The work presented in this dissertation was focused on developing an affordable, automated, upper extremity exercise system suitable for individuals with stroke and spinal cord injury (SCI). The three studies presented in this thesis demonstrated the efficacy of functional electrical stimulation-assisted exercise therapy (FES-ET). Furthermore a protocol was developed to implement FES-ET in participants homes via tele-rehabilitation. The protocol included the use of an improved version of the bionic glove, an FES device that enhanced hand grasp and release in SCI individuals in combination with a custom-built workstation that enabled task-oriented rehabilitation in the home setting, supervised over the Internet. In the course of these studies, an objective hand function assessment tool was developed to complement tele-supervised FES-ET and provide the therapist with an unbiased evaluation of the participants impairment. A major section of this dissertation is concerned with the development and testing of a novel exercise workstation named the ReJoyce (Rehabilitation Joystick for Computer Exercise), that can assess hand function electronically. The ReJoyce is an instrumented workstation that provides standardized upper extremity rehabilitation based on ADLs, in the guise of computer games played by manipulating attachments on the device. The three studies presented in this thesis focus on the scientific merits and the logistics of providing tele-supervised FES-ET with this workstation. The first study demonstrated the feasibility of treating and assessing individuals on the workstation who had recently suffered a stroke. The second study explored the relationship between the quantitative assessment of hand function with the workstation and two widely-used clinical tests. The last study involved daily, tele-supervised FES-ET or conventional exercises and therapeutic electrical stimulation (TES), maintained for 6 weeks, with SCI participants spread out over a large geographical area. FES-ET performed with the workstation resulted in statistically significant and clinically important improvements in hand function that were greater than those produced by the more conventional protocol. The results demonstrated the importance of including a range of exercises aimed at improving both strength and dexterity. It is concluded that tele-supervised FES-ET on a standardized workstation is feasible, effective and affordable in the current healthcare settin

Deep tissue injury (DTI) is a severe form of pressure ulcers resulting from ischemia and mechanical damage due to unrelieved pressure. Despite many preventative methods, none so far has significantly reduced the incidence of DTI. The use of a novel method of pressure ulcer prevention, intermittent electrical stimulation (IES), was investigated. The current study investigated the effects of IES on surface pressure and tissue oxygenation in individuals with SCI. The results demonstrated that IES induced contractions caused significant reductions in pressure around the ischial tuberosities, as well as significant and sustained increases in oxygenation. Direct measurements of oxygen in an invasive rodent model indicated that IES induced contractions resulted in a 20-100% increase in tissue oxygenation. The results indicate that IES directly targets the pathogenic factors contributing to the development of pressure ulcers and thereby may be an effective method for the prevention of DTI.

Injury to the cervical spinal cord results in complete or partial loss of arm and hand function, severely limiting the performance of daily activities. Deficits in hand function in individuals with cervical spinal cord injury (SCI) are primarily due to a loss of descending motor pathways that are vital for fine control of the hand and fingers. In addition to these deficits, secondary plastic reorganization may create further loss of function. This thesis will explore the following questions: 1. What are the similarities and differences between cortical organization of muscles affected by a cervical SCI to those not affected by the injury?; 2. Do individuals with cervical SCI improve in hand function and cortical organization after an intensive hand training intervention?; 3. Which physical therapy intervention provides the optimal conditions by which to improve hand function following cervical SCI? In chapter 2 we compare cortical motor maps of transcranial magnetic stimulation (TMS) evoked responses of muscles rostral and caudal to the injury to those of ND individuals. The cortical maps of the biceps brachii or the thenar muscles were constructed, and compared between ND individuals and individuals with SCI. The motor threshold (MT) for the thenar muscles in individuals with SCI was significantly higher than ND individuals. The purpose of the study described in chapter 3 was to compare the functional and cortical changes associated with two different interventions: unimanual or bimanual massed practice training, both combined with somatosensory stimulation. There was a significant difference between pre- and post-intervention scores on tests measuring unimanual hand function, bimanual hand function, and sensory function. This difference was associated with a difference between pre- and post-intervention cortical map area. The purpose of the study described in chapter 4 was to compare clinical and cortical changes associated with either a delayed intervention control period or a combined intervention of massed practice training with electrical stimulation. Participants were randomly assigned to one of two groups: delayed intervention control group or immediate intervention group. Participants were also randomly assigned to one of four groups: unimanual training with somatosensory stimulation, bimanual training with somatosensory stimulation, unimanual training with functional electrical stimulation, or bimanual training with functional electrical stimulation. There was a significant difference between the control and immediate intervention group on the test measuring unimanual hand function. Participants in the bimanual group performed significantly better on the test measuring bimanual hand function. There was a significant difference between the control group and immediate intervention group in cortical map area. In chapter 5 we discuss the clinical relevance of the results of the studies described in three prior chapters. Conclusions drawn include the idea that cortical maps of muscles caudal to the level of injury in individuals with SCI have higher motor thresholds than ND participants. Individuals with tetraplegia can improve in hand function and sensation with a physical therapy intervention of massed practice training combined with somatosensory stimulation. Finally, the type of training (unimanual massed practice or bimanual massed practice) influences the type of improvements gained, however the type of electrical stimulation does not influence the clinical outcome.

Intravesical electrical stimulation (IVES) has been used in treatment of patients with urinary bladder dysfunctions for more than four decades. While some investigators have reported excellent results others have observed less convincing effects or outright failures. The discrepancies may reflect differences in patient selection or stimulation procedure. A better theoretical understanding of the IVES working mechanism might help to improve the success rate of the treatment. The aims of the present study were to provide such information. Experiments were performed on adult female cats and rats under /alpha/-chloralose anesthesia. IVES was delivered by a catheter electrode in the bladder. At proper intensity and frequency, IVES evoked reflex detrusor contractions that were abolished by bilateral rhizotomy of sacral dorsal roots. Stimulation parameters and response characteristics revealed that bladder mechanoreceptor A/delta/ afferents were activated by the IVES, the same afferents that drive the normal micturition reflex. Five minutes of continues IVES at 20 Hz induced a prolonged, significant decrease in the micturition threshold volume of anesthetized rats. Similarly, selective bladder A/delta/ afferent stimulation induced a long-lasting enhancement of micturition reflex discharges in cats. A comparable prolonged inhibitory effect on the micturition reflex was demonstrated after ano-genital afferent stimulation. Both modulatory effects occurred without changes in response sensitivity of stimulated afferents. The IVES induced modulation was prevented by transient exposure of the bladder to a local anesthetic and by systemic administration of a glutamate NMDA receptor antagonist. In conclusion, IVES induces a prolonged modulation of the micturition reflex by an LTP like enhancement of excitatory synaptic transmission in the central micturition reflex pathway. The findings provide an experimental explanation for the neuronal mechanisms underlying the curative effect of IVES in patients with bladder evacuation problems. / On the day of the public defence the status of article V was: Accepted.

Orthostatic hypotension (OH) is a prevalent condition among individuals with spinal cord injury (SCI). After an injury, OH often reduces the benefit of neurorehabilitation and also prolongs periods of inactivity that lead to secondary complications. This study investigated whether the cardiovascular response to head-up tilting can be improved using functional electrical stimulation (FES) and rhythmic passive movements of the lower extremities. Participants with high thoracic and cervical SCI were recruited. While the participants were tilted head-up to 70 degrees, four conditions were applied in a random sequence: 1) no intervention, 2) rhythmic passive leg movements, 3) isometric FES, and 4) a combination of FES and passive leg movements. The measured cardiovascular parameters indicated that a combination of FES and passive leg movements induced the most desirable response to head-up tilting. The proposed intervention will enable more individuals with SCI to participate in beneficial neurorehabilitation that uses a novel tilt table.

Orthostatic hypotension (OH) is a prevalent condition among individuals with spinal cord injury (SCI). After an injury, OH often reduces the benefit of neurorehabilitation and also prolongs periods of inactivity that lead to secondary complications. This study investigated whether the cardiovascular response to head-up tilting can be improved using functional electrical stimulation (FES) and rhythmic passive movements of the lower extremities. Participants with high thoracic and cervical SCI were recruited. While the participants were tilted head-up to 70 degrees, four conditions were applied in a random sequence: 1) no intervention, 2) rhythmic passive leg movements, 3) isometric FES, and 4) a combination of FES and passive leg movements. The measured cardiovascular parameters indicated that a combination of FES and passive leg movements induced the most desirable response to head-up tilting. The proposed intervention will enable more individuals with SCI to participate in beneficial neurorehabilitation that uses a novel tilt table.

<p>Spinal cord injury (SCI) and other neurological diseases and disorders can cause urinary dysfunction that can cause serious health problems and reduce an individual's quality of life. Current methods for treating urinary dysfunction have major limitations or provide inadequate improvement in urinary symptoms. Pudendal nerve stimulation is a potential means of restoring control of bladder function in persons with neurological disease or spinal cord injury. Bladder contraction and relaxation can be evoked by pudendal afferent stimulation, and peripheral pudendal afferent branches may be ideal targets for a bladder control neural prosthesis. This dissertation investigates control of bladder function by selective activation of pudendal afferents.</p> <p>This study investigated the ability to improve both urinary continence and micturition by both direct and minimally-invasive electrical stimulation of selected pudendal afferents in &#945;-chloralose anesthetized male cats. Direct stimulation of the pudendal afferents in the dorsal nerve of the penis (DNP), percutaneous DNP stimulation, and intraurethral stimulation were used to investigate the bladder response to selective activation of pudendal afferents. Finite element modeling of the cat lower urinary tract was used to investigate the impact of intraurethral stimulation location and intraurethral electrode configuration on activation of pudendal afferents. Also, the impact of pharmacological and surgical block of sympathetic activity to the bladder on the bladder reflexes evoked by DNP stimulation was investigated to determine the role of the sympathetic bladder innervation on the mechanism of bladder activation by pudendal afferent stimulation.</p> <p>The DNP is an ideal target for restoring urinary function because stimulation at low frequencies (5-10 Hz) improves urinary continence, while stimulation at high frequencies (33-40 Hz) improves urinary voiding. Intraurethral stimulation is a valid method for clinical investigation of the ability to evoke bladder inhibition and activation via selective activation of the DNP or cranial sensory branch (CSN) of the pudendal nerve. In the cat, intraurethral stimulation can activate the bladder via two distinct neural pathways, a supraspinal pathway reflex activated by the CSN and a spinal reflex activated by the DNP. Finite element modeling revealed the importance of urethral location for selective pudendal afferent activation by intraurethral stimulation. Finally, the sympathetic bladder pathway does not play a significant role in the mechanism mediating bladder activation by DNP stimulation. These findings imply that selective pudendal afferent stimulation is a promising approach for restoring control of bladder function to individuals with SCI or other neurological disorders.</p> / Dissertation

Strip steaks from the McGregor genome project were used to evaluate the effects of sarcomere length, myofibrillar fragmentation index, 3 h postmortem pH, 24 h postmortem pH, marbling, electrical stimulation (ES), sarcoplasmic free calcium concentration, and collagen characteristics on tenderness as measured by Warner-Bratzler shear force (WBS). The WBS values were measured prior to this project so the animals were able to be separated into “tender” and “tough” groups using a WBS value of 30 N as the separating point, steaks with a WBS value less than 30 N being “tender” and the others being “tough”. It was found that ES sides had lower WBS values, however, “tough” steaks showed a greater response to ES than “tender” steaks. ES sides also had higher sarcoplasmic free calcium concentration and lower 3 h postmortem pH. Tenderness is best predicted by treatment (ES versus NON-ES), however, there is some efficacy in using total collagen and collagen solubility in conjunction with treatment.

A principal goal of neural engineering is to control the activation of neural circuits across space and time. The ability to control neural circuits with surrogate inputs is needed for the development of clinical neural prostheses and the experimental interrogation of connectivity between brain regions. Electrical stimulation provides a clinically viable method for activating neural tissue and the emergence of optogenetic stimulation has redefined the limitations on stimulating neural tissue experimentally. However, it remains poorly understood how these tools activate complex neural circuits. The goal of this proposed project was to gain a greater understanding of how to control the activity of neural circuits in-vivo using a combination of experimental and computational approaches. Voltage sensitive dye imaging was used to observe the spatiotemporal activity within the rodent somatosensory cortex in response to systematically varied patterns of sensory, electrical, and optogenetic stimulation. First, the cortical response to simple patterns of sensory and artificial stimuli was characterized and modeled, revealing distinct neural response properties due to the differing synchrony with which the neural circuit was engaged. Then, we specifically designed artificial stimuli to improve the functional relevance of the resulting downstream neural responses. Finally, through direct optogenetic modulation of thalamic state, we demonstrate control of the nonlinear propagation of neural activity within the thalamocortical circuit. The combined experimental and computational approach described in this thesis provides a comprehensive description of the nonlinear dynamics of the thalamocortical circuit to surrogate stimuli. Together, the characterization, modeling, and overall control of downstream neural activity stands to inform the development of central nervous system sensory prostheses, and more generally provides the initial tools and framework for the control of neural activity in-vivo.

The restoration of arm-free standing in paraplegic individuals can be accomplished with the help of functional electrical stimulation (FES). The key component of such a system is a controller that can modulate FES induced muscle contractions in real-time, such that artificially produced forces in the legs and abdominal muscles are able to generate stable standing posture. A 57 year-old individual with chronic ASIA-A (American Spinal Injury Association), T3/4 level spinal cord injury (SCI) participated in this study. The objective was to determine if a proportional-derivative (PD) or proportional-integral-derivative (PID) controller could be used to regulate FES induced muscle contractions in the ankle joint to allow it to maintain balance of the entire body during quiet standing, while exhibiting physiological dynamics seen in able-bodied individuals while doing so.