Dissertationen zum Thema „Limbic circuit“

Au sein du circuit cortico-limbique, des régions complémentaires seraient impliquées soit dans l’évaluation soit dans la régulation des états affectifs. Cependant, la contribution respective de ces mécanismes «bottom-up» et «top-down» lors du traitement émotionnel reste à clarifier. Premièrement, nous avons validé un nouveau paradigme d’IRMf conçu pour dissocier les composants du circuit cortico-limbique, c.-à-d. le circuit dorsal cognitif entrecroisé avec le circuit ventral affectif. Nous avons trouvé que l’amygdale et ses connexions avec le circuit dorsal étaient engagées par le traitement émotionnel bottom-up. Le cortex cingulaire antérieur (CCA) dorsal et ses connexions avec le cortex préfrontal dorso-latéral (CPFDL) et l’amygdale étaient recrutés par la résolution top-down du conflit émotionnel. Le CPFDL et ses connexions avec le CCA dorsal étaient engagés par le contrôle attentionnel top-down. Puis, nous avons examiné l’impact de l’anxiété sur le circuit. Nous avons montré qu’une forte anxiété était associée à une activation plus importante du CCA en réponse au conflit émotionnel mais à une connectivité réduite entre CCA et CPFL. Enfin, nous avons examiné la variation d’activité et de connectivité fonctionnelle chez des patients schizophrènes. Chez les patients comparativement aux témoins, les processus bottom-up étaient associés à une interaction réduite entre l’amygdale et le CCA ventral et dorsal ainsi que le CPFDL. La résolution du conflit émotionnel entraînait une plus forte connectivité entre CCA dorsal et CCA ventral ainsi que le CPFDL. L’augmentation du contrôle attentionnel provoquait une connectivité plus importante entre le CPFDL et le CCA ventral
Within the cortico-limbic circuit, complementary regions are believed to be involved in either the appraisal or the regulation of affective state. However, the respective contribution of these bottom-up and top-down mechanisms during emotion processing remains to be clarified. First, we validated a new fMRI paradigm designed to dissociate the components of the cortico-limbic circuit, that is, the dorsal cognitive circuit intertwined with the ventral affective circuit. We found that the amygdala and its connections to the dorsal circuit was engaged by bottom-up emotional processing. The dorsal anterior cingulate cortex (ACC) and its connections to the dorsolateral prefrontal cortex (DLPFC) and amygdala, was recruited by top-down resolution of emotional conflict. The DLPFC and its connections to dorsal ACC was engaged by top-down attentional control. Secondly, we investigated the impact of anxiety on the circuit. We demonstrated that higher levels of anxiety were associated with stronger conflict-related activation in ACC but with reduced connectivity between ACC and LPFC. Finally, we examined the variation in functional activity and connectivity in schizophrenia patients. In patients compared to controls, bottom-up processes were associated with reduced functional interaction between the amygdala and both dorsal and ventral ACC as well as DLPFC. Top-down resolution of emotional conflict led to stronger functional connectivity between the dorsal ACC and both ventral parts of ACC and DLPFC. Increased top-down attentional control caused higher functional coupling between the DLPFC and ventral ACC

L'anxiété dans la maladie de Parkinson (MP) est un symptôme non-moteur fréquent et invalidant dont la prise en charge est difficile. La faible connaissance des mécanismes impliqués est une limite à sa prise en charge. L'objectif de ce travail était d'identifier les mécanismes sous-jacents de l'anxiété liée à la MP, via une approche IRM cérébrale multimodale.Une revue systématique de la littérature portant sur les données d'imagerie dans l'anxiété liée à la MP a d'abord été réalisée, permettant de générer de premières hypothèses. Ensuite, plusieurs études incluant des analyses en IRM cérébrale structurale et fonctionnelle ont été menées chez des patients atteints de MP et présentant ou non une anxiété cliniquement significative. Nos analyses se sont focalisées sur le circuit de la peur, connu pour être impliqué dans les troubles anxieux, et le circuit cortico-striato-thalamo-cortical limbique, connu pour son implication dans les symptômes psycho-comportementaux de la MP.Nos résultats suggèrent que l'anxiété liée à la MP serait la conséquence d'un déséquilibre fonctionnel et structural entre ces deux circuits. Certaines structures communes, comme le thalamus, le striatum ou les noyaux du tronc cérébral, pourraient être des zones clés dont l'altération pourrait expliquer la forte prévalence de ces troubles dans la MP. D'autres travaux s'appuyant notamment sur les avancées technologiques en imagerie et sur de nouveaux concepts concernant la physiopathologie de la MP, seront nécessaires pour répondre à ces questions
Anxiety in Parkinson's disease (PD) is a frequent and disabilitating non-motor symptom. It is difficult to manage, partly due to a poor knowledge of the underlying mechanisms. The objective of this thesis was to identify the underlying mechanisms of PD-related anxiety, using multimodal brain MRI.A systematic review of the literature on imaging data in PD-related anxiety was first carried out, allowing the generation of initial hypotheses. Then, several studies including structural and functional brain MRI analyses were carried out in PD patients with or without clinically significant anxiety. Our analyses focused on the fear circuit, known to be involved in anxiety disorders and fear processing, and the limbic cortico-striato-thalamo-cortical circuit, known for its involvement in the neuropsychiatric symptoms of PD.Our results suggest that PD-related anxiety is the consequence of a functional and structural imbalance between these two circuits. Certain overlapping structures, such as the thalamus, the striatum or the brainstem nuclei, could be key areas whose alteration could explain the high prevalence of these disorders in PD. Further works based in particular on technological advances in imaging and new concepts concerning the pathophysiology of PD will be necessary to answer the remaining questions

The medial prefrontal cortex (mPFC} and hippocampus (HPC} are central to executive control, spatial learning and working memory. In order to enable behavioral control, the function of the mPFC and HPC is tuned by complex interplay between excitatory (glutamatergic) and inhibitory (GABAergic) neurotransmitter systems. This thesis has employed lesions, pharmacological and optogenetic methodologies to investigate how the relationship between excitation and inhibition within the adult mouse mPFC and HPC affects cognition, using a battery of touchscreen-based operant assays: the automated spatial array task (ASAT), Spatial Reversal (SR) and Visual Discrimination (VD). Behavioral testing following excitotoxic lesions showed that the HPC was strongly implicated in the performance of both spatial tests (ASAT and SR), while removal of the mPFC had only marginal effects on learning with several trends that did not reach significance. Additionally, in VD, effects were only present as trends towards an involvement of the mPFC in formations of new stimulus-reward relationships. Interdependent processing spanning the mPFC and HPC while not directly assessed can be considered likely to explain complex changes in task performance. Using the described assays helped validate their application to test mPFC and HPC function in mice.

ITC/USA 2012 Conference Proceedings / The Forty-Eighth Annual International Telemetering Conference and Technical Exhibition / October 22-25, 2012 / Town and Country Resort & Convention Center, San Diego, California
There are always some intrinsic tradeoffs among the performance characteristics: radiation efficiency, directivity, and bandwidth, of electrically small antennas (ESAs). A non-Foster enhanced, broad bandwidth, metamaterial-inspired, electrically small, Egyptian axe dipole (EAD) antenna has been successfully designed and measured to overcome two of these restrictions. By incorporating a non-Foster circuit internally in the near-field resonant parasitic (NFRP) element, the bandwidth of the resulting electrically small antenna was enhanced significantly. The measured results show that the 10 dB bandwidth (BW10dB) of the non-Foster circuit-augmented EAD antenna is more than 6 times the original BW10dB value of the corresponding passive EAD antenna.

Abstract Digital delta-sigma modulators are used in a broad range of modern electronic sub-systems, including oversampled digital-to-analogue converters, class-D amplifiers and fractional-N frequency synthesizers. This work addresses a well known problem of unwanted spurious tones in the modulator’s output spectrum. When a delta-sigma modulator works with a constant input, the output signal can be periodic, where short periods lead to strong deterministic tones. In this work we propose means for guaranteeing that the output period will never be shorter than a prescribed minimum value for all constant inputs. This allows a relationship to be formulated between the modulator’s bus width and the spurious-free range, thereby making it possible to trade output spectrum quality for hardware consumption. The second problem addressed in this thesis is related to the finite accuracy of frequencies generated in delta-sigma fractional-N frequency synthesis. The synthesized frequencies are usually approximated with an accuracy that is dependent on the modulator’s bus width. We propose a solution which allows frequencies to be generated exactly and removes the problem of a constant phase drift. This solution, which is applicable to a broad range of digital delta-sigma modulator architectures, replaces the traditionally used truncation quantizer with a variable modulus quantizer. The modulus, provided by a separate input, defines the denominator of the rational output mean. The thesis concludes with a practical example of a delta-sigma modulator used in a fractional-N frequency synthesizer designed to meet the strict accuracy requirements of a GSM base station transceiver. Here we optimize and compare a traditional modulator and a variable modulus design in order to minimize hardware consumption. The example illustrates the use made of the relationship between the spurious-free range and the modulator’s bus width, and the practical use of the variable modulus functionality.

In the field of neuroscience, being in love and feeling romantically attached to a partner is described as a dynamic process. Romantic love may be viewed as a motivational system, changing throughout time and place, fluctuating on the interest and motivation of the individual. Early memories and attachment towards a caregiver, lay the foundation for later attachment behavior, also known as attachment styles. In this thesis, an exploratory approach is present. The thesis aims to introduce and describe the neural correlates of romantic love and romantic attachment. Brain regions concerned with reward, emotion and thought processing, such as the reward circuitry network of the brain and the limbic system, are being investigated. So are other brain areas involved in romantic love and romantic attachment. Research findings suggest that brain areas responsible for affection, emotional control, learning, memory and social judgment are all involved in the complex processes of being in love and feeling romantically attached. These findings are represented by the involvement of the frontal lobe, cerebral cortex, limbic system, orbitofrontal cortex, and hippocampus, anterior cingulate cortex (ACC), ventral tegmental area (VTA), caudate tail, including the reward pathways of the brain. Distribution and regulation of neurotransmitters such as; vasopressin, oxytocin, dopamine, corticosterone and serotonin are all present in the state of romantic  attachment and romantic love. Overlapping evidence confirms the involvement of the reward circuitry network, together with the limbic system as crucial in the formation and maintenance of a romantic relationship.

Les amplificateurs paramétriques Josephson (JPA) se sont révélés être un outil indispensablepour l’étude expérimentale de dispositifs quantiques dans le régime micro-onde ; car ilsrajoutent uniquement le minimum de bruit imposé par la mécanique quantique[1]. Cependant,ces amplificateurs sont beaucoup plus difficiles à utiliser et optimiser que leurs homologuesclassiques. Récemment, plusieurs expériences réalisées avec des circuits supraconducteurs,composés d’une jonction Josephson polarisée en tension en série avec un résonateur microonde,ont montré qu’une paire de Cooper peut traverser la barrière de la jonction par effettunnel en émettant un ou plusieurs photons avec une énergie totale de 2e fois la tensionappliquée. Dans cette thèse, nous montrerons qu’un tel circuit permet de mettre en place unamplificateur micro-onde préservant la phase que nous appelons « Amplificateur basé sur letunneling inélastique de paires de Cooper » (ICTA). Il est alimenté par une tension continueet peut fonctionner avec un bruit très proche de la limite quantique.Nous commencerons en présentant le principe du fonctionnement de l’ICTA. Par analogieavec la théorie quantique des JPAs[2], nous avons étudié les performances de cet amplificateurcomme le gain, la bande passante et le bruit. Ensuite, nous présenterons la premièrepreuve expérimentale d’une amplification proche de la limite quantique sans utilisation d’unepompe micro-onde externe, mais simplement d’une tension continue dans une configurationextrêmement simple. Ces mesures ont été faites sur des échantillons avec des jonctionsen aluminium, dénommés ICTA de première génération. Selon nos résultats théoriques etexpérimentaux, nous avons conçu des circuits hyperfréquences où l’impédance présentéeà la jonction dépend de fréquences spécifiques afin d’optimiser les performances de notreamplificateur. Ces échantillons, dénommés ICTA de seconde génération, ont été fabriquésavec du nitrure de niobium. Une amélioration significative du gain et du bruit a été prouvée.Un tel amplificateur, alimenté par une simple tension continue, pourrait rendre la mesurede signaux micro-ondes au niveau du photon unique beaucoup plus faciles et permettred’intégrer plusieurs amplificateurs sur une seule puce. Il pourrait donc être un élémentimportant pour la lecture de qubit dans les processeurs quantiques à grande échelle
Josephson parametric amplifiers (JPA), have proven to be an indispensable tool for awide range of experiments on quantum devices in the microwave frequency regime, becausethey provide the lowest possible noise. However, JPAs remain much more difficult to use andoptimize than conventional microwave amplifiers. Recent experiments with superconductingcircuits consisting of a DC voltage-biased Josephson junction in series with a resonator,showed that a tunneling Cooper pair can emit one or several photons with a total energyof 2e times the applied voltage. In this thesis we show that such q circuit can be used toimplement a new type of phase preserving microwave amplifier, which we call InelasticCooper pair Tunneling Amplifier (ICTA). It is powered by a simple DC bias and offers nearquantum-limited noise performance.We start this work by presenting a brief and simple picture of the basic ICTA operatingprinciples. In analogy with the quantum theory of JPAs, we calculate the performances ofthis amplifier such as the gain, bandwidth and noise. Then, we present the first experimentalproof that amplification close to the quantum limit is possible without microwave drive inan extremely simple setup. These measurements are made on a first generation of samplesbased on aluminium junctions. According to our theoretical and experimental results, wehave designed microwave circuits presenting specific frequency-dependent impedances tothe junction in order to optimize the performances of our amplifier. This second generationof ICTA samples is fabricated from niobium nitride and provide significantly lower noiseand higher gain.We expect that once fully optimized, such an amplifier, powered by simple DC voltagescould then make measuring microwave signals at the single photon level much easier andallow to deploy many amplifiers on a chip. It could therefore be an important ingredient forqubit readout in large-scale quantum processors

The work describes the design and implementation of compact inverter for brushless DC motor, which have mechanical power 600 W and rated torque 1.6 Nm. Motor is designed for DC link voltage with value 300 V. The focus is placed on the cost and simplicity. On this basis, the inverter is designed for uses single purpose power and control circuit. The power part is solved using a circuit FSBB15CH60C. The circuit is placed on a separate board of power electronics. Cooling of the power circuit is performed by the surface structure of BLDC motor. Control of the inverter ensures circuits LB11696V and NE566. The both circuits are placed on separate board of control electronics. Circuit LB11696V contains a control algorithm, as well as protections, which are necessary for safe operation of the inverter. Power supply of electronics is performed using step-down converter from MYRRA company.

Tese de doutoramento Medicina
The endocannabinoid system has been implicated in the regulation of several physiological functions. The widespread distribution of the endocannabinoid system in the central nervous system (CNS) accounts for many effects attributed to cannabinoids. Importantly, cannabinoids have been shown to modulate mood, cognition and memory. There is growing evidence suggesting that cannabinoids can interact with the noradrenergic system. Noradrenergic transmission in the CNS has also been implicated in the regulation of mood, cognition and memory. In the present work, the hypothesis that cannabinoids can impact noradrenergic transmission in the limbic system was examined. Firstly, localization of the cannabinoid receptor type 1 (CB1r) was performed in the nucleus accumbens (Acb) and in the nucleus of the solitary tract (NTS), using immunohistochemical techniques, to clarify the anatomical substrates underlying potential interactions. It was shown that CB1r is present in noradrenergic neurons of the NTS. In addition, CB1r was found in the Acb but rarely in noradrenergic terminals. Furthermore, the effects of cannabinoid administration on adrenergic receptor (AR) expression in the Acb were studied. Western blot analysis of accumbal tissue revealed that exogenous administration of the synthetic cannabinoid WIN 55,212-2 decreases α2A- and β1-AR expression. Finally, the importance of norepinephrine (NE) in cannabinoid-induced behaviors was tested. Using the place conditioning paradigm and the elevated zero maze (EZM), the effects of cannabinoids on aversion and anxiety, respectively, were tested following depletion or blockade of noradrenergic transmission in the Acb or in the bed nucleus of the stria terminalis (BNST). Using an immunotoxin approach, NE depletion restricted to the Acb, but not BNST, blocked the expression of aversion to WIN 55,212-2. Depletion of NE had no effect on WIN 55,212-2-induced anxiety. Moreover, the fact that blockade of β1-AR in the Acb prevents WIN 55,212-2-induced aversion suggests that noradrenergic transmission via β1-AR is critical for eliciting this behavior. In conclusion, the present work provides new evidence supporting the idea that cannabinoids can impact noradrenergic transmission in the limbic system. In addition, cannabinoid-induced aversion is dependent on intact noradrenergic transmission in the Acb. Taken together, the studies provide herein clarify the anatomical and neurochemical substrates for cannabinoid actions in the CNS.
O sistema endocanabinóide tem sido implicado na regulação de várias funções fisiológicas. A dispersa distribuição do sistema endocanabinóide no sistema nervoso central (SNC) explica os muitos efeitos atribuídos aos canabinóides. De realçar que tem sido demonstrado que os canabinóides modelam o humor, cognição e memória. Existe uma crescente evidência sugerindo uma interacção entre o sistema endocanabinóide e o sistema noradrenérgico. Por seu lado, transmissão noradrenérgica no SNC tem sido implicada na regulação do humor, cognição e memória. No presente trabalho, a hipótese de que os canabinóides podem afectar a transmissão noradrenérgica no sistema límbico foi examinada. Inicialmente, a localização do receptor dos canabinóides tipo 1 (CB1r) no núcleo accumbens (Acb) e no núcleo do tracto solitário (NTS) foi efectuada utilizando técnicas de imunohistoquímica, de forma a clarificar os substratos anatómicos subjacente a potenciais interacções. Foi demonstrado que CB1r está presente em neurónios noradrenérgicos do NTS. Para além disso, CB1r foi encontrado no Acb mas raramente em terminais noradrenérgicos. Adicionalmente, os efeitos da administração de canabinóides na expressão de receptores adrenérgicos no Acb foram estudados. Análise por western blot de tecido do Acb revelou que administração exógenea do canabinóide sintético WIN 55,212-2 diminui a expressão dos receptores adrenérgicos α2A e β1. Finalmente, a importância da noradrenalina (NA) nos comportamentos induzidos pelos canabinóides foi testada. Utilizando o paradigma de “place conditioning” e o teste “elevated zero maze” (EZM), os efeitos dos canabinóides na aversão e anxiedade foram testados após depleção ou bloqueio da transmissão noradrenérgica no Acb ou no núcleo da estria terminalis (BNST). Utilizando uma imunotoxina, a depleção restrita de NA no Acb, mas não no BNST, bloqueou a aversão ao WIN 55,212-2. Enquanto que depleção de NA não teve nenhum efeito na anxiedade provocada por WIN 55,212- 2. Mais, o facto de o bloqueio do receptor adrenérgico β1 no Acb prevenir a aversão induzida por WIN 55,212-2 sugere que a transmissão noradrenérgica via este receptor é fundamental para a expressão deste comportamento. Em conclusão, o presente trabalho fornece nova evidência suportando a ideia de que os canabinóides podem afectar a transmissão noradrenérgica no sistema límbico. Mais, a aversão induzida por canabinóides é dependente da transmissão noradrenérgica no Acb. Em conjunto, os estudos apresentados neste trabalho esclarecem os substratos anatómicos e neuroquímicos das acções dos canabinóides no SNC.

博士
國立陽明大學
生理學研究所
101
The generation of epilepsy depends on the circuit transition from normal state to abnormal state, and this transition is involved in the changes of brain activities including neuronal firing patterns, coordination of neural populations, and correlation between single neurons and neural populations. However, the determinants and regulators prior to status epilepticus (SE) are not well understood. In this dissertation, different approaches to spatio-temporal dynamics of brain were used to study the transition factors from normal state to epileptic state. Firstly, to understand the transition of epilepsy, the neural activities in the hippocampus were measured by neuronal ensemble recording in Sprague Dawley rats treated with pilocarpine. According to the analysis of firing coincident from neuronal ensembles, a decrease of hippocampal coincidence was correlated with the development of SE. The hippocampal desynchronization might be a predicting factor of SE. However, we found a very heterogeneous change in the firing rate across putative hippocampal neurons. Secondly, the neural activities prior to SE in pilocarpine-treated rats were recorded in multiple regions of the limbic system including the CA1, CA3, dentate gyrus, anterior nucleus of thalamus, amygdala, entorhinal cortex, subiculum, and medial septum. The synchronization between different brain regions was computed by inter-structure coherence to assess the brain connection prior to SE. According to neural network analysis, we identified the enhanced beta synchrony in the limbic system prior to the occurrence of SE. Specifically, a significant beta synchrony between the amygdala and the anterior nucleus of thalamus was found. Therefore, the neural connection between the amygdala and the thalamus might involve in the development of SE. Thirdly, an imbalance between neural excitation and inhibition in the brain may underlie the transition from normal state to epileptic state. For example, a change in GABAergic transmission might participate in this transition process in pilocarpine model. To evaluate the involvement of GABAergic transmission, a pharmaceutical approach was used. In rats treated with diazepam, a GABAA receptor agonist, we found a decrease in the firing rate of high-spiking neurons in association with a lower rate of SE induction. This finding suggests that the GABAergic transmission plays an important role in generation of SE. In conclusion, these results suggest that hippocampal desynchronization is a key electrophysiological change prior to the occurrence of SE. The limbic hyper-synchronization at beta oscillation is a characteristic feature in rats with SE. Moreover, a blockade of GABAA receptors might prevent the development of SE by decreasing the firing rate of high-spiking neurons. Further studies are warranted to determine the exact biomarkers prior to SE and their underlying mechanisms in pilocarpine-treated rats.

碩士
國立成功大學
電機工程學系
104
Abstract This thesis mainly studies on a switch circuit with current limitation. When short circuit fault occurs, high short circuit current may damage devices and system. According to output characteristic of IGBT, collector current is proportional to its saturation voltage, and can be limited at a safe value while IGBT operating in active region, and it is related gate-to-emitter voltage. Integrate these characteristics to driver circuit of IGBT, a novel protection switch circuit is proposed. This protection switch circuit can inhibit fault current by operating IGBT in active region. Comparing with the conventional mechanical protection, it has a shorter response time, and can clear fault before fault current increases to maximum value. Eliminating difficulty of arc suppression of short current in a DC system. In a AC system, there is no delay to shut off the fault current. Standard of fault current withstanding for devices will be lower. Thus, cost can be reduced and reliability can be enhanced. In this thesis, this short circuit protection switch will be implemented to DC and AC applications. One is a digital control inverter, and the other is grid-connected solid state circuit breaker. These circuits can achieve short circuit protection, short circuit current limiting, and auto restarting.

碩士
長庚大學
基礎醫學研究所
91
The hypothalamo-pituitary-adrenal axis (HPA axis) response is the classical response when animals receive stressful challenges. The paraventricular nucleus of the hypothalamus (PVH) plays a key role in HPA axis response. PVH releases corticotrophin-releasing factor (CRF) to the anterior pituitary gland to increase plasma adrenocorticotrophin (ACTH) level, which in turn to raise the plasma corticosterone level. The efferent of PVH are well known, but the afferents of PVH are complicated and abstruse. Limbic system is the central structure involved in memory, learning and emotional regulations. The amygdala is involved in behavioral, autonomic, and neuroendocrine responses to stressful stimuli. Recent studies showed that lesion of the amygdala can attenuate the HPA axis response to stress, and infusion of corticosterone directly into the amygdala results in the opposite effects. On the other hand, the bed nucleus of the stria terminalis (BNST), the integrative center of the limbic system, receives afferents from the amygdala and hippocampus and projects to the PVH. The goal of my study was to determine the anatomical relationship among amygdala, BNST and PVH under stress. Male Sprague-Dawley rats received contexual conditioned fear paradigm of conditioned stimulus (CS) and unconditioned stimulus (US) for one, three, or five days. On the day of sacrifice, rats were exposed to CS only. Immunohistochemical staining of Fos-immunoreactivity (ir) was used to identify activated cells, and in situ hybridization was used to detect CRF mRNA and arginine vasopressin (AVP) mRNA in the hypothalamus. Tract tracing studies were conducted to characterize the anatomical relationship among amygdala, BNST and PVH. My findings showed that conditioned fear elevated Fos-ir expression in the PVH and medial nucleus of the amygdala (MeA), and decreased Fos-ir expression in the central nucleus of the amygdala (CeA) and dorsal lateral nucleus of the BNST. CRF mRNA level was upregulated in the PVH, BNST and CeA in conditioned rats. Conditioned fear also elevates AVP mRNA expression in the PVH. Tract tracing studies demostrated that CeA could project to PVH via the BNST, and MeA could project to the PVH directly. These studies provide evidences that conditioned fear could alter limbic cellular activity which might involved in HPA regulation, and the tract tracing studies further suggest an anatomical framework between limbic system and PVH under stress.

Autism spectrum disorders (ASDs) are characterized by phenotypic and genetic heterogeneity. Our analysis of functional networks perturbed in ASD suggests that both truncating and non-truncating de novo mutations contribute to autism. Moreover, we find that truncating mutations affecting the same exon lead to strikingly similar intellectual phenotypes in unrelated ASD probands and propose that exons, rather than genes, represent a unit of effective phenotypic impact for truncating mutations in autism. The phenotypic effects are likely mediated by nonsense-mediated decay of splicing isoforms and similar patterns may be observed in other genetic disorders. While multiple cell types and brain areas are affected, the impact of ASD mutations converge on a strongly interconnected system of neural structures that involve basal ganglia loops and the limbic system. We observe that distant projections constitute a disproportionately large fraction of the network composition, suggesting that the integration of diverse brain regions is a key property of the neural circuit. We demonstrate that individual de novo mutations impact several disparate components of the network and may further explain the phenotypic variability. Overall, our study presents a method that, to our knowledge, is the first unbiased approach using genetic variants to comprehensively discover and identify the neural circuitry affected in a psychiatric disorder.

The emergence of limbs in vertebrates represents a significant evolutionary innovation. Limbs facilitate diverse motor behaviors, yet require spinal networks that can coordinate the activities of many individual muscles within the limb. Here I describe several efforts to characterize the specification of spinal motor neurons and assembly of spinal circuits in higher vertebrates. I discuss the formation of selective presynaptic sensory inputs to motor pools, a process which has long been thought to occur in an activity-independent manner. I demonstrate an as yet unappreciated role of activity-dependent refinement in patterning the set of sensory-motor connections that link motor pools with synergist function. I also explore the genetic specification of motor pools that project to defined muscle targets. I show that the motor pools that control digits engage distinct developmental genetic programs which reflect underlying differences in Hox and retinoic acid signaling. The divergent mechanisms underlying the specification of digit-innervating motor neurons may reflect the unique status of digit control in the evolution of motor behavior.

The aim of this research is the occurrence of symptoms of the limbic dysfunction in patients suffering from headaches. By means of the questionnaire survey method was tested group of people with this diagnosis. The basic premise is the assumption that certain symptoms, specifically abnormalities in brain activity, occur more frequently in patients with this diagnosis. The theoretical part of this thesis concentrates on the function of the temporal lobe and the limbic system, a brief outline of the characteristics of temporo-limbic dysfunction and a summary overview of headaches. The research part is addressed to the evaluation questionnaire study and answers to the questions asked. Keywords Temporal lobe, limbic system, temporolimbic dysfunction, headaches, migraine, comorbidity,questionnaire

Dans l’hémiparésie consécutive à un AVC, une coactivation anormale des extenseurs du genou et de la cheville est souvent observée à la jambe atteinte lorsque la personne tente de bouger ou encore lors de la marche. Les mécanismes sous-jacents à cette coactivation sont mal compris. Bien que l’AVC entraîne une lésion supraspinale, des évidences démontrent le dysfonctionnement de certains circuits spinaux dans l’hémiparésie. Ce projet de doctorat visait à évaluer : 1) l’excitabilité des circuits spinaux intersegmentaires projetant des extenseurs du genou aux extenseurs de la cheville et 2) si un éventuel dysfonctionnement de ces circuits dans l’hémiparésie est associé à une coactivation anormale des extenseurs du genou et de la cheville lors de contractions statiques et au cours de la marche. La première étude compare la modulation de l’activité réflexe du soléaire suite à la stimulation du nerf fémoral entre des sujets hémiparétiques et sains. Une augmentation de la facilitation hétéronyme de courte latence et une diminution de l’inhibition ultérieure du réflexe H du soléaire ont été observées chez les sujets hémiparétiques. Ces résultats démontrent un dysfonctionnement des circuits intersegmentaires propriospinaux liant le quadriceps au soléaire suite à l’AVC. La deuxième étude démontre que ces changements dans la modulation hétéronyme des sujets hémiparétiques, évaluée au moyen de la méthode complexe basée sur l’activité réflexe du soléaire, sont similaires à ceux observés lorsque la modulation est évaluée en utilisant une méthode plus simple, soit celle de l’activité volontaire du soléaire. De plus, la modulation hétéronyme évaluée par les deux méthodes est corrélée avec l’atteinte motrice à la jambe parétique. La troisième étude a permis de quantifier une augmentation de la coactivation entre les extenseurs du genou et de la cheville lors de contractions volontaires statiques chez des personnes hémiparétiques par rapport à des personnes saines. De plus, le niveau accru de la coactivation involontaire des extenseurs de la cheville lors de l’activation volontaire des extenseurs du genou s’avère corrélé avec la modulation intersegmentaire du côté parétique. La quatrième étude a utilisé un indice temporel, soit l’intervalle entre les pics d’activation électromyographique (PAI), et un indice d’amplitude de coactivation (CAI) pour quantifier une augmentation de la coactivation entre les extenseurs du genou et de la cheville lors de la marche chez des personnes hémiparétiques par rapport à des personnes saines. Ces indices sont corrélés, pour certains groupes musculaires, avec la modulation intersegmentaire modifiée du côté parétique. Finalement, des résultats préliminaires montrent que la vibration mécanique du tendon rotulien (80 Hz) réduit la facilitation intersegmentaire accrue des sujets hémiparétiques. Ce projet doctoral a permis de mettre en lumière un dysfonctionnement de circuits spinaux liant le quadriceps et le soléaire dans l’hémiparésie consécutive à un AVC. Ce changement dans les mécanismes neurophysiologiques de la moelle épinière est corrélé avec des changements fonctionnels. Ainsi, ce dysfonctionnement pourrait contribuer à la coactivation involontaire entre les extenseurs du genou et de la cheville qui fait partie intégrante de la synergie pathologique en extension souvent rencontrée à la jambe parétique lors d’efforts en statique et pendant la marche. Finalement, une étude préliminaire suggère que la vibration mécanique serait une modalité sensorielle prometteuse pour réguler l’hyperexcitabilité des circuits spinaux qui contribuerait aux atteintes motrices chez les personnes hémiparétiques.
In stroke individuals, an abnormal coactivation of knee and ankle extensors is often observed when the paretic leg is voluntarily moved and during gait. The mechanisms underlying this abnormal coactivation are not well understood. Although, stroke is the result of a supraspinal lesion, studies have shown that spinal pathways might also be affected in hemiparesis. This doctoral project aims: 1) to assess intersegmental pathways projecting from knee extensors to ankle extensors in hemiparetic patients and 2) to evaluate whether a potential malfunction in these pathways after stroke is associated with an abnormal coactivation of leg extensors during static contractions and during gait. The first study of this project compares the effects of femoral nerve (FN) stimulation on soleus reflex activity in hemiparetic patients and healthy individuals. An increase of the early short-latency heteronymous facilitation and a decrease of the later inhibition of soleus H reflex induced by FN stimulation were observed in stroke patients. These results demonstrate the malfunction of intersegmental short propriospinal pathways linking quadriceps to soleus after stroke. The second study shows that these changes in the heteronymous modulation assessed with the complex method using soleus H reflex are similar to those found using a simpler method based on the modulation of soleus voluntary EMG. Moreover, changes in the propriospinal modulation observed with both methods were correlated with motor impairments of the paretic leg. The third study has quantified an increased coactivation of knee and ankle extensors during static contractions in stroke patients compared to healthy controls. Furthermore, the increased coactivation of ankle extensors during the voluntary contraction of knee extensors was related to the modified heteronymous modulation in the paretic leg. The fourth study has quantified an increased coactivation of knee and ankle extensors in hemiparetic gait using a temporal coactivation index, that was the peak activation interval (PAI) and a coactivation amplitude index (CAI). In some muscles, these indexes were correlated to the modified intersegmental modulation of soleus voluntary activity on the paretic side of stroke patients. Finally, preliminary results have shown that vibration of the patellar tendon (80 Hz) can reduce the enhanced heteronymous facilitation observed in the paretic leg. This doctoral project demonstrates the malfunction of intersegmental pathways linking quadriceps to soleus in hemiparesis following stroke. The neurophysiological alterations at the spinal level are correlated with functional changes. This malfunction could contribute to the abnormal involuntary coactivation of knee and ankle extensors often observed in the paretic leg while the person attempts to move or during gait. Finally, a preliminary study indicates that mechanical vibration could be a promising sensory modality in the regulation of the hyperexcitability of spinal reflex pathways, which is thought to participate in motor impairments after stroke.