29 research outputs found
Neural basis of motor control : study of the negative motor network with cortico-sub-cortical brain mapping
La vision classique et hiĂ©rarchique de lâorganisation du systĂšme moteur est remise en question par la dĂ©couverte dâautres structures que le cortex moteur primaire capables dâinfluer en parallĂšle sur la sortie motrice, dans le cadre dâun modĂšle hodotopique. Lâobjectif de ce travail a Ă©tĂ© dâĂ©tudier les rĂ©seaux de contrĂŽle du mouvement Ă lâaide de stimulations Ă©lectriques directes cĂ©rĂ©brales lors de chirurgies en condition Ă©veillĂ©e pratiquĂ©es pour lâexĂ©rĂšse de tumeurs cĂ©rĂ©brales. Cette mĂ©thode permet la prĂ©servation de la fonction motrice tout en apportant de nombreuses informations sur lâorganisation du systĂšme moteur en gĂ©nĂ©ral. Le contrĂŽle moteur a Ă©tĂ© Ă©tudiĂ© au travers du phĂ©nomĂšne moteur nĂ©gatif, qui consiste en un arrĂȘt du mouvement sans perte de tonus ou de conscience lors dâĂ©lectrostimulations. DĂ©crit initialement au niveau cortical, nos travaux ont montrĂ© quâil Ă©tait possible dâidentifier ce phĂ©nomĂšne dans la substance blanche de façon bilatĂ©rale et que les fibres supportant ces rĂ©ponses motrices nĂ©gatives sont organisĂ©es dâune maniĂšre somatotopique, Ă lâinstar de la voie pyramidale. Nous avons pu mettre en Ă©vidence une voie modulatrice motrice bilatĂ©rale capable dâinhiber les mouvements des deux membres supĂ©rieurs lors dâune stimulation sous-corticale unilatĂ©rale. Nous avons montrĂ© quâune lĂ©sion des sites gĂ©nĂ©rant des rĂ©ponses motrices nĂ©gatives conduisait Ă un syndrome de lâaire motrice supplĂ©mentaire et Ă des troubles dĂ©finitifs des mouvements fins et de la coordination bimanuelle. Ces rĂ©sultats expliquent les troubles observĂ©s lors de chirurgies des rĂ©gions prĂ©motrices rĂ©alisĂ©es sans cartographie motrice active, câest-Ă -dire cherchant uniquement Ă identifier les structures motrices primaires. Ils valident la nĂ©cessitĂ© de pratiquer une cartographie motrice en condition Ă©veillĂ©e et ce quelle que soit la dominance hĂ©misphĂ©rique. Ces rĂ©sultats Ă lâĂ©chelle sous-corticale nous ont conduit Ă dĂ©finir le concept de rĂ©seau moteur nĂ©gatif et son implication dans les rĂ©seaux de contrĂŽle moteur. Le preuve de lâexistence de tels rĂ©seaux nous a permis dâexplorer le niveau cortical et de mettre en Ă©vidence une organisation systĂ©matique des aires motrices nĂ©gatives, proposant ainsi une autre vision que celles dâune rĂ©partition alĂ©atoire ou somatotopique. Cette organisation en plusieurs aires effecteurs-dĂ©pendantes et redondantes a permis de confirmer par les stimulations Ă©lectriques directes la sĂ©grĂ©gation du gyrus prĂ©central en plusieurs gradient rostro-caudal et dorso-ventral. Lâensemble de ces Ă©lĂ©ments nous a permis dâĂ©mettre plusieurs hypothĂšses concernant le rĂŽle de ces rĂ©seaux. Nous supposons quâil sâagit de plusieurs rĂ©seaux interconnectĂ©s fonctionnant Ă lâaide de mĂ©canismes inhibiteurs internes, dont le rĂŽle va de la modulation du flux moteur dans le cadre de processus dĂ©cisionnels compĂ©titifs intĂ©grĂ©s aux aires nĂ©gatives Ă lâinhibition vraie dâun comportement moteur dans le cadre de circuits entre le cortex et les noyaux gris centraux. La carte probabiliste rĂ©alisĂ©e permettra de planifier les chirurgies cĂ©rĂ©brales mais aussi de servir de zone dâintĂ©rĂȘt pour les nouvelles thĂ©rapies par stimulations et la recherche en neurosciences.The classical and hierarchical view of the motor system has been challenged since the discovery of other structures able to modulate the motor output in the framework of a hodotopic model. The aim of this work was to study the motor control network thanks to direct electrostimulations performed during awake surgery for brain tumors. This method has shown its effectiveness to preserve motor functions while giving new highlights about the organization of the motor system. In our work, motor control has been studied through the negative motor phenomenon, which consists in a complete arrest of movement without loss of tonus or consciousness during electrostimulations. Initially described at a cortical level, our work demonstrated the possibility to elicit negative motor phenomenon in both hemispheres at a subcortical level. Moreover, we identified a bilateral modulatory motor pathway able to inhibit both upper limbs during unilateral subcortical stimulations. We also shown that fibers driving negative motor responses are organized in a somatotopic manner, like the pyramidal pathway. Resection of these fibers lead to a supplementary motor area syndrome with permanent deficit in fine motor skills and bimanual coordination. These results explain the neurological deficits which might occur after surgery in premotor areas when no active brain mapping is performed, that is, when only primary motor structures are sought. They emphasize the necessity to perform a motor mapping during awake surgery whatever the side and hemispheric dominance. These subcortical results led us to define the concept of negative motor networks and their involvement in motor control networks. Evidences of this network allowed us to explore the cortical level and to report a well-defined organization of the negative motor area, different from the random or somatotopic distributions previously described. This effector-dependent and redundant organization in several areas defined by direct electrostimulations has been helpful to confirm the rostro-caudal and dorso-ventral segregation of the precentral gyrus. Consequently, it was possible to propose several hypothesis about the role of these networks. We presume that they are constituted by several large-scale interconnected networks, based on internal inhibitor mechanisms, whose role goes from modulation of the motor output in a competitive model of decision-making integrated in the negative motor area to real inhibition of motor behaviors thanks to cortico-basal ganglia circuitry. The probabilistic map created with these works will be helpful to plan surgery but could also provide regions of interest for brain stimulations therapies as well as neuroscientific research
New insights into the neural foundations mediating movement/language interactions gained from intrasurgical direct electrostimulations
International audienceInteractions between language and motricity have been a topic of interest in brain development as well as in pathological models. The role of the motor system in language has been investigated through neuroimaging and non-invasive brain stimulation methods. However, little is known about the neural basis that might be involved in such interactions. Meanwhile, brain direct electrostimulations (DES) have provided essential knowledges about the connectomic organization of both motor and language systems. We propose here to review the literature about DES from the outlook of interactions between language and motricity and to investigate common cortico-subcortical structures shared by both networks. Then we will report an experimental study about the spatial distribution of DES eliciting simultaneous speech and contralateral upper limb negative motor response in a series of 100 patients operated on under awake condition for a low-grade glioma. From the probabilistic map obtained, a structural connectivity analysis was performed to reveal the cortico-subcortical networks involved in language and motricity interactions. The embodiment suggested by these results takes place in parallel and distributed bilateral fronto-temporo-parietal networks rather than in a single and somatopically well defined organization as previously suggested
Somatotopic organization of the white matter tracts underpinning motor control in humans: an electrical stimulation study
International audienceThe somatotopic organization of the primary motor cortex is well documented. However, a possible somatotopy of the network involved in motor control, i.e., eliciting negative motor phenomena during electrostimulation, is unknown in humans, particularly at the subcortical level. Here, we performed electrical stimulation mapping in awake patients operated for gliomas, to study the distribution of the white matter tracts subserving movement control of the lower limb, upper limb(s), and speech. Eighteen patients underwent awake surgery for frontal low-grade gliomas, by using intraoperative subcortical electrostimulation mapping to search interference with movement of the leg, arm(s), and face. We assessed the negative motor responses and their distribution throughout the tracts located under premotor areas. The corresponding stimulation sites were reported on a standard brain template for visual analysis and between-subjects comparisons. During stimulation of the white matter underneath the dorsal premotor cortex and supplementary motor area, rostral to the corticospinal tracts, all patients experienced cessation of the movement of lower and upper limbs, of bimanual coordination, and/or speech. These subcortical sites were somatotopically distributed. Indeed, stimulation of the fibers from mesial to lateral directions and from posterior to anterior directions evoked arrest of movement of the lower limb (mesially and posteriorly), upper limb(s), and face/speech (laterally and anteriorly). There were no postoperative permanent deficits. This is the first evidence of a somatotopic organization of the white matter bundles underpinning movement control in humans. A better knowledge of the distribution of this motor control network may be helpful in neurosciences and neurosurgery
Temporal Processing in Patients with Tumor Invading the Supplementary Motor Area Before and After Surgical Resection
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A Nonradiated Grade II Glioma That Underwent Delayed Malignant Transformation to a Gliosarcoma with Meningeal Growth and Dissemination
International audienceBackground: Secondary gliosarcomas are rare tumors, especially those arising from a World Health Organization (WHO) grade II glioma not irradiated. We report a case with subtotal resection for a WHO grade II oligoastrocytoma, without adjuvant treatment, whose metaplastic transformation into gliosarcoma suddenly occurred 4 years later with meningeal dissemination. We show a favorable outcome after therapeutic management of this rare entity.Patient: A 46 year-old woman underwent surgery for a right premotor WHO grade II oligoastrocytoma discovered incidentally. Because of a subtotal resection with only 1âcc of residue, no complementary therapy was given, and the patient enjoyed a normal life for 4 years. In the meantime, the magnetic resonance images performed every 6 months showed a very low growth rate. Suddenly, the tumor switched toward a gliosarcoma profile with meningeal dissemination.Results: Reoperation, radiotherapy, and chemotherapy were performed, enabling a control of the disease with 15 months of follow-up (i.e., with radiologic shrinkage of the multiple lesions and preservation of quality of life).Conclusion: A delayed sarcomatous transformation can acutely occur with a low proliferation index in a nonirradiated WHO grade II oligoastrocytoma. Furthermore, an aggressive therapeutic strategy can allow control of secondary gliosarcomas, even in cases of leptomeningeal spreading
Identification of Gender- and Subtype-Specific Gene Expression Associated with Patient Survival in Low-Grade and Anaplastic Glioma in Connection with Steroid Signaling
Low-grade gliomas are rare primary brain tumors, which fatally evolve to anaplastic gliomas. The current treatment combines surgery, chemotherapy, and radiotherapy. If gender differences in the natural history of the disease were widely described, their underlying mechanisms remain to be determined for the identification of reliable markers of disease progression. We mined the transcriptomic and clinical data from the TCGA-LGG and CGGA databases to identify male-over-female differentially expressed genes and selected those associated with patient survival using univariate analysis, depending on molecular characteristics (IDH wild-type/mutated; 1p/19q codeleted/not) and grade. Then, the link between the expression levels (low or high) of the steroid biosynthesis enzyme or receptors of interest and survival was studied using the log-rank test. Finally, a functional analysis of gender-specific correlated genes was performed. HOX-related genes appeared to be differentially expressed between males and females in both grades, suggesting that a glioma could originate in perturbation of developmental signals. Moreover, aromatase, androgen, and estrogen receptor expressions were associated with patient survival and were mainly related to angiogenesis or immune response. Therefore, consideration of the tight control of steroid hormone production and signaling seems crucial for the understanding of glioma pathogenesis and emergence of future targeted therapies
Une mĂ©thode originale basĂ©e sur lâIRM pour Ă©valuer le phĂ©notype infiltrant des gliomes de bas grade
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Effects of Carbidopa Premedication on 18F-FDOPA PET Imaging of Glioma: A Multiparametric Analysis
Purpose: This study aimed to determine the impact of carbidopa premedication on static, dynamic and radiomics parameters of 18F-FDOPA PET in brain tumors. Methods: The study included 54 patients, 18 of whom received carbidopa, who underwent 18F-FDOPA PET for newly diagnosed gliomas. SUV-derived, 105 radiomics features and TTP dynamic parameters were extracted from volumes of interest in healthy brains and tumors. Simulation of the effects of carbidopa on time-activity curves were generated. Results: All static and TTP dynamic parameters were significantly higher in healthy brain regions of premedicated patients (ÎSUVmean = +53%, ÎTTP = +48%, p < 0.001). Furthermore, carbidopa impacted 81% of radiomics features, of which 92% correlated with SUVmean (absolute correlation coefficient â„ 0.4). In tumors, premedication with carbidopa was an independent predictor of SUVmean (ÎSUVmean = +52%, p < 0.001) and TTP (ÎTTP = +24%, p = 0.025). All parameters were no longer significantly modified by carbidopa premedication when using ratios to healthy brain. Simulated data confirmed that carbidopa leads to higher tumor TTP values, corrected by the ratios. Conclusion: In 18F-FDOPA PET, carbidopa induces similarly higher SUV and TTP dynamic parameters and similarly impacts SUV-dependent radiomics in healthy brain and tumor regions, which is compensated for by correcting for the tumor-to-healthy-brain ratio. This is a significant advantage for multicentric study harmonization
YC-1 suppresses constitutive nuclear factor-kappa B activation and induces apoptosis in human prostate cancer cells
International audienceNegative motor responses (NMRs) are defined as movement arrests induced by direct electrical stimulation of the brain. The NMRs manifest themselves after the disruption of a corticosubcortical network involved in motor control, referred to as the ânegative motor networkâ. At present, the spatial topography of the negative motor areas (NMAs) is poorly known. Hence, the objectives of the present study were to establish the first probabilistic map of the NMAs of the upper limbs and face, identify potential subareas, and investigate the NMAsâ relationships with the primary motor cortex. A total of 117 patients with low grade glioma underwent awake surgery with direct electrostimulation. The Montreal Neurological Institute coordinates of sites eliciting NMRs (face and upper limbs) were registered. A probabilistic map was created, and subareas were identified in a cluster analysis. Each cluster was then plotted on the Glasser atlas and the 1200 Subjects Group Average Data from the Human Connectome Project, in order to study connectivity and compare the results with recent parcellation data. We elicited 386 NMRs (mean ± standard deviation current intensity: 2.26 ± 0.5 mA) distributed throughout the precentral gyrus in both hemispheres. In each hemisphere, we found two clusters for facial NMRs. For upper limb NMRs, we found two clusters in the right hemisphere; and three in the left. Each cluster overlapped with parcellations from the Glasser atlas. For the face, the NMAs were associated with areas 55b and 6v. For the upper limbs, the NMAs were linked to areas 6v, 6d, and 55b. Each NMA cluster showed a specific pattern of functionally connected areas, such as the inferior frontal gyrus, supplementary motor area, parietal areas, and posterior superior temporal gyrus. The white matter pathways projecting to these subareas involved the frontal aslant tract and the frontostriatal tractâboth of which are well known to be associated with NMRs. This study constitutes the largest series to date of NMRs mapped to the lateral surface of both hemispheres. Rather than being randomly distributed, the NMAs appeared to be well structured and corresponded to parcellations identified by functional neuroimaging. Moreover, the white matter pathways known to drive NMRs are also connected to regions encompassing NMAs. Taken as a whole, our results suggest that NMAs belong to a large-scale modulatory motor network. Our new probabilistic map might constitute a valuable tool for use in further clinical and fundamental studies of motor control
Turning-induced surface integrity for a fillet radius in a 316L austenitic stainless steel
International audienceTurning is a machining process extensively applied to produce revolution parts. Durability of these parts are known to depend on the turning process signature that is often referred as surface integrity. The surface integrity generated in a fillet radius has been barely studied in the literature so far, despite the well-known geometrical stress concentration factor of such singularities. Therefore this paper deals with the investigation of machining-induced surface integrity when turning a fillet radius in a 316L austenitic stainless steel. Different characterization methods are used for that purpose - SEM, EBSD, nanoindentation and X-Ray diffraction. It points out that the turning-induced consequences are not homogeneous along the machined profile. Residual stresses are strongly affected and microstructure is highly modified over a depth of 80 ÎŒm that leads to a mechanical properties gradient. It is evidenced that the average uncut chip thickness is the main governing parameter regarding surface integrity. It is also reported that deformation twins appear in the affected zone. It highlights that turning-induced microstructure evolution at a given depth is rather a consequence of severe plastic deformation at high strain rate than dynamic recrystallization