Dissertations / Theses on the topic 'Compound Motor Action Potential'

The recovery from prior stimulation of the compound action potential (CAP) was measured using a forward masking stimulus paradigm in four normal-hearing, human subjects. The CAP was recorded using a wick electrode placed on the tympanic membrane. The effects of a 4000-Hz, 97-dB SPL conditioning stimulus on CAP amplitude in response to a 4000-Hz probe were measured as a function of conditioner–probe interval for three probe levels. The normalized probe response amplitude was completely recovered to the control values at an average conditioner–probe interval of 1359 ms, similar to that observed in chinchilla (Relkin, E.M., Doucet, J.R., Sterns, A., 1995. Recovery of the compound action potential following prior stimulation: evidence for a slow component that reflects recovery of low spontaneous-rate auditory neurons, Hear. Res. 83, 183–189). The present results are interpreted as a consequence of the slow recovery of low spontaneous-rate (SR), high threshold neurons from prior stimulation (Relkin, E.M., Doucet, J.R., 1991. Recovery from prior stimulation. I: Relationship to spontaneous firing rates of primary auditory neurons. Hear. Res. 55, 215–222) and may provide indirect physiological evidence for the existence of a class of low-SR auditory neurons in humans.

El Glucagon-like peptide-1 (GLP-1), un pèptid derivat del processament del proglucagó en les cè_lules L del jejúnum i del colon, inhibeix la secreció àcida gàstrica i el buidament gàstric, a més de reduir la capacitat d'ingesta. Els mecanismes d'acció del GLP-1 no estan clars. Hi ha dades que suggereixen que la inhibició de les funcions gàstriques per part del GLP-1 estan mitjançades pel nervi vagus.<br/>L'acomodació o relaxació gàstrica en resposta a la ingesta és un reflex mitjançat pel vagus que dóna lloc a un increment del volum o capacitat gàstrica que impedeix l'increment de la pressió intragàstrica quan mengem, evitant així l'aparició de símptomes. La primera hipòtesi que vàrem plantejar va ser que el GLP-1 inhibeix el reflex d'acomodació gàstrica i que això explicaria en part la reducció de la capacitat d'ingesta que s'observa en administrar el GLP-1. Per provar aquesta hipòtesi vàrem comparar els efectes d'una infusió endovenosa de GLP-1 i placebo, en voluntaris sans, sobre l'acomodació gàstrica postprandial (mesurada amb la tècnica SPECT), l'increment postprandial del polipèptid pancreàtic (marcador de funció vagal abdominal) i el volum d'un nutrient líquid (Ensure®) ingerit fins atansar la sacietat màxima. Els resultats del primer estudi van demostrar que el GLP-1 no inhibeix l'acomodació gàstrica postprandial; al contrari, va augmentar el volum gàstric en dejú i després del menjar. Això es va acompanyar per una marcada inhibició de la secreció de polipèptid pancreàtic, la qual està sota control vagal colinèrgic. Degut a que el to gàstric està mantingut per influència colinèrgica vagal, els resultats obtinguts són compatibles amb la hipòtesi de que el GLP-1 indueix relaxació gàstrica (augment de volum gàstric) per inhibició de les vies colinèrgiques vagals. Si aquesta hipòtesi fos certa, en cas de disfunció vagal o vagotomia, el GLP-1 no produiria relaxació gàstrica (augment de volum gàstric). <br/>Per provar aquesta segona hipòtesi, vàrem estudiar l'efecte de la mateixa infusió endovenosa de GLP-1, comparada amb placebo, en els volums gàstrics de subjectes amb neuropatia vagal diabètica. Vàrem comparar també els volums gàstrics dels malalts diabètics que rebien placebo amb els dels subjectes sans estudiats en el primer estudi presentat en aquesta tesi. Al contrari del que vàrem observar en subjectes sans, el GLP-1 no va augmentar el volum gàstric en malalts diabètics amb neuropatia vagal. Això suggereix que l'efecte del GLP-1 sobre el volum gàstric està mitjançat pel nervi vagus.<br/>Els malalts diabètics avaluats presentaven volums gàstrics, tan en dejú com després del menjar, similars als dels subjectes sans. El nervi vagus participa en el control del to o volum gàstric, però hi ha altres mecanismes que també hi participen. Es més, hi ha evidència de que el to gàstric pot ser controlat adequadament en absència de innervació vagal extrínseca. De manera que la troballa de la existència de volums gàstrics normals en malalts amb neuropatia vagal s'afegeix a la evidència de que, en cas d'alteració del reflex principal vago-vagal, es produeix un mecanisme adaptatiu per preservar la resposta de relaxació gàstrica postprandial.<br>Glucagon-like peptide-1 (GLP-1), a peptide derived from the processing of the proglucagon molecule in L cells of the jejunum and colon, inhibits gastric acid secretion and gastric emptying rate and it also decreases food consumption. It is still not clear how these effects of GLP-1 are mediated. There are data that suggest that GLP-1 inhibition of upper gastrointestinal functions is mediated through the vagus nerve.<br/>The accommodation or relaxation of the stomach in response to meal ingestion is a vagally-mediated reflex that increases gastric volume. This prevents the increase in intragastric pressure when food and fluid enter in the stomach, avoiding the development of symptoms. <br/>We hypothesized that GLP-1 inhibits the gastric accommodation reflex and that this effect could partly explain the reduced food consumption with GLP-1. To test this hypothesis, we compared, in healthy volunteers, the effects of intravenous infusion of GLP-1 and placebo, on postprandial gastric accommodation (as measured by the SPECT technique), postprandial response of plasma human pancreatic polypeptide (a surrogate marker of vagal abdominal function) and the volume of a nutrient liquid meal (Ensure_) ingested at maximum satiation. The results of the first study showed that GLP-1 does not inhibit postprandial gastric accommodation; on the contrary, it increased fasting and postprandial gastric volumes. This was accompanied by a marked inhibition of the pancreatic polypeptide release, which is under vagal cholinergic control. Since gastric tone is maintained by vagal cholinergic input, the results observed in our first study suggested that GLP-1 could induce gastric relaxation (increase gastric volume) by inhibition of vagal cholinergic pathways. If this hypothesis were true, one would predict that in the presence of vagal dysfunction or vagotomy, GLP-1 would not induce gastric relaxation (increase gastric volume). <br/>To test this second hypothesis we studied the effect of the same intravenous infusion of GLP-1, compared to placebo, on gastric volumes in a sample of subjects with diabetes affected with vagal neuropathy. We also compared gastric volumes in diabetic patients on placebo to those in the healthy subjects who participated in the first study presented in this thesis. In contrast to effects in health, GLP-1 did not increase gastric volume in diabetics with vagal neuropathy. This suggests that the effect of GLP-1 on gastric volume is dependent on vagal function. <br/>The diabetic patients evaluated had gastric volumes similar to those of healthy controls. The vagus nerve participates in the control of gastric volume or tone; however, there are other mechanisms involved. Furthermore, there is increasing evidence that gastric tone may be adequately controlled in the absence of extrinsic vagal innervation. Thus, we believe that the normal gastric volume response to a meal observed in the presence of vagal neuropathy adds to the growing evidence of the existence of an adaptive response preserving postprandial gastric relaxation when the main vago-vagal reflex is impaired.

The purpose of this study was to investigate how design changes in Cochlear Nucleus cochlear implants (CIs) (CI24M, CI24R, CI24RE and CI422) affected electrode impedance and ECAP measures, and to determine if these design changes affected post-lingually deafened adults and children with congenital hearing loss in a similar way. Results of this study showed that electrode impedance was inversely related to the area of the electrode contacts in the array: lowest for the full-banded CI24M CI and highest for adults who used the CI422 device which has the smallest electrode contacts of all four devices. The noise floor of the NRT system likely plays a significant role in the finding that CI users with older devices (the CI24M, and CI24R CIs) had higher ECAP thresholds than individuals with the CI24RE electrode array. The position of the electrode array in the cochlea was also found to have a significant effect on ECAP measures. CI users with modiolar hugging (the CI24R and CI24RE CIs) electrode arrays were found to have lower ECAP thresholds than CI users whose electrode arrays were seated more laterally in the cochlear duct (e.g. the CI24M and CI422 implants). The position of the electrode contacts relative to the modiolus of the cochlea was found to be related to slope of the ECAP growth functions. The lowest slopes were found in CI24RE users. It also had a significant impact on the width of the channel interaction function. Electrode arrays seated further from the modiolus have significantly more channel interaction than electrode arrays that hug the modiolus of the cochlea. Differences between results recorded from post-lingually deafened adults and children with congenital hearing loss were minimal. The difference only reflected on the ECAP slopes. Slopes in children with congenital hearing loss were significantly steeper than those recorded from adults. This may indicate that children with congenital hearing loss may have better neural survival than adults with acquired hearing loss. In conclusion, the results of the current study show evidence of the effects of variations in design and function of the implanted components of the Nucleus CI. Perhaps the most significant finding from the current data set is that electrode arrays located closer to the modiolus of the cochlea have lower thresholds and exhibit less channel interaction than electrode arrays that are positioned more laterally. An argument could be made that lower stimulation levels and less channel interaction may result in better outcomes and/or longer battery life. For CI candidates who do not have significant residual acoustic hearing, the CI24RE implant might be a better choice than the more recently introduced CI422 electrode array.

The ability to perceive speech is related to the listener's ability to differentiate among frequencies (i.e. spectral resolution). Cochlear implant users exhibit variable speech perception and spectral resolution abilities, which can be attributed at least in part to electrode interactions at the periphery (i.e. spatial resolution). However, electrophysiological measures of peripheral spatial resolution have not been found to correlate with speech perception. The purpose of this study was to systematically evaluate auditory processing from the periphery to the cortex using both simple and spectrally complex stimuli in order to better understanding the underlying processes affecting spatial and spectral resolution and speech perception. Eleven adult cochlear implant users participated in this study. Peripheral spatial resolution was assessed using the electrically evoked compound action potential (ECAP) to measure channel interaction functions for thirteen probe electrodes. We evaluated central processing using the auditory change complex (ACC), a cortical response, elicited with both spatial (electrode pairs) and spectral (rippled noise) stimulus changes. Speech perception included a vowel-discrimination task and the BKB-SIN test of keyword recognition in noise. We varied the likelihood of electrode interactions within each participant by creating three experimental programs, or MAPs, using a subset of seven electrodes and varying the spacing between activated electrodes. Linear mixed model analysis was used to account for repeated measures within an individual, allowing for a within-subject interpretation. We also performed regression analysis to evaluate the relationships across participants. Both peripheral and central processing abilities contributed to the variability in performance observed across CI users. The spectral ACC was the strongest predictor of speech perception abilities across participants. When spatial resolution was varied within a person, all electrophysiological measures were significantly correlated with each other and with speech perception. However, the ECAP measures were the best single predictor of speech perception for the within-subject analysis, followed by the spectral ACC. Our results indicate that electrophysiological measures of spatial and spectral resolution can provide valuable information about perception. All three of the electrophysiological measures used in this study, including the ECAP channel interaction functions, demonstrated potential for clinical utility.

[Truncated abstract] The present study investigated whether any of the characteristics of the compound action potential (CAP) waveform or the spectrum of the neural noise (SNN) recorded from the cochlea, could be used to examine abnormal spike generation in the type I primary afferent neurones, possibly due to pathologies leading to abnormal hearing such as tinnitus or tone decay. It was initially hypothesised that the CAP waveform and SNN contained components produced by the local action currents generated at the peripheral ends of the type I primary afferent neurones, and that changes in these local action currents occurred due to changes in the membrane potential of these neurones. It was further hypothesised that the lateral olivo-cochlear system (LOCS) efferent neurones regulate the membrane potential of the primary afferent dendrites to maintain normal action potential generation, where instability in the membrane potential might lead to abnormal primary afferent firing, and possibly one form of tinnitus. We had hoped that the activity of the LOCS efferent neurones could be observed through secondary changes in the CAP waveform and SNN, resulting from changes in the membrane potential of the primary afferent neurones. The origins of the neural activity generating the CAP waveform and SNN peaks, and the effects of the LOCS on the CAP and SNN were experimentally investigated in guinea pigs using lesions in the auditory system, transient ischemia and asphyxia, focal and systemic temperature changes, and pharmacological manipulations of different regions along the auditory pathway. ... Therefore, the CAP and SNN are altered by changes in the propagation of the action potential along the primary afferent neurones, by changes in the morphology of the tissues surrounding the cochlear nerve, and by changes in the time course of the action currents. If the CAP waveform is not altered, the amplitude of the 1kHz speak in the spontaneous SNN can be used as an objective measure of the spontaneous firing rate of the cochlear neurones. However, because the SNN contains a complex mixture of neural activity from all cochlear neurones, and the amplitude of the spontaneous SNN is variable, it would be difficult to use the spontaneous SNN alone as a differential diagnostic test of cochlear nerve pathologies. To record extratympanic electrocochleography (ET ECochG) from humans, a custom-designed, inexpensive, low-noise, optically isolated biological amplifier was built. Furthermore, a custom-designed extratympanic active electrode and ear canal indifferent electrode were designed, which increased the signal-to-noise ratio of the ECochG recording by a factor of 2, decreasing the overall recording time by 75%. The human and guinea pig CAP waveforms recorded in the present study appeared similar, suggesting that the origins of the human and guinea pig CAP waveforms were the same, and that experimental manipulations of the guinea pig CAP waveform can be used to diagnose the cause of abnormal human ECochG waveforms in cases of cochlear nerve pathologies.

Este trabalho apresenta a modelagem matemática e a simulação de potenciais de ação de unidades motoras de músculos de vertebrados visando a posterior simulação do eletromiograma. Para conseguir isso, inicialmente se fez uma compilação de dados existentes para a distribuição das fibras musculares (FBs) nas unidades motoras (MUs) de vários músculos, e as modelagens matemáticas descritos na literatura para o potencial de ação de uma FB (SFAP) e de uma MU (MUAP). Com base nos dados fisiológicos, primeiro se localizou as FBs em um músculo, por meio de uma aproximação de que as FBs estão rodeadas de outras seis no músculo. Para conseguir isto se construiram hexágonos concêntricos por MU, e posteriormente se localizou as FBs nas MUs, cobrindo uma faixa entre 75 e 2000 FBs, o que corresponde a músculos distais de mamíferos. Depois se fez uma aproximação para a distribuição de 170000 FBs nas 272 MUs da cabeça medial do músculo gastrocnêmio (MG) do gato, conseguindo numa primeira simulação localizar cerca de 70% das FBs para cada MU. Com esta localização das FBs no músculo baseados nos dados da literatura se aproximaram os retardos axonais por uma distribuição gaussiana, com média de 2 ms (gato) ou 10 ms (homem) e com desvio padrão de menos de 0,5 ms, desprezando o atraso axonal nas ramificações axonais, que foi estimado no máximo 29 vezes menor. Para a geração do SFAP trabalhou-se com dois modelos, um analítico, o qual resulta em simulações numéricas demoradas, e, outro numérico baseado na convolução da corrente com uma função peso. Para o modelo numérico dobrou-se imaginariamente o comprimento das FBs, para levar em conta o erro computacional de fim de fibra. O modelo numérico resultou em um tempo de simulação 30 vezes menor que o analítico. Adicionalmente, para simular a captação externa (i.e. na pele), fez-se uma aproximação para a função que modela os eletrodos de superfície de secção circular localizados a uma distância maior que 1,79 mm das FBs, mostrando um espectro similar ao reportado na literatura. Finalmente, os MUAPs obtidos resultavam com formas de onda e espectros similares ao descrito na literatura. Além disto, em certos casos, obtiveram-se MUAPs com indentações, seja localizando as junções neuromusculares em bandas da ordem de 1 mm de espessura, seja quando o tempo de atraso axonal foi considerado junto com a velocidade de condução da FB em função da raiz quadrada do diâmetro da FB. Foram feitas simulações para os MG e bíceps braquial do homem. Neste último caso, foram obtidos MUAPs similares aos captados para pessoas saludáveis, e foi observada a freqüência de disparos dos potenciais de ação do motoneurônio no espectro do MUAP. Quanto às formas dos agrupamentos das FBs em uma MU, não se obtiveram diferenças significativas para as FBs posicionadas homogênea e aleatoriamente, exceto uma ligeira variação nas amplitudes. No entanto, ocurreu uma mudança na faixa espectral, quando as FBs estavam concentradas.<br>This work presents the mathematical model and simulation of motor unit action potentials of vertebrate muscles aiming at after simulation of the electromyogram. To obtain this, initially, it was made a compilation of several data about the distribution of muscle fibers (FBs) in motor units (MUs) of many muscles, and the mathematical models of the action potential of a single FB (SFAP) and MU (MUAP), reported in previous works. On the basis of this physiological data, first, the FB was located in a muscle, using an approximation in which the FBs are encircled with other six FBs in the muscle. To reach this, concentric hexagons were constructed to build the surface of the MU, and later the FBs were situated in the MU, covering a range between 75 and 2000 FBs, corresponding to mammals extremity muscles. Later, a new approximation were was madein order to distribute the 170000 FBs in the 272 MUs of the medial head of muscle medialis gastrocnemius (MG) of the cat, reaching, in a first simulation, the localization of almost 70% of the FBs at each MU. With the FBs lalready allocated in the muscle, and based in data of previous works, their axonal delay were approximated by a gaussian distribution, with mean of 2 ms (cat) or 10 ms (man) and standard deviation of less than 0,5 ms, discarding the axonal delay in the axonal branching, that were estimated to affectup to 29 times less. To SFAP generation, two models were used, the first analytical, resulting in delayed numerical simulations, and the other based on convolution of the second derivate of the current with a weight function, where the length of the FBs was imaginarily duplicated, in order to consider the end fiber effect. Using this, a simulation time 30 times lesser than the analytical one was obtained. Additionally, so as to simulate the external recording (i.e. in the skin), it was made an approximation to the function that models the circular shape surface electrodes located at distances greater than 1,79 mm of the FBs, showing a similar spectrum reported. Finally, the waves and spectrum of the simulated MUAPs resulted similar to the ones reported in the literature. Beyond this, in certain cases, MUAPs were simulated with some tuned, either locating the neuromuscular junctions with thickness bands of 1 mm, or, when the axonal delay and the FB muscle fiber conduction velocity were considered as a function of the square root fiber diameter. This was simulated for MUAPs of MG and biceps brachii muscles of human beings, in the last case it has reached the waveforms and tuned found in heath subjects, and it was visualized the mean frequency of firing rate at the spectrum. In order to know how much affects grouping for the FBs to waves a MU, they were not found significant differences with FBs located homogeneously and randomly, except a little variation in the amplitude of the MUAP. However, they presented a change in the spectral bandwidth when the FBs are more concentrated.

Submitted by Leonardo Cavalcante (leo.ocavalcante@gmail.com) on 2018-07-17T18:53:07Z No. of bitstreams: 1 Arquivototal.pdf: 3232624 bytes, checksum: 559aa25bbe9205467b3fdd737354219e (MD5)<br>Made available in DSpace on 2018-07-17T18:53:07Z (GMT). No. of bitstreams: 1 Arquivototal.pdf: 3232624 bytes, checksum: 559aa25bbe9205467b3fdd737354219e (MD5) Previous issue date: 2016-02-29<br>The high incidence of pain in the general population has encouraged research about this theme. Products derived from plant species have been widely used in the pharmacological treatment of pain relief. Recent studies have reported the important role of monoterpenes, active compounds found in the essential oils of aromatic plants, having relevant analgesic and anti-inflammatory potential. The geraniol (GER) is a monoterpenic alcohol, found in >160 essential oil of plant species, especially Cymbopogon gender. In the literature consulted, several biochemical and pharmacological properties are shown of GER: antitumor, antimicrobial, antiinflammatory, antioxidant, gastric and intestinal protector, neuroprotective and antiarrhythmic. In this study was evaluated the antinociceptive activity of GER, not yet reported, by animal behavioral and electrophysiological in vitro models. Male and female adult Swiss mice were used. Initially the acute toxicity of GER was investigated by calculating the lethal dose 50 (LD50) by intraperitoneal (i.p.) (= 199.9 mg/kg) and oral (p.o.) (> 1 g/kg). In psychopharmacological screening, after the administration of single doses of GER (i.p. and p.o.), behavioral changes were observed indicating a depressant profile on the central nervous system (CNS) and/or peripheral nervous system (SNP), and relevant antinociceptive effect of geraniol. Therefore, more specific antinociceptive property evaluation tests were performed. The GER (12.5, 25 or 50 mg/kg i.p. and 50 or 200 mg/kg p.o.) decreased (p<0.001) the number of abdominal contractions induced by i.p. injection of acetic acid, when compared with the control. The opioid antagonist naloxone (5 mg/kg) administered subcutaneously (s.c.) in mice, subsequently treated with GER (25 mg/kg i.p.), did not reverse its antinociceptive activity. The GER (12.5, 25 and 50 mg/kg i.p.) reduced (p<0.001) paw licking time in the second phase (15-30 min, inflammatory phase) of the formalin test. Also, in the glutamate test was reduced (p<0.01) paw licking time when GER 50 mg/kg i.p. administered. In a subsequent step, it was investigated the effect of GER on the excitability of peripheral nerve fibers through extracellular recording in the sciatic nerve in mice. The GER presented depressant effect of the compound action potential (CAP), which was reversed after washing and recovery period. The GER blocked components of the CAP concentration-dependent manner and exposure time to the drug: 1 mM after 120 min for the first component (Aγ and Aβ fibers) and 0.6 mM after 90 min for the second (Aγ and Aδ fibers). The concentration, which induces 50% inhibition of the peak-to-peak amplitude of the PAC (IC50) for the GER was calculated, being equal to 0.48±0.04 mM. The conduction velocity was also reduced by exposure to GER from the 0.3 mM concentration, for the 1st component [46.18±2.60 m/s to 36.04±1.60 m/s; p<0.05 (n=7)] and the 2nd component [18.37±1.31 m/s to 12.71±0.56 m/s; p<0.001 (n=7)]. In conclusion, the results obtained show that GER has antinociceptive activity, mainly in pain related to inflammation. Participation of the opioid pathway in its mechanism of action is unlikely, but the modulation of glutamatergic neurotransmission in a dose-dependent manner is a possible mechanism. Its antinociceptive activity is also related to the reduction in peripheral neuronal excitability, firstly in thinner fibers Aδ, which are directly connected to the conduction pain.<br>A elevada incidência da dor na população em geral tem incentivado as pesquisas entorno desse tema. Produtos oriundos de espécies vegetais têm sido amplamente utilizados no tratamento farmacológico de alívio da dor. Estudos recentes têm relatado o importante papel dos monoterpenos, princípios ativos encontrados nos óleos essenciais de plantas aromáticas, tendo relevante potencial analgésico e anti-inflamatório. O geraniol (GER) é um álcool monoterpênico, encontrado no óleo essencial de >160 espécies vegetais, especialmente do gênero Cymbopogon. Na literatura consultada, pesquisas apontam várias propriedades bioquímicas e farmacológicas para o GER: antitumoral, antimicrobiana, anti-inflamatória, antioxidante, de proteção gástrica e intestinal, neuroprotetora e antiarrítmica. Neste estudo foi avaliada a atividade antinociceptiva do GER, ainda não relatada, mediante modelos animais comportamentais e eletrofisiológicos in vitro. Foram utilizados camundongos machos e fêmeas Swiss adultos. Inicialmente, foi investigada a toxicidade aguda do GER mediante cálculo da dose letal 50 (DL50) pela via intraperitoneal (i.p.) (=199,9 mg/kg) e oral (v.o.) (>1 g/kg). Na triagem psicofarmacológica, após a subministração de doses únicas de GER (i.p. e v.o.) foram observadas alterações comportamentais que indicaram perfil depressor do sistema nervoso central (SNC) e/ou periférico (SNP), e relevante efeito antinociceptivo do geraniol. Portanto, foram realizados testes comportamentais de avaliação de propriedade antinociceptiva mais específicos. O GER (12,5; 25 e 50 mg/kg i.p. e 50 ou 200 mg/kg v.o.) reduziu (p<0,001) o número de contorções abdominais induzidas por injeção i.p. de ácido acético, quando comparado com o controle. O antagonista opióide naloxona (5 mg/kg) administrado pela via subcutânea (s.c.) em camundongos, subsequentemente tratados com GER (25 mg/kg i.p.), não reverteu sua atividade antinociceptiva. O GER (12,5; 25 e 50 mg/kg i.p.) reduziu (p<0,001) o tempo de lambida da pata na segunda fase (15-30 min, fase inflamatória) do teste da formalina. Também, no teste do glutamato houve redução (p<0,01) do tempo de lambida da pata quando administrado GER 50 mg/kg i.p. Em uma etapa subsequente, investigou-se o efeito do GER sobre a excitabilidade de fibras nervosas periféricas, mediante registro extracelular em nervo ciático de camundongo. O GER apresentou efeito depressor do potencial de ação composto (PAC), o qual foi parcialmente revertido após lavagem durante o período de recuperação. O GER bloqueou as componentes do PAC, de maneira dependente da concentração e do tempo de exposição à droga: 1 mM aos 120 min para a primeira componente (fibras Aγ e Aβ) e 0,6 mM aos 90 min para a segunda (fibras Aγ e Aδ). Foi calculada para o GER, a concentração que induz 50% de inibição da amplitude pico-a-pico do PAC (CI50), sendo igual a 0,48±0,04 mM. A velocidade de condução também, foi reduzida pela exposição ao GER, a partir da concentração de 0,3 mM para a 1ª componente [46,18±2,60 m/s para 36,04±1,60 m/s; p<0,05 (n=7)] e para a 2ª componente [18,37±1,31 m/s para 12,71±0,56 m/s; p<0,001 (n=7)]. Em conclusão, os resultados obtidos mostram que o GER tem atividade antinociceptiva, principalmente na dor relacionada à inflamação. A participação da via opióide no seu mecanismo de ação é pouco provável, mas a modulação da neurotransmissão glutamatérgica de maneira dependente da dose é um mecanismo possível. Sua atividade antinociceptiva tambèm, está relacionada à redução da excitabilidade neuronal periférica, primeiramente de fibras mais finas como Aδ, ligadas diretamente à condução da dor.

Current cochlear implant systems use fast pulsatile stimulation to deliver the temporal modulations of speech and to, potentially, improve the neural representation of such modulations by restoring the independence of neural firing. The realization of these benefits may vary with other pulse rate-dependent temporal interactions that occur at the neural membrane, e.g., per(i)stimulatory adaptation and its post-stimulatory or forward masking effects. This study attempted to characterize adaptation and recovery of the electrically evoked compound action potential (ECAP) using probe pulses delivered within and following brief (100 ms) high-rate masker (1800 pps) pulse trains at various current levels in adults and children. With this stimulus paradigm, the ECAP amplitude typically achieved a steady state during the course of pulse train stimulation. The ECAP amplitude at steady state was, on average, a similar proportion (50-70%) of the amplitude at onset for various stimulus levels and in both age groups. However, long-term adaptation effects, evidenced by the decrease in onset ECAP amplitude, were greater in adults particularly at lower levels in the ECAP dynamic range. Instances of alternation in ECAP amplitude were seen at stimulus levels that were higher in the ECAP dynamic range. The forward masking effects of pulse train stimulation were quantified by the ECAP amplitude in response to a subsequent probe pulse normalized by the response to the same pulse presented alone. Pulse train forward masking increased with the level of the masker pulse train and decreased with the level of the probe stimulus. The recovery of the ECAP for probes that were lower in level than the masker pulse train was incomplete at 600 ms after masker offset, consistent with long-term cumulative effects observed in the response to the probe alone. Masker pulse trains that are lower in level than the probe pulse produced proportionally small decrements in the ECAP amplitude with complete recovery within 250 ms of pulse train offset particularly in adults. ECAP recovery of a probe preceded by a masker pulse train of equal level followed a monotonic or non-monotonic pattern consistent with a hypothesis of both adaptation and facilitation occurring with pulse train stimulation. The various patterns of recovery may attest to the occurrence of more than a single process in the same subset of nerve fibers or in different fibers. We hypothesize that the variations in the recovery patterns may be attributable to individual differences in the status of the auditory nerve and possibly, the variations in temporal interactions across the spatial domain at different stimulus levels. Finally, the probe-evoked ECAP amplitude at steady state in children and briefly, e.g., 20 ms, after pulse train offset in both age groups could be predicted by the ECAP amplitude in response to the same probe pulse when preceded at a brief interval (1.2 or 2 ms) by a single masker pulse of the same level as the masker pulse train. Further investigation may reveal if the observed differences in neural responsiveness to pulsatile stimulation, among individuals account for differences in psychophysical measures, including speech perception and whether there may be an "optimal" neural output that could be evoked by an individually "optimized" signal.

Effective cochlear implant fitting (or programming) is essential for providing good hearing outcomes, yet it is a subjective and error-prone task. The initial objective of this research was to automate the procedure using the auditory nerve electrically evoked compound action potential (the ECAP) and machine intelligence. The Nucleus?? cochlear implant measures the ECAP via its Neural Response Telemetry (NRT™) system. AutoNRT™, a commercial intelligent system that measures ECAP thresholds with the Nucleus Freedom™ implant, was firstly developed in this research. AutoNRT uses decision tree expert systems that automatically recognise ECAPs. The algorithm approaches threshold from lower stimulus levels, ensuring recipient safety during postoperative measurements. Clinical studies have demonstrated success on approximately 95% of electrodes, measured with the same efficacy as a human expert. NRT features other than ECAP threshold, such as the ECAP recovery function, could not be measured with similar success rates, precluding further automation and loudness prediction from data mining results. Despite this outcome, a better application of the ECAP threshold profile towards fitting was established. Since C-level profiles (the contour of maximum acceptable stimulus levels across the implant array) were observed to be flatter than T-level profiles (the contour of minimum audibility), a flattening of the ECAP threshold profile was adopted when applied as a fitting profile at higher stimulus levels. Clinical benefits of this profile scaling technique were demonstrated in a 42 subject study. Data mining results also provided an insight into the ECAP recovery function and refractoriness. It is argued that the ECAP recovery function is heavily influenced by the size of the recruited neural population, with evidence gathered from a computational model of the cat auditory nerve and NRT measurements with 21 human subjects. Slower ECAP recovery, at equal loudness, is a consequence of greater neural recruitment leading to lower mean spike probabilities. This view can explain the counterintuitive association between slower ECAP recovery and greater temporal responsiveness to increasing stimulation rate. This thesis presents the first attempt at achieving completely automated cochlear implant fitting via machine intelligence; a future generation implant, capable of high fidelity auditory system measurements, may realise the ultimate objective.

Contexte: La réponse synchrone des fibres auditives, évaluée à partir de l'onde I des potentiels d'action évoqués auditifs (PEA), ou à partir du potentiel d'action composite (PAC) du nerf auditif, est l'élément clé du dépistage des neuropathies auditives. De récentes études ont toutefois montré que le seuil et l'amplitude de cette réponse pouvaient être absolument normaux malgré une perte importante de fibres du nerf auditif. Dans ce travail de thèse, nous proposons une nouvelle méthode d'exploration fonctionnelle, potentiellement applicable à l'homme, rendant mieux compte du nombre et de l'intégrité des fibres du nerf auditif. Cette méthode a été évaluée à l'aide d'un modèle pharmacologique de neuropathie physiologiquement pertinent.Matériel et méthodes: Chez des gerbilles, une perte sélective de fibres auditives a été induite par application d'une faible concentration d'ouabaïne dans la niche de la fenêtre ronde de la cochlée. Cette neuropathie a ensuite été caractérisée par des comptages de synapses (immunohistochimie/imagerie confocale 3D) et l'enregistrement de l'activité unitaire de fibres du nerf auditif. Les PAC et l'activité soutenue du nerf ont été enregistrés 6 jours après l'application d'ouabaïne, à l'aide d'une électrode de recueil disposée dans la niche de la fenêtre ronde. Résultats: L'application d'ouabaïne induit une perte spécifique des fibres à basse activité spontanée (AS&lt;0,5 potentiel d'action/sec) comme observé au cours du vieillissement et après une surexposition sonore. La disparition de cette population de fibres est indétectable à l'aide du PAC car leur réponse unitaire est à la fois retardée et désynchronisée. Par contre, l'amplitude de la réponse soutenue du nerf se révèle être un bien meilleur indicateur de la perte des fibres à basse activité spontanée. Pour aller plus loin, nous avons mis au point une méthode qui permet d'observer l'activité synchrone et soutenue du nerf auditif dans une même réponse. Cette approche rend compte des trois mécanismes de fusion vésiculaire (libération rapide, lente et soutenue) de la première synapse auditive.Conclusion: L'analyse de la réponse soutenue du nerf auditif est une approche fiable pour déterminer le nombre et le phénotype fonctionnel des fibres qui composent le nerf auditif. Cette méthode, applicable à l'homme, devrait améliorer le dépistage des neuropathies, avec une meilleure différenciation des atteintes d'origine synaptique et/ou neuronale.Mots clés: Cochlée, nerf auditif, potentiel d'action composite, activité soutenue du nerf auditif, enregistrement unitaires, ouabaïne, neuropathie<br>Background: The synchronous activation of the auditory nerve fibers (ANFs), is commonly studied through the compound action potential (CAP), or the auditory brainstem responses (ABR), to probe deafness in experimental and clinical settings. Recent studies have shown that substantial ANF loss can coexist with normal hearing threshold, and even unchanged CAP amplitude, making the detection of auditory neuropathies difficult. In this study, we took advantage of the round window neural noise (RWNN) to probe ANF loss in a physiologically-relevant model of neuropathy.Material and methods: ANF loss was induced by the application of ouabain onto the round window niche. CAP and RWNN of the gerbil's cochlea were recorded through an electrode placed onto the round window niche, 6 days after the ouabain application. Afferent synapse counts and single-unit recordings were carried-out to determine the degree and the nature of ANF loss, respectively. Results: Application of a low ouabain-dose into the gerbil RW niche elicits a specific degeneration of low spontaneous rate (SR) fibers, as shown by single-unit recordings. Simultaneous recordings (CAP/single-unit) demonstrate that low-SR fibers have a weak contribution to the CAP amplitude because of their delayed and broad first spike latency distribution. However, the RWNN amplitude decreases with the degree of synaptic loss. The RWNN method is therefore more sensitive than CAP to detect low-SR fiber loss, most probably because it reflects the sustained discharge rate of ANFs. Based on these data, we proposed a far-field method (Peri-stimulus time response-PSTR) to assess the fast, slow, and sustain vesicular release at the first auditory synapse.Conclusion: The round window neural noise is a faithful proxy to probe the degree and the SR-based nature of fiber loss. This method could be translated into the clinic to probe hidden hearing loss and orient the practitioner toward synaptopathy and/or neuropathy.Key words: Cochlea, auditory nerve, compound action potential, round window neural noise, single fiber recording, ouabain-induced neuropathy

A wide literature of predominantly behavioural experiments that use Stimulus Response Compatibility (SRC) have suggested that visual action information such as object affordance yields rapid and concurrent activation of visual and motor brain areas, but has rarely provided direct evidence for this proposition. This thesis examines some of the key claims from the affordance literature by applying electrophysiological measures to well established SRC procedures to determine the verities of the behavioural claims of rapid and automatic visuomotor activation evoked by viewing affording objects. The temporal sensitivity offered by the Lateralised Readiness Potential and by visual evoked potentials P1 and N1 made ideal candidates to assess the behavioural claims of rapid visuomotor activation by seen objects by examining the timecourse of neural activation elicited by viewing affording objects under various conditions. The experimental work in this thesis broadly confirms the claims of the behavioural literature however it also found a series of novel results that are not predicted by the behavioural literature due to limitations in reaction time measures. For example, while different classes of affordance have been shown to exert the same behavioural facilitation, electrophysiological measures reveal very different patterns of cortical activation for grip-type and lateralised affordances. These novel findings question the applicability of the label ‘visuomotor’ to grip-type affordance processing and suggest considerable revision to models of affordance. This thesis also offers a series of novel and surprising insights into the ability to dissociate afforded motor activity from behavioural output, into the relationship between affordance and early visual evoked potentials, and into affordance in the absence of the intention to act. Overall, this thesis provides detailed suggestions for considerable changes to current models of the neural activity underpinning object affordance.

Made available in DSpace on 2015-05-14T13:00:16Z (GMT). No. of bitstreams: 1 parte1.pdf: 4104748 bytes, checksum: 578975146349baff07079d6c3f9756b6 (MD5) Previous issue date: 2008-08-29<br>Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES<br>Snake venoms contain a complex arsenal of protein bio-active components, many of these being neurotoxins (NTXs). These snakes have high neurotoxic activity venom, corresponding to the Elapidae family, which includes coral snakes (Micrurus) whose venom contains circa 90-95% of low molecular mass protein components. Among these, several are postsynaptic neurotoxins or α- NTXs (MM = 6-9 kDa). The Micrurus ibiboboca (Merren, 1820) is a snake of the Elapidae family witch is quite common in the Northeast of Brazil. In spite of the great diversity of species of Micrurus, scarce works involving the nervous system with isolated and pure toxins of those serpents has been developed in level biochemical, pharmacological and electrophysiological. The aim of this study was to purify the toxin Mic6c7NTX of the Micrurus ibiboboca venom, characterize to biochemically and electrophysiologically the toxin Mic6c7NTX in the peripheral nervous system (PNS) of rats, evaluating alterations in the record of the Compound Action Potential (CAP) of the isolate nerve and the toxin activity on the voltage-dependent sodium channels (Nav) in the neurons of the dorsal root ganglion (DRG). The venom was extracted from the Micrurus ibiboboca collected in Paraiba State (Brazil). Initially, electrophysiological tests (current clamp method) using the single sucrose gap technique were accomplished with crude venom (100μg/mL). It was observed that in this concentration the crude venom caused reduction in the CAP amplitude (25%). This neurotoxity led into an intriguing question: what components of the venom would promote to reduction in the excitability of the nerve? Based upon this question, I decided to purify the venom throughout the Liquid Chromatography of the High Performance (HPLC) of the Cation Exchange Chromatography (CIEX) and the Reverse Phase Chromatography (RPC). The molecular mass (MM) of the raw toxin was determined by mass-spectrometry (MALDI-QTOF/ MS) and N-terminal sequence by means of Edman s Degradation. The search for similarity with other toxins was accomplished against proteomic data bank. The CIEX profile showed 19 fractions and the highest peak fraction was used for the second dimension. The toxin Mic6c7NTX obtained by RPC showed elution in 26.7%of the acetonitrile (ACN) and MM 7.047.56Da. The obtained partial N-terminal sequence showed 31 aminoacid residues. The search for similarity of structure and function showed great similarity (65%) with other short chain α-NTXs Australian elapids snakes. The electrophysiological studies (single sucrose gap technique) showed that the toxin Mic6c7NTX (1 μM) reduced the excitability of the isolate nerve similarly to the reduction observed in the crude venom about 21%. Other CAP parameters such as despolarization speed (DSCAP), repolarization time (τCAP) and peak of time (PTCAP) did not show alterations. This suggests that the toxin may be affecting the Nav channels. For the confirmation of that hypothesis experiments were accomplished with whole cell patch-clamp technique in DRG neurons. This results showed that the toxin Mic6c7NTX (1 WM) abolished completely the current of Nav channels sensitive the tetrodotoxin (TTX-S). Also the Nav channels TTX resistant (TTX-R) were investigated in the presence of the Mic6c7NTX toxin previously using TTX (100 nM). This results showed that the toxin Mic6c7NTX (100 nM) abolished completely the current of Nav channels TTX-R and IC50 = 30nM. However, reversion of this blocking was not observed. The present study biochemically and electrophysiologically characterized an α-NTX of the Micrurus ibiboboca elapid snake. Furthermore, it showed a potent toxin with affinity Nav channels TTX-S and TTX-R of the PNS. This is the first α-NTX isolated and identified of the venom from the Micrurus ibiboboca (Merrem, 1820) snake.<br>As serpentes da família Elapidae possuem uma peçonha com alta atividade neurotóxica e capacidade de letalidade. Fazem parte dessa família as serpentes corais americanas (gênero Micrurus) com suas peçonhas contendo cerca de 90-95% de componentes protéicos, sendo na sua maior parte neurotoxinas com baixa massa molecular (6-8 kDa), podendo ser destacadas as neurotoxinas com ação pós-sinápticas ou α-Neurotoxinas (α-NTX). A Micrurus ibiboboca (Merrem, 1820) é uma serpente da família Elapidae, comum na região Nordeste. Apesar da grande diversidade de espécies do gênero Micrurus sp., escassos trabalhos envolvendo atividade de toxinas isoladas e puras destas peçonhas e sistema nervoso têm sido desenvolvidos em nível bioquímico, farmacológico ou eletrofisiológico. O objetivo desse estudo foi purificar a toxina Mic6c7NTX da peçonha de M. ibiboboca, caracterizar bioquímicamente e investigar com ferramentas eletrofisiológicas a ação da toxina no Sistema Nervoso Periférico (SNP) de ratos avaliando alterações no Potencial de Ação Composto (PAC) do nervo isquiático isolado e a atividade da toxina nos canais para sódio dependentes de voltagem (Nav) em neurônios do gânglio da raiz dorsal (DRG). A peçonha da M. ibiboboca foi extraída de serpentes coletadas no Estado da Paraíba (Brasil). Inicialmente, ensaios eletrofisiológicos com o método de current clamp utilizando a técnica de single sucrose gap foram realizados com a peçonha bruta (100 Wg/mL). Os resultados mostraram que a peçonha bruta nessa concentração promoveu redução na amplitude do PAC (25%). Esse efeito da toxina na excitabilidade do nervo levantou o questionamento: Que componentes da peçonha estariam causando essa diminuição da excitabilidade? A peçonha foi purificada por meio de Cromatografia Líquida de Alta Performance (HPLC), de troca catiônica (CIEX) e fase reversa (RPC). Na sequência, os picos da CIEX foram submetidos à RPC e posteriormente analisados por espectrometria de massas (MALDI-TOF/MS) que detectou a massa molecular da toxina Mic6c7NTX de 7.047,56 Da. Em seguida, foi determinado o seu N-terminal por Degradação de Edman que apresentou 31 resíduos de aminoácidos e serviu de estudo para a bioinformática na busca por similaridade em banco de dados proteômicos com outras toxinas protéicas, demonstrando que a toxina Mic6c7NTX apresentou similaridade (65%) com α-NTXs de cadeia curta de serpentes elapídicas australianas. Posteriormente, foi investigado o efeito da toxina isolada no SNP. Os estudos eletrofisiológicos em single sucrose gap demonstraram que a toxina Mic6c7NTX (1 WM) reduziu a excitabilidade do nervo isolado de forma similar à observada pela peçonha bruta. Não foram observadas alterações significantes em outros parâmetros do PAC, como velocidade de despolarização (VDPAC), tempo de repolarização (τPAC) e tempo de pico (PTPAC), sugerindo que a toxina atuasse num sítio de ligação específico dos [Escreva uma citação do documento ou o 11 canais Nav no SNP. Para a confirmação dessa hipótese foram realizados experimentos de voltage clamp com a técnica de whole cell patch-clamp em cultura primária de neurônios DRG da medula espinhal de ratos. Os resultados mostraram que a toxina Mic6c7NTX (1 WM) aboliu completamente as correntes dos canais Nav sensíveis à tetrodotoxina (TTX-S). Também foi investigado o efeito da toxina sobre a população de canais Nav resistentes à TTX (TTX-R), utilizando previamente TTX (100 nM) para bloquear os canais Nav TTX-S. Os registros com a toxina Mic6c7NTX (100 nM) demonstraram um bloqueio total da corrente nos canais Nav TTX-R dos DRGs e uma IC50 da toxina em torno de 30 nM. Também foi observado que essa toxina se liga aos canais Nav de forma lenta e irreversível. O presente estudo caracterizou bioquímica e eletrofisiologicamente uma α-NTX da serpente elapídica Micrurus ibiboboca. Farmacologicamente, trata-se de uma potente toxina com afinidade aos canais Nav TTX-S e TTX-R do SNP. Essa é a primeira α-NTX isolada e caracterizada da peçonha da serpente Micrurus ibiboboca (Merrem, 1820).

Informações sobre as características funcionais e estruturais da unidade motora (UM) são altamente relevantes em investigações fisiológicas e nos estudos clínicos das disfunções neuromusculares. A eletromiografia (EMG) é um método adequado para obtenção dessas informações. Entretanto, devido à dificuldade na separação da atividade individual de uma unidade motora das outras que estão simultaneamente ativas, seu uso em clínica prática se dá comumente através de métodos invasivos, empregando eletrodos de agulha ou fios implantados. Apesar da EMG de superfície ser não-invasiva e, portanto mais apropriada para aplicações clínicas, não é usada em clínica porque não há até o presente um método satisfatório para decomposição do sinal EMG de superfície. Um EMG de superfície é muito mais difícil de decompor devido a significante superposição dos Potenciais de Ação das UMs (MUAPs) e a relação sinal-ruído relativamente baixa, se comparada aos métodos invasivos. Defendemos que a separação da atividade individual das UMs pode ser feita de modo não-invasivo aliando-se técnicas de aquisição altamente especializadas com técnicas usadas em reconhecimento de padrões. Desenvolvemos um método para decomposição de EMGs de superfície, a partir do qual foi possível extrair características relevantes das UMs, que permitem seu uso em avaliação e diagnóstico de desordens neuromusculares. Em nossa abordagem, o sinal EMG é inicialmente captado sob contração isométrica fraca usando eletrodos desuperfície. O sinal EMG bruto passa em seguida por um filtro Diferencial Passa-Baixas Ponderado (DPBP) em série com um detector de picos, que detecta os picos de MUAPs e extrai suas formas de onda. Na sequência, o conjunto de MUAPs extraído é classificado por uma rede neural SOM, e os MUAPs agrupados pela similaridade de suas formas de onda. No próximo passo a informação temporal dos disparos é checada, eliminando possíveis erros de classificação, e finalmente os Trens de MUAPs (MUAPTs) das UMs individuais são reconstituídos do EMG original. As estatísticas de disparos (IPI) bem como as formas de ondas dos MUAPs das respectivas UMs são então extraídas e armazenadas para estudos posteriores. Resultados preliminares obtidos com EMGs normais e patológicos, extraídos de membros superiores sob contração fraca, indicam que, o método mostrou-se apto a decompor EMGs de superfícies, além de potencial para aplicações em estudos clínicos não-invasivos de disfunções neuromusculares.Informações sobre as características funcionais e estruturais da unidade motora (UM) são altamente relevantes em investigações fisiológicas e nos estudos clínicos das disfunções neuromusculares. A eletromiografia (EMG) é um método adequado para obtenção dessas informações. Entretanto, devido à dificuldade na separação da atividade individual de uma unidade motora das outras que estão simultaneamente ativas, seu uso em clínica prática se dá comumente através de métodos invasivos, empregando eletrodos de agulha ou fios implantados. Apesar da EMG de superfície ser não-invasiva e, portanto mais apropriada para aplicações clínicas, não é usada em clínica porque não há até o presente um método satisfatório para decomposição do sinal EMG de superfície. Um EMG de superfície é muito mais difícil de decompor devido a significante superposição dos Potenciais de Ação das UMs (MUAPs) e a relação sinal-ruído relativamente baixa, se comparada aos métodos invasivos. Defendemos que a separação da atividade individual das UMs pode ser feita de modo não-invasivo aliando-se técnicas de aquisição altamente especializadas com técnicas usadas em reconhecimento de padrões. Desenvolvemos um método para decomposição de EMGs de superfície, a partir do qual foi possível extrair características relevantes das UMs, que permitem seu uso em avaliação e diagnóstico de desordens neuromusculares. Em nossa abordagem, o sinal EMG é inicialmente captado sob contração isométrica fraca usando eletrodos desuperfície. O sinal EMG bruto passa em seguida por um filtro Diferencial Passa-Baixas Ponderado (DPBP) em série com um detector de picos, que detecta os picos de MUAPs e extrai suas formas de onda. Na sequência, o conjunto de MUAPs extraído é classificado por uma rede neural SOM, e os MUAPs agrupados pela similaridade de suas formas de onda. No próximo passo a informação temporal dos disparos é checada, eliminando possíveis erros de classificação, e finalmente os Trens de MUAPs (MUAPTs) das UMs individuais são reconstituídos do EMG original. As estatísticas de disparos (IPI) bem como as formas de ondas dos MUAPs das respectivas UMs são então extraídas e armazenadas para estudos posteriores. Resultados preliminares obtidos com EMGs normais e patológicos, extraídos de membros superiores sob contração fraca, indicam que, o método mostrou-se apto a decompor EMGs de superfícies, além de potencial para aplicações em estudos clínicos não-invasivos de disfunções neuromusculares.<br>Information on the functional and structural characteristics of the motor unit (MU) they are highly important in physiologic investigations and in the clinical studies of the neuromuscular dysfunctions. The electromyography (EMG) it is an appropriate method for obtaining of that information. However, due to the difficulty in the separation of the individual activity of a motor unit of the another that are simultaneously active, your use in practical clinic happen commonly through methods invasive, employing needle electrodes or implanted threads. In spite of surface EMG to be non-invasive and, therefore more appropriate for clinical applications, it is not used at clinic because there is not until the present a satisfactory method for decomposition of the surface EMG sign. A surface EMG is much more difficult of decomposing due to significant overlap of the Motor Unit Action Potentials (MUAPs) and the relationship sign-noise relatively low, if compared to the invasive methods. We defended that the separation of the individual activity of MUs can be made in way non-invasive allying highly specialized acquisition techniques with techniques used in recognition of patterns. We developed a method for decomposition of surface EMGs, starting from which was possible to extract important characteristics of MUs, which allow your use in evaluation and diagnosis of neuromuscular disorders. In our approach, the sign EMG is captured initially under weak isometriccontraction using surface electrodes. The sign EMG raw raisin soon after for a Biased Low-Pass Differential filter (BLPD) in series with a detector of peaks, that detects the peaks of MUAPs and it extracts your wave forms. In the sequence, a SOM neural network classifies the set of extracted MUAPs, and MUAPs are clustered by the similarity in your wave shape. In the next step the temporal information of the discharges is checked, eliminating possible classification mistakes, and finally the MUAPs Trains (MUAPTs) of individual MUs they are reconstituted of original EMG. The statistics of discharges (IPI) as well as the forms of waves of MUAPs of respective MUs are then extracted and stored for subsequent studies. Results preliminaries obtained with normal and pathological EMGs, extracted of superior members under weak contraction, they indicate that, the method was shown capable to decompose surfaces EMGs, besides potential for applications in clinical studies non-invasive of neuromuscular dysfunctions.

It is important to have better evaluation and understanding of the motor neuron physiology, with the goal to early and objectively diagnose and treat patients with neurodegenerative pathologies. The Compound Muscle Action Potential (CMAP) scan is a non-invasive diagnosis technique for neurodegenerative pathologies, such as ALS, and enables a quick analysis of the muscle action potentials in response to motor nerve stimulation. This work aims to study the influence of different pulse modulated waveforms in peripheral nerve excitability by CMAP scan technique on healthy subjects. A total of 13 healthy subjects were submitted to the same test. The stimuli were applied in the medium nerve on the right wrist and electromyography signal collected on the Abductor Pollicis Brevis (APB) muscle surface on the right thumb. Stimulation was performed with an increasing intensities range from 4 to 30 mA, with varying steps, 3 stimuli per step. The procedure was repeated 4 times per subject, each repetition using a different single pulse stimulation waveform: monophasic square, monophasic triangular, monophasic quadratic and biphasic square. Results were retrieved from the averaging of the stimuli on each current intensity step. The square pulse needs less current intensity to generate the same response amplitude regarding the other waves and presents a more steep curve slope and this effect is gradually decreasing for the triangular and quadratic pulse,respectively, being the difference even more evident regarding the biphasic pulse. The control of the waveform stimulation pulse allows varying the stimulusresponse curve slope.

碩士<br>義守大學<br>電機工程學系<br>91<br>ABSTRACT A prosthetic device, called the cochlear implant, can be implanted in the inner ear and can restore partial hearing to profoundly deaf people. According to the clinical data, the effect is vary different from individual. Therefore, improved efficacy to cochlear implant is such a important work. There are two ways can ameliorate the situation. One is to find the new stimulation strategy, the other is to design new electrode dimension over again. When new stimulation strategy or new electrode be developed. Apply to patient is only way to distinguish weather the new design fine or inferior. We are going to find some method called modeling evoked compound action potential in cochlear implant that we can know the performance on new design without any surgery. Currently there is no easy ways to model evoked compound action potential (EAP) of the auditory nerve fibers. This thesis presents a method to model the EAP using finite element method, Schwarz-Eikhof nerve fiber model, and equivalent circuit models on a 3D cochlea model. The simulation results are validated by EAP measured in cochlear implant users.

碩士<br>國立交通大學<br>生醫工程研究所<br>105<br>With physiological dimensions of the cochlear implant (CI) patient’s cochlea from computed tomography (CT), it is possible to build a more accurate patient-specific electro-neural model of CI patients based on clinical measurements. One of such methods is proposed in this thesis. An accurate patient specific electro-neural model could be used for fine tuning the electrical stimulation parameters or “maps” of a CI patient without needing many CI mapping sessions. This has enormous implication for CI pediatric applications due to obvious reason. The goal of this thesis is to evaluate the relative spiral ganglion cells (SGC) density of a human CI patient. The electric potential along the cochlea in a CI patient can be measured via electric field imaging (EFI). Also, there is a significant correlation between evoked compound action potential (ECAP) threshold and behavior threshold (T) level for a CI patient. ECAP measurement approach is an objective and faster way to obtain the relative T level of a CI patient. This again has important implication for pediatric CI mapping application since it does not require feedback from pediatric CI patients. Due to a large stimulating range, we propose to use the idea of using “apple-core”-ECAP paradigm which can limit the auditory nerves being stimulated to a narrower volume between neighboring two electrodes. Since the volume of auditory nerves activated and the distance between electrode and SGC are fixed, we can obtain the relative SGC density through comparing with every SGC signal at different electrodes.

Indiana University-Purdue University Indianapolis (IUPUI)<br>This thesis describes a novel method to reversibly and safely block nerve conduction using a low frequency alternating current (LFAC) waveform at 1 Hz applied through a bipolar extrafascicular electrode. This work follows up on observations made on excised mammalian peripheral nerves and earthworm nerve cords. An in-situ electrophysiology setup was used to assess the LFAC waveform on propagating action potentials (APs) within the cervical vagus nerve in anaesthetized Sprague-Dawley rats (n = 12). Two sets of bipolar cuff or hook electrodes were applied unilaterally to the cervical vagus nerve, which was crushed rostral to the electrodes to exclude reflex effects on the animal. Pulse stimulation was applied to the rostral electrode, while the LFAC conditioning waveform was applied to the caudal electrode. The efferent volley, if unblocked, elicits acute bradycardia and hypotension. The degree of block of the vagal stimulation induced bradycardia was used as a biomarker. Block was assessed by the ability to reduce the bradycardic drive by monitoring the heart rate (HR) and blood pressure (BP) during LFAC alone, LFAC with vagal stimulation, and vagal stimulation alone. LFAC applied via a hook electrode (n = 7) achieved 86.6 +/- 11% block at current levels 95 +/- 38 uAp (current to peak). When applied via a cuff electrode (n = 5) 85.3 +/- 4.60% block was achieved using current levels of 110+/-65 uAp. Furthermore, LFAC was explored on larger vagal afferent fibers in larger human sized nerve bundles projecting to effects mediated by a reflex. The effectiveness of LFAC was assessed in an in-situ electrophysiological setup on the left cervical vagus in anaesthetized domestic swine (n = 5). Two bipolar cuff electrodes were applied unilaterally to the cervical vagus nerve, which was crushed caudal to the electrodes to eliminate cardiac effects. A tripolar extrafascicular cuff electrode was placed most rostral on the nerve for recording of propagating APs induced by electrical stimulation and blocked via the LFAC waveform. Standard pulse stimulation was applied to the left cervical vagus to induce the Hering-Breuer reflex. If unblocked, the activation of the Hering-Breuer reflex would cause breathing to slow down and potentially cease. Block was quantified by the ability to reduce the effect of the Hering-Breuer reflex by monitoring the breathing rate during LFAC alone, LFAC and vagal stimulation, and vagal stimulation alone. LFAC achieved 87.2 +/- 8.8% (n = 5) block at current levels of 0.8 +/- 0.3 mAp. Compound nerve action potentials (CNAP) were monitored directly. They show changes in nerve activity during LFAC, which manifests itself as the slowing and amplitude reduction of components of the CNAPs. Since the waveform is balanced, all forward reactions are reversed, leading to a blocking method that is similar in nature to DC block without the potential issues of toxic byproduct production. These results suggest that LFAC can achieve a high degree of nerve block in both small and large nerve bundles, resulting in the change in behavior of a biomarker, in-vivo in the mammalian nervous system at low amplitudes of electrical stimulation that are within the water window of the electrode.

碩士<br>國立台北護理學院<br>聽語障礙科學研究所<br>92<br>Several reports have shown the benefit in speech perception of cochlear implants. Determination of behavioral threshold levels (T-levels) and comfort levels (C-levels) of the cochlear implant users is very important for their performance of auditory perception. Either electrically evoked compound action potential (ECAP) or electrically evoked auditory brainstem response (EABR) has been studied to help with optimizing individual’s map parameters of cochlear implant users, particularly young children, in whom accurate behavioral T-levels and C-levels to electrical stimulation are difficult to obtain. The purpose of this study was to evaluate the efficacy of EABR and ECAP in programming children with Nucleus-24 cochlear implants by comparing their thresholds with behavioral T-levels and C-levels. Seventeen subjects (7 males and 10 females) with Nucleus 24 cochlear implant participated in this study. All subjects have received implantation at least for one year. Behavioral T-level and C-level were measured through the speech processor. Their auditory behavioral responses were reliable and stable MAPs were established. ECAP thresholds were recorded with the NRT 3.0v software (Cochlear, Australia). EABR thresholds were measured with evoked potential technique (Bravo, Nicolet, USA). SPSS 10.0 for Windows (SPSS Inc., Chicago, USA) was used for analysis. Regression models and paired t-tests were used to analyze the correlations between ECAP threshold, EABR threshold, behavioral T-level and C-level. ECAP thresholds were measured successfully in 64% of active electrodes measured, whereas EABR thresholds were measured in 71%. Unsuccessful recording of ECAP and EABR was observed mostly in subjects either with severe malformations or calcification of inner ear. Both ECAP and EABR could not be measured in four cases. When the subjects with severe malformations or calcification of inner ear were excluded, the rate of successful measurement raised to 94.2 % for EABR and 84.6 % for ECAP, respectively. EABR thresholds were on average 6.17 programming units (current levels) higher than ECAP thresholds. The correlation between EABR and ECAP thresholds was moderate (r = 0.755) and significant (p < 0.01). Paired t-tests revealed no significant difference between EABR and ECAP statistically (p = 0.051). The correlation between behavioral T-levels and ECAP thresholds or EABR thresholds was fair (r = 0.409 and 0.304, respectively). The correlation between behavioral C-levels and ECAP thresholds was moderate (r = 0.61), whereas the correlation between behavioral C-levels and EABR thresholds were fair (r = 0.283). The correlation between behavioral maps and EABR thresholds or ECAP thresholds is not strong. However, EABR and ECAP can be used as ancillary tools in programming MAP T-levels and C-levels of young children. In general, the rate of successful recording of EABR was higher than that of ECAP. Because recording of ECAP is easier and less time consuming than EABR, ECAP may be the choice of objective measurement. EABR measurement may be preferable for individuals whose ECAP can not be recorded successfully. Because of the very low rate of successful recording in young children either with severe malformations or calcification of inner ear, measurement of EABR and ECAP may not play a role in programming them.

<p>Deep brain stimulation (DBS) is an established surgical therapy for movement disorders. The mechanisms of action of DBS remain unclear, and selection of stimulation parameters is a clinical challenge and can result in sub-optimal outcomes. Closed-loop DBS systems would use a feedback control signal for automatic adjustment of DBS parameters and improved therapeutic effectiveness. We hypothesized that evoked compound action potentials (ECAPs), generated by activated neurons in the vicinity of the stimulating electrode, would reveal the type and spatial extent of neural activation, as well as provide signatures of clinical effectiveness. The objective of this dissertation was to record and characterize the ECAP during DBS to determine its suitability as a feedback signal in closed-loop systems. The ECAP was investigated using computer simulation and <italic>in vivo</italic> experiments, including the first preclinical and clinical ECAP recordings made from the same DBS electrode implanted for stimulation. </p><p>First, we developed DBS-ECAP recording instrumentation to reduce the stimulus artifact and enable high fidelity measurements of the ECAP at short latency. <italic>In vitro</italic> and <italic>in vivo</italic> validation experiments demonstrated the capability of the instrumentation to suppress the stimulus artifact, increase amplifier gain, and reduce distortion of short latency ECAP signals.</p><p>Second, we characterized ECAPs measured during thalamic DBS across stimulation parameters in anesthetized cats, and determined the neural origin of the ECAP using pharmacological interventions and a computer-based biophysical model of a thalamic network. This model simulated the ECAP response generated by a population of thalamic neurons, calculated ECAPs similar to experimental recordings, and indicated the relative contribution from different types of neural elements to the composite ECAP. Signal energy of the ECAP increased with DBS amplitude or pulse width, reflecting an increased extent of activation. Shorter latency, primary ECAP phases were generated by direct excitation of neural elements, whereas longer latency, secondary phases were generated by post-synaptic activation.</p><p>Third, intraoperative studies were conducted in human subjects with thalamic DBS for tremor, and the ECAP and tremor responses were measured across stimulation parameters. ECAP recording was technically challenging due to the presence of a wide range of stimulus artifact magnitudes across subjects, and an electrical circuit equivalent model and finite element method model both suggested that glial encapsulation around the DBS electrode increased the artifact size. Nevertheless, high fidelity ECAPs were recorded from acutely and chronically implanted DBS electrodes, and the energy of ECAP phases was correlated with changes in tremor. </p><p>Fourth, we used a computational model to understand how electrode design parameters influenced neural recording. Reducing the diameter or length of recording contacts increased the magnitude of single-unit responses, led to greater spatial sensitivity, and changed the relative contribution from local cells or passing axons. The effect of diameter or contact length varied across phases of population ECAPs, but ECAP signal energy increased with greater contact spacing, due to changes in the spatial sensitivity of the contacts. In addition, the signal increased with glial encapsulation in the peri-electrode space, decreased with local edema, and was unaffected by the physical presence of the highly conductive recording contacts.</p><p>It is feasible to record ECAP signals during DBS, and the correlation between ECAP characteristics and tremor suggests that this signal could be used in closed-loop DBS. This was demonstrated by implementation in simulation of a closed-loop system, in which a proportional-integral-derivative (PID) controller automatically adjusted DBS parameters to obtain a target ECAP energy value, and modified parameters in response to disturbances. The ECAP also provided insight into neural activation during DBS, with the dominant contribution to clinical ECAPs derived from excited cerebellothalamic fibers, suggesting that activation of these fibers is critical for DBS therapy.</p><br>Dissertation

This thesis describes a novel method to reversibly and safely block nerve conduction using a low frequency alternating current (LFAC) waveform at 1 Hz applied through a bipolar extrafascicular electrode. This work follows up on observations made on excised mammalian peripheral nerves and earthworm nerve cords. An<i> in-situ</i> electrophysiology setup was used to assess the LFAC<br>waveform on propagating action potentials (APs) within the cervical vagus nerve in anaesthetized Sprague-Dawley rats (n = 12). Two sets of bipolar cuff or hook electrodes were applied unilaterally to the cervical vagus nerve, which was crushed rostral to the electrodes to exclude reflex effects<br>on the animal. Pulse stimulation was applied to the rostral electrode, while the LFAC conditioning waveform was applied to the caudal electrode. The efferent volley, if unblocked, elicits acute bradycardia and hypotension. The degree of block of the vagal stimulation induced bradycardia<br>was used as a biomarker. Block was assessed by the ability to reduce the bradycardic drive by monitoring the heart rate (HR) and blood pressure (BP) during LFAC alone, LFAC with vagal stimulation, and vagal stimulation alone. LFAC applied via a hook electrode (n = 7) achieved 86.6 +/- 11% block at current levels 95 +/- 38 uAp (current to peak). When applied via a cuff electrode (n = 5) 85.3 +/- 4.60% block was achieved using current levels of 110 +/- 65 uAp. Furthermore, LFAC was explored on larger vagal afferent fibers in larger human sized nerve bundles projecting to effects mediated by a reflex. The effectiveness of LFAC was assessed in an <i>in-situ</i> electrophysiological setup on the left cervical vagus in anaesthetized domestic swine (n = 5). Two bipolar cuff electrodes were applied unilaterally to the cervical vagus nerve, which was crushed caudal to the electrodes to eliminate cardiac effects. A tripolar extrafascicular cuff electrode was placed most rostral on the nerve for recording of propagating APs induced by<br>electrical stimulation and blocked via the LFAC waveform.<br>Standard pulse stimulation was applied to the left cervical vagus to induce the Hering-Breuer reflex. If unblocked, the activation of the Hering-Breuer reflex would cause breathing to slow down and potentially cease. Block was quantified by the ability to reduce the effect of the Hering-Breuer<br>reflex by monitoring the breathing rate during LFAC alone, LFAC and vagal stimulation, and vagal stimulation alone. LFAC achieved 87.2 +/- 8.8% (n = 5) block at current levels of 0.8 +/- 0.3 mAp. Compound nerve action potentials (CNAP) were monitored directly. They show changes<br>in nerve activity during LFAC, which manifests itself as the slowing and amplitude reduction of components of the CNAPs. Since the waveform is balanced, all forward reactions are reversed, leading to a blocking method that is similar in nature to DC block without the potential issues of<br>toxic byproduct production. These results suggest that LFAC can achieve a high degree of nerve block in both small and large nerve bundles, resulting in the change in behavior of a biomarker, <i>in-vivo </i>in the mammalian nervous system at low amplitudes of electrical stimulation that are within the water window of the electrode.<br>

<div>Electrical nerve stimulation (ENS) is an emerging therapy for many neurological disorders. Compared with conventional one-way stimulations, closed-loop ENS approaches increase the stimulation efficacy and minimize patient's discomfort by constantly adjusting the stimulation parameters according to the feedback biomarkers from patients. Wireless neurostimulation devices capable of both stimulation and telemetry of recorded physiological signals are welcome for closed-loop ENS systems to improve the quality and reduce the costs of treatments, and real-time digital signal processing (DSP) engines processing and extracting features from recorded signals can reduce the data transmission rate and the resulting power consumption of wireless devices. Electrically-evoked compound action potential (ECAP) is an objective measure of nerve activity and has been used as the feedback biomarker in closed-loop ENS systems including neural response telemetry (NRT) systems and a newly proposed autonomous nerve control (ANC) platform. It's desirable to design a DSP engine for real-time processing of ECAP in closed-loop ENS systems. </div><div><br></div><div>This thesis focuses on developing the DSP architecture for real-time processing of ECAP, including stimulus artifact rejection (SAR), denoising, and extraction of nerve fiber responses as biomedical features, and its VLSI implementation for optimal hardware costs. The first part presents the DSP architecture for real-time SAR and denoising of ECAP in NRT systems. A bidirectional-filtered coherent averaging (BFCA) method is proposed, which enables the configurable linear-phase filter to be realized hardware efficiently for distortion-free filtering of ECAPs and can be easily combined with the alternating-polarity (AP) stimulation method for SAR. Design techniques including folded-IIR filter and division-free averaging are incorporated to reduce the computation cost. The second part presents the fiber-response extraction engine (FREE), a dedicated DSP engine for nerve activation control in the ANC platform. FREE employs the DSP architecture of the BFCA method combined with the AP stimulation, and the architecture of computationally efficient peak detection and classification algorithms for fiber response extraction from ECAP. FREE is mapped onto a custom-made and battery-powered wearable wireless device incorporating a low-power FPGA, a Bluetooth transceiver, a stimulation and recording analog front-end and a power-management unit. In comparison with previous software-based signal processing, FREE not only reduces the data rate of wireless devices but also improves the precision of fiber response classification in noisy environments, which contributes to the construction of high-accuracy nerve activation profile in the ANC platform. An application-specific integrated circuit (ASIC) version of FREE is implemented in 180-nm CMOS technology, with total chip area and core power consumption of 19.98 mm² and 1.95 mW, respectively. </div><div><br></div>