The precise neuroanatomical pathways underlying seizure genesis and propagation are largely unknown. Current evidence suggests that epileptiform activity may travel along preferred anatomical routes and that some structures may act as “gates” that funnel and spread seizure activity throughout the brain. Burchfiel and Applegate (1989a) have proposed a gating hypothesis to explain kindled seizure propagation. According to this hypothesis, kindling involves three distinct phases that are separated by two crucial gates. The first gate mediates the expression of partial seizures, and the second gate mediates the expression of fully generalized seizures. Little work has been done in determining which anatomical sites contain these gates, in particular the second gate. The following experiments set out to investigate the role that the claustrum may play in mediating the second gate, responsible for the expression of kindled generalized seizures. Experiments 1 and 2 utilized correlative strategies to address the claustrum's participation in kindling. In Experiment 1, kindling was evoked directly from claustrum and these properties were compared with the nearby structures of the amygdala, insular cortex, and perirhinal cortex. The claustrum generally exhibited much more potent epileptogenic attributes than the other structures, including quick progression to seizure generalization and more vigorous and sustained convulsions. However, the claustrum, shared many electrographic and convulsive properties with the insular and perirhinal cortices, including a two phase development of generalized seizures, rapid progression to seizure generalization, and quick onset to limb convulsions. In Experiment 2, further dissociations were detected between claustrum and amygdaloid kindling by changes in molecular products linked with neural plasticity. Claustrum kindling was associated with generally more intensive expression of claustrum in kindling. Experiments 3 and 4 used more direct approaches to address the role of the claustrum in kindling. In Experiment 3, alternating stimulation between the claustrum and amygdala demonstrated that the claustrum was capable of arresting amygdaloid kindling at the partial seizure stages. This kindling antagonism effect was not observed with stimulation of the superficial insular cortex, perirhinal cortex, or piriform cortex. In Experiment 4, lesions applied to the claustrum were effective in delaying, but not blocking amygdaloid kindling. These delays were in amygdaloid kindling were produced by small lesions restricted to the ipsilateral anterior claustrum. Taken together these data suggest that the claustrum may represent the crucial mediator of the second gate responsible for kindled seizure generalization. / Graduate

Thesis (Ph. D. in Neuroscience)--Vanderbilt University, Aug. 2008. / Title from title screen. Includes bibliographical references.

The claustrum (Cl) is a subcortical gray-matter structure housed between the external capsule medially and the extreme capsule laterally. Due to its extensive reciprocal connections throughout the brain, it has been implicated in consciousness and other higher order functions including linking behavior and emotion. Such linkage may be important in understanding the neurobiology of autism since other cortical and subcortical regions including the spatially and ontologically related basal ganglia, as well as limbic structures, have been implicated in the disorder. Participants were males with autism (n=16) and typically developing (TD; n=14) matched for head circumference and age. The Cl and other structures were identified in 3-Tesla MRI scans using ANALYZE®, then segmented and volume quantified. Four Cl volumes were traced (i.e., right, left, right ventral, left ventral) first in axial plane then in coronal plane for entire Cl visualization. Two-tailed single sample t-tests revealed significant differences in the right claustrum (p=.014), left claustrum (p = .041), right total claustrum (p = .018) and left total claustrum (p=.044). Right Cl volume was found to be significantly larger than left within each of the groups (Autism, p=.021; TD, p=.033). These preliminary results demonstrate that the Cl can be consistently identified in vivo using ROI tracing with apparent right-versus-left asymmetry documented. Smaller claustral volumes in autism support theories of a disconnect in long-range circuitry associated with autism.

<p>Humans and animals have remarkable capabilities in keeping time and using time as a guide to orient their learning and decision making. Psychophysical models of timing and time perception have been proposed for decades and have received behavioral, anatomical and pharmacological data support. However, despite numerous studies that aimed at delineating the neural underpinnings of interval timing, a complete picture of the neurobiological network of timing in the seconds-to-minutes range remains elusive. Based on classical interval timing protocols and proposing a Timing, Immersive Memory and Emotional Regulation (TIMER) test battery, the author investigates the contributions of the dorsal and ventral hippocampus as well as the dorsolateral and the dorsomedial striatum to interval timing by comparing timing performances in mice after they received cytotoxic lesions in the corresponding brain regions. On the other hand, a timing-based theoretical framework for the emergence of conscious experience that is closely related to the function of the claustrum is proposed so as to serve both biological guidance and the research and evolution of “strong” artificial intelligence. Finally, a new “Double Saturation Model of Interval Timing” that integrates the direct- and indirect- pathways of striatum is proposed to explain the set of empirical findings.</p> / Dissertation

Le traçage rétrograde des voies corticales chez le singe a permis d’étudier deux sujets liés. En premier lieu, des injections dans 40 aires d'un atlas cortical de 91 aires ont permis de constituer une base de données cohérente sur la connectivité corticale à l’échelle de l’hémisphère. Les structures sous-corticales favorisant la communication corticale via la formation de boucles cortico-sous-cortico-corticales ont été examinées. Nous montrons que la force des projections du claustrum (considéré comme ayant une affiliation étroite avec le cortex) vers chaque aire explorée est exceptionnelle. De plus, un chevauchement des neurones marqués dans le claustrum a été observé suite à des paires d'injections dans des aires largement éloignées, y compris dépourvues de connexions cortico-corticales directes. A l’aide d’outils de la théorie des graphes, nous avons examiné la centralité des 40 aires et du claustrum dans le réseau cortical. En particulier, le claustrum est le meilleur exemple d’une aire pouvant prétendre au statut de « hub ». Ces résultats soulignent l'importance d'étudier les principes organisationnels du cortex via l'analyse de la topologie de son réseau. En second lieu, nous avons étudié le développement de la voie corticospinale par laquelle le cortex influence la planification, l'exécution et le contrôle de la motricité fine. Nous montrons que la topologie des projections corticospinales chez l’adulte émerge suite à un processus développemental de raffinement des projections ipsi- et controlatérale étendues. Ces résultats suggèrent que le développement de la connectivité corticale pourrait être régulé de manière dynamique et spécifique aux primates / The retrograde tracing experiments in macaque cortex in this thesis had two related objectives. Firstly, injections in 40 cortical areas (from a 91-area atlas) allowed the construction of a hemisphere-wide consistent database of cortical connectivity. We examined which subcortical structures promote cortical communication via the formation of cortico-subcortical-cortical loops. The claustrum, which we argue has a tight affiliation with the cortex, showed uniquely strong outputs to every cortical area. Widely separated injection pairs led to overlapping labelled neurons in the claustrum including those pairs lacking direct cortico-cortical connections. Using graph theoretic tools, we examined how central the 40 areas and claustrum are in the cortical network, specifically with respect to hub status. This showed that the claustrum is, beyond doubt, the prime hub of the cortex. These findings emphasise the importance of studying the organizational principles of the cortex via the analysis of its network topology. Secondly, we investigated the development of the corticospinal pathway, a route over which the cortex directly influences the planning, execution and control of fine voluntary movements. We show that the adult pattern of corticospinal projections emerges via a developmental process from a widespread ipsi- and contralateral distribution. These findings suggest that the developmental refinement of cortical connectivity might be dynamically regulated and primate specific

No description available.

Le claustrum est une structure télencéphalique sous-corticale présente chez tous les mammifères. Il est réciproquement interconnecté avec tout le cortex cérébral. Le claustrum serait impliqué dans la synchronisation d’oscillations corticales et le maintien de l’attention. Les projections corticales sensorielles au claustrum de la souris forment des bandes longitudinales dédiées à chaque modalité sensorielle, qui peuvent également se chevaucher. Actuellement, il n'y a aucune étude de la morphologie des axones des projections corticales au claustrum. Les paramètres quantitatifs morphométriques des axones uniques permettent de comprendre comment l’information est distribuée à l’intérieur d’une structure. Pour visualiser les axones de la projection visuelle au claustrum, des injections iontophorétiques du traceur neuronal antérograde, la leucoagglutinine Phaseolus vulgaris (PHA-L) ont été réalisées dans le cortex visuel de souris adultes C57BL/6J. La révélation immunohistochimique du PHA-L a été réalisée pour reconstruire les axones individuels des projections des cortex visuels au claustrum en utilisant Neurolucida 360 (MBF Biosciences). Ces projections ont été montrées dans la région centrale le long de l’axe dorso-ventral du claustrum ipsi- et controlatéral. Il y a trois types de morphologie des axones : certains parcourent toute la longueur du claustrum sans ramification, d’autres sont longs et branchés, et d’autres sont courts. Les arborisations locales pourraient suggérer des modules plus petits au sein de l'organisation longitudinale du claustrum. Certaines collatérales de l'axone sortent du domaine visuel central pour se ramifier dans des domaines des autres modalités sensorielles. La projection du cortex visuel au claustrum est ainsi constituée d’axones dont la morphologie est peu diversifiée. Des axones individuels acheminent l’information sur toute l’étendue rostro-caudale du claustrum. La bifurcation des axones suggère que l’information visuelle peut être acheminée vers des territoires de d’autres modalités sensorielles dans le claustrum. La distribution des varicosités suggère que les contacts synaptiques s’établissent aléatoirement tout au long du trajet des axones. / The claustrum is a subcortical telencephalic structure present in all mammals. It is widely and reciprocally interconnected with the entire cerebral cortex. It has been suggested to be involved in the synchronization of cortical oscillations and in attention. The claustrum in mice exhibits a clear dorsoventral organization of longitudinal bands dedicated to different sensory cortical projections, that can also overlap. Presently, there are no studies of the cortical projections to the claustrum at the single axon level. Single axon quantitative morphometric parameters help understanding how information is distributed within a structure and how it interacts with the entire brain. To reveal axons of the visual cortex projection to the claustrum, iontophoretic injections of the anterograde neuronal tracer Phaseolus vulgaris leucoagglutinin (PHA-L) were performed in the visual cortex of adult C57BL/6J mice. Individual axons of the projections from the visual cortices to the claustrum were reconstructed using Neurolucida 360 (MBF Biosciences). These projections were shown in central region of the dorsoventral axis in the ipsi- and contralateral claustra. There were three morphological types of axon: some traveled all the length of the claustrum without significant branching, some were long and branched, and others were short. Local arborizations might suggest smaller modules within the longitudinal organization of the claustrum. Some collaterals of the main axon exit the central visual domain to branch into other sensory modalities. The visual projection to the claustrum is formed by poorly diversified axon regarding to their morphology. Individual axons route the information through all the rostro-caudal length of the claustrum. Axonal bifurcations suggest that visual information can be directed to other territories associated to other sensory modalities. The varicosity distribution suggest that synapses are established randomly.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24505号 / 医博第4947号 / 新制||医||1064(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 渡邉 大, 教授 林 康紀, 教授 井上 治久 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

[pt] A presente tese tem como objetivo investigar os desdobramentos do ódio na constituição subjetiva em sua dimensão transgeracional em função de falhas ambientais ocorridas nos primórdios da vida psíquica na relação com o objeto primário. A reflexão sobre o ódio no pensamento psicanalítico começa atrelada à neurose obsessiva e, posteriormente, é expandida para contemplar os primeiros movimentos psíquicos do ego em relação ao objeto. A radicalidade que tal sentimento pode assumir no psiquismo devido a severas falhas na rêverie materna ocasionam a interrupção da função comunicativa da identificação projetiva. Dessa maneira, o ódio revela sua face destrutiva, uma vez que o psiquismo se encontra colonizado por objetos bizarros impossíveis de serem metabolizados pelo continente materno. As derivações desses traumatismos precoces na formação do self afetam profundamente a modalidade identificatória em ação, prevalecendo o seu uso adesivo que impede a construção de espaços psíquicos. A manifestação do claustro como derivativo do ódio traumático possui profundos impactos na existência do indivíduo, que experimenta uma relação de encarceramento com o objeto primário. Investigamos de que maneira o ódio é passível de se perpetuar entre gerações ao assumir um caráter transgeracional, no qual prevalece a lógica do segredo e da identificação alienante, que impede a atuação da identificação projetiva como via de comunicação intergeracional. Defendemos que essa forma de perpetuação críptica e condensada do ódio se manifesta em uma configuração psicopatológica que nomeamos como claustro transgeracional, que provoca impasses no campo psicanalítico e convoca o psicanalista ao trabalho implicado e empático através da contratransferência enquanto instrumento clínico. / [fr] La présente thèse vise à étudier le déploiement de la haine dans la constitution subjective dans sa dimension transgénérationnelle en fonction des échecs environnementaux survenus aux premiers stades de la vie psychique dans la relation avec l objet primaire. La réflexion sur la haine dans la pensée psychanalytique commence liée à la névrose obsessionnelle et s élargit ensuite pour envisager les premiers mouvements psychiques du moi par rapport à l objet. La radicalité qu un tel sentiment peut assumer dans le psychisme en raison de graves failles dans la rêverie maternelle provoque l interruption de la fonction communicative de l identification projective. La haine révèle ainsi son visage destructeur, puisque le psychisme est colonisé par des objets bizarres, impossibles à métaboliser par le continent maternel. Les dérivations de ces traumatismes précoces dans la formation du moi affectent profondément la modalité identificatoire en action, prévalant son utilisation adhésive qui empêche la construction d espaces psychiques. La manifestation du claustrum comme dérivé de la haine traumatique a des impacts profonds sur l existence de l individu, qui vit une relation d emprisonnement avec l objet primaire. Nous étudions comment la haine est susceptible de se perpétuer entre les générations en assumant un caractère transgénérationnel, dans lequel la logique du secret et de l identification aliénante prévaut, empêchant l action de l identification projective comme moyen de communication intergénérationnelle. Nous soutenons que cette forme de perpétuation cryptique et condensée de la haine se manifeste dans une configuration psychopathologique que nous nommons claustrum transgénérationnel, qui provoque des impasses dans le champ psychanalytique et convoque le psychanalyste au travail implicite et empathique par le contretransfert comme instrument clinique.

Made available in DSpace on 2016-04-28T20:38:37Z (GMT). No. of bitstreams: 1 Andrea de Davide Ratto Morelli.pdf: 720847 bytes, checksum: f67ae12322be10f9bae642d62c44bd21 (MD5) Previous issue date: 2013-03-15 / This study aims to gather information on some types of pathological organizations of the personality, using psychoanalytic knowledge. Several authors underlie it, starting with Sigmund Freud, Melanie Klein, Joan Riviere, Wilfred Bion, Herbert Rosenfeld, Hanna Segal and getting to John Steiner, Donald Meltzer, Frances Tustin, Judith Mitrani and James Grotstein, whose works in these areas are discussed more deeply. Efforts are made to understand and identify points of convergence, divergence and/or intersection among concepts like claustrum, psychic retreats, autistic capsules and adhesive pseudo-object relations. Discussion of the importance of continence and the development of schizo paranoid and depressive positions, permeate all the work and are fundamental to the approach of the clinical material presented. Analyst's psychic continence is questioned in face of difficulties as the claustrum seduction, attraction of adhesive pseudo-object relations, embarrassment of tenderness and struggles for dominate or exclusion of the analyst. Facing the difficulties of handling complex defensive systems, such as pathological organizations, confidence in the existence of unconscious need of psychic truth remains encouraging and cherishing, both to continue the trajectory of psychoanalytic exercise, and to achieve the needs of patients / Este estudo tem por objetivo recolher informações sobre alguns tipos de organizações patológicas da personalidade, utilizando conhecimentos psicanalíticos. Vários autores embasam-no partindo de Sigmund Freud, Melanie Klein, Joan Riviere, Wilfred Bion, Herbert Rosenfeld, Hanna Segal e chegando a John Steiner, Donald Meltzer, Frances Tustin, Judith Mitrani e James Grotstein, cujos trabalhos nessas áreas são discutidos mais profundamente. Esforços são realizados para compreender e identificar pontos de convergência, divergência e/ou intersecção entre conceitos como claustros, refúgios psíquicos, cápsulas autistas e pseudorrelações objetais adesivas. Discussões da importância da continência e da elaboração das posições esquizoparanoides e depressivas perpassam todo o trabalho e são fundamentais para a abordagem do material clínico apresentado. A continência psíquica do analista é questionada em face de dificuldades como a sedução dos claustros e a atratibilidade de pseudorrelações objetais adesivas, o embaraço diante da ternura e lutas por dominar ou excluir o analista. Diante da dificuldade de manejo com sistemas defensivos complexos, como os das organizações patológicas, a confiança na existência da necessidade inconsciente da verdade psíquica permanece estimulante e acalentadora tanto para continuar a trajetória do exercício psicanalítico, quanto para alcançar as necessidades dos pacientes