Many electrophysiological experiments require the recording, stimulating, or both in the peripheral nervous system. There are many electrodes currently on the market, but they are either not designed for implantation or are not robust enough to be used multiple times in situ. The cost of buying these electrodes from a manufacturer can be prohibitive and many labs prefer to make their own. This introduces variability between studies, as different techniques and configurations in the design and fabrication of electrodes can create variance in electrical impedance, spatial arrangement, or other factors. This paper presents a detailed methodology for the construction of electrodes that are robust, have uniform impedance values of Z = 2.38 ± 0.906 kΩ. at 1 kHz alternating current (AC), and can be used in multiple in vitro or in situ experiments, or for chronic implantation in vivo. This method will reduce the amount of time and material needed to construct electrodes for experimental studies in animals.

Spinal cord injury results in life-long damage to sensory and motor functions. Recovery from these injuries is limited and often insufficient because the lack of stimulation from supraspinal systems results in further atrophy of the damaged neural pathways. Current studies have shown that repeated sensory activity obtained by applying stimulation enhances plasticity of neural circuits, and in turn increases the ability to create new pathways able to compensate for the damaged neurons. Functional electrical stimulation has been proven to show success in this form of rehabilitation, but it has its limitations. Stimulating neural pathways with electricity results in also stimulating surrounding neurons and muscle tissue. This results in attenuation of the intended effect. The use of optogenetics mitigates this issue, but comes with its own complications. Optogenetics is a growing method of neural stimulation which utilizes genetic modification to create light activated ion channels in neurons to allow for activation or suppression of neural pathways. In order to activate the neurons, light of the appropriate wavelength must be able to penetrate the nerves. Applying the light transcutaneously is insufficient, as the skin and muscle tissue attenuate the signal. The target nerve may also move relative to an external point on the body, creating further inconsistency. Specifically in the case of using a rat model, an external object will be immediately removed by the animal. This thesis seeks to address this issue for a rat model by designing a nerve cuff capable of both optical and electrical stimulation. This device will be scaled to fit the sciatic nerve of a rat and allow for both optical activation and inhibition of the neural activity. It will be wired such that each stimulus may be operated individually or in conjunction with each other. The simultaneous stimulation is required in order to validate the neural inhibition facet. The circuit itself will be validated through the use of an optical stimulation rig, using a photoreceptor in place of an EMG. The application of the cuff will be verified in a live naive rat. Aim 1: Design and build an implantable electrical stimulation nerve cuff for the sciatic nerve of rats. An electrical nerve cuff for the sciatic nerve of a rat will be designed and assembled such that it is able to reliably activate the H-reflex. For it to be used in a walking rat, the cuff must be compatible with a head mount in order to prevent the rat from being able to chew at the wiring or their exit point. The cuff will be controlled through a Matlab program that is able to output specified signals and compare these outputs directly with the resultant EMG inputs. Aim 2: Implement LEDs onto the cuff and perform validation experiments. Light delivery capability will be added to the cuff through the use of LEDs. The functionality of the cuff will be validated through tests on naive rats. If successful, only an electric stimulation will result in a muscle twitch. An optical stimulation should result in no twitches, which would then validate that no current is leaking from the nerve cuff, given that the rat does not express any light sensitive protein channels. Ultimately, with a rat expressing ChR2 opsins on the sciatic nerve, an activation of the nerve using a blue light of wavelength 470nm will result in activating an h-wave without an m-wave when optically stimulated. Similarly, using the nerve cuff with a rat expressing ArchT opsins will result in suppressing the h-wave from an electric stimulation once the sciatic nerve is illuminated with green light of a wavelength of 520 nm. / Bioengineering

Vagus nerve stimulation (VNS) is an approved therapy for patients suffering from refractory epilepsy. While VNS is currently an open loop system, making the system closed loop can improve the therapeutic efficacy. Electrical recording of peripheral nerve activity using a nerve cuff electrode is a potential long-term solution for implementing a closed-loop controlled VNS system. However, the clinical utility of this approach is significantly limited by various factors, such as poor signal-to-noise ratio (SNR) of the recorded electroneurogram (ENG). In this study, we investigated the effects of (1) modifying the electrode contact dimensions, (2) implementing an external shielding layer on the nerve cuff electrode and (3) exploring shielded bipolar nerve cuff designs on the recorded ENG. Findings from both computer simulations and animal experiments suggest that significant improvements in peripheral nerve recordings can be achieved.

Vagus nerve stimulation (VNS) is an approved therapy for patients suffering from refractory epilepsy. While VNS is currently an open loop system, making the system closed loop can improve the therapeutic efficacy. Electrical recording of peripheral nerve activity using a nerve cuff electrode is a potential long-term solution for implementing a closed-loop controlled VNS system. However, the clinical utility of this approach is significantly limited by various factors, such as poor signal-to-noise ratio (SNR) of the recorded electroneurogram (ENG). In this study, we investigated the effects of (1) modifying the electrode contact dimensions, (2) implementing an external shielding layer on the nerve cuff electrode and (3) exploring shielded bipolar nerve cuff designs on the recorded ENG. Findings from both computer simulations and animal experiments suggest that significant improvements in peripheral nerve recordings can be achieved.

No description available.

Currently there does not exist a type of peripheral nerve interface that adequately combines spatial selectivity, spatial coverage and low invasiveness. In order to address this lack, we investigated the application of bioelectric source localization algorithms, adapted from electroencephalography/magnetoencephalography, to recordings from a 56-contact “matrix” nerve cuff electrode. If successful, this strategy would enable us to improve current neuroprostheses and conduct more detailed investigations of neural control systems. Using forward field similarities, we first developed a method to reduce the number of unnecessary variables in the inverse problem, and in doing so obtained an upper bound on the spatial resolution. Next, a simulation study of the peripheral nerve source localization problem revealed that the method is unlikely to work unless noise is very low and a very accurate model of the nerve is available. Under more realistic conditions, the method had localization errors in the 140 μm-180 μm range, high numbers of spurious pathways, and low resolution. On the other hand, the simulations also showed that imposing physiologically meaningful constraints on the solution can reduce the number of spurious pathways. Both the influence of the constraints and the importance of the model accuracy were validated experimentally using recordings from rat sciatic nerves. Unfortunately, neither idealized models nor models based on nerve sample cross-sections were sufficiently accurate to allow reliable identification of the branches stimulated during the experiments. To overcome this problem, an experimental leadfield was constructed using training data, thereby eliminating the dependence on anatomical models. This new strategy was successful in identifying single-branch cases, but not multi-branches ones. Lastly, an examination of the information contained in the matrix cuff recordings was performed in comparison to a single-ring configuration of contacts. The matrix cuff was able to achieve better fascicle discrimination due to its ability to select among the most informative locations around the nerve. These findings suggest that nerve cuff-based neuroprosthetic applications would benefit from implanting devices with a large number of contacts, then performing a contact selection procedure. Conditions that must be met before source localization approaches can be applied in practice to peripheral nerves were also discussed.

Currently there does not exist a type of peripheral nerve interface that adequately combines spatial selectivity, spatial coverage and low invasiveness. In order to address this lack, we investigated the application of bioelectric source localization algorithms, adapted from electroencephalography/magnetoencephalography, to recordings from a 56-contact “matrix” nerve cuff electrode. If successful, this strategy would enable us to improve current neuroprostheses and conduct more detailed investigations of neural control systems. Using forward field similarities, we first developed a method to reduce the number of unnecessary variables in the inverse problem, and in doing so obtained an upper bound on the spatial resolution. Next, a simulation study of the peripheral nerve source localization problem revealed that the method is unlikely to work unless noise is very low and a very accurate model of the nerve is available. Under more realistic conditions, the method had localization errors in the 140 μm-180 μm range, high numbers of spurious pathways, and low resolution. On the other hand, the simulations also showed that imposing physiologically meaningful constraints on the solution can reduce the number of spurious pathways. Both the influence of the constraints and the importance of the model accuracy were validated experimentally using recordings from rat sciatic nerves. Unfortunately, neither idealized models nor models based on nerve sample cross-sections were sufficiently accurate to allow reliable identification of the branches stimulated during the experiments. To overcome this problem, an experimental leadfield was constructed using training data, thereby eliminating the dependence on anatomical models. This new strategy was successful in identifying single-branch cases, but not multi-branches ones. Lastly, an examination of the information contained in the matrix cuff recordings was performed in comparison to a single-ring configuration of contacts. The matrix cuff was able to achieve better fascicle discrimination due to its ability to select among the most informative locations around the nerve. These findings suggest that nerve cuff-based neuroprosthetic applications would benefit from implanting devices with a large number of contacts, then performing a contact selection procedure. Conditions that must be met before source localization approaches can be applied in practice to peripheral nerves were also discussed.

No description available.

No description available.

No description available.