For patients with focal drug-resistant epilepsy, surgical remediation can be a hopeful last resort treatment option, but only if enough clinical signs can point to an epileptogenic tissue region. Subdural grids offer ample cortical surface area coverage to evaluate multiple regions of interest, yet they lack the spatial resolution typical of penetrating electrodes. Additionally, subthreshold stimulation through subdural grids is a stable source for detecting eloquent cortex surrounding potential epileptic tissue. Researchers have each tried introducing microelectrodes to increase the spatial resolution but ran into connectivity challenges as the desired surface area increased. Meanwhile, clinical hybrid options have shown promise by combining multiple electrode sizes, maintaining surface area coverage with an increased spatial resolution where necessary. However, a benchtop method to quantify spatial resolution or test signal summation, without the complexity of an in vivo study, has not been found in the literature; a subdural grid in gel solution has functioned previously but without a published method. Thus, a novel hybrid electrode array with a telescopic configuration including three electrode geometries, called the M$^3$ array, is proposed to maintain cortical surface area coverage and provide spatial clarity in regions of interest using precision microfabrication techniques. Electrophysiological recording with this array should enhance the clinical signal portfolio without changing how clinicians interface with the broad surface data from macros. Additionally, this would provide a source for simultaneous recording and stimulation from the same location due to the telescopic nature of the design. A novel benchtop test method should remove complexity from in vivo tests while allowing direct comparison of recording capabilities of different cortical surface electrodes. Implementing the proposed M$^3$ electrode array in intracranial monitoring improves the current technology without much compromise, enhancing patient outcomes, reducing risks, and encouraging swift clinical translation.

Electrical stimulation of the human peripheral nervous system can be a powerful tool to treat various medical conditions and provide insight into nervous system processes. A critical challenge for many applications is to selectively activate neurons that have the desired effect while avoiding the activation of neurons that produce side effects. To stimulate peripheral fibers, the longitudinal intrafascicular electrode (LIFE) targets small groups of fibers inside the fascicle using low-amplitude pulses and is well-suited for chronic use. This work aims to understand better the ability to use intrafascicular stimulation with LIFEs to activate small groups of neurons within a fascicle selectively.A hybrid workflow was developed to simulate: 1) the production/propagation of the electric field induced by the stimulation pulse and 2) the effect of the electric field on fiber activation (recruitment). To create efficient and robust strategies for the selective recruitment of axons, recognizing the effect of each parameter on their recruitment and activation pattern is essential. Thus, using this hybrid workflow, the effects of various factors such as fascicular anatomy, electrode parameters, and stimulation pulse parameters on recruitment have been characterized, and the sensitivity of the recruitment patterns to these parameters has been explored. Results demonstrated the potential advantages of specific stimulation strategies and the sensitivity of recruitment patterns to electrode placement and tissue properties. For example, it is demonstrated: the significant effect of endoneurium conductivities on threshold levels; that a configuration with a LIFE as a local ground can be used to deselect its surrounding axons; the advantages of changing the delay between pulses in dual monopolar stimulation in targeting different axons clusters and increasing the activation frequency of some axons; how monopolar and bipolar configurations can be used to enhance spatial selectivity; the effect of longitudinal displacement of axons, electrode length and electrode movement on the recruitment and the activation pattern. In summary, this work forms the foundation for developing stimulation strategies to enhance the selectivity that can be achieved with intrafascicular stimulation.

Neuron models that behave like their biological counterparts are essential for computational neuroscience.Reduced neuron models, which abstract away biological mechanisms in the interest of speed and interpretability, have received much attention due to their utility in large scale simulations of the brain, but little care has been taken to ensure that these models exhibit behaviors that closely resemble real neurons.
In order to improve the verisimilitude of these reduced neuron models, I developed an optimizer that uses genetic algorithms to align model behaviors with those observed in experiments.
I verified that this optimizer was able to recover model parameters given only observed physiological data; however, I also found that reduced models nonetheless had limited ability to reproduce all observed behaviors, and that this varied by cell type and desired behavior.
These challenges can partly be surmounted by carefully designing the set of physiological features that guide the optimization. In summary, we found evidence that reduced neuron model optimization had the potential to produce reduced neuron models for only a limited range of neuron types.

Parkinson's disease (PD) is a neurodegenerative disorder that produces a characteristic set of neuromotor deficits that sometimes includes reduced amplitude and velocity of movement. Several studies have shown that people with PD improved their motor performance when presented with external cues. Other work has demonstrated that high velocity and large amplitude exercises can increase the amplitude and velocity of movement in simple carryover tasks in the upper and lower extremities. Although the cause for these effects is not known, improvements due to cueing suggest that part of the neuromotor deficit in PD is in the integration of sensory feedback to produce motor commands. Previous studies have documented some somatosensory deficits, but only limited information is available regarding the nature and magnitude of sensorimotor deficits in the shoulder of people with PD. The goals of this research were to characterize the sensorimotor impairment in the shoulder joint of people with PD and to investigate the use of visual feedback and large amplitude/high velocity exercises to target PD-related motor deficits. Two systems were designed and developed to use visual feedback to assess the ability of participants to accurately adjust limb placement or limb movement velocity and to encourage improvements in performance of these tasks. Each system was tested on participants with PD, age-matched control subjects and young control subjects to characterize and compare limb placement and velocity control capabilities. Results demonstrated that participants with PD were less accurate at placing their limbs than age-matched or young control subjects, but that their performance improved over the course of the test session such that by the end, the participants with PD performed as well as controls. For the limb velocity feedback task, participants with PD and age-matched control subjects were less accurate than young control subjects, but at the end of the session, participants with PD and age-matched control subjects were as accurate as the young control subjects. This study demonstrates that people with PD were able to improve their movement patterns based on visual feedback of performance and suggests that this feedback paradigm may be useful in exercise programs for people with PD.