Modulation de l'apprentissage visuel par stimulation électrique transcrânienne à courant direct du cortex préfrontal

Le traitement visuel répété d’un visage inconnu entraîne une suppression de l’activité neuronale dans les régions préférentielles aux visages du cortex occipito-temporal. Cette «suppression neuronale» (SN) est un mécanisme primitif hautement impliqué dans l’apprentissage de visages, pouvant être détecté par une réduction de l’amplitude de la composante N170, un potentiel relié à l’événement (PRE), au-dessus du cortex occipito-temporal. Le cortex préfrontal dorsolatéral (CPDL) influence le traitement et l’encodage visuel, mais sa contribution à la SN de la N170 demeure inconnue. Nous avons utilisé la stimulation électrique transcrânienne à courant direct (SETCD) pour moduler l’excitabilité corticale du CPDL de 14 adultes sains lors de l’apprentissage de visages inconnus. Trois conditions de stimulation étaient utilisées: inhibition à droite, excitation à droite et placebo. Pendant l’apprentissage, l’EEG était enregistré afin d’évaluer la SN de la P100, la N170 et la P300. Trois jours suivant l’apprentissage, une tâche de reconnaissance était administrée où les performances en pourcentage de bonnes réponses et temps de réaction (TR) étaient enregistrées. Les résultats indiquent que la condition d’excitation à droite a facilité la SN de la N170 et a augmentée l’amplitude de la P300, entraînant une reconnaissance des visages plus rapide à long-terme. À l’inverse, la condition d’inhibition à droite a causé une augmentation de l’amplitude de la N170 et des TR plus lents, sans affecter la P300. Ces résultats sont les premiers à démontrer que la modulation d’excitabilité du CPDL puisse influencer l’encodage visuel de visages inconnus, soulignant l’importance du CPDL dans les mécanismes d’apprentissage de base.Repeated visual processing of an unfamiliar face suppresses neural activity in face-specific areas of the occipito-temporal cortex. This "repetition suppression" (RS) is a primitive mechanism involved in learning of unfamiliar faces, which can be detected through amplitude reduction of the N170 event-related potential (ERP). The dorsolateral prefrontal cortex (DLPFC) exerts top-down influence on early visual processing. However, its contribution to N170 RS and learning of unfamiliar faces remains unclear. Transcranial direct current stimulation (tDCS) transiently increases or decreases cortical excitability, as a function of polarity. We hypothesized that DLPFC excitability modulation by tDCS would cause polarity-dependent modulations of N170 RS during encoding of unfamiliar faces. tDCS-induced N170 RS enhancement would improve long-term recognition reaction time (RT) and/or accuracy rates, whereas N170 RS impairment would compromise recognition ability. Participants underwent three tDCS conditions in random order at ~72 hour intervals: right anodal/left cathodal, right cathodal/left anodal and sham. Immediately following tDCS conditions, an EEG was recorded during encoding of unfamiliar faces for assessment of P100 and N170 visual ERPs. P300 was analyzed to detect prefrontal function modulation. Recognition tasks were administered ~72 hours following encoding. Results indicate the right anodal/left cathodal condition facilitated N170 RS and induced larger P300 amplitudes, leading to faster recognition RT. Conversely, the right cathodal/left anodal condition caused increases in N170 amplitudes and RT, but did not affect P300. These data are the first to demonstrate that DLPFC excitability modulation can influence early visual encoding of unfamiliar faces, highlighting the importance of DLPFC in basic learning mechanisms

L’orientation scolaire en Communauté française de Belgique

Le concept d’orientation est particulièrement problématique dans le contexte belge francophone où l’ensemble de l’enseignement et de la formation repose sur un quasi-marché hautement concurrentiel. Dans un tel contexte, on pourrait s’attendre à une offre très abondante et fortement sollicitée de services d’aide à l’orientation scolaire et professionnelle. Il n’en va pas ainsi. L’orientation, couplée à la sélection, s’effectue le plus souvent sur un mode informel, même s’il existe des organismes publics et privés chargés d’apporter leur aide en ce domaine. Dans de nombreux cas, dont la situation la plus dramatique prend place au début de l’enseignement secondaire, orientation et sélection se confondent à travers les avis des conseils de classe, baptisés « attestations d’orientation ». Dans les faits, ces attestations se résument dans leur grande majorité, à des « bons à poursuivre dans la filière générale » ou des invitations à quitter cette « voie royale » pour gagner des filières techniques et professionnelles actuellement beaucoup moins valorisées.The concept of careers advice is particularly troublesome in the francophone context of Belgium, where all teaching and training activities depend upon a highly competitive nearly market. In such a context we could assume the existence of and the strong demand for many advisory services for school and professional careers. However this is not what happens. Careers advice, coupled with selection, takes place most often in an informal fashion, even though public and private organisations, supposed to bring their help in that matter, actually exist. In many cases, which most dramatic situation takes place at the beginning of secondary school, careers advice and selection are very closely connected in the conseils de classe2 notifications, called “attestations d’orientation” (“careers advice certificates”). In fact, these certificates correspond for most of them to a sort of “ticket” to go on academic courses or to leave this “best” of paths for the presently far less esteemed vocational studies.El concepto de orientación es particularmente problemático en el contexto belga francófono en dónde el conjunto de la enseñanza y de la formación reposa sobre un cuasi-mercado altamente competitivo. En tal contexto, se podría esperar una oferta muy abundante y fuertemente solicitada de servicios de ayuda para la orientación escolar y profesional. Pero esto no es así. La orientación, aparejada a la selección, se efectúa más frecuentemente de una manera informal, incluso cuando existen organismos públicos y privados encargados de aportar su ayuda en este campo. En numerosos casos, y cuya situación más dramática ocurre al principio de la enseñanza secundaria, la orientación y la selección se confunden a través de los consejos de clase, bautizados « certificaciones de orientación ». En los hechos, estas certificaciones se resumen en su gran mayoría a « visto bueno para proseguir en la rama general » o a invitaciones a abandonar esta « vía real » para dirigirse a las ramas técnicas y profesionales actualmente mucho menos valorizadas

Prolonged and unprolonged complex febrile seizures differently affect frontal theta brain activity

Objective: Studies have identified persistent cognitive and functional deficits, which could be linked to each other, in children with complex febrile seizures (FS). Our aim was to investigate differences in brain activity in children with a history of complex FS, through a study paradigm associated with the development of learning capacities and using electroencephalographic (EEG) signal. To further increase our understanding of these differences, complex FS were studied separately depending on their type. Method: EEG was recorded in 43 children with past FS. Brain activity associated with auditory learning was investigated using a habituation paradigm, in which repetition suppression (RS) is typically found following stimulus repetition. Auditory stimuli were repeated three times, and each presentation were analysed separately in the time-frequency (TF) domain. A mixedanalysis of variance was used to assess differences in spectral power between stimulus repetition and FS type (simple vs complex prolonged; CP vs complex unprolonged; CUP). Results: Repetition effects were found in the 3-6 Hz during 150-600ms time window after stimulus onset at frontal sites (F(2, 40)=5.645, p=0.007, η2p=0.220). Moreover, an interaction effect between stimulus repetition and FS type (F(4, 80)=2.607, p=0.042, η2p=0.115) was found. Children with CP FS showed greater increase in spectral power in response to the first stimulus presentation, while children with CUP FS failed to show a RS pattern. Significance: Our results show distinct abnormalities in brain activity to a habituation paradigm. We argue that these changes suggest children with CP FS may be hyperexcitable, while children with CUP FS show impaired habituation processes. Still, these differences may be associated with other clinical features linked to complex FS as well. Hence, the role of these differences in complex FS incidence and prognosis should be the subject of future studies

DHX15-independent roles for TFIP11 in U6 snRNA modification, U4/U6.U5 tri-snRNP assembly and pre-mRNA splicing fidelity

International audienceThe U6 snRNA, the core catalytic component of the spliceosome, is extensively modified post-transcriptionally, with 2’-O-methylation being most common. However, how U6 2’-O-methylation is regulated remains largely unknown. Here we report that TFIP11, the human homolog of the yeast spliceosome disassembly factor Ntr1, localizes to nucleoli and Cajal Bodies and is essential for the 2’-O-methylation of U6. Mechanistically, we demonstrate that TFIP11 knockdown reduces the association of U6 snRNA with fibrillarin and associated snoRNAs, therefore altering U6 2′-O-methylation. We show U6 snRNA hypomethylation is associated with changes in assembly of the U4/U6.U5 tri-snRNP leading to defects in spliceosome assembly and alterations in splicing fidelity. Strikingly, this function of TFIP11 is independent of the RNA helicase DHX15, its known partner in yeast. In sum, our study demonstrates an unrecognized function for TFIP11 in U6 snRNP modification and U4/U6.U5 tri-snRNP assembly, identifying TFIP11 as a critical spliceosome assembly regulator

Multi-Institutional Evaluation of Pathologists' Assessment Compared to Immunoscore.

BACKGROUND The Immunoscore (IS) is a quantitative digital pathology assay that evaluates the immune response in cancer patients. This study reports on the reproducibility of pathologists' visual assessment of CD3+- and CD8+-stained colon tumors, compared to IS quantification. METHODS An international group of expert pathologists evaluated 540 images from 270 randomly selected colon cancer (CC) cases. Concordance between pathologists' T-score, corresponding hematoxylin-eosin (H&E) slides, and the digital IS was evaluated for two- and three-category IS. RESULTS Non-concordant T-scores were reported in more than 92% of cases. Disagreement between semi-quantitative visual assessment of T-score and the reference IS was observed in 91% and 96% of cases before and after training, respectively. Statistical analyses showed that the concordance index between pathologists and the digital IS was weak in two- and three-category IS, respectively. After training, 42% of cases had a change in T-score, but no improvement was observed with a Kappa of 0.465 and 0.374. For the 20% of patients around the cut points, no concordance was observed between pathologists and digital pathology analysis in both two- and three-category IS, before or after training (all Kappa < 0.12). CONCLUSIONS The standardized IS assay outperformed expert pathologists' T-score evaluation in the clinical setting. This study demonstrates that digital pathology, in particular digital IS, represents a novel generation of immune pathology tools for reproducible and quantitative assessment of tumor-infiltrated immune cell subtypes