Dissertations / Theses on the topic 'Maladie de Parkinson – imagerie diagnostique'
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Carey, Guillaume. "Imaging anxiety in Parkinson's disease." Electronic Thesis or Diss., Université de Lille (2022-....), 2024. https://pepite-depot.univ-lille.fr/ToutIDP/EDBSL/2024/2024ULILS023.pdf.
Full textAnxiety 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
Pinto, Serge. "Stimulation du noyau subthalamique et dysarthrie parkinsonienne : études biomécanique et par imagerie cérébrale." Université Joseph Fourier (Grenoble), 2002. http://www.theses.fr/2002GRE19008.
Full textSubthalamic nucleus stimulation and parkinsonian dysarthria : biomechanical and neuroimaging studies. The aim of this study is to determine the bilateral subthalamic nucleus (STN) stimulation effect on parkinsonian dysarthria (. . . ) These changes associated with speech production in PD might be explained by a compensatory phenomenon. When the STN stimulation was turned ON, the activation profiles were similar to those of the healthy subjects, except for the persistence of activation of the SMA
Menuel, Carole. "Vers la précision inframillimétrique en IRM en conditions stéréotaxiques : application au traitement par stimulation profonde de la maladie de Parkinson." Paris 11, 2005. http://www.theses.fr/2005PA112057.
Full textHigh-frequency stimulation of the subthalamic nucleus (STN) is an effective method for treating refractory idiopathic Parkinson disease (PD). MRI in stereotactic conditions is used by many teams to perform pre-operative targeting of the STN. The goal of this study is to analyze and correct the geometric observed on MR acquisitions used for targeting of the STN. Dedicated phantom of known geometry was used. We calculated existing shifts between measured points and theoretically defined points on the same T1 and T2-weighted sequences used to target STN. A shifting volume was built to correct the distorsion. A quantitative study of the correction was carried out on the phantom images and acquisitions done in patients. To quantify the distortion corrections in patients, we evaluated different anatomical structure. Results show that the distortions are greater in T2 and weak in T1-weighted acquisitions, of the size order of one pixel. The geometric distortion was significantly reduced and smaller than pixel size after distortion correction. Study of the patient’s scans showed a good correspondence between anatomical structure in T1 (not distorted) and T2 corrected. The MR distortions observed on a T1-weighted acquisition remains very low, this confirms that this type of sequence can be used with stereotactic precision,. T2-weighted acquisition can be used to obtain measurement at the center part of the field of view but cannot be used directly for stereotactic targets determination. Correction of the geometrical distortion observed on the T2-weighted sequence can be obtained with our method and could be used to the stereotactic procedure
Couronné, Raphaël. "Modélisation de la progression de la maladie de Parkinson." Electronic Thesis or Diss., Sorbonne université, 2021. http://www.theses.fr/2021SORUS363.
Full textIn this work, we developed statistical methods to model disease progression from patient’s repeated measurements, with a focus on Parkinson’s Disease (PD). A key challenge lies in the inherent heterogeneity of PD across patients, to the extent that PD is now suspected to encompass multiple subtypes or motor phenotypes. To gain insights on disease progression, research studies propose to gather a broad range of marker measurements, at multiple timepoints for each patients. These data allow to investigate the disease’s patterns of progression via statistical modeling. In a first part, we modeled the progression of scalar markers of PD. We extended on a disease progression model, namely the longitudinal spatiotemporal model. We then proposed to address data missingness, and to model the joint progression of markers of different nature, such as clinical scores, and scalar measurements extracted on imaging modalities. With this method, we modeled early motor progression in PD, and, in a second work, the heterogeneity of idiopathic PD progression, with a focus on sleep symptoms. In a second, independent, part of the manuscript, we tackled the longitudinal modeling of medical images. For these higher dimensionality data, Deep Learning is often used, but mostly in cross sectional setups, ignoring the possible inner dynamics. We proposed to leverage Deep Learning as a dimensionality reduction tool to build a spatiotemporal coordinate system of disease progression. We first took advantage of this flexibility to handle multimodal data. Then we leveraged the self-supervision induced by assuming monotonicity over time, to offer higher flexibility in modeling temporal variability
Emond, Patrick. "Développement de médicaments radiopharmaceutiques émetteurs de rayonnements gamma pour l'exploration du transporteur de la dopamine dans le système nerveux central." Tours, 1997. http://www.theses.fr/1997TOUR4016.
Full textHaegelen, Claire. "Construction et validation d’une base de données multimodales pour la stimulation cérébrale profonde." Thesis, Rennes 1, 2014. http://www.theses.fr/2014REN1B003/document.
Full textDeep brain stimulation (DBS) is an effective treatment for patients with severe disabled Parkinson’s disease refractory to medical treatments. DBS surgery consists of the accurate implantation of an electrode in a deep brain nucleus. The quality of the surgical planning can be improved by developing a multimodal database based on anatomical, clinical and electrophysiologial data. The first step was to develop a specific magnetic resonance imaging (MRI) template of Parkinson’s disease patients’ anatomy, and to validate the segmentation of the 24 deep brain structures made on this template. Secondly, we focused on identifying optimum sites for subthalamic nucleus (STN) stimulation by studying symptomatic motor improvement along with neuropsychological side effects in 30 patients with PD. Each clinical score produced one anatomo-clinical atlas, associating the degree of improvement or worsening of the patient with its active contacts.We showed a discrepancy between a good motor improvement and an invevitable deterioration of the fluencies by targeting the postero-superior region of the STN. Finally, we developed new statistical anatomo-clinical maps the better to visualize the motor and neuropsychological consequences at 6 months of GPm stimulation in 20 patients with PD. These maps provided us with the motor improvement of GPm stimulation without cognitive impairments. We also proposed a new more lateral targeting of the GPm in PD because of the cortico-subcortical atrophy induced by the disease. Our goal is to use these statistical maps prospectively in further patients to improve their targeting, thus ensuring a shorter planning step on the day of the surgery as well as better outcomes from motor and neuropsychological point of view
Debilly, Bérengère. "Comparaison de l'atrophie cérébrale évaluée en R. M. N dans la maladie de Parkinson idiopathique et dans les autres syndromes parkinsoniens." Bordeaux 2, 1992. http://www.theses.fr/1992BOR2M143.
Full textStauber, Jonathan. "Imagerie MALDI : nouveaux développements et applications cliniques." Lille 1, 2007. https://pepite-depot.univ-lille.fr/LIBRE/Th_Num/2007/50376-2007-379.pdf.
Full textThe recent innovations in molecular biology were realized with the evolution of the imaging techniques in the field of Genomics, Transcriptomics, and recently in Proteomics with an essential tool, the mass spectrometry. This imaging technique create characteristic protein profiles of the cellular states, and appears today as an undissociable tool for research in biology and medicine. The last developments look to emerge the mass spectrometry to a molecular imaging to identify pathologies, to observe the drugs distributions in tissues, or the diseases diagnosis or prognosis. This unique and recent technology should be developed, improved, and standardized. It's in this point of view the my PhD training named MALDI imaging new developments and clinical applications was defined. The different results obtained during my PhD were permits to create a concept of Specific Imaging Mass Spectrometry, to develop Molecular MALDI imaging of frozen and FFPE tissues with many applications in the research of specific biomarkers in Parkinson disease and ovarian cancer. The evolution of this unique molecular imaging technique should be in the next years a complementary method of others in vivo imaging technique
Maia, Serge. "Imagerie moléculaire de la neuroinflammation dans la maladie de Parkinson : étude préclinique dans un modèle animal de rat." Thesis, Tours, 2012. http://www.theses.fr/2012TOUR3302/document.
Full textAlthough the precise molecular mechanisms causing the dopaminergic neurodegeneration are still not totally understood, a body of epidemiological, clinical and experimental evidence indicates that neuroinflammation may have an important role in the pathogenesis of PD. Study of spatio-temporal links between neuroinflammation and neurodegeneration during the course of PD would improve understanding of the physiopathological mechanism and also accessibility to early diagnosis and/or new antiinflammatory therapeutic approaches. The current development of non-invasive molecular imaging methods allowing direct monitoring of the neuroinflammation process should be valuable for this purpose. The molecular target of choice in this field is the 18 kDa translocator protein (TSPO), a sensitive biomarker associated with neuroinflammation, which is over-expressed in activated microglia. In the study presented here we achieved the longitudinal evaluation of both physiopayhological mechanisms in parallel with the modifications of dopaminergic function at several time-points after 6-OHDA lesion in the rat that mimics an early stage of PD. After unilateral intra-striatal 6-OHDA administration, we quantified the temporal evolution of the TSPO, TH immunoreactivity and DAT in the striatum and the SNc from 3 to 56 days post-lesion (dpl). Increased binding of TSPO ligands used, i.e. [3H]PK11195 and [125I]CLINDE, was observed in the lesioned striatum at 3, 7 and 14 dpl, followed by a progressive return to the basal level at 56 dpl. The binding profile in the SNc showed progressive binding beginning at 3 dpl, peaking at 14 dpl, and progressively decreasing until 56 dpl. In this rodent model of PD, the neuroinflammatory and neurodegenerative processes occurred concomitantly. The transitory occurrence of microglial activation could be involved in the advent and the lasting installation of dopaminergic neuron loss. This study supports the link between neuroinflammation and neurodegeneration and emphasizes the interest of CLINDE as potent in vivo tracer of neuroinflammation by providing valuable information for early diagnosis and longitudinal follow-up of disease progression, with potential applications to human patients. Indeed, early detection of neuroinflammation, prior to a clinically significant loss of neurons, could become a major issue in the management of pre-symptomatic PD. To support this idea, we demonstrate the existence of a therapeutic window, occurring just after the lesion, which may be proposed for the introduction of anti-inflammatory treatments that aimed to slow the neurodegenerative process. Further exploration of the relationship between neuroinflammation and neurodegeneration in vivo in the same animal model with the method of micro-PET imaging, transposable to humans, using in parallel the [18F]-DPA714 for TSPO and [18F]-LBT999 for DAT is pending
Poisson, Alice. "Plasticité anormale et maladie de Parkinson : de l'akinésie à l'hyperkinésie." Thesis, Lyon 1, 2014. http://www.theses.fr/2014LYO10261/document.
Full textMirror movements and akinesia can be both found during Parkinson’s disease. Although very different, they may both reflect an abnormal cerebral plasticity during the disease and the perturbation of the motor inhibitory control. This work reveals that mirror movements are linked to a1/ disruption of the reactive inhibitory control and 2/ to the overactivation of numerous cortical areas. The latter could be the result of a compensatory recruitment aiming at improving the movement. But they could as well reflect a deleterious loss of cerebral activation specificity during Parkinson’s disease. The second experience shows that in healthy subject, the proactive inhibitory control is underpinned by the noradrenergic system. Last but not least the third part of this work reveals an abnormal implementation of the proactive inhibitory control in Parkinson’s disease and suggests its involvement in akinesia. Brought together these results suggest that an abnormal plasticity phenomenon underlies the mirror movements and the akinesia in Parkinson’s disease. More precisely, we observed a default of the reactive inhibitory control associated to mirror movements in Parkinson’s disease and an excess of proactive inhibitory control that seems to be linked to akinesia. The finding of an adrenergic modulation of the proactive inhibitory control opens the fields for the development of noradrenergic therapeutics in akinesia
Bhattacharjee, Manik. "Une nouvelle méthode de recalage en imagerie cérébrale adaptée à la cartographie individuelle des ganglions de la base par déformation d’atlas anatomiques." Paris 11, 2009. http://www.theses.fr/2009PA112269.
Full textDeep Brain Stimulation (DBS) involves the implantation of electrodes in basal ganglia structures. This thesis is part of a project to improve the precision of this surgery, frequently used to treat Parkinson disease. Despite MR-Imaging progress, some structures are not directly visible on images. A basal ganglia atlas combining MRI and 3D histological structures was developped in the laboratory. A linear method to adapt this atlas to patients was validated against per-operative electrophysiology recordings in the subthalamic region. However this method is not precise enough in other locations. A new elastic registration method, CBBM (Confidence-Based Block-Matching) was developped. This is a block-matching method using the notion of confidence, highly constrained to preserve the shape of atlas structures. CBBM was evaluated and compared to four other methods on a standard image set. Results show that the method is well-suited to our registration problem. CBBM was then applied to atlas registration on patients and shown to improve results compared to the previous linear method. Lastly, the influence on surgery precision of the pneumocephalus, a per-operative deformation of the brain, was assessed using CBBM
Bellot, Emmanuelle. "Le colliculus supérieur dans la maladie de Parkinson : un biomarqueur possible ?" Thesis, Université Grenoble Alpes (ComUE), 2017. http://www.theses.fr/2017GREAS043/document.
Full textSome visuo-motor impairments observed in the early stages of Parkinson’s disease (PD) might be related to a dysfunction of a subcortical structure connected to the basal ganglia, the superior colliculus (SC). The aim of this PhD thesis was to explore the functional state of the SC in newly diagnosed (de novo) PD patients before and after dopaminergic treatment intake, in order to evaluate the potential value of the SC functioning as a biomarker. To do this, we developed a functional Magnetic Resonance Imaging (fMRI) experimental protocol, which successfully imaged the SC and also the lateral geniculate nucleus (LGN) and primary visual area V1 functional activity and modulate their activity by using visual stimuli with low luminance contrast levels (<10%). Additionally, we estimated the perceptual response to contrast by using a psychophysical task. We tested in a first time this experimental protocol on healthy subjects with varying age in order to evaluate the effect of normal aging on the functioning of these regions of interest (ROIs) and to distinguish the effects related to age from those potentially related to the pathology (Study 1). A significant progressive decrease of the BOLD amplitude with age was observed in the LGN and V1. These data were consistent with the response functions obtained with the psychophysical task. These results indicate a significant luminance contrast sensitivity decline with age of both the magnocellular and parvocellular pathways. In a second time, we tested our protocol on de novo PD patients before and after the introduction of the first dopaminergic treatment in order to assess the effects of PD and treatment on the ROIs functioning (Study 2). Our results highlighted an early alteration of the contrast processing for the SC and LGN in PD patients, with no normalization after dopaminergic treatment introduction. These findings indicate a functional deficit of the SC and LGN that appears early in the disease course, in line with our effective connectivity analyses. These results could favor the identification of deficits linked to sensory dysfunction of these structures as well as the development of paraclinical and clinical tests involving this system for an early diagnosis of the disease
Corkidi, Blanco Gabriel. "Système d'analyse de préparations histologiques par imagerie numérique : Histo 200 : application à l'étude physiopathologique de la maladie de Parkinson." Paris 12, 1989. http://www.theses.fr/1989PA120058.
Full textPrange, Stéphane. "Physiopathologie de l'hétérogénéité phénotypique et pronostique de la maladie de Parkinson : études de cohortes et imagerie multimodale in vivo." Thesis, Lyon, 2020. http://www.theses.fr/2020LYSE1015.
Full textPas de résumé en anglais
Tir, Fazia Mélissa. "Apport de l'imagerie du tenseur de diffusion dans l'atrophie multisystématisée." Thesis, Lille 2, 2011. http://www.theses.fr/2011LIL2S025/document.
Full textA definite diagnosis of Parkinson’s disease (PD) and multiple system atrophy (MSA) can only be confirmed neuropathologically. The clinical differentiation of the parkinsonian variant of multiple system atrophy (MSA-P) from PD is challenging, especially during the early stages of the disease. Early differentiation of these diseases is particularly important because the disorders differ in terms of progression, prognosis, and treatment responses. The aim of the first part of the study was to evaluate in vivo changes in the brain’s macro- and microstructure in MSA-P and in PD and to characterize the cerebral anatomical differences between the two conditions. We used a combination of voxel-based morphometry (VBM) and whole-brain, voxel-based diffusion tensor imaging analysis (VB-DTI). In MSA-P patients, VBM analysis revealed a lower density of grey matter (GM) in a motor related circuit (especially in the left primary motor cortex, PMC), relative to PD patients, and in the left supplementary motor area (SMA), relative to controls). Diffusion tensor imaging analysis revealed lower fractional anisotropy (FA) values in the left PMC and the right cerebellum in MSA-P patients, compared with controls. Using a volumetric diffusion technique, our study revealed selective tissue degeneration in motor circuits, regardless of the volume loss detected in VBM and in agreement with pathology reports and clinical motor characteristics. Our findings suggest that MSA-P is characterized by both macro- and microstructural changes in the sensorimotor circuit. The aim of the second part of the study was to evaluate brain connectivity especially cortico putaminal connectivity using probabilistic tractography. We assessed volumetric and microstructural changes that occur within each of these subregions and try to establish the potential value of these changes in differential diagnosis.DTI and T1-weighted images were obtained using 1.5 T MRI. Putamen was manually segmented. The cortex was segmented using Freesurfer software and cortical regions were classified in three functional systems: motor, associative and limbic. Then, we calculated the connection probability between putamen and ipsilateral cortical target. Volumes and DTI parameters (fractional anisotropy FA, mean diffusivity MD) of the resulting DTI-based parcellations of the putamen were compared between groups. Comparisons between groups were carried out using bivariate non parametrics tests. Putamen microstructural changes were present in the two variants of MSA according to anatomopathological knowledge. Loss of motor connectivity in MSA-P patients can be explained partially by important volume loss of putamen. Statistical multivariate model combining few clinical criteria and data obtained by MRI-based parcellation allows discriminating MSA-P from MSA-C from PD patients and controls in more than 75% of cases.The third part’s aim was to study the cognitive profile of MSA patients compared to PD patients and to evaluate the cognitive clinical correlations with VBM and VB-DTI brain MRI data. The contribution of standard neuropsychological examination to the differential diagnosis of both syndromes remains still limited. Our study revealed the main involvement of motor cortex in cognitive functions. From our knowledge, there is no study of cognitive correlations and DTI parameters in PD or in MSA
Coatnoan, Nicolas. "La Trypanosoma cruzi proline racemase, un marqueur diagnostique et de suivi pour la Maladie de Chagas ?" Electronic Thesis or Diss., Sorbonne université, 2018. http://www.theses.fr/2018SORUS315.
Full textChagas disease caused by Trypanosoma cruzi occurs in Latin and Central America. The parasite is difficult to detect outside the acute phase of infection. No diagnostic means is 100% reliable and does not allow detection of the parasite in the tissues and no vaccine is available. The laboratory characterized the first eukaryotic proline racemase which is also a mitogen for B cells: Trypanosoma cruzi proline racemase (TcPRAC). It is a virulence factor for the parasite, essential for its survival. TcPRAC genes are present in all genotypes of the parasite and are absent in other infectious trypanosomatids. TcPRAC could be a specific marker for the disease. We have demonstrated, using the experimental model, that TcPRAC is indeed a specific diagnostic marker of the infection but especially a marker that would make it possible to assert the effectiveness of a treatment. We were able to follow the infectious process in real time by in vivo imaging. We have produced anti-TcPRAC VHHs capable of binding to intracellular TcPRAC expressed by live parasites in vitro. We have initiated the development of a prototype for the detection of intracellular parasites in vivo. We have been able to optimize new trypanocidal compounds in order to develop new chemotherapies against the disease
Sharman, Michael. "Neuroimaging biomarkeurs of structural and functional connectivity in Parkinson's disease." Paris 6, 2011. http://www.theses.fr/2011PA066644.
Full textLa maladie de Parkinson (MDP) est une maladie neurodégénérative qui atteint le plus souvent les personnes âgées et qui se manifeste par des troubles moteurs qui s’aggravent au cours du temps. L'objectif de cette thèse était d'identifier et d'évaluer des biomarqueurs de la MDP grâce à l'imagerie par résonance magnétique (IRM). Ce travail est constitué de trois différentes études. La première étude visait à mieux comprendre l'influence de la qualité des données acquises sur les mesures de biomarqueurs candidats en IRM pondérée en diffusion (IRM-DW) en utilisant un jeu de données simulées dans un premier temps, puis un jeu de données réelles dans un deuxième temps. Dans la deuxième étude, les patrons de connectivité structurelle et fonctionnelle ont été évalués en IRM-DW et en IRM fonctionnelle au repos (IRMf-rs) pour déterminer leur efficacité en tant que biomarqueurs candidats. Un paradigme multimodal unique a permis d'isoler des déficits anatomiques et fonctionnels qui concernaient des connexions isolées du circuit sensorimoteur particulièrement touchées dans la MDP. Dans la troisième étude, la validation des biomarqueurs candidats identifiés précédemment a été effectuée dans un groupe de volontaires sains. Les changements de connectivité anatomiques liés à l'âge affectaient différemment les trois circuits corticales-souscorticales. Dans l'ensemble, cette thèse a permis d'une part d'identifier et d'évaluer plusieurs nouveaux biomarqueurs dans la MDP, d'autre part d'approfondir notre compréhension du rapport entre les anomalies structurelles et fonctionnelles du cerveau en ce qui concerne la MDP, tout en développant de nouveaux outils analytiques de neuroimagerie
Macia, Frédéric. "Paralysie supranucléaire progressive : histoire naturelle, marqueurs cliniques et neuroradiologiques." Bordeaux 2, 2000. http://www.theses.fr/2000BOR23006.
Full textQuinlivan, Mitchell. "Rôles du système cholinergique dans le disfonctionnement cognitif associé à la maladie Alzheimer et évaluation d'outils pour l'imagerie moléculaire." Tours, 2007. http://www.theses.fr/2007TOUR3324.
Full textCholinergic neuron degeneration is a prominent hallmark of Alzheimer’s disease (AD). Using a specific immunotoxin (SAP), basal forebrain cholinergic neurons in the rat were lesioned, as assessed by immunohistochemistry (IHC), to model this facet of AD. Behavioural testing, utilising models with two different routes of SAP administration, further demonstrated the necessity of this system for normal attentional function and its relatively minor role in mnemonic function, cognitive domains greatly affected by AD. Studies with radioligands specific for the nicotinic receptor (nAChR) or the Vesicular Acetylcholine Transporter were both able to demonstrate the lesion validated by IHC, the first time a nAChR radioligand has done this in a SAP model. Although eventually it was unable to be used for the in vivo continuation of this work, studies for the development of a small-animal molecular imaging system initially intended for such a continuation are also reported
Maillet, Audrey. "Etude des réseaux neuronaux impliqués dans les troubles de la marche et le freezing dans la maladie de Parkinson." Thesis, Grenoble, 2012. http://www.theses.fr/2012GRENV083.
Full textGait disorders, including freezing of gait are frequent and disabling symptoms that lead to severe decrease of the quality of life on patients from Parkinson's disease (PD). This is emphasized by the fact that those difficulties respond poorly to current medical and surgical treatments. The underlying pathophysiology remains largely unknown. However, the resistance to actual treatments suggests the extension of the degenerative process towards non-dopaminergic structures. Involvement of the pedonculopontine nucleus (PPN) has been proposed. The aim of the study was to better understand the neural networks involved in those troubles, as well as their modulation by dopaminergic drugs and PPN stimulation. The constraints related to stillness of the head during Positron Emission Tomography (PET) exclude, necessarily, the realization of an effective gait. This task has been accomplished using mental moor imagery. The same mural networks are, indeed, activated during the actual execution and the mental representation of movement, under the assumption that motor mental imaging is undertaken from a kinesthetic perspective. Thus, it was necessary, preliminarily to this study, to control the ability of patients to imagine themselves walking from a kinesthetic point of view. Our data validate this condition. Moreover, they show that it is possible to improve this ability through a specific training. What is more, the use of a behavioral protocol, based on Fitt's law, helped the patients to familiarize themselves with this approach, before PET acquisitions, but also to control their correct performance during PET scan. The results, which have been obtained in cerebral imaging confirm the complexity of the underlying mechanisms of gait disorders, and suggest notably different levels of deregulation, on a cortical, sub-cortical and brainstem. In particular, frontal deregulation appears to be confirmed. Moreover, a deregulation of the brainstem could be more particularly involved in gait disorders apparition. We have also evidenced parietal implication, but its exact compensatory or pathologic role remains to be determined. Levodopa-responsive freezing seems to be a consequence of worsened parkinsonian bradykinesia. PPN stimulation seems able to restore a functional cortico-cerebello-cortical loop, facilitating movement. Complementarily studies, on a larger selection of patients, are thus necessary to complete those results. A better understanding of pathophysiology is, as a matter of fact, necessary for the development of new therapeutics in order to improve the therapy of patients from those very invalidating troubles, and thus, to reduce their impact on public health
Nezzar, Hachemi. "Etude in vivo du connectome des saccades oculomotrices chez l'Homme par imagerie structurelle." Thesis, Clermont-Ferrand 1, 2016. http://www.theses.fr/2016CLF1MM15/document.
Full textVisual system is complex by its anatomy and its function. Neuro-anatomists have been interested in understanding the link between the visual pathways and the brain for centuries. Classical brain fixation and dissection methods were used to describe the visual pathways identifiable macroscopically. Non–image visual pathway, particularly the part involves in saccadic eye movements network in human is still not mastered. Our current knowledge in SCM is based on animal studies, anatomic dissection and brain histopathology examination of specimens from patients with clinical basal ganglia (BG) disorders. Saccadic eye movements (SCM) are under the control of the basal ganglia (BG) and SCM circuitry within the BG represents a good model for studying pathology in the extra-pyramidal system. The diagnosis of Parkinson’s disease (PD), which affects SEM and its distinction from non-dopaminergic, essential tremor (ET) where SEM are not impaired can be challenging and still relies on clinical observations. Diffusion tensor imaging and fiber tractography (DTI-FT), a new MRI technology, can be used to evaluate the presence and integrity of white matter tracts using directional diffusion patterns of water. The purpose of this study is to use DTI-FT to analyse SEM networks within BG and compare the SEM neural pathways or connectome of patients clinically diagnosed with PD and ET. To date, there are no studies, using DTI-FT for the extensive exploration of non-image visual pathways and SCM circuits, notably the deep brain connections. For this goal, we introduced the concept of SCM connectomes, derived from the general concept of connectome. Our study used structural MRI to identify nuclei and fascicles of the SCM connectome in PD and ET patients; imageries were acquired in routine clinical conditions fitted for DBS surgery. We found a reduction of the fiber number in two fascicles of the connectome in PDcompared to ET group
Hudry, Julie Laure. "Etude des processus cérébraux impliqués dans le traitement de l'information olfactive chez l'homme : données anatomo-fonctionnelles, électrophysiologiques et comportementales." Lyon 1, 2002. http://www.theses.fr/2002LYO10009.
Full textNeumane, Sara. "Mécanismes de compensation dans la maladie de Parkinson : approches comportementale, pharmacologique, de neuro-imagerie et immunohistochimique chez le singe intoxiqué au MPTP après récupération des symptômes moteurs." Thesis, Lyon 1, 2011. http://www.theses.fr/2011LYO10045.
Full textPayoux, Pierre. "Imagerie fonctionnelle et syndromes extrapyramidaux." Toulouse 3, 2006. http://www.theses.fr/2006TOU30092.
Full textActivation studies using PET or fMRI allow to describe a functional cartography of the brain. The modulation of cortical activity might be due to the presence of selective activator systems, the dysfunction of which could explain the activation abnormalities often highlighted in motor disorders. The objective of this work is to describe the variety of the mechanisms of activation encountered in extrapyramidal patients. From a strictly motor point of view, we thus studied the cortical activation in subjects with idiopathic Parkinson's disease (PD) treated by deep brain stimulation. We also studied cerebral motor activation in patients presenting with Multi Systemic Atrophy. These results were confronted with those of patients with PD and normal subjects. We also investigated non degenerative extrapyramidal diseases such as the parkinson's syndrome induced by neuroleptics in schizophrenia. Finally, the study of activation may not only address movements disorders. Thus we studied activation related to pain which is another component of Parkinson's disease. This work points out the predominant involvement of basal ganglia in the modulation of motricity while integrating emotional and motivational dimensions. The treatments, when they are effective, can involve extra-striatal networks and in particular cortico-cerebellar rather than frontal mesial
Gardier, Camille. "Etude de la coopération de l'alpha-synucléine et de LRRK2 dans les dysfonctions mitochondriales dans la Maladie de Parkinson." Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS405.
Full textThe proteins alpha-synuclein (αsyn) and Leucine-Rich Repeat Kinase 2 (LRRK2) both play major roles in the physiopathology of sporadic and genetic forms of Parkinson’s Disease (PD). In particular, the G2019S mutation of LRRK2, located in its kinase domain, is the most prevalent cause of genetic forms of PD. It has been suggested that αsyn and LRRK2 could act together to induce the selective loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) in the pathogenesis of this disease. In our laboratory, it has been shown that G2019S LRRK2 could increase the dopaminergic cell loss induced by αsyn in the SNpc of rats, confirming the existence of a functional interaction between the two proteins. Moreover, it has been known for years that mitochondrial dysfunction played a major role in PD. Many studies showed that both LRRK2 and αsyn induced mitochondrial dysfunction. Therefore, we hypothesized that the functional interaction between αsyn and LRRK2 could take place through a common effect on mitochondria. We showed in vitro, in primary rat neurons, that G2019S LRRK2, but not the wild type (WT) form nor the dead kinase mutant (DK), significantly increased the number of neurons expressing a pathological form of αsyn (phospho-S129). This was not associated with any cell loss. At the cellular and molecular levels, there was a significant decrease in the mitochondrial ATP production rate in cells co-expressing LRRK2 (WT, G2019S and even more pronounced with DK) with αsyn, without any change in total ATP levels. The mean distance travelled by mitochondria along neurites was higher in neurons co-expressing αsyn and LRRK2 than in neurons only expressing αsyn. To summarize, in this in vitro model LRRK2 increases the somatic accumulation of a pathologic form of αsyn, in a kinase-dependent manner. In these conditions, mitochondria are able to maintain their homeostasis, in particular by adapting their ATP production rate. This seems to indicate a moderate mitochondrial stress induced by the co-expression of αsyn and LRRK2
Jeancolas, Laetitia. "Détection précoce de la maladie de Parkinson par l'analyse de la voix et corrélations avec la neuroimagerie." Electronic Thesis or Diss., Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLL019.
Full textVocal impairments, known as hypokinetic dysarthria, are one of the first symptoms to appear in Parkinson's Disease (PD). A large number of articles exist on PD detection through voice analysis, but few have focused on the early stages of the disease. Furthermore, to our knowledge, no study had been published on remote PD detection via speech transmitted through the telephone channel. The aim of this PhD work was to study vocal changes in PD at early and preclinical stages, and develop automatic detection and monitoring models. The long-term purpose is to build a cheap early diagnosis and monitoring tool, that doctors could use at their office, and even more interestingly, that could be used remotely with any telephone. The first step was to build a large voice database with more than 200 French speakers, including early PD patients, healthy controls and idiopathic Rapid eye movement sleep Behavior Disorder (iRBD) subjects, who can be considered at PD preclinical stage. All these subjects performed different vocal tasks and were recorded with a professional microphone and with the internal microphone of a computer. Moreover, they called once a month an interactive voice server, with their own phone. We studied the effect of microphone quality, speech tasks, gender, and classification analysis methodologies. We analyzed the vocal recordings with three different analysis methods, covering different time scale analyses. We started with cepstral coefficients and Gaussian Mixture Models (GMM). Then we adapted x-vectors methodology (which never had been used in PD detection) and finally we extracted global features classified with Support Vector Machine (SVM). We detected vocal impairments at PD early and preclinical stages in articulation, prosody, speech flow and rhythmic abilities. With the professional microphone recordings, we obtained an accuracy (Acc) of 89% for male early PD detection, just using 6min of reading, free speech, fast and slow syllable repetitions. As for women, we reached Acc = 70% with 1min of free speech. With the telephone recordings, we achieved Acc = 75% for men, with 5min of rapid syllable repetitions, and 67% for women, with 5min of free speech. These results are an important first step towards early PD telediagnosis. We also studied correlations with neuroimaging, and we were able to linearly predict DatScan and Magnetic Resonance Imaging (MRI) neuromelanin sensitive data, from a set of vocal features, in a significant way. This latter result is promising regarding the possible future use of voice for early PD monitoring
Yapo, Cédric. "Adaptations de la cascade de signalisation AMPc/PKA dans le striatum au cours de la maladie de Parkinson et de son traitement par la L-DOPA : étude par imagerie de biosenseurs sur un modèle animal Detection of phasis dopamine by D1 and D2 striatal medium spiny neurons Switch-like PKA responses in the nucleus of striatal neuron." Thesis, Sorbonne université, 2018. http://www.theses.fr/2018SORUS603.
Full textNeuromodulatory signals trigger adaptations in neuronal functions via complex integrative properties. Among the various existing intracellular signaling pathways, the cAMP/PKA cascade plays a critical role in the cellular response to dopamine. To analyze these integrative processes, we combine biosensor imaging in mouse brain slices with in silico modelisation of the intracellular signaling in D1 and D2 medium-sized spiny neurons. In a first part of my thesis work, we analyze the dynamics of cAMP/PKA signaling in striatal neurons stimulated by transient dopaminergic signals, such as those associated with reward. With imaging we show that the dopamine D2 receptors can sense phasic dopamine signals at the level of cAMP, a thought that has been argued for long. Moreover in silico simulations suggest that D2 spiny neurons could sense the interruptions in tonic dopamine levels associated with aversion in the animal. This work was published in (Yapo et al., J Physiol 2017). In a second part, we analyzed the effect of such brief dopaminergic signals on the nuclear PKA-dependent signaling. In comparison to cortical neurons, we show that the striatal neurons display a positive feedforward mechanism which strengthens the nuclear responses. This peculiar situation, which contrasts with the usual homeostatic feedback mechanisms found in biology, leads to all-or-nothing and extremely sensitive responses. We believe that this mechanism allows for the detection of transient dopaminergic signals. This work was published in (Yapo et al., J Cell Science 2018). Lastly a third part, that will be introduced as preliminary data, consisted in analyzing the adaptations of the striatal neurons following a dopamine depletion, such as the one found in Parkinson’s disease. We observed in our mouse model an hypersensitivity of the D1 spiny neurons to dopamine, already described by other groups. Additionally we show that striatal neurons display an increased phosphodiesterase activity. A better understanding of these pathological adaptations could lead to the emergence of new therapeutic strategies
Gargouri, Fatma. "Etude de la connectivité fonctionnelle dans les pathologies de mouvement de Parkinson et de Huntington en utilisant l’approche par graine et la théorie des graphes." Thesis, Paris 6, 2017. http://www.theses.fr/2017PA066487/document.
Full textFunctional magnetic resonance imaging (fMRI) is a technique that allows exploring neuronal activity using an endogenous contrast based on the oxygenation level of hemoglobin. This contrast is called BOLD (Blood oxygenated Level Dependent). It has been shown that fluctuations in the BOLD signal at rest, correlated in distant brain regions, defining long-distance brain functional networks. This is called functional connectivity. The latter represents the spontaneous activity of the brain and it is measured by fMRI at rest. Our research project has therefore combined a methodological aspect and two applications in the field of movement pathologies. In the first part of our project we studied data preprocessing strategies. The objective was to study the influence of the preprocessing steps and their order of application on the brain networks’ topology. We compared 12 different pretreatment strategies. In these strategies we applied the standard and most used techniques but with a different order of application. The following two studies used resting-state fMRI to study: Huntington's disease and Parkinson's disease. In these pathologies, we focused on the study of the brain networks addressed through the study of functional connectivity. We determined whether resting-state fMRI and graph theory measures were able to identify robust biomarkers of Huntington's disease progression in a longitudinal study. In the second study, we investigated the role of cholinergic basal nuclei of the forebrain and their connections in the onset of cognitive problems presented in Parkinson's disease. The seed-based analysis is a suitable method for this type of question
Artero, Sylvaine. "Détection des troubles cognitifs légers (MCI) : algorithmes diagnostiques, dépistage et validité prédictive." Montpellier 1, 2004. http://www.theses.fr/2004MON1T004.
Full textPrevot, Geoffrey. "Plateforme de nanoémulsions destinées au diagnostic et à la thérapeutique." Thesis, Bordeaux, 2018. http://www.theses.fr/2018BORD0195.
Full textOil in water (O/W) nanoemulsions have been used for over 50 years in human clinics as a lipids source in parenteral nutrition. Even if nanoemulsions have recently emerged as vehicles for lipophilic active pharmaceutical ingredient (API) their use as a therapeutic or diagnostic agent is still under-exploited. The objective of this Ph.D thesis was to develop an nanoemulsions platform as an alternative to conventionally used nanosystems. In this work, 2 applications have been studied: the diagnosis of vulnerable plaque in atherosclerosis, and the treatment of Parkinson's disease. Nanoemulsions have been functionalized with humanized antibody targeting atheroma and loaded with magnetic particles as molecular contrast agents for magnetic resonance imaging (MRI) and an emerging technique: magnetic particle imaging (MPI). The successful plaque targeting has been demonstrated in atheromatous mice. The inclusion of original and ultra-bright lipophilic chromophores as well as the loading of API have paved the way to the development of multimodal and theranostic formulations. Therapeutic nanoemulsions against Parkinson’s disease have been developed to restore lysosomal pH of dopaminergic neurons with acidic polymer (PLGA). Acidification dysfunction leads to cell death due to the accumulation of waste inside neurons. The formulation has been optimized for brain delivery through intravenous or intranasal administration. The results show brain delivery in vivo trough intravenous injection associated with a pH rescue in vitro. The perspectives will focus on optimizing this platform and use it for new applications such as magnetic hyperthermia in cancers
Devignes, Quentin. "The dual cognitive syndrome hypothesis in Parkinson’s disease : MRI studies of structural and functional correlates." Thesis, Université de Lille (2018-2021), 2021. https://pepite-depot.univ-lille.fr/ToutIDP/EDBSL/2021/2021LILUS064.pdf.
Full textParkinson’s disease (PD) is a neurodegenerative disease characterized by motor disorders. However, non-motor symptoms, including cognitive impairment, are also part of the clinical presentation. According to the severity of cognitive impairment, three presentations are usually distinguished in PD: (a) the absence of significant cognitive impairment despite possible symptoms, (b) mild cognitive impairment (MCI) and (c) PD dementia. MCI refers to significant cognitive deficits without global cognitive decline nor impact on activities of daily living. This condition is common in Parkinson’s disease (PD-MCI), can affect one or several cognitive functions and is heterogenous. According to the dual syndrome hypothesis, PD-MCI can be subdivided into two cognitive subtypes: a frontostriatal one, characterized by attentional and/or executive deficits, and a posterior cortical one, characterized by visuospatial, memory and/or language deficits. The latter has been associated with a higher risk of developing dementia earlier. To date, only few studies have considered the cognitive heterogeneity in PD-MCI and no study defined PD-MCI subtypes based on the dual syndrome hypothesis. Besides, in-vivo biomarkers of these cognitive subtypes are lacking.The main objectives of this thesis were (a) to propose a state-of-the-art on neuroimaging outcomes associated with distinct PD-MCI cognitive subtypes, and (b) to identify structural and functional MRI brain changes associated with the frontostriatal and posterior cortical subtypes.Therefore, we performed a systematic review which showed a gap in the scientific literature given that only ten neuroimaging studies considering PD-MCI subtypes were identified. Thereafter, we conducted two studies to identify structural and resting-state functional MRI modifications in PD-MCI subtypes. We used data from non-demented PD patients (n=114) whose cognitive subtype was determined by their cognitive performance at a comprehensive neuropsychological test battery: (a) patients with normal cognition (PD-NC) (n=41), (b) patients with a frontostriatal subtype (PD-FS) (n=16), (c) patients with a posterior cortical subtype (PD-PC) (n=25) and (d) patients with a mixed subtype (PD-MS) (i.e. combination of frontostriatal and posterior cortical deficits) (n=32). For functional analyses, data from 24 age-matched healthy controls were also used.Our results showed (a) more abundant and more extensive structural alterations in patients with posterior cortical deficits (PD-PC and PD-MS), (b) increased functional connectivity within the basal ganglia in PD-PC patients and (c) decreased functional connectivity in various resting-state networks in patients with frontostriatal deficits (PD-FS and PD-MS). Further longitudinal studies are needed to assess the progression of these structural and functional modifications and to determine the predictive potential of these markers regarding the risk of developing dementia
Horn, Jean-François. "Diagnostic des maladies neurodégénératives à partor d'images obtenues par tomographie d'émission monophotonique et à l'aide de méthodes de classement avec apprentissage supervisé." Paris 6, 2009. http://www.theses.fr/2009PA066454.
Full textVetel, Steven. "Neuroinflammation et neuroprotection dans un modèle de maladie de Parkinson précoce (lésion à la 6-hydroxydopamine chez le rat)." Thesis, Tours, 2018. http://www.theses.fr/2018TOUR3309/document.
Full textCurrently, therapeutic strategies in Parkinson’s disease are symptomatic and the progression of the disease is uncontrolled, requiring the development of new neuroprotective approaches. Neuroinflammation plays a major role in the neurodegenerative process where it occurs early through the activation of glial cells (microglia and astrocytes). Based on the use of animal models mimicking the early stages of the disease, the development of anti-inflammatory strategies is therefore a promising therapeutic approach. This thesis work consisted in the development and the characterisation of a partial 6-hydroxydopamine lesion model in rats in order to evaluate the effects of an original therapeutic strategy based on the combined use of a α7 nicotinic receptors agonist and a σ1 receptors agonist. Using different experimental approaches, we first evaluated the neurodegenerative and neuroinflammation processes in the model that we developped. Our results showed a partial and reproductible degeneration of nigro-striatal dopaminergic neurons associated with a marked neuroinflammation. Our metabolic analyses have also revealed several specific alterations, providing new insight on the mechanisms involved in the neurodegenerative process. Using positron emission tomography imaging, we then evaluated longitudinally the expression profile of α7 nicotinic receptors in the key structures of the nigro-striatal pathway. Our results showed transient changes in the density of these receptors that may be linked to biphasic microglial responses in association with the kinetics of neuronal degeneration. Thus, these results reinforce the hypothesis of specifically targeting α7 nicotinic receptors in order to reduce the neuroinflammatory processes. Finally, we evaluated the effects of our therapeutic strategy in the model and our results showed that this type of combination partially preserves the integrity of nigro-striatal dopaminergic neurons and reduces glial reactions in lesioned animals. Although it is necessary to confirm and extend these results, this type of combination could represent a promising new pharmacological approach in the treatment of Parkinson’s disease
Pyatigorskaya, Nadya. "Etude de lésions du tronc cérébral à l'aide de l'imagerie par résonance magnétique dans les syndromes parkinsoniens." Thesis, Paris 6, 2016. http://www.theses.fr/2016PA066477.
Full textIn recent years numerous biomarkers of nigro-striatal damage were proposed in Parkinson's disease (PD). These markers are able to detect and quantify neurodegenative changes in the substantia nigra (SN) of patients with PD as well as in subjects with premotor conditions. Their diagnostic performances to detect PD as well as the extent of extranigral pathology remain incompletely understood.In this work we observed the damage of the substantia nigra in preclinical and premotor forms of PD. Iron load was increased in both symptomatic and asymptomatic mutations carriers, suggesting the interest of the biomarker in PD related genetic mutations. In addition, we found a pre-clinical impairment of the SN in subjects affected by idiopathic sleep in REM behavioral disorders (iRBD) who have not yet converted to Parkinsonism. In these subjects, the SN damage was best demonstrated by neuromelanin-sensitive imaging and diffusion tensor imaging (DTI) with fractional anisotropy measure, suggesting an interest of these measures in the prodromal characterization of PD. These same markers had the best performance for PD diagnosis.Finally, we found medulla oblongata damage patients with PD using DTI. This damage was correlated with cardiac and respiratory autonomic symptoms, suggesting the importance of this biomarker in medulla oblongata damage exploration. It also opens a possibility of medulla oblongata study in presymptomatic subjects as medulla oblongata damage should appear before motor symptoms based on the Braak model.These biomarkers may be the first step towards a presymptomatic diagnosis of PD in clinical practice
Arribarat, Germain. "Approche par IRM multiparamétrique pour le tronc cérébral." Thesis, Toulouse 3, 2018. http://www.theses.fr/2018TOU30334.
Full textConnecting the brain to the spinal cord, the brain stem Brainstem (BST) is an area of convergence of motor and sensory pathways. It has different nuclei, responsible for various functions such as motor skills, regulation of respiratory and cardiac rhythms, the origin of cranial nerves. Despite its importance in various neurodegenerative diseases, in vivo exploration of BST is still a challenge today. The resolution used, the low contrast and its location make it difficult to study in conventional magnetic resonance imaging (MRI). Based on various advanced MRI sequences, we carried out a study of the substantia nigra (SN) in a population of Parkinson's patients, an area located in the upper part of the BST. The results show that iron imaging combined with free water imaging suggests different underlying pathophysiological processes. Nevertheless, given the size of the structures studied, the need for precision remains necessary for more reliable identification. The originality of the proposal is to develop a method dedicated to BST, in order to best overcome the difficulties of its observation. By optimizing MRI acquisitions and several image processing, the results obtained show the possibility of easily identifying certain structures and stabilizing quantitative values. To conclude, still with the objective of improving MRI measurements, we were interested in MRI on human anatomical parts. Post-mortem MRI is used in this thesis for the detection and quantification of metals (iron) and correlation with histological techniques
Jacquelet, Yann. "Contribution à la définition de mécanismes coopératifs par système multiagent pour la segmentation et l'étiquetage d'objets multiples de la scène : application aux syndromes parkinsoniens." Rennes 1, 2005. http://www.theses.fr/2005REN1S171.
Full textCarrière, Nicolas. "Troubles du contrôle des impulsions au cours de la maladie de Parkinson, étude électro-encéphalographique de l’intégration de la récompense et modifications de la connectivité fonctionnelle cérébrale de repos en imagerie par résonance magnétique." Thesis, Lille 2, 2015. http://www.theses.fr/2015LIL2S060/document.
Full textBackgroundIn Parkinson’s disease, dopamine agonists are associated with an increased risk of impulse control disorders (ICD). Their occurrence is supposed to be related with a deregulation of the dopaminergic meso-limbic pathway, involved in the processing of the consequences of previous action to adapt future behaviors. Dopamine agonists, through a tonic stimulation of the dopamine receptors would lead to an overestimation of the positive consequences of actions, and therefore, continuation of a harmful behavior.Method:We investigated (i) the resting-state striato-cortical functional connectivity using functional MRI, and (ii) electro-encephalographic (EEG) markers of feedback processing during a gambling task : the feedback related negativity (FRN), the feedback related positivity, (FRP), and the theta band oscillations (4-7 Hz) in 20 Parkinson’s disease patients with an active ICD, 19 Parkinson’s disease patients without ICD, and 19 healthy subjects.Functional MRI: The ventral striatum, dorsal caudate, and anterior and posterior putamen were semi-automatically segmented. For each region of interest, a seed-based connectivity analysis was performed on preprocessed fMRI data mapped on the ipsilateral cortical surface.Neurophysiological approach: The subjects underwent an EEG while performing a gambling task. The EEG was averaged for each condition and each subject. The FRP amplitude was measured in Cz, and the FRN amplitude was measured in Fz on the difference wave between the potential evoked by losses and by gains. The power spectra were computed by using a sinusoidal Morlet wavelet transform and averaged by condition. The maximum power in the theta frequency band was computed for each participant and each condition.Results:Cortico-striatal connectivity analysis: The presence of an ICD in patients with PD was associated with functional disconnection between the left anterior putamen and both the left inferior temporal and anterior cingulate gyrus. ICD patients also displayed a trend toward a functional disconnection between (i) the left anterior putamen and the inferior frontal gyrus, (ii) the posterior putamen and the inferior temporal gyrus, superior frontal gyrus, posterior cingulate, and medial frontal gyrus on the left, as well as the medial frontal gyrus, middle frontal gyrus, and cingulate gyrus on the right, (iii) the dorsal caudate and the gyrus rectus and orbitofrontal cortex, and the middle frontal and inferior temporal gyrus on the left.Evoked potentials: In Parkinson’s disease patients without ICD and healthy controls, the FRP was greater after gains that after losses following a non-risky choice. There was no difference in FRP amplitude after losses and gains in Parkinson’s disease patients with ICD.Time-frequency analysis: At Cz, positive outcomes (gains) were associated with greater theta power than negative outcomes (losses) in Parkinson’s disease patients without ICD and in healthy controls, but not in Parkinson’s disease patients with ICD. There was an increase in theta power after unexpectedly high outcomes, at Fz in healthy controls and in FCz in Parkinson’s disease patients with ICD, whereas theta power was not modulated by the magnitude of the outcome in PD patients without ICDs.Conclusions:Parkinson’s disease patients with ICD have an alteration in EEG markers of reward in line with an altered discrimination of gains and losses and a greater sensitivity to unexpectedly high outcomes, supposed to lead to a significant activation in the dopaminergic meso-limbic pathways. These findings are in line with a dysfunction in reward processing in ICD in Parkinson’s disease. This dysfunction is associated, at rest, with an alteration in striato-cortical connectivity that goes beyond a pure dopaminergic meso-limbic dysfunction
Criaud, Marion. "Évaluation des modèles psychologiques du contrôle inhibiteur au moyen de l’IRM fonctionnelle : Plausibilité physiologique, bases neurales et applications cliniques dans la maladie de parkinson." Thesis, Lyon 1, 2015. http://www.theses.fr/2015LYO10346/document.
Full textThe inhibition is a key function of the cognitive control. But its assessment is made difficult by its very definition. Indeed, if the inhibition is properly implemented, the observable outcomes are suppressed. In consequences, the existing psychological models are fragile, and the imaging results inconsistent. A meta-analysis was first used to prove that the classical studies confound activations related to the reactive and selective inhibition and the activity elicited by parallel functions involved in experimental tasks. This led us to propose a new model of inhibition, defined as proactive mechanisms implemented in anticipation of stimulation. This model was first tested with two behavioral experiments. The results suggest that proactive inhibition is the default mode of the executive control. The proactive model was then assessed together with its two competing models (reactive selective and reactive non-selective) in an fMRI study. The results confirmed that the reactive selective model is less plausible than the two non-selective models. Finally we focused on the clinical consequence of this theoretical upheaval. When the standard model predicts that the impulsivity is the only consequence of inhibition deficit, the proactive model also predicts a deficit in movement initiation. This is what we showed by associating a hyperactivation of the proactive control network and the akinesia in Parkinson’s disease
Girard, Romuald. "Combinaison des approches psychopharmacologiques et d'imagerie cérébrale pour l’étude de la prise de décision individuelle et sociale chez l’Homme." Thesis, Lyon 1, 2013. http://www.theses.fr/2013LYO10205/document.
Full textThe aim core of this thesis is to investigate different aspects of decision-making and flexibility in healthy and clinical populations. Specifically, we investigated the neural correlates of social decision-making in young healthy individuals, the influence of steroid hormones on cognitive flexibility in early menopausal women and cerebral dysfunctions involved in reward devaluation during decision-making process in individuals suffering of Parkinson disease. First, we studied the neural correlates of iniquity aversion when making a decision for oneself or on behalf of his own group and when facing a single individual or another group. Our results highlight influence of two distinct neural network involved in iniquity aversion during complex social exchange, outlining a neuronal explanation to interindividualintergroup discontinuity effect. Our second study, described the influence of hormone replacement therapy (i.e., HRT) on cognitive flexibility in early menopausal women. Many studies described a deleterious effect of steroid supplementation on executive cognitive functions, if it delayed after the onset of the menopause. However, “windows of opportunity” hypothesis suggests a benefic and neuroprotective effect against psychiatric disorders, if hormonal replacement therapy starts close to the beginning of menopause. Combining pharmacological and neuroimaging approaches, we showed a neuroprotective effect in brain structures involved in cognitive flexibility, in young menopausal women. Finally, our last study highlights the effect of dopaminergic treatment in Parkinsonians patients developing impulsive control disorder (i.e., hypersexuality). Preliminary results showed influence of these two factors on distinct subsystems involved in evaluation of different types of costs (i.e., effort/delay) associated with subsequent rewards. This thesis demonstrates the value of combining pharmacology studies and fMRI in order to better understand to which extent hormonal and dopaminergic treatments affect the brain mechanisms during individual and social decision-making
Caire, François. "Imagerie per-opératoire des électrodes de stimulation cérébrale profonde et proposition d’une nouvelle modalité de repérage stéréotaxique indirect de la cible subthalamique." Thesis, Bordeaux 2, 2012. http://www.theses.fr/2012BOR22015/document.
Full textThe clinical efficacy of subthalamic deep brain stimulation is now well established. Nevertheless, progress is possible, regarding especially (1) the accuracy of electrodes implantation and (2) the definition of the surgical target. In the first part of this work, we worked on the optimization of DBS electrodes implantation. First, we analyzed retrospectively the results obtained by using intra-operative 3D imaging for the control of microelectrodes and definite leads placement. Thereafter, we considered the possibility to use a radiological landmark for intraoperative controls. To this end, we studied the cases of patients who underwent reimplantation of DBS electrodes. The initial electrode (still implanted) was used as a landmark: (1) for the deifntion of the reimplantation target and (2) for the radiological control of the new lead positioning. In the second part, we worked on the optimization of the surgical target. First, we assessed the interest of the mamillothalamic tract as a landmark of the anteroposterior coordinate of the anterior border of the STN in MR axial images. Thereafter, we tried to identify MR landmarks for tridimensionnal normalization of the stereotactic space. Finally, we tried to correlate the coordinates of active contacts with MR-defined landmarks in a series of patients that had been operated with good clinical results. Based on our results, we can propose the following coordinates for a new normalized subthalamic target : x = 0.44xlat edge 3rd ventricle + 10.71mm; y = 0.69xmamillo-thalamic tract + 1.62 mm or 0.34 ACPC length + 2.52 mm; z = 0.72xthalamus height – 16 mm. We will assess this target in a future prospective study
Haegelen, Claire. "Construction et validation d'une base de données multimodales pour la stimulation cérébrale profonde." Phd thesis, Université Rennes 1, 2014. http://tel.archives-ouvertes.fr/tel-01073108.
Full textHett, Kilian. "Multi-scale and multimodal imaging biomarkers for the early detection of Alzheimer’s disease." Thesis, Bordeaux, 2019. http://www.theses.fr/2019BORD0011/document.
Full textAlzheimer’s disease (AD) is the most common dementia leading to a neurodegenerative process and causing mental dysfunctions. According to the world health organization, the number of patients having AD will double in 20 years. Neuroimaging studies performed on AD patients revealed that structural brain alterations are advanced when the diagnosis is established. Indeed, the clinical symptoms of AD are preceded by brain changes. This stresses the need to develop new biomarkers to detect the first stages of the disease. The development of such biomarkers can make easier the design of clinical trials and therefore accelerate the development of new therapies. Over the past decades, the improvement of magnetic resonance imaging (MRI) has led to the development of new imaging biomarkers. Such biomarkers demonstrated their relevance for computer-aided diagnosis but have shown limited performances for AD prognosis. Recently, advanced biomarkers were proposed toimprove computer-aided prognosis. Among them, patch-based grading methods demonstrated competitive results to detect subtle modifications at the earliest stages of AD. Such methods have shown their ability to predict AD several years before the conversion to dementia. For these reasons, we have had a particular interest in patch-based grading methods. First, we studied patch-based grading methods for different anatomical scales (i.e., whole brain, hippocampus, and hippocampal subfields). We adapted patch-based grading method to different MRI modalities (i.e., anatomical MRI and diffusion-weighted MRI) and developed an adaptive fusion scheme. Then, we showed that patch comparisons are improved with the use of multi-directional derivative features. Finally, we proposed a new method based on a graph modeling that enables to combine information from inter-subjects’ similarities and intra-subjects’ variability. The conducted experiments demonstrate that our proposed method enable an improvement of AD detection and prediction
Jardin-Mathé, Olivia. "Développement d'un logiciel universel d'imagerie par spectrométrie de masse et application au modèle sangsue et aux maladies neurodégénératives." Thesis, Lille 1, 2008. http://www.theses.fr/2008LIL10033/document.
Full textDirect analysis of tissues by MALDI mass spectrometry is a growing approach, and very important especially conceming biopsy analysis. It offers the interest to avoid extraction, purification and preparation of the sample. Moreover it allows to get additional information by preserving composite localization in the tissue thanks to the analysis realized in situ by a laser beam scan. The automation ofthis scan enables creation ofa matrix (signal intensity versus X y coordinates); thus data conversion by bioinformatics' software is the keystone of this technology. Access to direct data, independently from the manufacturer, accessibility to computing parameters allowing the creation of the picture and transparency have been our priorities during the creation of our new imaging software: MITrCS. ln order to illustrate the efficiency of this pro gram, the survey of the medicinal leech embryos proteome versus medicinal leech adult proteome was undertaken in order to search peptides presents in the embryo that are re-expressed in the adult during nervous regeneration. This work on this invertebrate has next been compared to studies realized on 6hydroxydopamin-treated animaIs in order to simulate Parkinson disease. Research of biomarkers and achievement of a molecular map linked with the Parkinson pathology should allow a correlation between biomarkers from nervous regeneration. But identified peptides still needs to be named, so 1 participated to the annotation of medicinal leech nervous system EST. Thanks to these EST, it williater be possible with MITrCS to correlate the picture to the name of the identified biomolecule in order to better apprehend its function
Puy, Laurent. "Mécanismes et Conséquences de l’Oedème Cérébral sur le Pronostic des Hémorragies IntraCérébrales Spontanées." Thesis, Université de Lille (2018-2021), 2021. http://www.theses.fr/2021LILUS058.
Full textSpontaneous intracerebral haemorrhage (ICH) is associated with a dramatic prognosis and remains devoid of specific treatment. Therefore, understanding the mechanisms of ICH pathology and repair is a matter of high priority. The peri-haemorrhagic zone, commonly called "peri-haematomal oedema" (PHE), might be a promising candidate for therapeutic interventions. However, its underlying mechanisms, natural evolution and prognostic value remain to date unclear. This thesis aimed at studying the mechanisms and consequences of this PHE. To do so, we combined an experimental (animal model of ICH) and a neuropathological (post-mortem study on human tissue) approach.We used the double autologous blood injection model to reproduce ICH in a large cohort of male and female rats. In a first study, we showed how multimodal MRI is a reliable tool to track the dynamic progression of peri-haematomal injuries and we characterized the kinetics of different PHE components (water content, [micro]-vessel injuries, neuro-inflammation and iron deposits). In a second study, we investigated the short and long-term consequences of ICH. We reported that a deep ICH provokes long term cognitive impairments in rats that affects both hippocampal and non hippocampal aspects of cognition contrasting with early spontaneous locomotor recovery. We also showed that focal striatal ICH induces distant brain atrophy and hypometabolism involving limbic system structures and cortical areas. We included 19 cases of patients who died from ICH in a post-mortem study. We provided evidence for Neutrophil extracellular Traps (NETs) infiltration within the haematoma core but also and within the PHE. We also investigated the natural kinetic of natural blood clearance process after ICH in human brain tissue with a focus on the monocyte-macrophage scavenger receptor (CD163)/hemoxygenase-1 (HO-1) pathway. Our findings contribute to refine our perception of PHE, to optimize the translational pipeline and, hopefully, to identify innovative therapeutic strategies for ICH
Mallah, Khalil. "In depth systemic biology analysis of central nervous system injuries." Thesis, Lille 1, 2018. http://www.theses.fr/2018LIL1S108/document.
Full textIn the context of studying biological alterations occurring post impact to the central nervous system, my thesis was focused on studying the proteomic and lipid changes occurring post injury to the brain and spinal cord. A fundamental spatio-temporal study was conducted on an open-head rat TBI model to identify potential injury-specific markers. Using MALDI MSI, we performed 3D reconstruction of the injured brain at 3 days after injury and depicted lesion-specific m/z lipid molecules. After, MALDI MSI was applied on the acute/sub-acute time frame post impact: 1 day, 3 days, 7 days, and 10 days. In parallel, a microproteomic analysis was carried out on tissue segments directly consecutive to the imaged ones in an approach to correlate both lipid and protein changes. Our results yielded the identification of a family of lipids, acylcarnitines, which are expressed within the injured cortex with maximum intensity 3 days post impact. These lipid molecules also were found to be expressed in the substantia nigra and microproteomics data showed an upregulation in expression of Parkinson’s related proteins. Taken altogether, our results depict a role of link between mild-TBI and Parkinson’s disease as early as 3 days post impact, with a possible role of acylcarnitine. This same family of molecules was also present in SCI. In a therapeutic approach previous results showed RhoA protein as a major candidate post impact in SCI. After using RhoA inhibitor treatment, a proteomic study was carried out to investigate its impact on SCI. The results showed that both in-vivo and in-vitro treatment with RhoA inhibitor stimulated neurite outgrowth and helped in axonal regeneration