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The radiologically isolated syndrome (RIS) was defined in 2009 as the presence of asymptomatic, incidentally identified demyelinating-appearing white matter lesions in the CNS within individuals lacking symptoms typical of multiple sclerosis (MS). The RIS criteria have been validated and predict the transition to symptomatic MS reliably. The performance of RIS criteria that require fewer MRI lesions is unknown. 2009-RIS subjects, by definition, fulfil three to four of four criteria for 2005 dissemination in space (DIS) and subjects fulfilling only one or two lesions in at least one 2017 DIS location were identified within 37 prospective databases. Univariate and multivariate Cox regression models were used to identify predictors of a first clinical event. Performances of different groups were calculated. Seven hundred and forty-seven subjects (72.2% female, mean age 37.7 ± 12.3 years at the index MRI) were included. The mean clinical follow-up time was 46.8 ± 45.4 months. All subjects had focal T2 hyperintensities suggestive of inflammatory demyelination on MRI; 251 (33.6%) fulfilled one or two 2017 DIS criteria (designated as Groups 1 and 2, respectively), and 496 (66.4%) fulfilled three or four 2005 DIS criteria representing 2009-RIS subjects. Group 1 and 2 subjects were younger than the 2009-RIS group and were more likely to develop new T2 lesions over time (P < 0.001). Groups 1 and 2 were similar regarding survival distribution and risk factors for transition to MS. At 5 years, the cumulative probability for a clinical event was 29.0% for Groups 1 and 2 compared to 38.7% for 2009-RIS (P = 0.0241). The presence of spinal cord lesions on the index scan and CSF-restricted oligoclonal bands in Groups 1–2 increased the risk of symptomatic MS evolution at 5 years to 38%, comparable to the risk of development in the 2009-RIS group. The presence of new T2 or gadolinium-enhancing lesions on follow-up scans independently increased the risk of presenting with a clinical event (P < 0.001). The 2009-RIS subjects or Groups 1 and 2 with at least two of the risk factors for a clinical event demonstrated better sensitivity (86.0%), negative predictive value (73.1%), accuracy (59.8%) and area under the curve (60.7%) compared to other criteria studied. This large prospective cohort brings Class I evidence that subjects with fewer lesions than required in the 2009 RIS criteria evolve directly to a first clinical event at a similar rate when additional risk factors are present. Our results provide a rationale for revisions to existing RIS diagnostic criteria.

The recollection of sensory information and subjective experience related to a personal past event depends on our episodic memory (EM). At the neural level, EM retrieval is linked with the reinstatement of hippocampal activity thought to recollect the sensory information experienced and stored in the cortex. At encoding, the sensory information also includes many bodily cues (i.e., touch, proprioception). Such integrated bodily signals are the basis of a sensorimotor form of self-consciousness called bodily self-consciousness (BSC). BSC consists of subjective experiences like the sense of ownership, first-person perspective, and the sense of agency, recruiting a distributed neural system consisting of premotor (PMC), supplementary motor (SMA), and posterior parietal regions. However, although both BSC and EM rely on the integration of sensory stimuli, the neural mechanism associating BSC and EM are still not known. In my thesis, I designed a new experimental procedure using virtual reality (VR) and motion tracking to investigate the behavioral and neural correlates of BSC, EM, and their interactions. I fully adapted the procedures to fMRI in order to test the impact of BSC manipulation at encoding on EM retrieval and its subjective components. The first part of my thesis investigated how different levels of BSC (visuomotor and perspectival congruency) during encoding impacted EM (Study 1) and the subjective re-experience of the memory called autonoetic consciousness (ANC; Study 2). In Study 1, I found that hippocampal reinstatement was enhanced and coupled with key BSC areas (PMC, SMA) only for preserved BSC characterized by visuomotor and perspectival congruency. Study 2 showed that the strength of recollection correlated with the strength of the subjective experience at encoding only under visuomotor and perspectival congruency. This relationship between ANC and BSC was mediated by the insula, a structure related to BSC and also linked with emotions in the EM field. In the second part of my thesis, I investigated the paradigm used in Studies 1 and 2 in clinical populations presenting damage to the medial temporal lobe (Study 3) or cortical areas (Study 4). In Study 3, I tested a rare case of amnestic patient with bilateral damage to the hippocampal complex. Despite preserved BSC, the patient showed a decreased EM when encoded under a BSC characterized by visuomotor and perspectival congruency. In Study 4, I tested whether damage to frontal cortex, including PMC, in motor stroke patients alters the impact of BSC state in EM. Preliminary results indicated that memory performance for scene encoded under visuomotor and perspectival congruency was not enhanced in stroke patients with impaired BSC. Finally, in the last part of my thesis (Study 5), I discuss the importance of VR technology in the study of BSC and what to improve in VR aesthetics to boost BSC effects in future studies. In summary, I designed a new experimental protocol using VR and motion tracking to investigate the impacts of BSC and its related subjective experience on EM. I adapted the design to fMRI to investigate the neural correlates of the association of these two processes. I linked these results in light of a rare case of an amnestic patient with a specific EM deficit and a group of motor stroke patients with lesions involved in BSC processes. My thesis contributes to linking sensory information processing, self-consciousness, and EM within a common framework: BSC.

© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC. The presence of white matter lesions in patients with cerebral small vessel disease (SVD) is among the main causes of cognitive decline. We investigated the relation between white matter hyperintensity (WMH) locations and executive and language abilities in 442 SVD patients without dementia with varying burden of WMH. We used Stroop Word Reading, Stroop Color Naming, Stroop Color-Word Naming, and Category Fluency as language measures with varying degrees of executive demands. The Symbol Digit Modalities Test (SDMT) was used as a control task, as it measures processing speed without requiring language use or verbal output. A voxel-based lesion–symptom mapping (VLSM) approach was used, corrected for age, sex, education, and lesion volume. VLSM analyses revealed statistically significant clusters for tests requiring language use, but not for SDMT. Worse scores on all tests were associated with WMH in forceps minor, thalamic radiations and caudate nuclei. In conclusion, an association was found between WMH in a core frontostriatal network and executive-verbal abilities in SVD, independent of lesion volume and processing speed. This circuitry underlying executive-language functioning might be of potential clinical importance for elderly with SVD. More detailed language testing is required in future research to elucidate the nature of language production difficulties in SVD.

Carbohydrates are an important source of renewable materials which can be converted into high added-value products. Sugar transformations should ideally be carried out with recyclable catalysts, in water, with the highest possible selectivity in the desired product. The aim of the present work was to explore the microstructural properties of the heterogeneous catalysts needed to carry out selectively lactose oxidation into lactobionic acid and lactose hydrogenation into lactitol. The first part consisted in the investigation of the influence of two functionalized supports (γ-Al2O3 and Cxerogel) modified by metallic precursor grafting and activation on the catalytic performances in lactose oxidation. The oxygenated functions were shown to be detrimental. This was confirmed by the results obtained with an inert support, boron nitride, which can be a promising alternative support, ensuring high selectivity. Subsequently, the optimal range of particle size within Pd/h-BN catalysts for high activity and selectivity was investigated and the optimal size was determined between 3 and 15 nm with no particles inferior to 3 nm. The effectiveness of Au/h-BN was also evaluated and it exhibited spectacular performances. Au/h-BN was shown to be a good candidate for thermal regeneration for recycling. Lactose hydrogenation was finally investigated with Pd/h-BN and particles inferior to 3 nm were also undesired. The selectivity obtained in lactose hydrogenation seems to be greatly dependent on the mechanism of each possible side reaction. (SC - Sciences) -- UCL, 2014