Doctor of Philosophy

dissertationToday, we are implanting electrodes into many different parts of the peripheral and central nervous systems for the purpose of restoring function to people with nerve injury or disease. As technology and manufacturing continue to become more advanced, ne

Intraneural stimulation elicits discrimination of textural features by artificial fingertip in intact and amputee humans.

Restoration of touch after hand amputation is a desirable feature of ideal prostheses. Here, we show that texture discrimination can be artificially provided in human subjects by implementing a neuromorphic real-time mechano-neuro-transduction (MNT), which emulates to some extent the firing dynamics of SA1 cutaneous afferents. The MNT process was used to modulate the temporal pattern of electrical spikes delivered to the human median nerve via percutaneous microstimulation in four intact subjects and via implanted intrafascicular stimulation in one transradial amputee. Both approaches allowed the subjects to reliably discriminate spatial coarseness of surfaces as confirmed also by a hybrid neural model of the median nerve. Moreover, MNT-evoked EEG activity showed physiologically plausible responses that were superimposable in time and topography to the ones elicited by a natural mechanical tactile stimulation. These findings can open up novel opportunities for sensory restoration in the next generation of neuro-prosthetic hands

Changed vibration threshold and loss of nerve movement in patients with repetitive strain injury; the peripheral neuropathology of RSI

Changed vibration threshold and loss of nerve movement in patients with repetitive strain injury; the peripheral neuropathology of RSI Repetitive strain injury (RSI) is a chronic pain condition affecting the upper limbs. It has been associated with tasks that require repetitive and intensive hand activities, particularly when these are carried out in constrained postures. Patients present with significant symptoms, but when examined, lack signs of specific inflammatory conditions or single peripheral nerve disorder. In consequence there have been considerable problems in the diagnosis of RSI and in designing effective treatment. Partial injury to peripheral nerves can produce significant symptoms and allodynic changes in the presence of normal nerve conduction studies. It therefore seemed possible that minor neuropathy might be an important contributor to RSI. To test this, vibration threshold was measured in patients with RSI and in a group of "at risk" office workers. Significantly raised thresholds were found, particularly affecting the median nerve, in both the patients and office workers. Following five minutes of keyboard use the patients showed a further rise in vibration threshold. Patients also showed reduced tolerance to non noxious suprathreshold vibration. These sensory changes are consistent with the changes observed in patients with diagnosed neuropathy. In further studies we imaged the median nerve at the carpal tunnel using MRI and high frequency ultrasound. The dynamics of the median nerve were studied during 30 degrees of wrist flexion and extension. A significant quantitative reduction of nerve movement was seen in patients. A correlation was found between nerve movement measured objectively and a clinical test of median nerve dynamics. How loss of normal nerve dynamics could contribute to the symptoms experienced by these patients is discussed. It is concluded that minor nerve injury forms part of the pathology of RSI and that testing vibration threshold and examining nerve movement could contribute to diagnosis and prove useful in evaluating treatment outcomes

Neural Interfacing with Dorsal Root Ganglia: Anatomical Characterization and Electrophysiological Recordings with Novel Electrode Arrays

Dorsal root ganglia (DRG), the hubs of neurons conducting sensory information into the spinal cord, are promising targets for clinical and investigative neural interface technologies. DRG stimulation is currently a tertiary therapy for chronic pain patients, which has an estimated prevalence of 11-40% of adults in the United States. In pre-clinical studies, combined neural recording and stimulation at DRG has been used as part of closed-loop systems to drive activity of the limbs and the urinary system. This suggests a role for clinical DRG interfaces to assist, among other patient groups, the nearly 300,000 spinal cord injured patients in the United States. To maximize the utility of DRG interfaces, however, there remains a strong need to improve our understanding of DRG structure. Neural interface technologies for both stimulation and recording rely heavily on the spatial organization of their neural targets. To record high-fidelity neural signals, a microelectrode must be placed within about 200 µm of a neural cell body. Likewise, effective neural stimulation is believed to act on a subset of DRG axons based on their size and target. The spatial organization of DRG, however, has not been previously quantified. In this thesis, I demonstrate a novel algorithm to transform histological cross-sections of DRG to a normalized circular region for quantifying trends across many samples. Using this algorithm on 26 lumbosacral DRG from felines, a common preclinical DRG model, I found that the highest density of neural cell bodies was in the outer 24% radially, primarily at the dorsal aspect. I extended this analysis to a semi-automated cross-DRG analysis in 33 lower lumbar DRG from 10 human donors. I found that the organization of human DRG was similar to felines, with the highest density of cell bodies found in the outer 20-25% of the DRG, depending on spinal level. I also found a trend toward lower small-axon density at the dorsal aspect of L5 DRG, a key region for stimulation applications. To take advantage of this quantitative knowledge of DRG organization, future neural interfaces with DRG will require more advanced technologies. Standard silicon-based electrode arrays, while useful for short-term DRG recordings, ultimately fail in chronic use after several weeks as a result of mechanical mismatch with neural tissue. In this thesis, I demonstrate sensory recording from the surface and interior of sacral DRG during acute surgery using a variety of flexible polyimide microelectrode arrays 4-μm thick and minimum site separation 25 to 40 μm. Using these arrays, I recorded from bladder and somatic afferents with high fidelity. The high density of sites allowed for neural source localization from surface recordings to depths 25 to 107 µm. This finding supports the anatomical analysis suggesting a high density of cell bodies in the dorsal surface region where the surface array was applied. The high site density also allowed for the use of advanced signal processing to decrease analysis time and track neural sources during movement of the array which may occur during future behavioral experiments. This thesis represents significant advances in our understanding of DRG and how to interface with them, particularly related to the way anatomy can inform development of future technologies. Going forward, it will be important to expand the anatomical maps based on organ function and to test the novel flexible arrays in chronic implant experiments.PHDBiomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/153477/1/zsperry_1.pd

Doctor of Philosophy

dissertationHands are so central to the human experience, yet we often take for granted the capacity to maneuver objects, to form a gesture, or to caress a loved-one’s hand. The effects of hand amputation can be severe, including functional disabilities, chronic phantom pain, and a profound sense of loss which can lead to depression and anxiety. In previous studies, peripheral-nerve interfaces, such as the Utah Slanted Electrode Array (USEA), have shown potential for restoring a sense of touch and prosthesis movement control. This dissertation represents a substantial step forward in the use of the USEAs for clinical careâ€"ultimately providing human amputees with widespread hand sensation that is functionally useful and psychologically meaningful. In completion of this ultimate objective, we report on three major advances. First, we performed the first dual-USEA implantations in human amputees; placing one USEA in the residual median nerve and another USEA in the residual ulnar nerve. Chapter 2 of this dissertation shows that USEAs provided full-hand sensory coverage, and that movement of the implant site to the upper arm in the second subject, proximal to nerve branch-points to extrinsic hand muscles, enabled activation of both proprioceptive sensory percepts and cutaneous percepts. Second, in Chapter 3, we report on successful use of USEA-evoked sensory percepts for functional discrimination tasks. We provide a comprehensive report of functional discrimination among USEA-evoked sensory percepts from three human subjects, including discrimination among multiple proprioceptive or cutaneous sensory percepts with different hand locations, sensory qualities, and/or intensities. Finally, in Chapter 4, we report on the psychological value of multiple degree of freedom prosthesis control, multisensor prosthesis sensation, and closed-loop control. This chapter represents the first report of prosthesis embodiment during closed-loop and open-loop prosthesis control by an amputee, as well as the most sophisticated closed-loop prosthesis control reported in literature to-date, including 5-degree-of-freedom motor control and sensory feedback from 4 hand locations. Ultimately, we expect that USEA-evoked hand sensations may be used as part of a take-home prosthesis system which will provide users with both advanced functional capabilities and a meaningful sense of embodiment and limb restoration

Respiratory Control: Central and Peripheral Mechanisms

Understanding of the respiratory control system has been greatly improved by technological and methodological advances. This volume integrates results from many perspectives, brings together diverse approaches to the investigations, and represents important additions to the field of neural control of breathing. Topics include membrane properties of respiratory neurons, in vitro studies of respiratory control, chemical neuroanatomy, central integration of respiratory afferents, modulation of respiratory pattern by peripheral afferents, respiratory chemoreception, development of respiratory control, behavioral control of breathing, and human ventilatory control. Forty-seven experts in the field report research and discuss novel issues facing future investigations in this collection of papers from an international conference of nearly two hundred leading scientists held in October 1990. This research is of vital importance to respiratory physiologists and those in neurosciences and neurobiology who work with integrative sensory and motor systems and is pertinent to both basic and clinical investigations. Respiratory Control is destined to be widely cited because of the strength of the contributors and the dearth of similar works. The four editors are affiliated with the University of Kentucky: Dexter F. Speck is associate professor of physiology and biophysics, Michael S. Dekin is assistant professor of biological sciences, W. Robert Revelette is research scientist of physiology and biophysics, and Donald T. Frazier is professor and chairman of physiology and biophysics. Experts in the field report current research and discuss novel issues facing future investigations. —SciTech Book Newshttps://uknowledge.uky.edu/upk_biology/1002/thumbnail.jp