Microstructural damage of the posterior corpus callosum contributes to the clinical severity of neglect

One theory to account for neglect symptoms in patients with right focal damage invokes a release of inhibition of the right parietal cortex over the left parieto-frontal circuits, by disconnection mechanism. This theory is supported by transcranial magnetic stimulation studies showing the existence of asymmetric inhibitory interactions between the left and right posterior parietal cortex, with a right hemispheric advantage. These inhibitory mechanisms are mediated by direct transcallosal projections located in the posterior portions of the corpus callosum. The current study, using diffusion imaging and tract-based spatial statistics (TBSS), aims at assessing, in a data-driven fashion, the contribution of structural disconnection between hemispheres in determining the presence and severity of neglect. Eleven patients with right acute stroke and 11 healthy matched controls underwent MRI at 3T, including diffusion imaging, and T1-weighted volumes. TBSS was modified to account for the presence of the lesion and used to assess the presence and extension of changes in diffusion indices of microscopic white matter integrity in the left hemisphere of patients compared to controls, and to investigate, by correlation analysis, whether this damage might account for the presence and severity of patients' neglect, as assessed by the Behavioural Inattention Test (BIT). None of the patients had any macroscopic abnormality in the left hemisphere; however, 3 cases were discarded due to image artefacts in the MRI data. Conversely, TBSS analysis revealed widespread changes in diffusion indices in most of their left hemisphere tracts, with a predominant involvement of the corpus callosum and its projections on the parietal white matter. A region of association between patients' scores at BIT and brain FA values was found in the posterior part of the corpus callosum. This study strongly supports the hypothesis of a major role of structural disconnection between the right and left parietal cortex in determining 'neglect'

FMRI resting slow fluctuations correlate with the activity of fast cortico-cortical physiological connections

Recording of slow spontaneous fluctuations at rest using functional magnetic resonance imaging (fMRI) allows distinct long-range cortical networks to be identified. The neuronal basis of connectivity as assessed by resting-state fMRI still needs to be fully clarified, considering that these signals are an indirect measure of neuronal activity, reflecting slow local variations in de-oxyhaemoglobin concentration. Here, we combined fMRI with multifocal transcranial magnetic stimulation (TMS), a technique that allows the investigation of the causal neurophysiological interactions occurring in specific cortico-cortical connections. We investigated whether the physiological properties of parieto-frontal circuits mapped with short-latency multifocal TMS at rest may have some relationship with the resting-state fMRI measures of specific resting-state functional networks (RSNs). Results showed that the activity of fast cortico-cortical physiological interactions occurring in the millisecond range correlated selectively with the coupling of fMRI slow oscillations within the same cortical areas that form part of the dorsal attention network, i.e., the attention system believed to be involved in reorientation of attention. We conclude that resting-state fMRI ongoing slow fluctuations likely reflect the interaction of underlying physiological cortico-cortical connections

Noradrenergic mechanisms of arousal’s bidirectional effects on episodic memory

Arousal’s selective effects on cognition go beyond the simple enhancement of emotional stimuli, sometimes enhancing and other times impairing processing of proximal neutral information. Past work shows that arousal impairs encoding of subsequent neutral stimuli regardless of their top-down priority via the engagement of β-adrenoreceptors. In contrast, retrograde amnesia induced by emotional arousal can flip to enhancement when preceding neutral items are prioritized in top-down attention. Whether β-adrenoreceptors also contribute to this retrograde memory enhancement of goal-relevant neutral stimuli is unclear. In this pharmacological study, we administered 40mg of propranolol or 40mg of placebo to healthy young adults to examine whether emotional arousal’s bidirectional effects on declarative memory relies on β-adrenoreceptor activation. Following pill intake, participants completed an emotional oddball task in which they were asked to prioritize a neutral object appearing just before an emotional or neutral oddball image within a sequence of 7 neutral objects. Under placebo, emotional oddballs impaired memory for lower priority oddball+1 objects but had no effect on memory for high priority oddball-1 objects. Propranolol blocked this anterograde amnesic effect of arousal. Emotional oddballs also enhanced selective memory trade-offs significantly more in the placebo than drug condition, such that high priority oddball-1 objects were more likely to be remembered at the cost of their corresponding lower priority oddball+1 objects under arousal. Lastly, those who recalled more high priority oddball-1 objects preceding an emotional versus neutral oddball image showed greater increases in salivary alpha-amylase, a biomarker of noradrenergic system activation, across the task. Together these findings suggest that different noradrenergic mechanisms contribute to the anterograde and retrograde mnemonic effects of arousal on proximal neutral memoranda

Development of gas systems for gaseous detector operation at HL-LHC

Après les résultats très remarquables obtenus au cours des premières décennies par Large Hadron Collider (LHC) du CERN, le complexe d’accélérateurs fait actuellement l’objet d’importantes mises à niveau et l’augmentation substantielle de la luminosité posera également des défis techniques majeurs pour les Expériences. Un long programme de consolidation et de mise à niveau est en cours de réalisation pendant le Long Shutdown 2, concernant entre autres les systèmes à muon, composés de détecteurs à gaz pour lesquels une composition correcte et stable du mélange gazeux est une condition essentielle pour garantir de performances bonnes et stables à long terme. Les gaz à effet de serre (Greenhouse gases, GHGs) étant largement utilisés comme composants de mélanges gazeux dans les détecteurs à gaz du LHC, leur fonctionnement doit tenir compte des dernières exigences du CERN quant à la réduction des émissions de GHGs et du coût des systèmes à gaz. Ce travail de thèse s’inscrit dans deux axes de recherche portant sur le développement et la mise à jour de techniques pour contribuer aux stratégies du CERN visant à minimiser la consommation de GHGs. Le premier est le fonctionnement des systèmes à gaz avec recirculation de gaz, en particulier pour le cas des détecteurs Triple-GEM, dont les performances ont été validées dans un environnement de rayonnement de type HL-LHC, quant à la stabilité à long terme, l’efficacité de détection des muons et la production d’impuretés de mélanges à base de CF4. Une stratégie possible pour limiter davantage les émissions de GHG est la récupération de composants de gaz précieux après leur utilisation dans les détecteurs, dans le but de les réinjecter dans le système de gaz. Cette thèse se concentre en particulier sur la récupération de deux GHGs utilisés dans les détecteurs gazeux des expériences LHC, le CF4 et le C2H2F4. La conception et l’exploitation des modules de récupération de CF4 sur les systèmes de gaz RICH2 de LHCb et CSC de CMS sont discutées, montrant comment de bons rendements de récupération peuvent être atteints avec une bonne pureté du CF4 récupéré. En outre, le développement d’une module prototype de récupération du C2H2F4 est présenté, dont la caractérisation a prouvé une efficacité de séparation très élevée (80% - 95%) et une très bonne qualité du C2H2F4 récupéré.After the highly remarkable results achieved in the first decades of operation of the CERN Large Hadron Collider (LHC), the accelerator complex is currently facing major upgrades, and the substantial increase in luminosity will pose major technical challenges also for the Experiments. A long consolidation and upgrade program is being realized during the Long Shutdown 2, concerning among others the Muon systems, composed of gaseous detectors for which a correct and stable gas mixture composition is a key requirement to guarantee good and stable long-term performance. As Greenhouse gases (GHGs) are widely used as gas mixture components in LHC gaseous detectors, their operation shall keep into account the latest CERN requirements in terms of reduction of GHGs emission and gas systems cost. This work delineates the development and upgrades of two different research lines put in place to contribute to the CERN strategies to minimize GHGs consumption. The first is the operation of gas systems with gas recirculation, in particular for the Triple-GEM detectors case, which performance was validated in a HL-LHC-like radiation environment, in terms of long-term stability, Muon detection efficiency and CF4-based impurities production. A possible strategy to further limit GHG emission is the recuperation of valuable gas components after their usage in the detectors, with the aim of re-injecting them in the gas system. This thesis focuses in particular on the recuperation of two GHGs used in LHC Experiments gaseous detectors, CF4 and C2H2F4. The design and operation of CF4 recuperation plants on the LHCb RICH2 and CMS CSC gas systems is discussed, showing how good recuperation efficiencies can be reached with a good purity of the recuperated CF4. Furthermore, the development of a C2H2F4 recuperation prototype plant is presented, which characterization proves a very high separation efficiency (80% - 95%) and an extremely good quality of the recuperated C2H2F4

Studies on Gas Mixture and Gas Recirculation Effects on GEM Detectors Operation at the CERN GIF++ Facility

The future Physics Program established for the Large Hadron Collider (LHC), with the upgrade of the accelerator, sets important challenges for all detector systems. Several upgrades will affect Muon Systems, including the ones on the gas mixture in use, since their stability and correct composition are at the basis of safe long-term operation. The aim is to lower operational costs and gas emission, while maintaining high performance levels. Gas systems are therefore operated in recirculation mode. The purpose of this thesis is a detailed study of the performances of Gas Electron Multiplier detectors (GEM), commonly operated with Ar/CO$_2$ gas mixtures, but also the addition of CF$_4$, to obtain an improved time resolution. The use of CF$_4$, that is considered a greenhouse gas, force the operation in recirculated gas systems, that makes fundamental to guarantee optimal detector operation in such condition. A Triple-GEM detector characterization was realized in different gas mixture conditions. Studies on GEM performance when operated in a gas recirculation system and under high irradiation rate were realized at the CERN Gamma Irradiation Facility (GIF++), that provides irradiation with gamma emission (662 keV photons) from a $^{137}$Cs source (activity 14 TBq). Two Triple-GEM detectors are installed inside the GIF++ facility with R&D purposes. The aim of the measurement campaign at GIF++ is to progress with the validation of their operation in a system as close as possible to the ones in LHC experiments

Développement de systèmes de gaz pour le fonctionnement des détecteurs gazeux au HL-LHC

After the highly remarkable results achieved in the first decades of operation of the CERN Large Hadron Collider (LHC), the accelerator complex is currently facing major upgrades, and the substantial increase in luminosity will pose major technical challenges also for the Experiments. A long consolidation and upgrade program is being realized during the Long Shutdown 2, concerning among others the Muon systems, composed of gaseous detectors for which a correct and stable gas mixture composition is a key requirement to guarantee good and stable long-term performance. As Greenhouse gases (GHGs) are widely used as gas mixture components in LHC gaseous detectors, their operation shall keep into account the latest CERN requirements in terms of reduction of GHGs emission and gas systems cost. This work delineates the development and upgrades of two different research lines put in place to contribute to the CERN strategies to minimize GHGs consumption. The first is the operation of gas systems with gas recirculation, in particular for the Triple-GEM detectors case, which performance was validated in a HL-LHC-like radiation environment, in terms of long-term stability, Muon detection efficiency and CF4-based impurities production. A possible strategy to further limit GHG emission is the recuperation of valuable gas components after their usage in the detectors, with the aim of re-injecting them in the gas system. This thesis focuses in particular on the recuperation of two GHGs used in LHC Experiments gaseous detectors, CF4 and C2H2F4. The design and operation of CF4 recuperation plants on the LHCb RICH2 and CMS CSC gas systems is discussed, showing how good recuperation efficiencies can be reached with a good purity of the recuperated CF4. Furthermore, the development of a C2H2F4 recuperation prototype plant is presented, which characterization proves a very high separation efficiency (80% - 95%) and an extremely good quality of the recuperated C2H2F4.Après les résultats très remarquables obtenus au cours des premières décennies par Large Hadron Collider (LHC) du CERN, le complexe d’accélérateurs fait actuellement l’objet d’importantes mises à niveau et l’augmentation substantielle de la luminosité posera également des défis techniques majeurs pour les Expériences. Un long programme de consolidation et de mise à niveau est en cours de réalisation pendant le Long Shutdown 2, concernant entre autres les systèmes à muon, composés de détecteurs à gaz pour lesquels une composition correcte et stable du mélange gazeux est une condition essentielle pour garantir de performances bonnes et stables à long terme. Les gaz à effet de serre (Greenhouse gases, GHGs) étant largement utilisés comme composants de mélanges gazeux dans les détecteurs à gaz du LHC, leur fonctionnement doit tenir compte des dernières exigences du CERN quant à la réduction des émissions de GHGs et du coût des systèmes à gaz. Ce travail de thèse s’inscrit dans deux axes de recherche portant sur le développement et la mise à jour de techniques pour contribuer aux stratégies du CERN visant à minimiser la consommation de GHGs. Le premier est le fonctionnement des systèmes à gaz avec recirculation de gaz, en particulier pour le cas des détecteurs Triple-GEM, dont les performances ont été validées dans un environnement de rayonnement de type HL-LHC, quant à la stabilité à long terme, l’efficacité de détection des muons et la production d’impuretés de mélanges à base de CF4. Une stratégie possible pour limiter davantage les émissions de GHG est la récupération de composants de gaz précieux après leur utilisation dans les détecteurs, dans le but de les réinjecter dans le système de gaz. Cette thèse se concentre en particulier sur la récupération de deux GHGs utilisés dans les détecteurs gazeux des expériences LHC, le CF4 et le C2H2F4. La conception et l’exploitation des modules de récupération de CF4 sur les systèmes de gaz RICH2 de LHCb et CSC de CMS sont discutées, montrant comment de bons rendements de récupération peuvent être atteints avec une bonne pureté du CF4 récupéré. En outre, le développement d’une module prototype de récupération du C2H2F4 est présenté, dont la caractérisation a prouvé une efficacité de séparation très élevée (80% - 95%) et une très bonne qualité du C2H2F4 récupéré

Développement de systèmes de gaz pour le fonctionnement des détecteurs gazeux au HL-LHC

After the highly remarkable results achieved in the first decades of operation of the CERN Large Hadron Collider (LHC), the accelerator complex is currently facing major upgrades, and the substantial increase in luminosity will pose major technical challenges also for the Experiments. A long consolidation and upgrade program is being realized during the Long Shutdown 2, concerning among others the Muon systems, composed of gaseous detectors for which a correct and stable gas mixture composition is a key requirement to guarantee good and stable long-term performance. As Greenhouse gases (GHGs) are widely used as gas mixture components in LHC gaseous detectors, their operation shall keep into account the latest CERN requirements in terms of reduction of GHGs emission and gas systems cost. This work delineates the development and upgrades of two different research lines put in place to contribute to the CERN strategies to minimize GHGs consumption. The first is the operation of gas systems with gas recirculation, in particular for the Triple-GEM detectors case, which performance was validated in a HL-LHC-like radiation environment, in terms of long-term stability, Muon detection efficiency and CF4-based impurities production. A possible strategy to further limit GHG emission is the recuperation of valuable gas components after their usage in the detectors, with the aim of re-injecting them in the gas system. This thesis focuses in particular on the recuperation of two GHGs used in LHC Experiments gaseous detectors, CF4 and C2H2F4. The design and operation of CF4 recuperation plants on the LHCb RICH2 and CMS CSC gas systems is discussed, showing how good recuperation efficiencies can be reached with a good purity of the recuperated CF4. Furthermore, the development of a C2H2F4 recuperation prototype plant is presented, which characterization proves a very high separation efficiency (80% - 95%) and an extremely good quality of the recuperated C2H2F4.Après les résultats très remarquables obtenus au cours des premières décennies par Large Hadron Collider (LHC) du CERN, le complexe d’accélérateurs fait actuellement l’objet d’importantes mises à niveau et l’augmentation substantielle de la luminosité posera également des défis techniques majeurs pour les Expériences. Un long programme de consolidation et de mise à niveau est en cours de réalisation pendant le Long Shutdown 2, concernant entre autres les systèmes à muon, composés de détecteurs à gaz pour lesquels une composition correcte et stable du mélange gazeux est une condition essentielle pour garantir de performances bonnes et stables à long terme. Les gaz à effet de serre (Greenhouse gases, GHGs) étant largement utilisés comme composants de mélanges gazeux dans les détecteurs à gaz du LHC, leur fonctionnement doit tenir compte des dernières exigences du CERN quant à la réduction des émissions de GHGs et du coût des systèmes à gaz. Ce travail de thèse s’inscrit dans deux axes de recherche portant sur le développement et la mise à jour de techniques pour contribuer aux stratégies du CERN visant à minimiser la consommation de GHGs. Le premier est le fonctionnement des systèmes à gaz avec recirculation de gaz, en particulier pour le cas des détecteurs Triple-GEM, dont les performances ont été validées dans un environnement de rayonnement de type HL-LHC, quant à la stabilité à long terme, l’efficacité de détection des muons et la production d’impuretés de mélanges à base de CF4. Une stratégie possible pour limiter davantage les émissions de GHG est la récupération de composants de gaz précieux après leur utilisation dans les détecteurs, dans le but de les réinjecter dans le système de gaz. Cette thèse se concentre en particulier sur la récupération de deux GHGs utilisés dans les détecteurs gazeux des expériences LHC, le CF4 et le C2H2F4. La conception et l’exploitation des modules de récupération de CF4 sur les systèmes de gaz RICH2 de LHCb et CSC de CMS sont discutées, montrant comment de bons rendements de récupération peuvent être atteints avec une bonne pureté du CF4 récupéré. En outre, le développement d’une module prototype de récupération du C2H2F4 est présenté, dont la caractérisation a prouvé une efficacité de séparation très élevée (80% - 95%) et une très bonne qualité du C2H2F4 récupéré

Studies on Triple-GEM Detectors in high radiation environment with gas recirculation

At the CERN LHC experiments, several gaseous detector technologies are operated in gas recirculation mode to lower operational costs and gas emissions. In the next years, Micro Pattern Gaseous Detector (MPGD) technologies will be largely implemented in the LHC experiments, with dedicated gas systems, and they will experience a significantly increased background radiation rate, especially in the HL-LHC phase. It is therefore fundamental to study MPGD operated with LHC gas systems, especially under gas recirculation, to be able to guarantee their safe long-term operation. In this context, the performance of Gas Electron Multiplier (GEM) detectors operated in gas recirculating systems have been studied at the CERN Gamma Irradiation Facility (GIF ++ ), which provides an intense gamma irradiation along with a Muon beam from the SPS accelerator. Triple-GEM detectors performance has been studied in relation to operation stability during long-term high rate irradiation, as well as in terms of Muon detection efficiency with different gamma background rates. Both tests were realized with various gas mixtures and gas system conditions. A complete overview of the results obtained at the GIF ++ is presented, showing the successful operation of Triple-GEM detectors during long-term high-rate irradiation and good Muon detection efficiency in HL-like background radiation

Triple-GEM detectors operation under gas recirculation in high-rate radiation environment

At the CERN LHC experiments, several gaseous detector technologies are operated in gas recirculation mode to lower operational costs and gas emissions. In the next years, Micro Pattern Gaseous Detector (MPGD) technologies will be largely implemented in the LHC experiments, with dedicated gas systems, and they will experience a significantly increased background radiation rate, especially in the HL-LHC phase. It is therefore fundamental to study MPGD operated with LHC gas systems, especially under gas recirculation, to be able to guarantee their safe long-term operation. In this context, the performance of Gas Electron Multiplier (GEM) detectors operated in gas recirculating systems have been studied at the CERN Gamma Irradiation Facility (GIF++), which provides an intense gamma irradiation along with a Muon beam from the SPS accelerator. Triple-GEM detectors performance has been studied in relation to operation stability during long-term high rate irradiation, as well as in terms of Muon detection efficiency with different gamma background rates. Both tests were realized with various gas mixtures and gas system conditions. A complete overview of the results obtained at the GIF++ is presented, showing the successful operation of Triple-GEM detectors during long-term high-rate irradiation and good Muon detection efficiency in LHC HL-like background radiation