Central nervous system microstimulation: Towards selective micro-neuromodulation

Electrical stimulation technologies capable of modulating neural activity are well established for neuroscientific research and neurotherapeutics. Recent micro-neuromodulation experimental results continue to explain neural processing complexity and suggest the potential for assistive technologies capable of restoring or repairing of basic function. Nonetheless, performance is dependent upon the specificity of the stimulation. Increasingly specific stimulation is hypothesized to be achieved by progressively smaller interfaces. Miniaturization is a current focus of neural implants due to improvements in mitigation of the body's foreign body response. It is likely that these exciting technologies will offer the promise to provide large-scale micro-neuromodulation in the future. Here, we highlight recent successes of assistive technologies through bidirectional neuroprostheses currently being used to repair or restore basic brain functionality. Furthermore, we introduce recent neuromodulation technologies that might improve the effectiveness of these neuroprosthetic interfaces by increasing their chronic stability and microstimulation specificity. We suggest a vision where the natural progression of innovative technologies and scientific knowledge enables the ability to selectively micro-neuromodulate every neuron in the brain

Spatial Resolution of Local Field Potential Signals in Macaque V4

A main challenge for the development of cortical visual prostheses is to spatially localize individual spots of light, called phosphenes, by assigning appropriate stimulating parameters to implanted electrodes. Imitating the natural responses to phosphene-like stimuli at different positions can help in designing a systematic procedure to determine these parameters. The key characteristic of such a system is the ability to discriminate between responses to different positions in the visual field. While most previous prosthetic devices have targeted the primary visual cortex, the extrastriate cortex has the advantage of covering a large part of the visual field with a smaller amount of cortical tissue, providing the possibility of a more compact implant. Here, we studied how well ensembles of Multiunit activity (MUA) and Local Field Potentials (LFPs) responses from extrastriate cortical visual area V4 of a behaving macaque monkey can discriminate between two-dimensional spatial positions. We found that despite the large receptive field sizes in V4, the combined responses from multiple sites, whether MUA or LFP, has the capability for fine and coarse discrimination of positions. We identified a selection procedure that could significantly increase the discrimination performance while reducing the required number of electrodes. Analysis of noise correlation in MUA and LFP responses showed that noise correlations in LFP responses carry more information about the spatial positions. Overall, these findings suggest that spatial positions could be localized with patterned stimulation in extrastriate area V4

Doctor of Philosophy

dissertationThe goal of this work is to construct a simulation toolset for studying and improving neuroprosthetic devices for restoring neural functionality to patients with neural disorders or diseases. This involves the construction and validation of coupled electromagnetic-neural computational models of retina and hippocampus, compiling knowledge from a broad multidisciplinary background into a single computational platform, with features specific to implant electronics, bulk tissue, cellular and neural network behavior, and diseased tissue. The application of a retina prosthetic device for restoring partial vision to patients blinded by degenerative diseases was first considered. This began with the conceptualization of the retina model, translating features of a connectome, implant electronics, and medical images into a computational model that was "degenerated." It was then applied to the design of novel electrode geometries towards increasing the resolution of induced visual percept, and of stimulation waveform shapes for increasing control of induced neural activity in diseased retina. Throughout this process, features of the simulation toolset itself were modified to increase the precision of the results, leading to a novel method for computing effective bulk resistivity for use in such multiscale modeling. This simulation strategy was then extended to the application of a hippocampus prosthetic device, which has been proposed to restore and/or enhance memory in patients with memory disorders such as Alzheimer's disease or dementia. Using this multiscale modeling approach, we are able to provide recommendations for electrode geometry, placement, and stimulation magnitude for increased safety and efficacy in future experimental trials. In attempt to model neural activity in dense hippocampal tissue, a simulation platform for considering the effects the electrical activity of neural networks have on the extracellular electric field, and therefore have on their neighboring cells, was constructed, further increasing the predictive ability of the proposed methodology for modeling electrical stimulation of neural tissue

Titania nanotube arrays as potential interfaces for neurological prostheses

2014 Summer.Includes bibliographical references.Neural prostheses can make a dramatic improvement for those suffering from visual and auditory, cognitive, and motor control disabilities, allowing them regained functionality by the use of stimulating or recording electrical signaling. However, the longevity of these devices is limited due to the neural tissue response to the implanted device. In response to the implant penetrating the blood brain barrier and causing trauma to the tissue, the body forms a to scar to isolate the implant in order to protect the nearby tissue. The scar tissue is a result of reactive gliosis and produces an insulated sheath, encapsulating the implant. The glial sheath limits the stimulating or recording capabilities of the implant, reducing its effectiveness over the long term. A favorable interaction with this tissue would be the direct adhesion of neurons onto the contacts of the implant, and the prevention of glial encapsulation. With direct neuronal adhesion the effectiveness and longevity of the device would be significantly improved. Titania nanotube arrays, fabricated using electrochemical anodization, provide a conductive architecture capable of altering cellular response. This work focuses on the fabrication of different titania nanotube array architectures to determine how their structures and properties influence the response of neural tissue, modeled using the C17.2 murine neural stem cell subclone, and if glial encapsulation can be reduced while neuronal adhesion is promoted

Doctor of Philosophy

dissertationThe development of devices to electrically interact with the brain is a challenging task that could potentially restore motion to paralyzed patients and sight to those with profound blindness. Neural engineers have designed many types of microelectrode arrays (MEAs) with this challenge in mind. These MEAs can be implanted into brain tissue to both record neural signals and electrically stimulate neurons with high selectivity and spatial resolution. Implanted MEAs have allowed patients to control of a variety of prosthetic devices in clinical trials, but the longevity of such motor prostheses is limited to a few years. Performance decreases over time as MEAs lose the ability to record neuronal signals, preventing their widespread clinical use. Microstimulation via intracortical MEAs has also not achieved broad clinical implementation. While microstimulation for the restoration of vision is promising, human clinical trials are needed. Chronic in vivo functionality assays in model systems will provide key insight to facilitate such trials. There are three goals that may help address insufficient MEA longevity, as well as provide insight on microstimulation functionality. First, thorough characterizations of how performance decreases over time, both with and without stimulation, will be needed. Next, factors that affect the chronic performance of microstimulating MEAs must be further investigated. Finally, intervention strategies can be designed to mitigate these factors and improve long term MEA performance. This dissertation takes steps towards meeting these goals by means of three studies. First, the chronic performance of intracortically implanted recording and stimulating MEAs is examined. It is found that while performance of implanted MEAs in feline cortex is dynamic, catastrophic device failure does not occur with microstimulation. Next, a variety of factors that affect microstimulation studies are investigated. It is found that many factors, including device iv damage, anesthesia depth, the application of microstimulation, and the use of impedance as a reporter play a role in observations of performance variability. Finally, a promising intervention strategy, a carbon nanotube coating, is chronically tested in vivo, indicating that carbon nanotubes do not cause catastrophic device failure and may impart benefits to future generations of MEAs

The Electrically Evoked Compound Action Potential: From Laboratory to Clinic

The electrically evoked compound action potential (eCAP) represents the synchronous firing of a population of electrically stimulated auditory nerve fibers. It can be directly recorded on a surgically exposed nerve trunk in animals or from an intra-cochlear electrode of a cochlear implant. In the past two decades, the eCAP has been widely recorded in both animals and clinical patient populations using different testing paradigms. This paper provides an overview of recording methodologies and response characteristics of the eCAP, as well as its potential applications in research and clinical situations. Relevant studies are reviewed and implications for clinicians are discussed