Les prothèses myoélectriques modernes peuvent être dotées de plusieurs degrés de liberté ce qui nécessite plusieurs signaux musculaires pour en exploiter pleinement les capacités. Pour obtenir plus de signaux, il nous a semblé prometteur d'expérimenter si les 6 compartiments du biceps brachial pouvaient être mis sous tension de façon volontaire et obtenir ainsi 6 signaux de contrôle au lieu d'un seul comme actuellement. Des expériences ont donc été réalisées avec 10 sujets normaux. Des matrices d'électrodes ont été placées en surface au-dessus du chef court et long du biceps pour recueillir les signaux électromyographiques (EMG) générés par le muscle lors de contractions effectuées alors que les sujets étaient soit assis, le coude droit fléchi ~ 100 ° ou debout avec le bras droit tendu à l'horizontale dans le plan coronal (sur le côté). Dans ces deux positions, la main était soit en supination, soit en position neutre, soit en pronation. L'amplitude des signaux captés au-dessus du chef court du muscle a été comparée à ceux obtenus à partir du chef long. Pour visualiser la forme du biceps sous les électrodes l'imagerie ultrasonore a été utilisée. En fonction de la tâche à accomplir, l'activité EMG a était plus importante soit dans un chef ou dans l'autre. Le fait de pouvoir activer préférentiellement l'un des 2 chefs du biceps, même si ce n'est pas encore de façon complètement indépendante, suggère que l'utilisation sélective des compartiments pourrait être une avenue possible pour faciliter le contrôle des prothèses myoélectriques du membre supérieur. / The latest myoelectric prostheses have several degrees of freedom and therefore require a large number of myoelectric signals to fully exploit their capabilities. Muscle compartments, which are intra-muscular subdivisions innervated by an individual muscle nerve branch, can be exploited to provide additional independent muscle control sites to operate such prostheses. This research presents a work to investigate the activation of the 6 biceps brachii compartments in healthy subjects to see if they have the ability to activate those compartments voluntarily. Therefore, electromyographic (EMG) signals were recorded from an array of seven and ten pairs of equally spaced surface electrodes positioned across the short and long head of the biceps of ten healthy subjects. The EMG signals are collected in two positions: 1) with the subject seated, right elbow flexed ~100°, and 2) with the subject standing with the right arm extended horizontally in the coronal plane (90°shoulder abduction). In both positions, the hand is either fully supinated, neutral, or fully pronated. The average root mean square value of the EMG signals obtained from the pairs of electrodes positioned over the short head are compared with the average obtained for the other pairs placed over the biceps long head. Ultrasound imaging also used to visualize the long and short heads of the biceps in flexed and extended arm while the hand was in different postures. Depending on the task to be accomplished, activity was larger in one head or in the other. Being able to activate either head of the biceps, while not yet completely independently, suggests that the selective use of compartments could be a possible avenue for controlling upper limb myoelectric prostheses.

L'hétérotopie en bande sous-corticale (SBH) est une malformation caractérisée par la présence d'une bande de neurones ectopiques en regard du cortex normal ou normotopique. La plupart des patients ont une mutation d'un gène encodant une protéine indispensable à la migration des neurones. Les patients présentent une épilepsie pharmacorésistante. La chirurgie ne donne pas de résultats satisfaisants, le foyer épileptogène n'étant jamais clairement délimité. Un modèle de rat reproduisant les caractéristiques observées chez les patients à pu être généré. Même s'il est clair que le cortex normotopique et l'hétérotopie participent aux évènements épileptiformes, leur zone de genèse reste néanmoins inconnue. Le but de cette thèse a été de localiser l'origine de l'activité épileptiforme in vitro sur tranches de cerveau à l'aide d'une technique d'enregistrement multisite.Des activités épileptiformes (ILEs) ont été enregistrées à l'aide d'une technique d'enregistrement extracellulaire multisite à 60 canaux. Un outil d'analyse développé sous Matlab a ensuite permis de caractériser les ILEs et notamment leur origine et étendues spatiales. Après avoir identifié l'importance du cortex normotopique dans la genèse des ILEs, nous en avons supprimé l'excitabilité in vivo. Nous montrons que la surexpression de ces canaux dans les neurones ectopiques n'altère pas la susceptibilité aux crises des animaux concernés alors que la surexpression de ces canaux dans l'hétérotopie et dans le cortex normotopique améliore le phénotype épileptique. Nos résultats suggèrent ainsi un rôle majeur du cortex normotopique dans la genèse des activités épileptiques dans le syndrome du double cortex. / Subcortical Band Heterotopia (SBH) is a cortical malformation formed when neocortical neurons prematurely stop their migration in the white matter, forming a heterotopic band below the normotopic cortex, and is generally associated with intractable epilepsy. Although it is clear that the band heterotopia and the overlying cortex both contribute to creating an abnormal circuit prone to generate epileptic discharges, it is less understood which part of this circuitry is the most critical. Here, we sought to identify the origin of epileptiform activity in a targeted genetic model of SBH in rats.Rats with SBH were generated by knocking‐down the Dcx gene into neocortical progenitors of rat embryos. Origin, spatial extent and laminar profile of bicuculline‐induced interictal‐like activity on neocortical slices were analyzed by using extracellular recordings from 60‐channels microelectrode arrays. Susceptibility to pentylenetetrazole‐induced seizures was assessed by electrocorticography in head‐restrained nonanaesthetized rats. We show that the band heterotopia does not constitute a primary origin for interictal‐like epileptiform activity in vitro and is dispensable for generating induced seizures in vivo. Further, we report that most interictal‐like discharges originating in the overlying cortex secondarily propagates to the band heterotopia. Importantly, we found that in vivo suppression of neuronal excitability in SBH does not alter the higher propensity of Dcx‐KD rats to display seizures. These results suggest a major role of the normotopic cortex over the band heterotopia in generating interictal epileptiform activity and seizures in brains with SBH.

Melanopsin (Opn4) is the opsin photopigment of intrinsically photosensitive retinal ganglion cells (ipRGCs). It has a conserved opsin structure and activation mechanism, yet demonstrates unusual functional properties that suggest it will possess unique structure-function relationships. The aim of this thesis was to characterise key OPN4 residues by examining the impact of non-synonymous mutations on melanopsin function. A genotype-driven screen of a chemically-mutagenized mouse archive led to the identification of a novel Opn4 mutant, S310A, located at a known opsin spectral tuning site. Action spectra from ipRGC and pupil light responses (PLR) of Opn4^S310A mice revealed no change in wavelength of peak sensitivity. However, Opn4^S310A PLR was significantly less sensitive at longer wavelengths, consistent with a short-wavelength shift in spectral sensitivity. This suggests S310A acts as a spectral tuning site in melanopsin. Next, the impact of naturally-occurring missense variants in human melanopsin (hOPN4) was examined in vitro. Fluorescent calcium imaging of 16 hOPN4 variants expressed in HEK293 cells revealed four hOPN4 variants abolished or attenuated responses to light (Y146C, R168C, G208S and S308F). These variants were located in conserved opsin motifs for chromophore binding or hydrogen-bond networks, functional roles apparently shared by melanopsin. Finally, two hOPN4 single nucleotide polymorphisms (SNPs) P10L and T394I, associated with abnormal non-image forming behaviour in humans, were explored in vivo. Using targeted viral-delivery of hOPN4 SNPs to mouse ipRGCs, a range of OPN4-driven behaviours, such as circadian photoentrainment and pupil light responses, were found to be comparable with hOPN4 WT control. Multi-electrode array recordings of ipRGCs transduced with hOPN4 T394I virus had significantly attenuated sensitivity and faster response offset, indicating this site may be functionally important for melanopsin activity but compensatory rod and cone input limits changes to non-image forming behaviour.

Comme dans beaucoup de domaines, la sécurité dépend du développement de méthodes analytiques très sensibles et fiables pour pouvoir détecter des molécules dangereuses. C'est pourquoi il est important de développer des méthodes simples afin de diagnostiquer rapidement un composé dangereux dans notre environnement. Dans ce contexte, les techniques électrochimiques offrent une alternative intéressante puisqu'elles permettent d'atteindre de grandes sensibilités et une bonne sélectivité, elles sont peu coûteuses et facilement adaptables pour la création de dispositifs portables. Récemment, notre équipe a développé un nouveau concept basé sur de la voltammétrie par échantillonnage de courant sur un réseau d'électrodes (EASCV), lequel est compatible avec la miniaturisation. Ce système permet de renouveler la surface et la solution au voisinage de l'électrode pendant l'analyse. Le projet de cette thèse a été d'étendre l'application de cette technique à des méthodes électrochimiques utilisant une étape de préconcentration. Une première étude, appliquée à la détection du phénol, a permis de montrer que l'EASCV offre une solution intéressante pour diminuer les phénomènes de passivation ayant lieu pendant l'analyse. En effet, une étude expérimentale associée à une étude théorique a montré que si un temps d'échantillonnage court était appliqué, le phénomène de passivation pouvait être évité. Enfin, pour la première fois, il a été possible de coupler la voltammétrie par échantillonnage de courant à la redissolution anodique. Cette étude, appliquée à la détection du plomb, a permis de mettre en place une courbe d'étalonnage et d'obtenir une intensité élevée de courant, 300 fois plus importante qu'avec les techniques classiques de redissolution anodique. Les premiers essais pour adapter ce nouveau concept aux méthodes pulsés se sont également montrés très encourageants. Afin d'améliorer la sensibilité et la sélectivité du capteur, le réseau d'électrodes a été fonctionnalisé. La modification dépend de la nature de l'espèce cible. Ainsi des polymères à empreintes moléculaires (pour des molécules comme la mélamine) ou des ligands (pour des ions comme le plomb) ont été testés. Dans les deux cas, une méthode d'électrogreffage a été mise au point pour fonctionnaliser la surface. Les premiers résultats obtenus sont encourageants puisqu'une courbe courant-potentiel a pu être tracée montrant une sensibilité 10 fois plus grande pour le plomb que celle obtenue avec une préconcentration par électrodépôt. / As in many fields, safety is primarily based on the development of reliable and highly sensitive analytical methods to detect hazardous molecules. Therefore there is a need for developing simple methods for the diagnosis of harmful molecules in our environment. In this context, electrochemical detection systems seems very promising because they are highly sensitive, require short analysis time, are easy to implement and economic to fabricate. Moreover, our team has recently developed a new concept of device based on sampled-current voltammetry performed on an electrode array (EASCV) which is compatible with miniaturization and portability. The system allows the renewal of the electrode surface and of the analytical solution during the analysis. The present project addresses these issues and aims to extend it to methods involving a preconcentration step. A first study, for the detection of phenol, showed that EASCV offers a versatile solution to decrease fouling effect during the analysis. Indeed experimental and theoretical studies show that the renewable of electrode surface and of the solution in the vicinity of the electrode associated with the use of a short sampled time can avoid electrode fouling. For the first time, it was possible to combine sampled-current voltammetry with anodic stripping voltammetry. In this study, we were able to create a calibration curve, for the detection of lead, and we obtained current intensities 300 times higher than with usual linear stripping voltammetry.First attempts to adapt this new concept to pulse methods were promising.. To increase the sensitivity and selectivity of the sensor, the electrode array is chemically modified. The nature of this modification depends on the nature of the analyte. Thus, molecular imprinted polymer (for molecules) or macrocyclic ligands (for ions) are tested In both cases, an electrografting method is achieved to functionalize the surface. The first results are promising since a current-potential curve is obtained with a sensibility ten times higher than with a preconcentration by electrodeposition.

Dopamine replacement therapy is the main method of treating Parkinson’s Disease (PD), however over time this treatment causes increasingly abnormal, involuntary movements. This symptom, known as Levodopa-Induced-Dyskinesia (LID) is associated with aberrant, high frequency oscillations (HFOs) in the motor cortex and basal ganglia, as demonstrated with implanted electrodes in human Parkinson’s patients as well as in a rat model of Parkinson’s Disease. However, despite efforts to determine if the same high frequency oscillations are also present during dyskinesia in the widespread 6-OHDA mouse model of Parkinson’s Disease, studies have been unable to do so. By building and implanting a 64-channel multi-electrode array into a unilateral 6-OHDA lesioned mouse, we were able to record HFOs at 80Hz and >100Hz in the motor cortex, basal ganglia and thalamus in the lesioned hemisphere during LID. We also recorded bilateral HFOs at >100Hz in the intact hemisphere. With this work we show that the same HFOs that are present in the motor cortex and basal ganglia of rats and humans are also present in mice during dyskinesia. This work will act to further validate the 6-OHDA PD-model in mice and provide opportunities to investigate new treatments for Parkinson’s Disease, dyskinesia and other neurological conditions. It will also serve as a model to study a purposed mechanism underlying the information processing in populations of neurons. / Dopaminbehandling är den mest förekommande metoden för att behandla Parkinsons sjukdom men detta orsakar dessvärre en bieffekt i form av gradvis förvärrande ofrivilliga rörelser. Detta beteendemönster kallas för Levodopa-Inducerad-Dyskinesi (LID) och med hjälp av elektrodimplantat i hjärnan, på parkinsonpatienter och djurmodeller av parkinsons, har man kunnat se att beteendet är förknippat med högfrekventa oscilleringar (HFO) av hjärnaktivitet i motorcortex och basala ganglierna. Trots försök att kartlägga om dessa högfrekventa oscilleringar också är närvarande i den populära 6-OHDA musmodellen av Parkinsons sjukdom, så har man hittills inte lyckats demonstrera detta. Genom att bygga och implantera ett elektrodimplantat med 64 kanaler i en ensidigt-leisonerad 6-OHDA musmodell av Parkinsons sjukdom så kunde vi åskådliggöra HFO i motor cortex, basala ganglierna och thalamus i den lesionerade hjärnhalvan under LID. Vi kunde också påvisa HFO som sträckte sig över till den intakta hjärnhalvan, med frekvenser över 100 Hz. Denna forskning ger stöd att 6-OHDA modellen för Parkinsons i möss är valid och ger möjlighet till nya metoder att utforska och behandla Parkinsons, dyskinesi och andra neurologiska åkommor. Studien lägger också grunden för framtida studier som ämnar att undersöka föreslagna mekanismer bakom sättet populationer av neuroner bearbetar information. / ingår i ett projekt finansierat av Vetenskapsrådet #2018-02717

Parkinson’s Disease affects 10 million people worldwide, with 40% of patients developing an associated psychosis which has been identified by studies as the number one source of caretaker distress and is related to increased mortality. This is further complicated by the fact that typical antipsychotic drugs worsen many of the motor symptoms implicated in Parkinson’s Disease, with only one commercially available drug able to ameliorate both symptoms. This problem ushers the development of novel drugs to treat these symptoms, as first tested on research animals. Complicating matters, drug effectiveness on the degree of psychosis is hard to obtain in animals without a reliable biomarker. However, a hallmark of psychotic states is thought to be the reduced coordination between brain structures, through neuronal synchronization, as demonstrated by steady-state responses and is suggested to be a potential biomarker of psychosis. By building a MATLAB software we were able to analyze the degree of neural synchronization between structures, during an auditory steady-state response, in rats that had been unilaterally lesioned by the 6-Hydroxydopamine model of Parkinson’s Disease, before and after administration of the psychotomimetic drug MK801. These rats had been chronically implanted with 128-channel multi electrode array, enabling us to measure the strength of coherence between several limbic structures, associated with auditory processing, from the sampled local field potential, identifying the degree of synchronization in the animal brain. As our data demonstrate that coherence levels dropped in the psychotic drug state, for structures in both the healthy and the Parkinsonian hemisphere, we are able to further demonstrate the validity of coherence measures as a biomarker for psychosis. These results demonstrate that our software can be used as a tool to assess the therapeutic response of drugs developed, aimed at treating Parkinson’s associated psychosis. / Parkinsons sjukdom drabbar 10 miljoner världen över, där 40% av patienterna utvecklar en associerad psykos vilket har visats vara en av de största stressfaktorerna för deras vårdgivare och är även förknippat med en högre dödlighetsgrad. Denna situation förvärras av det faktum att de vanliga antipsykotiska drogerna kan förvärra många av de motoriska symptom som utgörs av Parkinsons sjukdom och det finns i dagsläget enbart en enda kommersiell drog som kan dämpa bägge symptom samtidigt. Detta problem frammanar vidare utveckling av nya läkemedel som kan behandla dessa symptom, som innebär att de först måste testas på försöksdjur. En komplikation som uppstår i relation till detta är svårigheten att utvärdera om läkemedel har någon terapeutisk effekt på de psykotiska tillstånden, enbart genom att observera försöksdjurens beteenden, och en pålitlig biomarkör krävs istället. En lösning kan dock finnas i det faktum att psykotiska tillstånd karaktäriseras av en reducerad förmåga för olika hjärnområden att koordinera genom neural synkronisering vilket demonstreras av ‘steady- state’ responser. Detta föreslår att ett mått på graden av koordineringsförmåga kan agera som en möjlig biomarkör för psykotiska tillstånd. Genom att konstruera ett MATLAB-program kunde vi analysera graden av synkronicitet mellan hjärnstrukturer, under den auditiva steady- state responsen i råttor som hade blivit ensidigt lesionerade genom 6-Hydroxiddopamin modellen av Parkinsons sjukdom, före och efter administration av den psykotomimetiska drogen MK801. Dessa råttor hade blivit kroniskt implanterade med 128 elektroder vilket möjliggjorde att vi kunde mäta styrkan i koherens i den lokala fält potentialen mellan limbiska strukturer, som är associerade med auditiv processering, vilket möjliggjorde identifiering av3dessa strukturers synkronicitet. Vår data demonstrerar att koherensen minskade under det psykotiska drogtillståndet för limbiska strukturer både i den intakta och den lesionerade hjärnhalvan. Detta är en vidare demonstration av att koherensnivåer kan agera som en biomarkör för det psykotiska tillståndet, liksom att vår mjukvara kan nyttjas som ett verktyg för att utvärdera nya läkemedels behandlingsförmåga på Parkinsons psykos.

Electrophysiological measures such as impedance telemetry and Neural Response Telemetry (NRT™) were developed by Cochlear™ in 1992 as clinical tools allowing the objective setting of stimulus levels for cochlear implant users. Extensive research proved the usefulness of NRT™’s as an aid in the programming process of audible and comfortable stimulus levels for children younger than six years. The Nucleus® Freedom™, launched in 2005, introduced new developments in cochlear implantation. Approval from the FDA for this system was obtained in March 2005 and for the first time included children from age 12 months with profound hearing loss. The Joint Committee on Infant Hearing suggested that children be diagnosed and that treatment commenced by the age of six months. The new features of the Nucleus Freedom™ give clinicians the necessary tools to treat this challenging population. An urgent need exists to ascertain the stability and accuracy of the new features introduced by this system, especially the Auto-NRT™ software, to validate its use within the paediatric population. A longitudinal descriptive design was utilized implementing quantitative research methods to critically describe the behaviour of impedance telemetry and NRT™’s in a group of young cochlear implant users. The quantitative method included the application of the Custom Sound™ software and the Auto-NRT™ feature for this group at implantation, device activation, and then at determined follow-up visits. Nine young children between nine months and five years and eleven months were used as participants during the twelve months of research. Impedance telemetry was described in terms of the mean Common Ground (CG) and Monopolar 1+2 (MP1+2) values calculated from measurement data collected on the basal, medial, and apical electrodes of the electrode array. The electrodes identified for statistical procedures for both measurement types were E3, E6, E8, E11, E13, E16, E19 and E21. Friedman’s ANOVA was used as a statistical measure to determine the level of significance in changes among the measurement modes and conditions. The Wilcoxon signed-rank test was indicated in the presence of significant changes identified by Friedman’s ANOVA to calculate the level of significance in a pair-wise comparison. Results indicate that impedance telemetry remained consistent over the electrode array and over time in both measurement modes. A slight increase in mean values was observed during the first three months, followed by a gradual decrease at the six months interval. These changes were statistically nonsignificant. No specific trends were evident in impedance telemetry over time. NRT™-measurements remained consistent across the electrode array over time. Significant changes were present between the intra-operative to device activation measurement intervals. This trend is also described in studies of adult cochlear implant users. NRT™-measurements were stable during the first year postimplantation within the paediatric population. A comparison between the mean impedance telemetry and NRT™’s disclosed an inverse trend during the first six months post-implantation. Most changes were non-significant, indicating that these measures can be used effectively in the new semi-automated fitting software. The implementation of these measurements can lead to streamlined and accountable service delivery to young cochlear implant users. AFRIKAANS : In 1992 is elektrofisiologiese metings soos impedanstelemetrie en Neurale Respons Telemetrie (NRT™) deur Cochlear™ ontwikkel as kliniese hulpmiddels om objektiewe instelling van stimulasievlakke vir kogleêre gebruikers moontlik te maak. Navorsing het bewys dat NRT™’s ‘n effektiewe hulpmiddel is tydens programmering van hoorbare en gemaklike stimulasievlakke by kinders jonger as ses jaar. Die Nucleus® Freedom™ met nuwe ontwikkelings ten opsigte van kogleêre inplantings is in 2005 bekendgestel. Die FDA het in Maart 2005 hierdie sisteem goedgekeur vir gebruik by kinders selfs so jonk as 12 maande met uitermatige gehoorverlies. Die Joint Committee on Infant Hearing het voorgestel dat diagnose en aanvang van rehabilitasie teen ses maande ouderdom moet plaasvind. Die nuwe funksies van die Nucleus® Freedom™ stel oudioloë in staat om hierdie uitdagende bevolking te hanteer. ‘n Dringende behoefte bestaan om te bepaal of hierdie sagteware, veral Auto-NRT™ wat saam met hierdie sisteem bekendgestel is, oor voldoende akkuraatheid en stabiliteit beskik om in die hantering van die pediatriese bevolking te gebruik. ‘n Longitudinale, beskrywende ontwerp, wat kwantitatiewe metodes implementeer, is aangewend om die beweging van impedanstelemetrie en NRT™’s by ‘n groep jong gebruikers van kogleêre inplantings krities te beskryf. Dit het die gebruik van die Custom Sound™ sagteware en die ingeslote Auto- NRT™ funksie behels. Dit is tydens inplantering, by aktivering van die toestel, en bepaalde opvolgsessies uitgevoer. Nege jong kinders tussen die ouderdomme van nege maande en vyf jaar en 11 maande is tydens die 12 maande navorsingsperiode as proefpersone benut. Die impedansmetings is beskryf in terme van die Common Ground (CG) en Monopolar 1+2 (MP1+2) stimulasiemodaliteite. Data is verkry vanaf geselekteerde elektrodes op die basale, mediale en apikale gedeeltes van die elektrode. Vir statistiese ontledings van impedans en NRT™ is hierdie elektrodes geselekteer: E3, E6, E8, E11, E13 E16, E19 en E21. As statistiese ontledingsmetode, is Friedman se ANOVA toegepas om die vlakke van beduidenheid van beweging tussen die verskillende toetsmodaliteite en -omstandighede te bepaal. Die Wilcoxon signed-rank toets is aangedui in die teenwoordigheid van statisties beduidende veranderinge. Die doel van hierdie toets was om die vlak van beduidenheid paarsgewys te verifieer. Resultate dui op konstante impedansmetings oor die elektrode asook oor tyd in beide toetsmodaliteite. ‘n Geringe, statisties nie-beduidende, verhoging in gemiddelde waardes is waargeneem tydens die eerste drie maande na inplantering, waarna die waardes weer geleidelik afgeneem het tot en met die ses maande opvolginterval. Geen spesifieke neiging kon vir impedanstelemetrie bepaal word nie. NRT™-metings het konstant gebly oor die elektrode en met tyd. Statisties beduidende veranderinge is gemeet tussen die intra-operatiewe en aktiveringsintervalle. Hierdie neiging is ook beskryf in studies van volwasse gebruikers van kogleêre inplantings. NRT™-metings, binne die pediatriese populasie, het dus stabiel gebly oor die 12 maande periode post-inplantering. ‘n Vergelyking tussen die gemiddelde impedans- en NRT™-metings het ‘n inverse neiging geïdentifiseer gedurende die eerste ses maande na inplantering. Veranderinge was oor die algemeen statisties nie-beduidend, wat daarop dui dat hierdie metings effektief gebruik kan word. Die implementering van hierdie metings kan meer doeltreffende dienslewering aan die jong gebruikers van kogleêre inplantings tot gevolg hê. / Dissertation (MCommunication Pathology)--University of Pretoria, 2010. / Speech-Language Pathology and Audiology / unrestricted