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京都大学 / 新制・課程博士 / 博士(人間健康科学) / 甲第23829号 / 人健博第100号 / 新制||人健||7(附属図書館) / 京都大学大学院医学研究科人間健康科学系専攻 / (主査)教授 黒木 裕士, 教授 山田 重人, 教授 森田 智視 / 学位規則第4条第1項該当 / Doctor of Human Health Sciences / Kyoto University / DFAM

<p> Alterations in neural tissues associated with environmental variables have been studied for many years. Anatomical changes in the neocortex of rats in response to exposure to complex environments were observed and replicated in a number of studies both within and across species. These changes are not dependent on the age of the animal or on the duration of exposure, and have been demonstrated in structures outside of the cortex. Due to the undisputed involvement of both the neocortex and the hippocampus in learning and memory, researchers applied a widely used model system of a synaptic mechanism for learning, long-term potentiation (LTP), to the environmental enrichment paradigm and demonstrated significant enhancements in hippocampal field potentials in enriched rats. The present study examines whether the neocortex also showed evidence of plasticity in synaptic transmission. No effects for environmental enrichment were observed on the maximum amplitude of neocortical field responses evoked from the corpus callosum. To assess the plasticity of the chronic preparation used in the study, the animals were exposed to trains of pulses previously shown to induce electrical LTP in the cortex, but revealed only a slight, although significant, depression of the evoked response amplitude. An alteration in the stimulation parameters did not result in an enhanced response. Cortical depth measures suggested that the enriched environment was indeed sufficient to produce plastic changes in anatomy, if not in the efficacy of synaptic transmission. The importance of these findings in the neocortex leads us to question the validity of the LTP model of learning and memory.</p> / Thesis / Master of Science (MSc)

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BACKGROUND: Accurate prediction of electromyographic (EMG) signals associated with a variety of motor behaviors could, in theory, serve as activity templates needed to evoke movements in paralyzed individuals using functional electrical stimulation. Such predictions should encompass complex multi-joint movements and include interactions with objects in the environment. METHODS: Here we tested the ability of different artificial neural networks (ANNs) to predict EMG activities of 12 arm muscles while human subjects made free movements of the arm or grasped and moved objects of different weights and dimensions. Inputs to the trained ANNs included hand position, hand orientation, and thumb grip force. RESULTS: The ability of ANNs to predict EMG was equally as good for tasks involving interactions with external loads as for unloaded movements. The ANN that yielded the best predictions was a feed-forward network consisting of a single hidden layer of 30 neural elements. For this network, the average coefficient of determination (R2 value) between predicted and actual EMG signals across all nine subjects and 12 muscles during movements that involved episodes of moving objects was 0.43. CONCLUSION: This reasonable accuracy suggests that ANNs could be used to provide an initial estimate of the complex patterns of muscle stimulation needed to produce a wide array of movements, including those involving object interaction, in paralyzed individuals.

The advancement of technologies that interface with electrically excitable tissues, such as the cortex and muscle, has the potential to lend greater mobility to the disabled, and facilitate the study of the central and peripheral nervous systems. Myoelectric interfaces are currently limited in their signal fidelity, spatial resolution, and interfacial area. Such interfaces are either implanted in muscle or applied to the surface of the muscle or skin. Thus far, the former technology has been limited in its applications due to the stiffness (several orders of magnitude greater than muscle) of its substrates, such as silicon and polyimide, whereas the latter technology suffers from poor spatial resolution and signal quality due to the physical separation between the electrodes and the signal source. We have developed a stretchable microneedle electrode array (sMEA) that can function while stretching and flexing with muscle tissue, thereby enabling multi-site muscle stimulation and electromyography (EMG) measurement across a large interfacial area. The scope of this research encompassed: (i) the development of a stretchable and flexible array of penetrating electrodes for the purposes of stimulating and measuring the electrical activity of excitable tissue, (ii) the characterization of the electrical, mechanical, and biocompatibility properties of this electrode array, (iii) the measurement of regional electrical activity of muscle via the electrode array, (iv) the study of the effect of spatially distributed stimulation of muscle on the fatigue and ripple of muscle contractions, and (v) the assessment of the extent to which the stretch response of electrically stimulated muscle behaves in a physiological manner.

Thesis (MScAgric (Animal Sciences))--University of Stellenbosch, 2009. / ENGLISH ABSTRACT: The two main determinants of post-slaughter processing outcomes are rates of pH and temperature decline. Muscle pH and temperature interact continuously during rigor development to affect both the muscle contracture and proteolytic enzyme activity. The pH, however, can be manipulated independently of temperature by electrical inputs applied to the carcass. Electrical inputs that should be considered range from electrical stunning to the various forms of electrical immobilisation (EI) and stimulation (ES) that occur during and after the dressing procedures. EI is used to suppress convulsions that occur after electrical stunning to ensure operator safety to maintain high throughputs speeds while ES is used to induce rapid tenderisation, although having other biochemical and biophysical effects on meat. The objective of the study was to supply information on the effect of different EI and ES treatments, frequencies and pulse widths on the meat quality of beef. There are very little data on the effect of EI when it is combined with ES on meat quality. This study used two different EI frequencies (high – 800 Hz; HFI and low – 15 Hz; LFI) combined with either high (1040 V; HVS) or medium (300 V; MVS) voltage ES to study the effect of these treatments on meat quality. In the following experiment the EI waveform and ES was standardised using HFI with MVS with the frequency being changed to either 5, 15 or 50 Hz. Then the pulse width of the waveform was changed to 0.1, 0.5, 1 and 10 ms to optimise the ES system. Meat quality measurements were made from the Longisimmus dorsi (LD) and Semimembranosus (SM) after 1, 5 and 9 days of chilled storage at 0 C. The LD (shear force = 94.3±2.2; cooking loss = 26.85±0.29; retail drip = 0.996±0.037; storage drip = 2.78±0.155; WBC (water binding capacity) = 45.4±0.36) had significantly lower shear force and higher water binding capacity than the SM (shear force = 103.7±2.5; cooking loss = 34.63±0.25; retail drip = 2.12±0.103; storage drip = 3.63±0.245; WBC = 59.3±0.57). Day of assessment (Day 1 = 122.7±2.9; Day 5 = 87.7±2.2; Day 9 = 81.0±2.4) had a significant effect on tenderness of the LD as shear force declined with an increase of day of assessment. The LFI HVS (storage drip = 3.30±0.223; shear force = 102.9±4.5) produced significantly greater drip during storage and shear force values when compared to the HFI followed by either HVS (storage drip = 2.45±0.261; shear force = 85.2±4.0) or MVS (storage drip = 2.60±0.178; shear force = 94.2±4.2) in the LD, probably attributable to different rates of pH decline post mortem. LFI HVS (a* = 20.79±0.31; chroma = 22.92) and LFI MVS (a* = 20.24±0.27; chroma = 22.23±0.30) had a redder and more vivid bloomed colour than HFI HVS (a* = 19.71±0.33; chroma = 21.49±0.37) and HFI MVS (a* = 20.00±0.27; chroma = 21.98±0.31), while LFI HVS (a* = 15.27±0.40) and HFI MVS (a* = 14.64±0.29) had a redder colour compared to HFI HVS (13.85±0.35) at day 9 for the LD. The oxygen consumption rate (MTT assay) correlated inversely linear (r = -0.63 and -0.73) with the a* values 24 hrs post mortem allowing for 3 hrs of bloom. Stimulation with 15 Hz (0.47±0.040) and 5 Hz (0.41±0.045) had a higher pH decline (ΔpH) during stimulation than 50 Hz (0.29±0.027). Shear force measurements and cooking loss percentage were obtained from the LD after 24 hrs of chilled storage at 0 C. There were no difference between the stimulation treatments for shear force (15 Hz = 121.3±3.3; 5 Hz = 123.8±7.6; 50 Hz =114.8±7.94), while cooking loss was higher in 15 Hz (28.8±0.47) than 50 Hz (25.9±0.71) which correlated (r = 0.43; p = 0.01) with ΔpH. There were no differences between 10 ms (0.46±0.020), 1 ms (0.43±0.020) and 0.5 ms (0.44±0.019) pulse widths on the ΔpH while 0.1 ms (0.33±0.020) had a lower decline. Stimulation with a 1 ms (94.6±5.6) pulse width had the lowest shear force that varied from 10 (111.3±3.8) and 0.1 ms (111.3±5.8). While cooking loss (0.1 = 25.3±0.48; 0.5 = 26.9±0.67; 1 = 25.9±0.63; 10 = 25.5±0.66) and water-holding capacity (0.1 = 36.1±1.60; 0.5 = 37.3±1.42; 1 = 37.5±1.15; 10 = 36.9±1.45) was not affected in the LD after 24 hrs of chilled storage at 0 C. Colour measurements on the SM indicated that a 0.1(a* = 19.38±0.50; chroma = 22.70±0.51), 0.5 (a* = 20.89±0.49; chroma = 24.34±0.56) and 10 ms (a* = 19.69±0.46; chroma = 22.98±0.58) pulse width had a deeper red and a more vivid colour than 1 ms (a* = 16.66±0.37; chroma = 19.99±0.32) at day nine of retail display. In conclusion, HFI improves meat quality when combined with either HVS or MVS and that MVS either improves (colour stability) or has no adverse effects on meat quality (tenderness and WBC) in relation to HVS when combined HFI. In addition, it shows that there are alternative electrical parameters to voltage that can be used to change the pH decline and by changing frequency and pulse width, subtle changes can be made to an ES system. Since every abattoir is different due to layout, chiller space and cooling regime these electrical parameters can be modulated to optimise an electrical stimulation system without expensive modification to the whole system. / AFRIKAANSE OPSOMMING: Die tempo van pH en temperatuur daling is die twee hoof bepalings van na-slag prosseserings uitkomste. Spier pH en temperatuur het ’n gedurige interaksie tydens rigor ontwikkeling en beïvloed die spier sametrekking en proteolitiese ensiem aktiwiteit. Die spier pH kan onafhanklik van temperatuur gemanipuleer word, deur elektriese golfvorms deur die karkas te stuur. Die elektriese golfvorms wat in ag geneem moet word varieer van elektriese impulse tydens bedwelming tot die verskeie golfvorms van elektriese immobilisasie (EI) en stimulasie (ES) wat gebruik kan word gedurende en na die slagproses. EI word gebruik om konvulsies te beheer wat onstaan na elektriese bedwelming om werker veiligheid en hoë deurvloei tempos te verseker, terwyl ES die verouderings proses versnel, alhoewel dit ander biochemiese en biofisiese uitwerkings het op vleis. Die studie het verneem om inligting te verskaf oor die effek van verskillende EI en ES kombinasies, frekwensie en puls wydtes op die kwaliteit van beesvleis. Daar is baie min inligting van EI in kombinasie met ES se effek op vleis kwaliteit. Die studie het gebruik gemaak van twee verskillende (EI) frekwensies (hoog – 800 Hz; HFI and laag – 15 Hz; LFI) wat gekombineer is met of hoë (1040 V; HVS) of medium (300 V; MVS) spanning ES se effek op vleis kwaliteit. In die volgende eksperiment was die EI golfvorm en die ES gestandardiseer en HFI met MVS was gebruik met die frekwensie wat verander is tussen 5, 15 en 50 Hz. Daarna was die pulse wydte van die golfvorm verander tussen 0.1, 0.5, 1en 10 ms om die ES sisteem te optimiseer. Vleis kwaliteit van die Longisimmus dorsi (LD) en Semimembranosus (SM) spiere was bepaal na 1, 5 en 9 dae van verkoelde storing teen 0°C. Die LD (skeurkrag = 94.3±2.2; kookverlies = 26.85±0.29; kleinhandel drup verlies = 0.996±0.037; storing drip verlies = 2.78±0.155; WBV (water bindings vermoë) = 45.4±0.36) het ‘n betekenisvolle laer skeurkrag waardes en hoër water bindings vermoë gehad in vergelyking met die SM (skeurkrag = 103.7±2.5; kookverlies = 34.63±0.25; kleinhandel drupverlies = 2.12±0.103; bergings drupverlies = 3.63±0.245; WBV = 59.3±0.57). Die dag van assesering (Dag 1 = 122.7±2.9; Dag 5 = 87.7±2.2; Dag 9 = 81.0±2.4) het ’n betekenisvolle effek gehad op die skeur krag waardes en het afgeneem met ’n toename in die dag van assesering. LFI HVS (storing drupverlies = 3.30±0.223; skeurkrag = 102.9±4.5) het betekenisvolle hoër vog verliese gehad tydens verkoelde storing en skeur krag wanneer dit vergelyk word met HFI gevolg deur of HVS (storing drupverlies = 2.45±0.261; skeurkrag = 85.2±4.0) of MVS (storing drupverlies = 2.60±0.178; skeurkrag = 94.2±4.2). LFI HVS (a* = 20.79±0.31; chroma = 22.92) en LFI MVS (a* = 20.24±0.27; chroma = 22.23±0.30) het ‘n helder en dieper rooi kleur gehad in vergelyking met HFI HVS (a* = 19.71±0.33; chroma = 21.49±0.37) en HFI MVS (a* = 20.00±0.27; chroma = 21.98±0.31), terwyl LFI HVS (a* = 15.27±0.40) en HFI MVS (a* = 14.64±0.29) ’n rooier en helderer kleur as HFI HVS (13.85±0.35) gehad het in die LD. Die suurstof verbruik tempo (MTT analise) korreleer omgekeerd (r = -0.63 en -0.73) met die a* waardes 24 hr post mortem na 3 hr van blootstelling van lug. Stimulasie met 15 (0.47±0.040) en 5 Hz (0.41±0.045) het ’n hoër pH daling (ΔpH) tydens stimulasie as 50 Hz (0.29±0.027). Skeurkrag waardes en kookverliese is verkry vanaf die LD na 1 dag van verkoelde storing teen 0 C. Daar was geen verskil tussen stimulasie frekwensie se effek of skeurkrag (15 Hz = 121.3±3.3; 5 Hz = 123.8±7.6; 50 Hz =114.8±7.94) nie, terwyl die kookverliese hoër was in die 15 Hz (28.8±0.47) as 50 Hz (25.9±0.71) behandeling wat gekorreleer (r = 0.43; p = 0.01) het met ΔpH. Daar was geen verskill tussen 10 (0.46±0.020), 1 (0.43±0.020) en 0.5 ms (0.44±0.019) puls wydtes se effek op ΔpH nie, terwyl 0.1 (0.33±0.020) ms ‘n kleiner afname tot gevolg gehad het. Stimulasie met ‘n 1 ms (94.6±5.6) puls wydte het die laagste skeurkrag gehad wat verskil het van die 10 (111.3±3.8) and 0.1 ms (111.3±5.8) puls wydtes, terwyl kookverliese (0.1 = 25.3±0.48; 0.5 = 26.9±0.67; 1 = 25.9±0.63; 10 = 25.5±0.66) en waterbindingsvermoë (0.1 = 36.1±1.60; 0.5 = 37.3±1.42; 1 = 37.5±1.15; 10 = 36.9±1.45) nie beïvloed was nie. Kleur metings van die SM het getoon dat ‘n 0.1 (a* = 19.38±0.50; chroma = 22.70±0.51), 0.5 (a* = 20.89±0.49; chroma = 24.34±0.56) en 10 ms (a* = 19.69±0.46; chroma = 22.98±0.58 puls wydtes die helder en dieper rooi kleur gehad het as 1 ms (a* = 16.66±0.37; chroma = 19.99±0.32) teen dag 9 van kleinhandel vertoning. Ter opsomming, lei HFI tot beter vleis kwaliteit wanneer dit gekombineer word met of HVS of MVS. Verder lei MVS tot of ’n verbetering (kleur stabiliteit) of geen nadelige effek op vleis kwaliteit (sagtheid en WBV) in vergelyking met HVS wanneer dit gekombineer word met HFI. Die studie bewys ook dat daar ander elektriese parameters bestaan as spanning, wat verander kan word om die pH daling te beïvloed. Deur die frekwensie en pulswydte te verander, kan klein veranderinge aangebring word aan ’n ES sisteem. Elke abattoir is verskillend as gevolg van uitleg, koelkamer spasie en verkoelings tempo en hierdie elektriese parameters kan verander word om ’n ES sisteem te optimiseer sonder enige duur veranderinge aan die hele sisteem.

<p>Modulation of neural activity with electrical stimulation is a widespread therapy for treating neurological disorders and diseases. Two notable applications that have had striking clinical success are deep brain stimulation (DBS) for the treatment of movement disorders (e.g., Parkinson's disease) and spinal cord stimulation (SCS) for the treatment of chronic low back and limb pain. In these therapies, the battery life of the stimulators is much less than the required duration of treatment, requiring patients to undergo repeated battery replacement surgeries, which are costly and obligate them to incur repeatedly the risks associated with surgery. Further, deviations in lead position of 2-3 mm can preclude some or all potential clinical benefits, and in some cases, generate side-effects by stimulation of non-target regions. Therefore, despite the success of DBS and SCS, their efficiency and ability to activate target neural elements over non-target elements, termed selectivity, are inadequate and need improvement.</p><p>We combined computational models of volume conduction in the brain and spine with cable models of neurons to design novel electrode configurations for efficient and selective electrical stimulation of nervous tissue. We measured the efficiency and selectivity of prototype electrode designs in vitro and in vivo. Stimulation efficiency was increased by increasing electrode area and/or perimeter, but the effect of increasing perimeter was not as pronounced as increasing area. Cylindrical electrodes with aspect (height to diameter) ratios of > 5 were the most efficient for stimulating neural elements oriented perpendicular to the axis of the electrode, whereas electrodes with aspect ratios of < 2 were the most efficient for stimulating parallel neural elements.</p><p>Stimulation selectivity was increased by combining two or more electrodes in multipolar configurations. Asymmetric bipolar configurations were optimal for activating parallel axons over perpendicular axons; arrays of cathodes with short interelectrode spacing were optimal for activating perpendicular axons over parallel axons; anodes displaced from the center of the target region were optimal for selectively activating terminating axons over passing axons; and symmetric tripolar configurations were optimal for activating neural elements based on their proximity to the electrode. The performance of the efficient and selective designs was not be explained solely by differences in their electrical properties, suggesting that field-shaping effects from changing electrode geometry and polarity can be as large as or larger than the effects of decreasing electrode impedance.</p><p>Advancing our understanding of the features of electrode geometry that are important for increasing stimulation efficiency and selectivity facilitates the design of the next generation of stimulation electrodes for the brain and spinal cord. Increased stimulation efficiency will increase the battery life of IPGs, increase the recharge interval of rechargeable IPGs, and potentially reduce stimulator volume. Greater selectivity may improve the success rate of DBS and SCS by mitigating the sensitivity of clinical outcomes to malpositioning of the electrode.</p> / Dissertation

Muscular fatigue limits athletic performance as well as activities of daily living that require repetitive or sustained contractile activity. The decrease in force output or inability to maintain a given force level during fatigue occurs as the result of neural and muscle physiological factors. In contrast to muscle fatigue, potentiation is an increase in muscle force following voluntary muscle activity. The simultaneously occurring processes of potentiation and fatigue influence force output. The aims of this research were to investigate parameters used to potentiate muscle via electrical stimulation and voluntary contraction, and to better understand how muscle force is sustained, we studied single motor unit firing patterns and force potentiation following muscular endurance training. In study 1, electrical stimulation trains matched for pulse number of various frequencies and of increasing pulse number at a given frequency were administered to determine the effects of these stimulation parameters and of the force-time integral (FTI) produced during the train on potentiation magnitude. No difference in potentiation magnitude was found across trains of matched pulse number for frequencies of 15, 25, 30 and 50 Hz. Potentiation increased as pulse number increased and there was a positive correlation between potentiation and the FTI. In study 2, we measured maximal potentiation following conditioning contractions (CC) of 25%, 50% and 100% maximal voluntary contraction (MVC) and during a 25% MVC fatigue task, pre-post 8 weeks of muscular endurance training. Results showed significant potentiation for all CC intensities. Potentiation increased as CC intensity increased and CC duration required to achieve maximal potentiation decreased as CC intensity increased. Muscular endurance training resulted in increased maximal potentiation, and potentiation was greater during the fatigue task after training. Potentiation was also correlated to endurance time. In study 3, the effects of muscular endurance training on motor unit firing rates were investigated. There was a small increase in mean motor unit firing rates during the course of the fatigue task after training. This research contributes to our understanding of muscular force production and muscular endurance. The findings suggest that motor unit firing frequency and force potentiation may contribute to enhanced muscular endurance. / text

Individuals with stroke often demonstrate impaired ankle-foot function, commonly termed dropped foot that affects their ability to walk safely at home and within their community. While interventions are available to improve gait function, they have inconsistency demonstrated positive effects due to the lack of evidence-based practice guidelines and a limited understanding of the mechanisms leading to dropped foot. The aim of this dissertation was to 1) determine the relationship between dropped foot gait deviations and impaired sensorimotor control, 2) compare gait biomechanics between stroke survivors with and without dropped foot impairment, and 3) evaluate the immediate effects of an ankle-foot orthotic (AFO) and functional electrical stimulation (FES) device among stroke survivors with dropped foot impairment. Our evaluation combined standardized clinical measures of ankle-foot function (i.e. sensorimotor control, strength, spasticity and range of motion) and gait analysis using advanced laboratory techniques (i.e. electromyography and electrical goniometers) to quantify mechanisms of dropped foot impairment. Fifty-five stroke survivors completed the assessment prior to discharge from inpatient rehabilitation. Individuals with poor generation of isometric dorsiflexor force and reduced passive ankle range of motion were likely to demonstrate greater plantarflexion in swing and limited stance phase ankle joint excursion, respectively. Results from the gait analysis revealed a delayed onset and reduced activation time of the ankle dorsiflexors, and decreased co-activation time in the stance phase as possible mechanisms leading to dropped foot. A detailed case series was performed with four stroke survivors with dropped foot currently using an AFO. Application of an AFO immediately improved peak dorsiflexion in the swing phase and limited ankle range of motion during stance. When walking with the FES device, individuals with moderate dorsiflexor muscle weakness improved their ankle position at initial contact and increased peak dorsiflexion during stance, while no significant changes were observed among individuals with greater impairment. Overall, the results highlighted individual differences in response to interventions aimed at improving dropped foot gait deviations. These findings contribute to a greater understanding of gait dysfunction post stroke, and may lead to the development of a more effective clinical assessment and intervention strategies to improve dropped foot impairment.