Nicotinic Acetylcholine Receptor Kinetics of the Neuromuscular Junction Simulated Using SPICE: An Illustration of Physiological Process Simulation with Conventional Circuit Simulation Software

With the advent of modern day computational power, there is a great deal of interest in the simulation and modeling of complex biological systems. A significant effort is being made to develop generalized software packages for the simulation of cellular processes, metabolic pathways and complex biochemical reaction systems. The advantages to being able to implement and simulate complex biological systems in a virtual environment are several. Simulations of this type, if sufficiently detailed, provide experimental physiologists with the ability to visualize the dynamics of a given biological system of interest. The validity of hypotheses related to the system under study can be tested in a virtual environment prior to carrying out experimental studies. We discuss a systematic approach by which certain reaction balance equations can be transformed into equivalent circuit models that may then be implemented and simulated using SPICE (Simulation Program with Integrated Circuit Emphasis). To introduce the methodology, we develop a simulation for a single ligand-receptor interaction and then we utilize this framework to implement a simulation of nicotinic acetylcholine receptor kinetics at the postsynaptic membrane of the neuromuscular junction. Although the example studies that we present are specific to biochemical reaction systems associated with cellular processes, the procedure is equally applicable to any biochemical or chemical process for which analogous systems of mass balance equations exist that have an equivalent circuit analog. The overall approach described above is useful from the biomedical engineering educational perspective because SPICE simulators are readily accessible to students in freeware versions that they can use to simulate and visualize relatively complex physiological processes such as neurotransmitter/receptor dynamics

Varying the Time Delay of an Action Potential Elicited with a Neural-Electronic Stimulator

There have been various theoretical and experimental studies presented in the literature that focus on interfacing neurons with discrete electronic devices such as transistors. It has also been demonstrated experimentally that neural-electronic devices can be used to elicit action potentials in a target neuron in close proximity to the neural-electronic stimulator. The time delay between stimulus and the onset of the neural action potential can be varied by varying the pulse amplitude and width generated by the neural-electronic stimulator (transistor)

A Novel Method for Characterization of Peripheral Nerve Fiber Size Distributions by Group Delay Measurements and Simulated Annealing Optimization

The ability to determine the characteristics of peripheral nerve fiber size distributions would provide additional information to clinicians for the diagnosis of specific pathologies of the peripheral nervous system. Investigation of these conditions, using electro-diagnostic techniques, is advantageous in the sense that such techniques tend to be minimally invasive yet provide valuable diagnostic information. One of the principal electro-diagnostic tools available to the clinician is the nerve conduction velocity test. While the peripheral nerve conduction velocity test can provide useful information to the clinician regarding the viability of the nerve under study, it is a single parameter test that yields no detailed information about the characteristics of the functioning nerve fibers within the nerve trunk. In this study we present a technique based on a decomposition of the maximal compound evoked potential and subsequent determination of the group delay of the contributing nerve fibers. The fiber group delay is then utilized as an initial estimation of the nerve fiber size distribution and the concomitant temporal propagation delays of the associated single fiber evoked potentials to a reference electrode. Subsequently the estimated single fiber evoked potentials are optimized against the template maximal compound evoked potential using a simulated annealing algorithm. Simulation studies, based on deterministic single fiber action potential functions, are used to demonstrate the robustness of the proposed technique in the presence of noise associated with variations in distance between the nerve fibers and the recording electrodes between the two recording sites

The Impact of Variations in Membrane Capacitance on the Detected Neural-Electronic Signal

There have been various theoretical and experimental studies presented in the literature that focus on interfacing neurons with discrete electronic devices such as transistors. The demonstrated lack of reproducible fidelity of the nerve cell action potential at the device junction would make it impractical to implement these devices in any neural prosthetic application where reliable detection of the action potential was a pre-requisite. In this study, the impact of typical variations in membrane capacitance on the detected neural signal is investigated

A Novel Method for Characterization of Peripheral Nerve Fiber Size Distributions by Group Delay

The ability to determine the characteristics of peripheral nerve fiber size distributions would provide additional information to clinicians for the diagnosis of specific pathologies of the peripheral nervous system. Investigation of these conditions, using electrodiagnostic techniques, is advantageous in the sense that such techniques tend to be minimally invasive yet provide valuable diagnostic information. One of the principal electrodiagnostic tools available to the clinician is the nerve conduction velocity test. While the peripheral nerve conduction velocity test can provide useful information to the clinician regarding the viability of the nerve under study, it is a single-parameter test that yields no detailed information about the characteristics of the functioning nerve fibers within the nerve trunk. In this study, we present a technique based on decomposition of the maximal compound evoked potential and subsequent determination of the group delay of the contributing nerve fibers. The fiber group delay is then utilized as an initial estimation of the nerve fiber size distribution and the associated temporal propagation delays of the single-fiber-evoked potentials to a reference electrode. Simulation studies, based on deterministic single-fiber action potential functions, are used to demonstrate the robustness of the proposed technique in the presence of simulated noise associated with the recording process

Strategies for Improving Neural Signal Detection Using a Neural-Electronic Interface

There have been various theoretical and experimental studies presented in the literature that focus on interfacing neurons with discrete electronic devices, such as transistors. From both a theoretical and experimental perspective, these studies have emphasized the variability in the characteristics of the detected action potential from the nerve cell. The demonstrated lack of reproducible fidelity of the nerve cell action potential at the device junction would make it impractical to implement these devices in any neural prosthetic application where reliable detection of the action potential was a prerequisite. In this study, the effects of several different physical parameters on the fidelity of the detected action potential at the device junction are investigated and discussed. The impact of variations in the extracellular resistivity, which directly affects the junction seal resistance, is studied along with the impact of variable nerve cell membrane capacitance and variations in the injected charge. These parameters are discussed in the context of their suitability to design manipulation for the purpose of improving the fidelity of the detected neural action potential. In addition to investigating the effects of variations in these parameters, the applicability of the linear equivalent circuit approach to calculating the junction potential is investigated

Biomedical Engineering Virtual Circuit Simulation Laboratories

Circuit simulators, such as SPICE (Simulation Program with Integrated Circuit Emphasis) are useful tools that can enhance the educational experience of students in many subject areas within a biomedical engineering curriculum. Courses on biomedical instrumentation are venues for which virtual laboratory experiments, using circuit simulators, can be readily developed. The instructor can use the circuit simulation platform to illustrate relatively complex concepts, such as differential amplification, which have wide applicability to biomedical instrumentation. More advanced courses that focus on the physiology of excitable cells or neural modeling and simulation are also venues for which circuit simulators may be applied to study the dynamics of related physiological models such as the Hodgkin-Huxley model. The equivalent circuit paradigm provides the student with an alternative to developing an understanding of complex physiological models. Application of SPICE based circuit simulators for neural modeling and simulation require the development of excitable membrane equivalent circuit models. Such models have been implemented by the author using SPICE primitive circuit elements in the form of a netlist sub-circuit. More advanced approaches have involved the implementation of neuron models using the SPICE code model paradigm. This alternative approach facilitates the implementation of the neuron model whereby it can be referenced from within a SPICE netlist program in the same way as any other device model would be referenced. At California Polytechnic State University (CalPoly), students at both the undergraduate and graduate levels are exposed to circuit simulation tools that are integrated into the course content as virtual labs in the biomedical engineering instrumentation course. More advanced courses at CalPoly in neural modeling and simulation also make use of the SPICE circuit simulation platform

A modification to the group delay and simulated annealing technique for characterization of peripheral nerve fiber size distributions for non-deterministic sampled data

The ability to determine the characteristics of peripheral nerve fiber size distributions would provide additional information to clinicians for the diagnosis of specific pathologies of the peripheral nervous system. Investigation of these conditions, using electro-diagnostic techniques, is advantageous in the sense that such techniques tend to be minimally invasive yet provide valuable diagnostic information. One of the principal electro-diagnostic tools available to the clinician is the nerve conduction velocity test. While the peripheral nerve conduction velocity test can provide useful information to the clinician regarding the viability of the nerve under study, it is a single parameter test that yields no detailed information about the characteristics of the functioning nerve fibers within the nerve trunk. In previous work, the efficacy of the group delay and simulated annealing approach was demonstrated in the context of a simulation study where deterministic functions were used to represent the single fiber evoked potentials. In this study we present a modification to the approach discussed previously that is applicable to non-deterministic functions of sampled data