huxley model (HHM). for a single-compartment (space-clamp) and continuous variation of the voltage-gated sodium channels (Na-v) half-activation-voltage parameter Delta V-1/2, which controls the window of sodium-influx currents. Unlike the baseline HHM, its parametric extension exhibits a richer multitude of dynamic regimes, such as multiple fixed points (FP's), bi- and multistability (coexistence of FP's and/or periodic orbits). Such diversity correlates with a number of functional properties of excitable neural tissue, such as the capacity or not to evoke an action potential (AP) from the resting state, by applying a minimal absolute rheobase current amplitude. The utility of the HHM rooted in the giant squid for the descriptions of the mammalian nervous system is of topical interest. We conclude that the model's fundamental principles are still valid (up to using appropriate parameter values) for warmer-blooded species, without a pressing need for a substantial revision of the mathematical formulation. We demonstrate clearly that the continuous variation of the Delta V-1/2 parameter comes close to being equivalent with recent HHM 'optimizations'. The neural dynamics phenomena described here are nontrivial. The model family analyzed in this work contains the classical HHM as a special case. The validity and applicability of the HHM to mammalian neurons can be achieved by picking the appropriate Delta V-1/2 parameter in a significantly broad range of values. For such large variations, in contrast to the classical HHM, the h and n gates' dynamics may be uncoupled - i.e. the n gates may no longer be considered in mere linear correspondence to the h gates. Delta V-1/2 variation leads to a multitude of dynamic regimes-e.g models with either 1 fixed point (FP) or with 3 FP's. These may also coexist with stable and/or unstable periodic orbits. Hence, depending on the initial conditions, the system may behave as either purely excitable or as an oscillator. Delta V-1/2 variation leads to significant changes in the metabolic efficiency of an action potential (AP). Lower Delta V-1/2 values yield a larger range of AP response frequencies, and hence provide for more flexible neural coding. Such lower values also contribute to faster AP conduction velocities along neural fibers of otherwise comparable-diameter. The 3 FP case brings about an absolute rheobase current. In comparison in the classical HHM the rheobase current is only relative - i.e. excitability is lost after a finite amount of elapsed stimulation time. Lower Delta V-1/2 values translate in lower threshold currents from the resting state

Energy-Optimal Electrical-Stimulation Pulses Shaped by the Least-Action Principle

Electrical stimulation (ES) devices interact with excitable neural tissue toward eliciting action potentials (AP's) by specific current patterns. Low-energy ES prevents tissue damage and loss of specificity. Hence to identify optimal stimulation-current waveforms is a relevant problem, whose solution may have significant impact on the related medical (e. g. minimized side-effects) and engineering (e. g. maximized battery-life) efficiency. This has typically been addressed by simulation (of a given excitable-tissue model) and iterative numerical optimization with hard discontinuous constraints - e.g. AP's are all-or-none phenomena. Such approach is computationally expensive, while the solution is uncertain - e. g. may converge to local-only energy-minima and be model-specific. We exploit the Least-Action Principle (LAP). First, we derive in closed form the general template of the membrane-potential's temporal trajectory, which minimizes the ES energy integral over time and over any space-clamp ionic current model. From the given model we then obtain the specific energy-efficient current waveform, which is demonstrated to be globally optimal. The solution is model-independent by construction. We illustrate the approach by a broad set of example situations with some of the most popular ionic current models from the literature. The proposed approach may result in the significant improvement of solution efficiency: cumbersome and uncertain iteration is replaced by a single quadrature of a system of ordinary differential equations. The approach is further validated by enabling a general comparison to the conventional simulation and optimization results from the literature, including one of our own, based on finite-horizon optimal control. Applying the LAP also resulted in a number of general ES optimality principles. One such succinct observation is that ES with long pulse durations is much more sensitive to the pulse's shape whereas a rectangular pulse is most frequently optimal for short pulse durations

Contribution of Direct Heating, Thermal Conduction and Perfusion During Radiofrequency and Microwave Ablation

Both radiofrequency (RF) and microwave (MW) ablation devices are clinically used for tumor ablation. Several studies report less dependence on vascular mediated cooling of MW compared to RF ablation. We created computer models of a cooled RF needle electrode, and a dipole MW antenna to determine differences in tissue heat transfer

Peripheral Nervous System Reconstruction Reroutes Cortical Motor Output—Brain Reorganization Uncovered by Effective Connectivity

Cortical reorganization in response to peripheral nervous system damage is only poorly understood. In patients with complete brachial plexus avulsion and subsequent reconnection of the end of the musculocutaneous nerve to the side of a phrenic nerve, reorganization leads to a doubled arm representation in the primary motor cortex. Despite, homuncular organization being one of the most fundamental principles of the human brain, movements of the affected arm now activate 2 loci: the completely denervated arm representation and the diaphragm representation. Here, we investigate the details behind this peripherally triggered reorganization, which happens in healthy brains. fMRI effective connectivity changes within the motor network were compared between a group of patients and age matched healthy controls at 7 Tesla (6 patients and 12 healthy controls). Results show the establishment of a driving input of the denervated arm area to the diaphragm area which is now responsible for arm movements. The findings extend current knowledge about neuroplasticity in primary motor cortex: a denervated motor area may drive an auxilliary area to reroute its motor output

REQUITE: A prospective multicentre cohort study of patients undergoing radiotherapy for breast, lung or prostate cancer

Purpose: REQUITE aimed to establish a resource for multi-national validation of models and biomarkers that predict risk of late toxicity following radiotherapy. The purpose of this article is to provide summary descriptive data. Methods: An international, prospective cohort study recruited cancer patients in 26 hospitals in eight countries between April 2014 and March 2017. Target recruitment was 5300 patients. Eligible patients had breast, prostate or lung cancer and planned potentially curable radiotherapy. Radiotherapy was prescribed according to local regimens, but centres used standardised data collection forms. Pre-treatment blood samples were collected. Patients were followed for a minimum of 12 (lung) or 24 (breast/prostate) months and summary descriptive statistics were generated. Results: The study recruited 2069 breast (99% of target), 1808 prostate (86%) and 561 lung (51%) cancer patients. The centralised, accessible database includes: physician-(47,025 forms) and patient-(54,901) reported outcomes; 11,563 breast photos; 17,107 DICOMs and 12,684 DVHs. Imputed genotype data are available for 4223 patients with European ancestry (1948 breast, 1728 prostate, 547 lung). Radiation-induced lymphocyte apoptosis (RILA) assay data are available for 1319 patients. DNA (n = 4409) and PAXgene tubes (n = 3039) are stored in the centralised biobank. Example prevalences of 2-year (1-year for lung) grade >= 2 CTCAE toxicities are 13% atrophy (breast), 3% rectal bleeding (prostate) and 27% dyspnoea (lung). Conclusion: The comprehensive centralised database and linked biobank is a valuable resource for the radiotherapy community for validating predictive models and biomarkers. Patient summary: Up to half of cancer patients undergo radiation therapy and irradiation of surrounding healthy tissue is unavoidable. Damage to healthy tissue can affect short-and long-term quality-of-life. Not all patients are equally sensitive to radiation "damage" but it is not possible at the moment to identify those who are. REQUITE was established with the aim of trying to understand more about how we could predict radiation sensitivity. The purpose of this paper is to provide an overview and summary of the data and material available. In the REQUITE study 4400 breast, prostate and lung cancer patients filled out questionnaires and donated blood. A large amount of data was collected in the same way. With all these data and samples a database and biobank were created that showed it is possible to collect this kind of information in a standardised way across countries. In the future, our database and linked biobank will be a resource for research and validation of clinical predictors and models of radiation sensitivity. REQUITE will also enable a better understanding of how many people suffer with radiotherapy toxicity

Stochastic synaptic plasticity in deterministic aVLSI networks of spiking neurons

Chicca E, Fusi S. Stochastic synaptic plasticity in deterministic aVLSI networks of spiking neurons. In: Rattay F, ed. Proceedings of the World Congress on Neuroinformatics. Vienna: ARGESIM/ASIM Verlag; 2001: 468-477.Stochastic learning solves the stability-plasticity problem (Fusi et al., 2000a) but raises new issues related to the generation of the proper noise driving the synaptic dynamics. Here we show that a simple, fully deterministic, spike-driven synaptic device can make use of the network generated vari- ability in the neuronal activity to drive the required stochastic mechanism. Randomness emerges naturally from the interaction of deterministic neu- rons, and no extra source of noise is needed. Learning and forgetting rates of the network can be easily controlled by changing the statistics of the spike trains without changing any inherent parameter of the synaptic dynamics

Stochastic synaptic plasticity in deterministic aVLSI networks of spiking neurons

Chicca E, Fusi S. Stochastic synaptic plasticity in deterministic aVLSI networks of spiking neurons. In: Rattay F, ed. Proceedings of the World Congress on Neuroinformatics. Vienna: ARGESIM/ASIM Verlag; 2001: 468-477.Stochastic learning solves the stability-plasticity problem (Fusi et al., 2000a) but raises new issues related to the generation of the proper noise driving the synaptic dynamics. Here we show that a simple, fully deterministic, spike-driven synaptic device can make use of the network generated vari- ability in the neuronal activity to drive the required stochastic mechanism. Randomness emerges naturally from the interaction of deterministic neu- rons, and no extra source of noise is needed. Learning and forgetting rates of the network can be easily controlled by changing the statistics of the spike trains without changing any inherent parameter of the synaptic dynamics

Cochlear implants in man and cat: different spiking is predicted by simulation

Lutter P, Rattay F, Felix H. Cochlear implants in man and cat: different spiking is predicted by simulation. Presented at the World Congress on Neuroinformatics, Vienna

Modeling the Electrical Excitation of the Mammalian Auditory Nerve

Stüger V, Rattay F, Lutter P. Modeling the Electrical Excitation of the Mammalian Auditory Nerve. In: Rattay F, ed. ARGESIM Report. Vol 10. 1998: 53-56