Cette thèse doctorale, qui prend la forme de quatre articles, est une étude corrélationnelle mettant en relation le raisonnement moral et la légitimation des dynamiques d’intimidation par les pairs chez des adolescents de 3ème secondaire. L’objectif principal poursuivi était d’examiner la contribution de la désensibilisation morale aux conduites adoptées par les adolescents lors d’incidents d’intimidation à l’école. L’objectif secondaire était d’examiner l’importance accordée respectivement à des standards de conduite issus des domaines moral, conventionnel et personnel chez les adolescents impliqués dans des incidents d’intimidation. Le premier article expose la problématique de la légitimation des dynamiques d’intimidation par les jeunes en faisant état des croyances normatives et des caractéristiques des environnements scolaires qui y sont associées. L’article discute de l’écart qui s’observe entre l’opposition affirmée de la majorité des adolescents face aux conduites d’intimidation et leur récurrence dans les milieux scolaires et vient compléter une première section décrivant les conséquences de l’intimidation pour les communautés scolaires. Le deuxième article s’inscrit dans le cadre théorique de cette thèse et fait état des connaissances sur le raisonnement moral des élèves impliqués dans des dynamiques d’intimidation. Il présente une explication des conduites d’intimidation dans la perspective de la théorie des domaines de la connaissance sociale et dans celle de la théorie de l’agentivité morale. Ces approches ont été retenues pour opérationnaliser le concept de désensibilisation morale afin de rencontrer les objectifs de recherche poursuivis. Le troisième article rapporte la démarche utilisée pour vérifier l’hypothèse d’une relation positive entre les conduites d’intimidation et l’acceptabilité d’incidents d’intimidation hypothétiques, de même que l’hypothèse d’une relation positive entre les conduites d’intimidation et le désengagement moral chez les adolescents impliqués. Le quatrième article rapporte la démarche utilisée pour examiner les justifications sociomorales émises par différents profils d’adolescents impliqués dans des incidents d’intimidation de façon à associer leur conduite avec les domaines de connaissances normatives auxquels se rattachent leurs justifications. Les résultats obtenus sont ensuite discutés au chapitre suivant afin de mettre en évidence la contribution de chacune des approches morales retenues à l’explication des conduites en contexte d’intimidation et les caractéristiques du raisonnement moral associées aux rôles adoptés et des pistes d’intervention sont offertes. Finalement, cette thèse doctorale conclue que seul le niveau moyen de désengagement moral, un indice global de l’adhésion à des croyances normatives antisociales, contribue statistiquement à l’explication des conduites adoptées lors d’incident d’intimidation au-delà du sexe des participants. Quant au raisonnement sociomoral, il informe davantage sur la façon dont les circonstances d’incidents d’intimidation sont reliées à la désensibilisation morale des jeunes impliqués. Les adolescents qui prennent activement la défense de pairs intimidés étaient caractérisés par un raisonnement moral plus uniforme, tandis que le raisonnement des élèves qui intimident et de ceux qui demeurent passifs était caractérisé par la subordination de principes moraux, respectivement en faveur d’impératifs à caractère conventionnel et d’impératifs à caractère personnel. / This doctoral thesis, presented as four scientific articles, is a correlational study about moral reasoning and the legitimization of school bullying in third-year high school students. The primary objective was to investigate the contribution of moral disinhibition to the bullying incident roles adopted by teenagers. The secondary objective was to investigate the relative importance given to moral, conventional, and personal standards of conduct in students involved in bullying incidents. The first article acknowledges the problem that is the legitimization of bullying conducts by school communities and exposes related normative beliefs and school environment characteristics. It mainly discusses the gap between the vocal opposition to bullying conducts shown by most students and the occurrence of bullying incidents in schools. This completes a section exposing the consequences associated with bullying. The second article reviews recent literature about moral reasoning and its link to bulling incident roles. It also gives an explanation of bullying conducts from the viewpoints of the social domains theory and of the sociocognitive theory of moral agentivity. These theoretical paradigms were used in operationalizing the concept of moral disinhibition in order to meet study goals. The third article reports on the methodology used in order to verify the hypothesis of a positive relation between bullying conducts and acceptability of hypothetical bullying incidents, as well as the hypothesis of a positive relation between bullying conducts and moral disengagement in involved adolescents. The forth article reports on the methodology used in the investigation of sociomoral justifications from adolescents adopting different bullying incident roles in order to ascertain the relation between their conduct and the social domains from which stem their justifications. Results are discussed as to show the contribution of each approach to the explanation of bullying incident roles and the moral reasoning characteristics related to each role. Intervention guidelines are proposed as well. This doctoral thesis concludes that only moral disengagement mean scores, which work as a global indication of antisocial normative beliefs, explain bullying incident roles beyond participants’ gender. Sociomoral reasoning is better suited to understanding how bullying incidents’ characteristics promote moral disinhibition. Actively defending bullied peers wad linked to more uniform moral reasoning. On the other hand, bullying and pro-bullying conducts were linked to moral subordination in favor of conventional standards of conduct, and passive bystanding was linked to moral subordination in favor of personal standards of conducts.

No description available.

Objetivos: O transtorno de déficit de atenção/hiperatividade (TDAH), o transtorno de conduta (TC) e o transtorno opositor desafiante (TOD) frequentemente ocorrem juntos na infância. No entanto, a existência e importância destes transtornos na vida adulta ainda é motivo de discussão. Este estudo tem como objetivo avaliar a extensão do impacto da história de TOD e TC na saúde mental global de indivíduos com TDAH persistente. Visa também avaliar a relação desses achados com o modelo de desinibição comportamental, considerando os perfis de desenvolvimento neurológico, personalidade e comorbidades. Métodos: Os pacientes foram selecionados consecutivamente a partir de uma amostra de conveniência no ambulatório de pesquisa do TDAH em adultos do Hospital de Clínicas de Porto Alegre (n=458). O grupo controle foi composto de voluntários doadores de sangue no Hemocentro do mesmo hospital (n=121). Os diagnósticos foram realizados com base nos critérios do DSM-IV, sendo os sujeitos avaliados para o TDAH e o TOD através do K-SADS-E; para o TC e o transtorno de personalidade anti-social através do MINI; e através do SCID para as demais comorbidades. A gravidade do TDAH foi avaliada utilizando o SNAP, e a personalidade avaliada com o TCI (Cloninger). Na análise foram comparados os pacientes com TDAH e os controles. No caso das variáveis com diferenças significativas, comparamos três grupos: TDAH sem história de TC ou de TOD (n=178); TDAH com história de TOD (sem TC) (n=184) e TDAH com história de TC (com ou sem TOD) (n=96). Resultados: Pacientes com TDAH apresentaram um perfil mais grave na comparação com os controles em diversas variáveis, incluindo todas as comorbidades. Internamente ao grupo com TDAH, uma história positiva de TC (e, em grau menor, de TOD) associou-se a maior gravidade e a um perfil mais externalizador. Conclusão: Uma história positiva de TOD e TC na infância ou adolescência associa-se a um impacto negativo na saúde mental de sujeitos com TDAH persistente, reforçando o valor preditivo destes transtornos para a saúde mental do adulto. Estes achados sugerem uma ligação entre déficits do desenvolvimento, características de personalidade, e desdobramentos de psicopatologias, que é consistente com o conceito de cascada de desinibição comportamental. / Objective: Attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD) and conduct disorder (CD) are frequently co-occurring disorders in children and adolescents. However, their clinical status among adults is disputed. This study analyzes how the clinical presentation of persistent ADHD might be influenced by a childhood or adolescence history of CD and ODD, and how these findings fit in the behavioral disinhibition framework. Methods: Patients were ascertained in an ADHD outpatient clinic. Diagnoses were based on the DSM-IV criteria and all subjects were evaluated using the KSADS- E for ADHD and ODD, MINI for CD/ASPD, SCID-I for other comorbidities, SNAP-IV for ADHD severity and Cloninger’s Temperament and Character Inventory (TCI) for personality. We compared patients with ADHD (n= 458) with controls (n=121). For those variables with significant differences, we compared three groups of patients: ADHD without history of CD or ODD (n=178); ADHD + history of ODD (without CD) (n=184) and ADHD + history of CD (with or without ODD) (n=96). Results: Patients with ADHD presented a worse profile than controls in several variables, including a higher frequency of all comorbidities. Within the ADHD group, a history of CD (and to a lower extent ODD) is associated with a more severe and externalizing profile. Conclusion: A history of CD and ODD entail a significant negative mental health impact on persistent ADHD, reinforcing the predictive validity of these entities in adulthood mental health. These findings suggest a link among neurodevelopmental deficits, personality characteristics, and unfolding of psychopathology consistent with the behavioral disinhibition cascade.

Objetivos: O transtorno de déficit de atenção/hiperatividade (TDAH), o transtorno de conduta (TC) e o transtorno opositor desafiante (TOD) frequentemente ocorrem juntos na infância. No entanto, a existência e importância destes transtornos na vida adulta ainda é motivo de discussão. Este estudo tem como objetivo avaliar a extensão do impacto da história de TOD e TC na saúde mental global de indivíduos com TDAH persistente. Visa também avaliar a relação desses achados com o modelo de desinibição comportamental, considerando os perfis de desenvolvimento neurológico, personalidade e comorbidades. Métodos: Os pacientes foram selecionados consecutivamente a partir de uma amostra de conveniência no ambulatório de pesquisa do TDAH em adultos do Hospital de Clínicas de Porto Alegre (n=458). O grupo controle foi composto de voluntários doadores de sangue no Hemocentro do mesmo hospital (n=121). Os diagnósticos foram realizados com base nos critérios do DSM-IV, sendo os sujeitos avaliados para o TDAH e o TOD através do K-SADS-E; para o TC e o transtorno de personalidade anti-social através do MINI; e através do SCID para as demais comorbidades. A gravidade do TDAH foi avaliada utilizando o SNAP, e a personalidade avaliada com o TCI (Cloninger). Na análise foram comparados os pacientes com TDAH e os controles. No caso das variáveis com diferenças significativas, comparamos três grupos: TDAH sem história de TC ou de TOD (n=178); TDAH com história de TOD (sem TC) (n=184) e TDAH com história de TC (com ou sem TOD) (n=96). Resultados: Pacientes com TDAH apresentaram um perfil mais grave na comparação com os controles em diversas variáveis, incluindo todas as comorbidades. Internamente ao grupo com TDAH, uma história positiva de TC (e, em grau menor, de TOD) associou-se a maior gravidade e a um perfil mais externalizador. Conclusão: Uma história positiva de TOD e TC na infância ou adolescência associa-se a um impacto negativo na saúde mental de sujeitos com TDAH persistente, reforçando o valor preditivo destes transtornos para a saúde mental do adulto. Estes achados sugerem uma ligação entre déficits do desenvolvimento, características de personalidade, e desdobramentos de psicopatologias, que é consistente com o conceito de cascada de desinibição comportamental. / Objective: Attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD) and conduct disorder (CD) are frequently co-occurring disorders in children and adolescents. However, their clinical status among adults is disputed. This study analyzes how the clinical presentation of persistent ADHD might be influenced by a childhood or adolescence history of CD and ODD, and how these findings fit in the behavioral disinhibition framework. Methods: Patients were ascertained in an ADHD outpatient clinic. Diagnoses were based on the DSM-IV criteria and all subjects were evaluated using the KSADS- E for ADHD and ODD, MINI for CD/ASPD, SCID-I for other comorbidities, SNAP-IV for ADHD severity and Cloninger’s Temperament and Character Inventory (TCI) for personality. We compared patients with ADHD (n= 458) with controls (n=121). For those variables with significant differences, we compared three groups of patients: ADHD without history of CD or ODD (n=178); ADHD + history of ODD (without CD) (n=184) and ADHD + history of CD (with or without ODD) (n=96). Results: Patients with ADHD presented a worse profile than controls in several variables, including a higher frequency of all comorbidities. Within the ADHD group, a history of CD (and to a lower extent ODD) is associated with a more severe and externalizing profile. Conclusion: A history of CD and ODD entail a significant negative mental health impact on persistent ADHD, reinforcing the predictive validity of these entities in adulthood mental health. These findings suggest a link among neurodevelopmental deficits, personality characteristics, and unfolding of psychopathology consistent with the behavioral disinhibition cascade.

Objetivos: O transtorno de déficit de atenção/hiperatividade (TDAH), o transtorno de conduta (TC) e o transtorno opositor desafiante (TOD) frequentemente ocorrem juntos na infância. No entanto, a existência e importância destes transtornos na vida adulta ainda é motivo de discussão. Este estudo tem como objetivo avaliar a extensão do impacto da história de TOD e TC na saúde mental global de indivíduos com TDAH persistente. Visa também avaliar a relação desses achados com o modelo de desinibição comportamental, considerando os perfis de desenvolvimento neurológico, personalidade e comorbidades. Métodos: Os pacientes foram selecionados consecutivamente a partir de uma amostra de conveniência no ambulatório de pesquisa do TDAH em adultos do Hospital de Clínicas de Porto Alegre (n=458). O grupo controle foi composto de voluntários doadores de sangue no Hemocentro do mesmo hospital (n=121). Os diagnósticos foram realizados com base nos critérios do DSM-IV, sendo os sujeitos avaliados para o TDAH e o TOD através do K-SADS-E; para o TC e o transtorno de personalidade anti-social através do MINI; e através do SCID para as demais comorbidades. A gravidade do TDAH foi avaliada utilizando o SNAP, e a personalidade avaliada com o TCI (Cloninger). Na análise foram comparados os pacientes com TDAH e os controles. No caso das variáveis com diferenças significativas, comparamos três grupos: TDAH sem história de TC ou de TOD (n=178); TDAH com história de TOD (sem TC) (n=184) e TDAH com história de TC (com ou sem TOD) (n=96). Resultados: Pacientes com TDAH apresentaram um perfil mais grave na comparação com os controles em diversas variáveis, incluindo todas as comorbidades. Internamente ao grupo com TDAH, uma história positiva de TC (e, em grau menor, de TOD) associou-se a maior gravidade e a um perfil mais externalizador. Conclusão: Uma história positiva de TOD e TC na infância ou adolescência associa-se a um impacto negativo na saúde mental de sujeitos com TDAH persistente, reforçando o valor preditivo destes transtornos para a saúde mental do adulto. Estes achados sugerem uma ligação entre déficits do desenvolvimento, características de personalidade, e desdobramentos de psicopatologias, que é consistente com o conceito de cascada de desinibição comportamental. / Objective: Attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD) and conduct disorder (CD) are frequently co-occurring disorders in children and adolescents. However, their clinical status among adults is disputed. This study analyzes how the clinical presentation of persistent ADHD might be influenced by a childhood or adolescence history of CD and ODD, and how these findings fit in the behavioral disinhibition framework. Methods: Patients were ascertained in an ADHD outpatient clinic. Diagnoses were based on the DSM-IV criteria and all subjects were evaluated using the KSADS- E for ADHD and ODD, MINI for CD/ASPD, SCID-I for other comorbidities, SNAP-IV for ADHD severity and Cloninger’s Temperament and Character Inventory (TCI) for personality. We compared patients with ADHD (n= 458) with controls (n=121). For those variables with significant differences, we compared three groups of patients: ADHD without history of CD or ODD (n=178); ADHD + history of ODD (without CD) (n=184) and ADHD + history of CD (with or without ODD) (n=96). Results: Patients with ADHD presented a worse profile than controls in several variables, including a higher frequency of all comorbidities. Within the ADHD group, a history of CD (and to a lower extent ODD) is associated with a more severe and externalizing profile. Conclusion: A history of CD and ODD entail a significant negative mental health impact on persistent ADHD, reinforcing the predictive validity of these entities in adulthood mental health. These findings suggest a link among neurodevelopmental deficits, personality characteristics, and unfolding of psychopathology consistent with the behavioral disinhibition cascade.

Background: The human Aldoketoreductase 1B10 gene (AKR1B10) encodes one of the enzymes belonging to the family of aldoketoreductases and may be involved in detoxification of nutrients during digestion. Further, AKR1B10 mRNA (messenger ribonucleic acid) expression was diminished in brain regions potentially involved in the regulation of eating behavior in rats which are more sensitive to cocaine and alcohol. We hypothesized that the human AKR1B10 gene may also play a role in the regulation of human eating behavior.

Allt fler i världen spelar onlinespel, men i samma takt ökar även antalet spelare som utsätts för trakasserier online. Den reducerade återhållsamhet individer känner inför att yttra sig online jämfört med vid fysiskt samtal kallas för the Online disinhibition effect, översatt till avhämningseffekten. Denna studie undersöker huruvida det går att reducera negativ påverkan av avhämningseffekten, så kallad elakartad avhämning, i onlinespel eftersom att spelare som påverkas av den är mer benägna att kommunicera trakasserier och glåpord. Frågan är av intresse för spelföretag med online-chatt; att förhindra trakasserier och glåpord skulle innebära att företag behöver lägga mindre resurser på moderering. Dessutom är frågan av intresse för privatpersoner som chattar online eftersom att deras välbefinnande skulle öka om den sociala spel-miljön blev bättre. En interaktiv pop-up utformades och testades i frågesportspelet Primetime. Pop-up:en syftade till att reducera elakartad avhämning hos spelarna. Inledningsvis hade vi fokus på att minska känslan av anonymitet, med färgval och emoticons som stärker ett lugnande budskap. Vi genomförde därefter ett A/B-test där spelomgångar utan pop-up jämfördes med spelomgångar med pop-up. Skillnaderna analyserades genom att vi mätte innehåll och kvantitet av meddelanden i Primetimes blockordsfunktion. Blockordsfunktionen samlar in de chattmeddelanden som består av flaggat innehåll, bland annat trakasserande meddelanden och glåpord. Ingen signifikant skillnad observerades med respektive utan pop-up:en i andelen blockordsmeddelanden per spelomgång. Vi kunde därmed inte dra någon slutsats om att andelen skulle ha förändrats av vår interaktiva pop-up. Likväl observerades en statistiskt säkerställd minskning av antalet chattmeddelanden som inte fångats upp av Primetimes blockordsfunktion om 49%. För sammanräknade antalet blockordsmeddelanden hade dessa minskat med 39%, men utan statistisk signifikans. Därmed drogs slutsatsen att vår pop-up delvis har reducerat avhämningseffekten, men inte med säkerhet trakasserande meddelanden och glåpord. / More and more people in the world are playing online games, however, the number of players who are being harassed online is also increasing. The reduced restraint one can experience when expressing oneself online compared to physical conversations is called the Online disinhibition effect. This study examines whether it is possible to reduce the negative aspects of the Online disinhibition effect, so called Toxic disinhibition, in online games. Gamers who are influenced by this effect are more prone to utter harassments and swearing in online games chats. The question is of interest for gaming companies that pursue online chat; preventing harassment and profanity would mean that companies need to spend less resources on moderation. In addition, the issue is of interest to individuals who chat online, as their well-being would increase if the social environment in games improved. An interactive pop-up was designed and tested in a quiz application called Primetime. The pop-up aimed to reduce toxic disinhibition among the players. Initially, we focused on reducing the feeling of anonymity, with color choices and emoticons that reinforce a calming message. We then performed an A/B-test where game rounds without pop-up were compared with game rounds with pop-up. The differences were analyzed by measuring the content and quantity of messages in Primetime's blockword function. The blockword function collects the chat messages that consist of flagged content, including harassing messages and profanity. No significant difference was observed with or without the pop-up in the proportion of blockword messages per game round. We could therefore not draw any conclusion that the proportion would have changed by our interactive pop-up. Nevertheless, a statistically significant reduction in the number of chat messages not captured by Primetime's blockword function was observed with a 49% decline. For the aggregate number of blockword messages, these had decreased by 39%, but without statistical significance. Thus, it was concluded that our pop-up has partially reduced the Online disinhibition effect, but not harassing messages and profanity

Text in Afrikaans / Hierdie studie ondersoek die moontlikheid dat aandagtekort versteuring met hiperaktiwiteit(ATHV/H) verband hou met probleme met voortgesette aandag, terwyl aandagtekort versteuring sander hiperaktiwiteit(ATHV/SO) verband hou met probleme met gefokusde aandag. Neurosielkundige toetse waarmee voortgesette- en gefokusde aandag gemeet word, word gebruik om drie groepe, naamlik ATHV/H(n=24), ATHV/SO(n=l5) en 'n kontrole groep(n=21), met mekaar te vergelyk. Resul tate dui daarop dat die groep ATHV/SO beduidend swakker presteer as die ander twee groepe op sommige van die toetse van gefokusde aandag, en ook neig om swakker te presteer op die toets van voortgesette aandag. Die groep ATHV/SO se probleme blyk gekoppel te wees aan 'n stadiger spoed van kognitiewe prosessering en 'n toestand van hipoopwekking. Die groep ATHV/H presteer nie beduidend swakker as die ander twee groepe op die toets van voortgesette aandag nie, maar presteer wel swakker as die kontrole groep op die Stroop Colour-Word Test waar inhibisie van ontoepaslike response vereis word. Die groep ATHV /H se probleme blyk verband te hou met frontale disfunksie wat manifesteer as 'n neighing tot impulsiwiteit en gebrekkige gedragsregulering. / This study examined the possibility that attention deficit disorder with hyperactivity(ADHD/H) is related to problems with sustained attention, while attention deficit disorder without hyperactivity (ADHD/WO) is related to problems with focussed attention. The performance of three groups: ADHD/H (n=24), ADHD/WO(n=15) and a control group(n=21) were compared. Results indicated that the ADHD/WO group performed significantly poorer than the other two groups on some of the tests of focussed attention and also tended to perform poorer on the test assessing sustained attention. This groups' symtoms appear to be related to a slowed speed of processing and a state of hypo-arousal. The ADHD/H group did not perform poorer than the other two groups on the test assessing sustained attention. The ADHD/H groups' symptoms appear to be related to frontal dysfunction resulting in impulsivity and poor behavioural control. / Psychology / M.A. (Sielkunde)

Les processus d'apprentissage et de mémoire sont contrôlés par des circuits et éléments neuronaux spécifiques. De nombreuses études ont récemment mis en évidence que les circuits corticaux jouent un rôle important dans la régulation des comportements de peur, cependant, leurs caractéristiques anatomiques et fonctionnelles restent encore largement inconnues. Au cours de ma thèse, en utilisant des enregistrements unitaires et des approches optogénétiques chez la souris libre de se comporter, nous avons pu montrer que les interneurones inhibiteurs du cortex auditif et du cortex préfrontal médian forment un microcircuit désinhibiteur permettant respectivement l'acquisition et l'expression de la mémoire de peur conditionnée. Dans les deux cas, les interneurones parvalbuminergiques constituent l'élément central du circuit et sont inhibés de façon phasique. D’un point de vue fonctionnel, nous avons démontré que cette inhibition était associée à la désinhibition des neurones pyramidaux par un mécanisme de réduction de l'inhibition continue exercée par les interneurones parvalbuminergiques. Ainsi, les interneurones parvalbuminergiques peuvent contrôler temporellement l'excitabilité des neurones pyramidaux. En particulier, nous avons montré que l'acquisition de la mémoire de peur conditionnée dépend du recrutement d'un microcircuit désinhibiteur localisé dans le cortex auditif. En effet, au cours du conditionnement de peur, la présentation du choc électrique induit l'inhibition des interneurones parvalbuminergiques, ce qui a pour conséquence de désinhiber les neurones pyramidaux du cortex auditif et de permettre l’apprentissage du conditionnement de peur. Dans leur ensemble, ces données suggèrent que la désinhibition est un mécanisme important dans l'apprentissage et le traitement de l'information dans les circuits corticaux. Dans un second temps, nous avons montré que l'expression de la peur conditionnée requière l'inhibition phasique des interneurones parvalbuminergiques du cortex préfrontal médian. En effet, leur inhibition désinhibe les cellules pyramidales préfrontales et synchronise leur activité en réinitialisant les oscillations thêta locales. Ces résultats mettent en évidence deux mécanismes neuronaux complémentaires induits par les interneurones parvalbuminergiques qui coordonnent et organisent avec précision l’activité neuronale des neurones pyramidaux du cortex préfrontal pour contrôler l'expression de la peur conditionnée. Ensemble, nos données montrent que la désinhibition joue un rôle important dans les comportements de peur en permettant l’association entre des informations comportementalement pertinentes, en sélectionnant les éléments spécifiques du circuit et en orchestrant l'activité neuronale des cellules pyramidales. / Learning and memory processes are controlled by specific neuronal circuits and elements. Numerous recent reports highlighted the important role of cortical circuits in the regulation of fear behaviour, however, the anatomical and functional characteristics of their neuronal components remain largely unknown. During my thesis, we used single unit recordings and optogenetic manipulations of specific neuronal elements in behaving mice, to show that both the auditory cortex and the medial prefrontal cortex contain a disinhibitory microcircuit required respectively for the acquisition and the expression of conditioned fear memory. In both cases, parvalbumin-expressing interneurons constitute the central element of the circuit and are phasically inhibited during the presentation of the conditioned tone. From a functional point of view, we demonstrated that this inhibition induced the disinhibition of cortical pyramidal neurons by releasing the ongoing perisomatic inhibition mediated by parvalbumin-expressing interneurons onto pyramidal neurons. Thereby, this disinhibition allows the precise temporal regulation of pyramidal neurons excitability. In particular, we showed that the acquisition of associative fear memories depend on the recruitment of a disinhibitory microcircuit in the auditory cortex. Fear-conditioning-associated disinhibition in auditory cortex is driven by foot-shock-mediated inhibition of parvalbumin-expressing interneurons. Importantly, pharmacological or optogenetic blockade of pyramidal neuron disinhibition abolishes fear learning. Together, these data suggest that disinhibition is an important mechanism underlying learning and information processing in cortical circuits. Secondly, in the medial prefrontal cortex, we demonstrated that expression of fear behaviour is causally related to the phasic inhibition of prefrontal parvalbumin-expressing interneurons. Inhibition of parvalbumin-expressing interneuron activity disinhibits prefrontal pyramidal neurons and synchronizes their firing by resetting local theta oscillations, leading to fear expression. These results identify two complementary neuronal mechanisms both mediated by prefrontal parvalbumin-expressing interneurons that precisely coordinate and enhance the neuronal efficiency of prefrontal pyramidal neurons to drive fear expression. Together these data highlighted the important role played by neuronal disinhibition in fear behaviour by binding behavioural relevant information, selecting specific circuit elements and orchestrating pyramidal neurons activity.

Les mouvements sont le résultat de contractions musculaires dont l’organisation spatio-temporelle est régie par des structures cérébrales et médullaires. Etudier les circuits qui les sous-tendent est une étape indispensable pour renforcer nos connaissances des mécanismes à l’origine de la commande des mouvements volontaires et pour mieux comprendre la pathophysiologie des mouvements anormaux. Les muscles squelettiques sont innervés par les motoneurones alpha de la moelle épinière qui à leur out sont influencés par des neurones des aires corticales motrices. Cette voie descendante constitue la voie corticomotoneuronale (CM) et est responsable de l’exécution des mouvements volontaires. Le cortex moteur primaire est considéré comme une structure clé, au cœur du système, permettant l’intégration complexe de nombreuses influences multi-régions pour conduire aux comportements moteurs adéquats. Les interactions qui existent entre les différents groupes de neurones au sein de M1 influent en dernier lieu sur la sortie motrice. De la balance complexe entre ces influences inhibitrices et excitatrices, locales ou à distance va dépendre l’état d’excitabilité des cellules CM contrôlant les différents muscles. L'objectif de ce travail de thèse était d'étudier comment évoluent certains de ces mécanismes excitateurs ou inhibiteurs du cortex moteur primaire lorsque la commande motrice volontaire d’un muscle de l’index est modifiée. Nous avons étudié le rôle de ces mécanismes dans les changements d’excitabilité de la voie CM qui accompagnent la contraction tonique volontaire du muscle premier interosseus dorsalis (FDI) en comparant une tâche simple mais peu naturelle : l’abduction de l'index, une tâche naturelle plus complexe: la pince pouce-index et la condition de repos musculaire. Nous avons également étudié l’effet de la commande motrice sur l’interaction entre deux de ces mécanismes inhibiteurs l’un à longue latence, la LICI, l’autre à courte latence, la SICI. Enfin nous avons souhaité évaluer le décours temporel de ces mécanismes dans un cadre pathologique tâche-dépendant: la crampe de l’écrivain. Pour cela, nous avons utilisé la technique d’electromyographie de surface pour enregistrer les potentiels moteurs évoqués par la Stimulation Magnétique Transcrânienne. Nous avons mis en évidence une modulation tâche-dépendante de la LICI. Par rapport à la tâche d’abduction simple, la LICI s’estompait plus tôt lors de la tâche de pince pouce-index, traduisant une désinhibition plus précoce lors d’un mouvement plus complexe. Nous avons observé, et ce pour la première fois dans la littérature, une phase de facilitation nette qui suivait cette désinhibition, et qui était absente lorsque le muscle était au repos. Ces résultats sont également visibles dans un muscle voisin du FDI, non engagé dans la tâche; cela suggère que les mécanismes à l’origine de la facilitation sont impliqués dans l’activité volontaire sans spécificité topographique. L’interaction entre la LICI et la SICI n’a pas été modifiée par la tâche effectuée, laissant penser qu’elle n’est pas impliquée dans les changements d’excitabilité tâche-dépendants. Enfin, il apparaît que la désinhibition est retardée chez les sujets dystoniques quand le muscle est engagé dans un mouvement complexe de pince pouce-index mais pas dans une tâche simple d’abduction de l’index en comparaison à des sujets contrôles. Ces résultats illustrent le fait que lors d’un mouvement plus complexe, l’efficacité des circuits inhibiteurs du cortex moteur primaire est modifiée, ce qui permet de réguler l’activité des cellules CM, afin d’adapter la commande motrice au mouvement souhaité. Le fait que cette désinhibition soit retardée dans une tâche complexe (proche de la tâche affectée) mais pas dans une tâche simple chez les patients atteints d’une crampe de l’écrivain suggère que les mécanismes à l’origine de la désinhibition pourraient participer aux troubles moteurs qui caractérisent la maladie. / Movements are evoked by muscles contractions whose spatial organization is mediated by both spinal and cortical components. It is important to investigate the underlying circuitry of movements to extend our knowledge on how voluntary movement are controlled and to better understand the pathophysiology of movements disorders. The spinal alpha motoneurons innervating distal muscles are controlled at least in parts by corticomotoneuronal neurons located in the motor cortical areas. Among them, the primary motor cortex is considered as a key structure, performing a complex integration of multi-regional influences leading to appropriate motor behaviors. Axons from corticomotoneuronal (CM) cells of the primary motor cortex reach the spinal cord via descending motor pathway. CM neurons are influenced by local or distant, inhibitory and excitatory components which determine the balance of excitability. The aim of this thesis was to explore changes of some of the excitatory and inhibitory mechanisms of motor cortex as a function of the task being performed. We assessed the time course of Long-interval Intracortical Inhibition (LICI), Late Cortical Disinhibition (LCD) and Long interval Intracortical Facilitation (LICF), which are mechanisms that potentially act to modulate the output of CM controlling the first dorsal interosseus (FDI) muscle. We compared three conditions : index finger abduction (a simple but not natural task), precision grip between index and thumb ( amore natural and complex task), and rest. We also evaluated the effect of task on interaction between LICI and Short Interval Intracortical Inhibition (SICI). Finally, we assessed the time course of LICI in patients suffering from writer’s cramp. For this purpose, we used surface electromyography to record motor potentials evoked by Transcranial Magnetic Stimulation.We showed a task-dependent change in late inhibitory and disinhibitory components. Compared with abduction task, the LICI induced during precision grip was shorter, suggesting an early disinhibition in more complex task. The disinhibition was followed by a period of facilitation only during the active tasks, i.e. facilitation was not observed when all muscles were at restat rest. However, long interval intracortical facilitation can be observed in a muscle at rest not engaged in an active task if a neighboring muscle is activated. It is therefore likely that mechanisms underlying facilitation are associated with voluntary contraction albeit with lack of topographic specificity. Interaction between LICI and SICI was not modified between tasks, suggesting that it was not involved in task-dependent changes of cortical excitability. Lastly, disinhibition was shown to be delayed in dystonic patients when the FDI was actively engaged in a precision grip but not in index abduction, compared with control subjects. An explanation might be that mechanisms underlying disinhibition are impaired in thumb-index precision grip (a task similar to that inducing unwanted contractions in writer’s cramp). Task-specidic disruption of LICI and late cortical disinhibition may therefore be at least in part responsible for pathophysiology of dystonia. It is likely that during complex task, the efficacy of LICI, and more generally of motor cortex inhibitory mechanisms, is modified to allow adaptation of CM neurons activity to the functional requirements of the motor task being performed.