abstract: In most of the work using event-related potentials (ERPs), researchers presume the function of specific components based on the careful manipulation of experimental factors, but rarely report direct evidence supporting a relationship between the neural signal and other outcomes. Perhaps most troubling is the lack of evidence that ERPs correlate with related behavioral outcomes which should result, at least in part, from the neural processes that ERPs capture. One such example is the NoGo-N2 component, an ERP component elicited in Go/NoGo paradigms. There are two primary theories regarding the functional significance of this component in this context: that the signal represents response inhibition and that the component reflects conflict. In this paper, a trial-level method of analysis for the relationship between ERP component potentials and downstream behavioral outcomes (in this case, response accuracy) using a multi-level modeling framework is proposed to provide discriminatory evidence for one of these theories. Following a description of the research on the NoGo-N2, preliminary data supporting the conflict monitoring theory are presented, noting important limitations. Next, an EEG simulation study is presented in which NoGo-N2 data are generated with a known relationship to fabricated reaction time data, showing that, with added levels of complexity and noise within the data, the MLM approach is consistently successful at extracting the known relationships that occur in real NoGo-N2 data. Next, using independent components analysis (ICA) to extract spatiotemporal components that best represent the signal of interest, a well-powered analysis of the relationship between the NoGo-N2 and response accuracy is used to provide strong discriminatory evidence for the conflict monitoring theory of the NoGo-N2. Finally, implications for the NoGo-N2, as well as all ERP components, are discussed with a focus on how this approach can and should be used. the paper concludes with potential expansions of this approach to areas beyond identifying the function of ERP components. / Dissertation/Thesis / Doctoral Dissertation Psychology 2019

Abstract The aim of this study was to discover attention- and inhibitory control-related differences in the electrical activity of the brain in 6- to 9-year-old children who stutter (CWS) compared to typically developed children (TDC). For studies I and II, the study group consisted of 11 CWS (mean age 8.1 years, age range 6.3–9.5 years; all boys) and 19 fluently speaking children (mean age 8.1 years, age range 5.8–9.6 years; 7 girls). In study III, the participants were twelve boys who stutter (mean age 7.97 years, range 6.3–9.5 years) and 12 typically developed, fluently speaking boys (mean age 8.01 years, range 5.8–9.6 years). The CWS were recruited through local speech therapists and special teachers and newspaper advertisements, while controls were recruited from schools and preschools and among families of department staff and friends. Electroencephalography (EEG) was recorded during a visual Go/Nogo task, which forms a conflict between the pre-potent Go-response and inhibition of response in the Nogo condition, demanding inhibitory control. This EEG data was investigated with conventional event-related potentials (ERP) analysis, potential map and global field power (GFP) analysis and a time-frequency analysis including the periods between tasks. In the ERP analysis, the CWS had a delayed N2 component in the Go condition and a poorly defined P3 component. The potential maps and GFP waveforms confirmed the findings in the Go condition, but also revealed differences in the Nogo condition, described as a prolonged and excessive N2component and an absent P3 component in the CWS. These results indicate problems in the evaluation and classification of the stimulus and the response preparation and inhibition of the response. In the time-frequency analysis, the CWS showed reduced occipital alpha power in the “resting” or preparatory period between visual stimuli, particularly in the Nogo condition. Therefore, the CWS demonstrate reduced inhibition of the visual cortex in the absence of visual stimuli, which is likely related to problems in attentional gating. This newly discovered lack of occipital alpha modulation indicates elementary differences in the regulation of visual information processing in CWS. These findings support the view of stuttering as part of an extensive brain dysfunction involving also attentional and inhibitory networks. / Tiivistelmä Tutkimuksen tavoitteena oli tunnistaa tarkkaavuuteen ja inhibitiokontrolliin liittyviä eroja aivojen sähköisessä toiminnassa 6–9-vuotiailla lapsilla, jotka änkyttävät verrattuna tavanomaisesti kehittyviin lapsiin. Osatöissä I ja II koeryhmässä oli 11 änkyttävää lasta (iän keskiarvo 8.1 vuotta, ikäjakauma 6.3–9.5 vuotta) ja verrokkiryhmässä 19 sujuvasti puhuvaa lasta (keskiarvo 8.1 vuotta, jakauma 5.8–9.6 vuotta; 7 tyttöä). Osatyössä III koeryhmässä oli 12 änkyttävää poikaa (keskiarvo 7.97, jakauma 6.3–9.5 vuotta) ja verrokkiryhmässä 12 sujuvasti puhuvaa poikaa (keskiarvo 8.01 vuotta, jakauma 5.8–9.6 vuotta). Koehenkilöitä haettiin puheterapeuttien ja erityisopettajien välityksellä sekä lehti-ilmoituksilla. Verrokkiryhmän osallistujat rekrytoitiin kouluista, esikouluista sekä henkilökunnan ja ystävien perheiden joukosta. Elektroenkefalografia (EEG) rekisteröitiin visuaalisen Go/Nogo-tehtävän aikana. Tehtävässä ennakoidun Go-vasteen ja Nogo-tilanteessa vaadittavan reaktiosta pidättäytymisen välille syntyvä ristiriita kuormittaa inhibitiokontrollia. EEG-dataa arvioitiin herätevasteiden avulla, tutkimalla jännitekarttojen ja koko pään jännitevaihteluiden eroja sekä käyttämällä aika-taajuusanalyysia, mihin sisältyi myös tehtävien välinen aika. Herätevasteanalyysissä änkyttävillä lapsilla oli viivästynyt N2-vaste Go-tilanteessa ja huonosti erottuva P3-vaste. Jännitekarttojen ja koko pään jännitevaihteluiden perusteella tämä löydös vahvistui, mutta ryhmät erosivat toisistaan myös Nogo-tilanteessa. Änkyttävillä lapsilla N2-vaste oli pidentynyt ja voimakkaampi ja P3-vaste puuttui. Löydökset viittaavat ongelmiin ärsykkeen arvioinnissa ja luokittelussa sekä reaktion valmistelussa ja inhibitiossa. Aika-taajuusanalyysissa änkyttävillä lapsilla oli okkipitaalialueilla merkittävästi vähemmän alfataajuista toimintaa tehtävien välisen ”lepotilan” tai valmistautumisvaiheen aikana erityisesti Nogo-tilanteessa. Änkyttävillä lapsilla näköaivokuoren inhibitio ärsykkeen puuttuessa on näin ollen heikentynyt, mikä viittaa häiriöön tarkkaavuuden suuntaamisessa. Tämä todettu alfatoiminnan säätelyn puuttuminen ilmentää perustavanlaatuisia eroja näköärsykkeen käsittelyssä änkyttävillä lapsilla. Löydökset tukevat näkemystä änkytyksestä osana laaja-alaista aivojen toiminnan häiriötä, joka käsittää todennäköisesti myös tarkkaavuuteen ja inhibitiokontrolliin liittyviä verkostoja.

La maladie d’Alzheimer à forme tardive, exempte de mutations, représente près de 99% des 850 000 cas répertoriés en France. Hormis l’âge, des facteurs génétiques comme BIN1 apparaissent déterminant dans l’établissement de l’amyloïdopathie et de la tauopathie, marqueurs constitutifs de cette maladie. Le travail de thèse est basé sur l’étude d’une surexpression du gène humain de BIN1 et de son impact dans un contexte murin de tauopathie. La surexpression seule de BIN1 entraine des défauts mnésiques à court terme associés à des anomalies cellulaires et moléculaires au niveau de la voie temporo-hippocampique. Ces altérations sont exacerbées par la combinaison de la souris TgBIN1 avec le modèle de tauopathie, à la fois chez les mâles et les femelles. Pour autant il apparait que la surexpression de BIN1 préserve la mémoire spatiale dépendamment de l’âge et du sexe. L’hippocampe apparait en grande partie préservé des inclusions intracellulaires de Tau et la myéline des fibres axonales est retrouvé intacte. Ces éléments mettent en évidence que BIN1 est un acteur important dans l’établissement de la tauopathie et que son activité neuro-protectrice peut être médiée par un complexe moléculaire direct impliquant à la fois Tau et RNT4-A/Nogo-A. / Late Onset Alzheimer Disease represents more than 99% of total Alzheimer cases and it is not caused by genetic mutations. Among risk factors such as age, genetic compounds as BIN1 appear to be determinant for the pathological process establishment. This study aims to determine the BIN1 overexpression effect in mice and in a tauopathy context. In this study, BIN1 overexpression alone caused short term memory impairments linked with the cellular and molecular abnormalities. These disorders are exacerbated by a combination of TgBIN1 mice with a tauopathy model, both in males and females. Surprisingly, BIN1 overexpression rescued long term and spatial memory regarding the age and sex. Hippocampus appeared to be preserved from intracellular Tau inclusions. Moreover, fornix myelin is found intact. These elements highlighted BIN1 which is a key gene in tauopathie establishment. BIN1 neuroprotective activity is mediated by direct molecular interactions both with Tau and RTN4-A/Nogo-A.

No description available.

Schizophrenia may result from altered gene expression leading to abnormal neurodevelopment. In a search for genes with altered expression in schizophrenia, cDNA library subtractive hybridization experiments using post-mortem human frontal cerebral cortices from schizophrenia individuals and neurological controls were performed. I found the mRNA of two neurodevelopmentally important genes, Nogo (RTN4) and calcium/calmodulin-dependent protein kinase II beta (CaMKIIβ), to be overexpressed in post-mortem frontal cortex tissues from patients who suffered with schizophrenia. I used the quantitative real-time polymerase chain reaction method to determined the mRNA levels of these genes in tissues from age- and sex-matched individuals. Nogo is a myelin-associated protein which inhibits the outgrowth of neurites and nerve terminals. The gene produces three splice variants, Nogo-A, B and C. I found Nogo-C mRNA to be overexpressed by 26% in schizophrenia. I also found a 17% reduction of Nogo-B mRNA in samples from individuals who had been diagnosed with severe depression. Furthermore, I showed that there is a direct correlation between the expression of both Nogo-A and -C and the presence of a CAA insert in the 3’UTR of the Nogo gene. CaMKII is a kinase localized at the postsynaptic density. The holoenzyme is primarily composed of the subunits α and β, encoded by two separate genes. It influences the expression of many neuroreceptors, in particular receptors of the glutamatergic pathway. CaMKII also mediates neural maturation during puberty, a time of onset of schizophrenia. The expression of CaMKIIα was elevated 29% in frontal cortex tissues of patients who suffered from depression. The expression of CaMKIIβ was elevated 27% in tissues of schizophrenia patients and 36% in tissues of patients diagnosed with depression. Upregulation of CaMKIIβ was associated with the presence of the CAA insert in at least one copy of the Nogo gene in a group containing both healthy subjects and patients with mental illness, possibly linking the CaMKII and Nogo pathways. The values for the expression of Nogo, CaMKIIα and CaMKIIβ were normalized to β-glucuronidase expression to minimize the effects of mRNA degradation. These results confirm that upregulation of Nogo-C and CaMKIIβ is likely associated with schizophrenia.

Schizophrenia may result from altered gene expression leading to abnormal neurodevelopment. In a search for genes with altered expression in schizophrenia, cDNA library subtractive hybridization experiments using post-mortem human frontal cerebral cortices from schizophrenia individuals and neurological controls were performed. I found the mRNA of two neurodevelopmentally important genes, Nogo (RTN4) and calcium/calmodulin-dependent protein kinase II beta (CaMKIIβ), to be overexpressed in post-mortem frontal cortex tissues from patients who suffered with schizophrenia. I used the quantitative real-time polymerase chain reaction method to determined the mRNA levels of these genes in tissues from age- and sex-matched individuals. Nogo is a myelin-associated protein which inhibits the outgrowth of neurites and nerve terminals. The gene produces three splice variants, Nogo-A, B and C. I found Nogo-C mRNA to be overexpressed by 26% in schizophrenia. I also found a 17% reduction of Nogo-B mRNA in samples from individuals who had been diagnosed with severe depression. Furthermore, I showed that there is a direct correlation between the expression of both Nogo-A and -C and the presence of a CAA insert in the 3’UTR of the Nogo gene. CaMKII is a kinase localized at the postsynaptic density. The holoenzyme is primarily composed of the subunits α and β, encoded by two separate genes. It influences the expression of many neuroreceptors, in particular receptors of the glutamatergic pathway. CaMKII also mediates neural maturation during puberty, a time of onset of schizophrenia. The expression of CaMKIIα was elevated 29% in frontal cortex tissues of patients who suffered from depression. The expression of CaMKIIβ was elevated 27% in tissues of schizophrenia patients and 36% in tissues of patients diagnosed with depression. Upregulation of CaMKIIβ was associated with the presence of the CAA insert in at least one copy of the Nogo gene in a group containing both healthy subjects and patients with mental illness, possibly linking the CaMKII and Nogo pathways. The values for the expression of Nogo, CaMKIIα and CaMKIIβ were normalized to β-glucuronidase expression to minimize the effects of mRNA degradation. These results confirm that upregulation of Nogo-C and CaMKIIβ is likely associated with schizophrenia.

Traumatic Brain Injury (TBI) mainly affects young persons in traffic accidents and the elderly in fall accidents. Improvements in the clinical management have significantly improved the outcome following TBI but survivors still suffer from depression, memory problems, personality changes, epilepsy and fatigue. The initial injury starts a series of events that give rise to a secondary injury process and despite several clinical trials there is no drug available for clinical use that targets secondary brain injury mechanisms. Some recovery of function is seen during the first months following injury but is usually limited and there are no drugs that stimulate the recovery of lost function. Some of the recovery is attributed to plasticity, the brains ability to adapt to new circumstances, and enhancing plasticity via increased axonal growth has the potential to partly restore lost function. In this thesis mice were subjected to the controlled cortical impact model of TBI and functional outcome was evaluated using Morris water maze, the cylinder test and the rotarod. Brain tissue loss was measured in all Papers but the additional histological analyses differ among the Papers. Attempts to increase axonal growth were made by interfering with Nogo receptor function in Paper I and by conditional knockout of ephA4 in Paper II. Contrary to the hypothesis cognition was impaired in Paper I but otherwise no effects of treatment were detected in Paper I and II. Much is still unknown about plasticity and despite the discouraging results of Papers I and II this treatment approach is still worth further exploration. It is firmly established that TBI results in an inflammatory response and some aspects of it may damage brain tissue. In Papers III and IV the inflammatory response was attenuated using an IL-1β directed antibody which resulted in reduced tissue loss and edema while improving cognitive function. The results from Papers III and IV are encouraging and the possibility to find a treatment based on IL-1β inhibition appears promising.

La jouissance est un des champs dont la psychanalyse fait usage pour rendre compte de ce qui pourrait expliquer le boitement structurel de la condition humaine, son paradoxe fondamental. Partant d'une épistémologie transcendantale, nous envisageons que, bien que le corps et la psyché ne revêtent pas les mêmes réalités, ils ont certains points d'accroche dont fait partie la jouissance et, bien que le corps ne détermine pas le psychisme, il le contraint. Il est alors proposé ici une hypothèse neuropsychanalytique de la jouissance, l'articulant autour du corps et de l'histoire. La jouissance serait la marque de ce qui a fait événement pour le sujet. Cette description permet de relier ce concept à la neurophysiologie des circuits dopaminergiques qui marquent physiologiquement tant la dimension pulsionnelle, que la dimension événementielle et donc historique.À partir de cette conceptualisation, un paradigme expérimental a été constitué afin d'investiguer cette possibilité d'une accroche entre le psychique et le biologique chez des sujets dépendants, lorsqu'ils sont confrontés à leur objet d'addiction. Concrètement, nous 'osons' l'hypothèse que plus un sujet manifeste d'indices repérables d'une mobilisation pulsionnelle dans son discours libre amorcé par l’objet addictif (dans ce cas-ci, la cigarette pour des fumeurs), plus il aura le geste rapide et sûr pour l’attraper ou des difficultés à inhiber son appétence vers cet objet. Ceci est investigué à travers un outil constitué à partir de la théorie psychanalytique d’une part, et à travers deux tâches de type Go-NoGo (évaluées par des mesures comportementales –temps de réaction et erreurs- et électrophysiologiques -la N2 et la P3, deux marqueurs considérés comme reflétant la signature des processus attentionnels et des biais d’inhibition-, d’autre part. La particularité du paradigme, outre cet usage d’outils issus de champs distincts, réside dans le fait que, à aucun moment, ce n’est le sens du discours des sujets, qui est investigué. L’outil psychanalytique évalue effectivement la façon dont les sujets s’expriment, et ce sont des juges naïfs (à l’égard de l’étude et de la psychanalyse) qui évaluent leur discours. Nos résultats mettent en évidence que les personnes dépendantes manifestent une tendance à l’impulsivité de façon générale. Mais, lorsque leur objet d’addiction est en place de support attentionnel, les sujets démontrent une augmentation significative de leurs performances et de l’amplitude de la P3, signe d’un investissement attentionnel. Les résultats des associations libres révèlent que la forme du discours des fumeurs est évaluée comme plus transgressive (comparativement aux non-fumeurs). Enfin, on retrouve une corrélation entre les indices psychiques (la transgression) et neurophysiologiques (la latence de la NoGo-N2). En conclusion, il semble que l’addiction dépasse la simple réalité pharmacologique de l’effet du toxique puisqu’il est repéré ici que l’effet de stimulant cognitif (manifeste par l’amélioration des performances) est induit par la simple représentation de la cigarette et non par la consommation de celle-ci. Ensuite, au regard de notre proposition épistémologique, nous semblons avoir réussi, sur base d’une lecture rapprochée des séminaires de Lacan, à construire un outil qui distingue de façon cohérente, consistante et valide une dimension pulsionnelle d’une dimension affective (valencée) dans ce qui peut s’entendre. Grâce à cet outil, nous avons trouvé des corrélations entre certains de ces marqueurs psychiques et certains paramètres physiologiques - les paramètres corrélant étant précisément des plus probants et la corrélation s’avérant être dans le sens prédit par notre construction hypothétique. Sur ce 'succès’, nous osons une conclusion épistémologique plus large qui propose que si l’univers du représentationnel, c'est-à-dire, du mental, est bien accroché au niveau de repères physiologiques, ceci n’est démontrable sur un plan mental que si l’on se borne à la forme des contenus mentaux – et, qui plus est, et de façon spéculative, en évitant toute hérméneutique au niveau des contenus mentaux. / Doctorat en Sciences psychologiques et de l'éducation / info:eu-repo/semantics/nonPublished

The aim of this thesis is to evaluate the level of motor skills in children and adolescents dealing with judo and taekwondo and to determine whether the level of motor skills differs between children with a suspected risk of ADHD (Attention Deficit Hyperactivity Disorder) compared to children without this risk. Another aim of this study is to evaluate the level of attention and find out whether it correlates with the level of motor skills. A total of 65 probands aged 9-13 years participated in the study. The experimental groups consisted of children competing in judo (n = 35), children practicing taekwondo (n = 19) and children attending taekwondo classes in physical education and hobby groups (n = 11). The Movement Assessment Battery for Children 2 test was chosen to test motor skills. To detect a suspected risk of ADHD was used the Test Go / NoGo and the level of attention was tested by theTest of attention d2. A significant difference in favour of judists was found between the results of motor skills of children and adolescents in comparison with the racing group of taekwondists (p = 0.045) and also in the results of individual components, namely in the balance component (p = 0.051). A significant difference was found in motor skills among children with a suspected risk of ADHD compared to...

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