A simulation study of the combined thermoelectric extracellular stimulation of the sciatic nerve of the Xenopus laevis: the localized transient heat block

The electrical behavior of the Xenopus laevis nerve fibers was studied when combined electrical (cuff electrodes) and optical (infrared laser, low power sub-5 mW) stimulations are applied. Assuming that the main effect of the laser irradiation on the nerve tissue is the localized temperature increase, this paper analyzes and gives new insights into the function of the combined thermoelectric stimulation on both excitation and blocking of the nerve action potentials (AP). The calculations involve a finite-element model (COMSOL) to represent the electrical properties of the nerve and cuff. Electric-field distribution along the nerve was computed for the given stimulation current profile and imported into a NEURON model, which was built to simulate the electrical behavior of myelinated nerve fiber under extracellular stimulation. The main result of this study of combined thermoelectric stimulation showed that local temperature increase, for the given electric field, can create a transient block of both the generation and propagation of the APs. Some preliminary experimental data in support of this conclusion are also shown

Neutral coding - A report based on an NRP work session

Neural coding by impulses and trains on single and multiple channels, and representation of information in nonimpulse carrier

Variability in the Firing of Nerve Impulses in Eccentric Cells of the Limulus Eye

Thesis is concerned with the source and characteristics of variability in the discharge of impulses by neurons. The neuron in which variability was studied is the eccentric cell in the compound eye of the horseshoe crab, Limulus polyphemus. In Part I a theory is presented which accounts for the variability in the response of an eccentric cell to light. The main idea of this theory is that the source of randomness in the impulse rate is noise in the generator potential. Another essential aspect of the theory is the view that the process which codes the generator potential into the impulse rate may be treated as a linear filter. These ideas lead directly to Fourier analysis of the fluctuations of the generator potential and fluctuations of the impulse rate. Experimental verification of theoretical predictions was obtained by measurement of the fluctuations and calculation of their variance spectrum. The variance spectrum (or power spectrum) of the impulse rate is shown to be the filtered variance spectrum of the generator potential. Another verification of the theory is the finding that in many cells the signal-to-noise ratio is constant for responses to sinusoidally modulated light, at all modulation frequencies. Inhibition from neighboring eccentric cells will have an effect on the variability of firing of a given eccentric cell. The effects of inhibition are discussed in Part II. The reduction in the average impulse rate which is caused by inhibition decreases the variance of the impulse rate. However, this reduction of the average impulse rate increases the coefficient of variation of the impulse rate. Inhibitory synaptic noise adds to the low frequency portion of the variance spectrum of the impulse rate. This occurs because of the Ill slow time course of the inhibitory synaptic potentials. As a consequence, inhibition decreases the signal-to-noise ratio for low frequency modulated stimuli. The net effect of inhibition is to increase the coefficient of variation of the impulse rate. This effect is predicted by the linear model of the eccentric cell. The same qualitative effect is predicted by other theories of neuronal variability, although its importance is stressed here for the first time

Restoring Upper Extremity Mobility through Functional Neuromuscular Stimulation using Macro Sieve Electrodes

The last decade has seen the advent of brain computer interfaces able to extract precise motor intentions from cortical activity of human subjects. It is possible to convert captured motor intentions into movement through coordinated, artificially induced, neuromuscular stimulation using peripheral nerve interfaces. Our lab has developed and tested a new type of peripheral nerve electrode called the Macro-Sieve electrode which exhibits excellent chronic stability and recruitment selectivity. Work presented in this thesis uses computational modeling to study the interaction between Macro-Sieve electrodes and regenerated peripheral nerves. It provides a detailed understanding of how regenerated fibers, both on an individual level and on a population level respond differently to functional electrical stimulation compared to non-disrupted axons. Despite significant efforts devoted to developing novel regenerative peripheral interfaces, the degree of spatial clustering between functionally related fibers in regenerated nerves is poorly understood. In this thesis, bioelectrical modeling is also used to predict the degree of topographical organization in regenerated nerve trunks. In addition, theoretical limits of the recruitment selectivity of the device is explored and a set of optimal stimulation paradigms used to selectively activate fibers in different regions of the nerve are determined. Finally, the bioelectrical model of the interface/nerve is integrated with a biomechanical model of the macaque upper limb to study the feasibility of using macro-sieve electrodes to achieve upper limb mobilization

Electrophysiology

The outstanding evolution of recording techniques paved the way for better understanding of electrophysiological phenomena within the human organs, including the cardiovascular, ophthalmologic and neural systems. In the field of cardiac electrophysiology, the development of more and more sophisticated recording and mapping techniques made it possible to elucidate the mechanism of various cardiac arrhythmias. This has even led to the evolution of techniques to ablate and cure most complex cardiac arrhythmias. Nevertheless, there is still a long way ahead and this book can be considered a valuable addition to the current knowledge in subjects related to bioelectricity from plants to the human heart

Biophysical Determinants of the Behaviour of Human Myelinated Axons

This thesis investigates the role of the hyperpolarization-activated current, Ih, on the excitability of human axons. It exploits the unique characteristics of the underlying hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels to improve existing and create new techniques for studying Ih. An isolated amplifier with low-noise and high common-mode rejection was developed, and threshold tracking techniques were modified to allow the measurement of the excitability of low-threshold sensory axons and of cutaneous afferents close to their receptors. These developments open up the possibility of studying changes in polyneuropathies, where symptoms and possibly the underlying pathology are more apparent distally in the limbs. Strong and long-lasting hyperpolarization was used to open more HCN channels and to examine their contribution to the excitability of motor and sensory axons. A mathematical model of myelinated motor axons was adapted to account for the response to strong and long-lasting hyperpolarization. Without structural changes the model was then modified to fit the observed excitability of sensory axons. Changes in the excitability and safety margin during focal hyperthermia were studied in both motor and sensory axons of the median nerve, and the underlying mechanisms were explored using the new mathematical model. Finally, the involvement of Ih in the frequency preference of oscillation in human axons was investigated by developing resonance techniques that have hitherto never been used to study axonal function

Simulating and optimizing electrical current flow and neuronal activation in retinal implants

© 2018 Dr Timothy Bede Esler[Abstract Withheld

Noninvasive Neuromodulation: Modeling and Analysis of Transcranial Brain Stimulation with Applications to Electric and Magnetic Seizure Therapy

Bridging the fields of engineering and psychiatry, this dissertation proposes a novel framework for the rational dosing of electric and magnetic seizure therapy, including electroconvulsive therapy (ECT) and magnetic seizure therapy (MST), for the treatment of psychiatric disorders such as medication resistant major depression and schizophrenia. The objective of this dissertation is to develop computational modeling tools that allow ECT and MST stimulation paradigms to be biophysically optimized ex vivo, prior to testing safety and efficacy in preclinical and clinical trials. Despite therapeutic advances, treatment resistant depression (TRD) remains a largely unmet clinical need. ECT is highly effective for TRD, but its side effects limit its real-world clinical utility. Modifications of treatment technique (e.g., electrode placement, stimulus parameters, novel paradigms such as MST) significantly improve the tolerability of convulsive therapy. However, we know relatively little about the distribution of the electric field (E-field) induced in the brain to inform spatial targeting of ECT and MST. Lacking an understanding of biophysical and physiological mechanisms, refinements in ECT/MST technique rely exclusively on time-consuming and costly clinical trials. Consequently, key questions remain unanswered about how to position the ECT electrodes or MST coil for targeted brain stimulation. Addressing this knowledge gap, this dissertation proposes a new platform that will inform an improved spatial targeting of ECT and MST through state-of-the-art computer simulations of the E-field distribution in human and nonhuman primate (NHP) brain. Part I of this dissertation aims to develop anatomically realistic finite element models of transcranial electric and magnetic stimulation in human and NHPs incorporating tissue heterogeneity and anisotropy derived from structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) data. The NHP models of ECT and MST are created alongside the human model since NHPs are used in preclinical studies on the mechanisms of seizure therapy. Part II of this dissertation aims to apply the model developed in Part I to electric and magnetic seizure therapy. We compute the strength and spatial distributions of the E-field induced in the brain by various ECT and MST paradigms. The relative E-field strength among various regions of interest (ROIs) is examined to select electrode/coil configurations that produce most focal stimulation of target ROIs that are considered to mediate the therapeutic action of ECT and MST. Since E-field alone is insufficient to account for individual differences in neurophysiological response, we calibrate the E-field maps relative to the neural activation threshold via in vivo measurements of the corticospinal tract response to single pulses (motor threshold, MT). We derive an empirical estimate of the neural activation threshold by coupling simulated E-field strength with individually measured MT. The E-field strength relative to an empirical neural activation threshold and corresponding volume of suprathreshold stimulation (focality) is examined to inform the selection of ECT and MST stimulus pulse amplitude that will result in focal ROI stimulation. We contrast the ECT/MST stimulation strength and focality with conventional fixed and individually titrated pulse amplitude necessary to induce a seizure (seizure threshold, ST) to study pulse amplitude adjustment as a novel means of controlling stimulation strength and focality. This work provides a basis for rational dosing of seizure therapies that could help improve their risk/benefit ratio and guide the development of safer alternatives for patients with severe psychiatric disorders