Dose-dependent effects of high intensity focused ultrasound on compound action potentials in an ex vivo rodent peripheral nerve model: comparison to local anesthetics.

BACKGROUND: In animal models, focused ultrasound can reversibly or permanently inhibit nerve conduction, suggesting a potential role in managing pain. We hypothesized focused ultrasound's effects on action potential parameters may be similar to those of local anesthetics. METHODS: In an ex vivo rat sciatic nerve model, action potential amplitude, area under the curve, latency to 10% peak, latency to 100% peak, rate of rise, and half peak width changes were assessed after separately applying increasing focused ultrasound pressures or concentrations of bupivacaine and ropivacaine. Focused ultrasound's effects on nerve structure were examined histologically. RESULTS: Increasing focused ultrasound pressures decreased action potential amplitude, area under the curve, and rate of rise, increased latency to 10% peak, and did not change latency to 100% peak or half peak width. Increasing local anesthetic concentrations decreased action potential amplitude, area under the curve, and rate of rise and increased latency to 10% peak, latency to 100% peak, and half peak width. At the highest focused ultrasound pressures, nerve architecture was altered compared with controls. DISCUSSION: While some action potential parameters were altered comparably by focused ultrasound and local anesthetics, there were small but notable differences. It is not evident if these differences may lead to differences in clinical pain effects when focused ultrasound is applied in vivo or if focused ultrasound pressures that result in clinically relevant changes damage nerve structures. Given the potential advantages of a non-invasive technique for managing pain conditions, further investigation may be warranted in an in vivo pain model.

Neural-electronic inhibition simulated with a neuron model implemented in SPICE.

There have been numerous studies presented in the literature related to the simulation of the interaction between biological neurons and electronic devices. A complicating factor associated with these simulations is the algebraic complexity involved in implementation. This complication has impeded simulation of more involved neural-electronic circuitry and consequently has limited potential advancements in the integration of biological neurons with synthetic electronics. In this paper, we describe a modification to a previously proposed SPICE based Hodgkin-Huxley neuron model that demonstrates more physiologically relevant electrical behavior. We utilize this SPICE based neuron model in conjunction with an external circuit that allows for artificial selective inhibition of neural spiking. The neural firing control scheme proposed herein would allow for action potential frequency modulation of neural activity that, if developed further, could potentially be applied to suppress undesirable neural activity that manifests symptomatically as the tremors or seizures associated with specific pathologies of the nervous system.

A Perturbation Based Decomposition of Compound-Evoked Potentials for Characterization of Nerve Fiber Size Distributions.

The characterization of peripheral nerve fiber distributions, in terms of diameter or velocity, is of clinical significance because information associated with these distributions can be utilized in the differential diagnosis of peripheral neuropathies. Electro-diagnostic techniques can be applied to the investigation of peripheral neuropathies and can yield valuable diagnostic information while being minimally invasive. Nerve conduction velocity studies are single parameter tests that yield no detailed information regarding the characteristics of the population of nerve fibers that contribute to the compound-evoked potential. Decomposition of the compound-evoked potential, such that the velocity or diameter distribution of the contributing nerve fibers may be determined, is necessary if information regarding the population of contributing nerve fibers is to be ascertained from the electro-diagnostic study. In this work, a perturbation-based decomposition of compound-evoked potentials is proposed that facilitates determination of the fiber diameter distribution associated with the compound-evoked potential. The decomposition is based on representing the single fiber-evoked potential, associated with each diameter class, as being perturbed by contributions, of varying degree, from all the other diameter class single fiber-evoked potentials. The resultant estimator of the contributing nerve fiber diameter distribution is valid for relatively large separations in diameter classes. It is also useful in situations where the separation between diameter classes is small and the concomitant single fiber-evoked potentials are not orthogonal.

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.

Computational modeling to evaluate helical electrode designs.

Finite element models of helical electrodes were utilized in conjunction with nerve fiber models to determine the efficacy of various changes in helical electrode design in improving nerve fiber recruitment. It was determined that an increase in the helical overlap angle does not facilitate recruitment of smaller diameter nerve fibers. The simulations led to some strategies that could potentially improve the electrode design.

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.

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.

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.

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).