No / The right temporoparietal cortex plays a critical role in body representation. Here, we applied repetitive transcranial magnetic stimulation (rTMS) over right extrastriate body area (EBA) and temporoparietal junction (TPJ) to investigate their causative roles in perceptual representations of one's own and others' body. Healthy women adjusted size-distorted pictures of their own body or of the body of another person according to how they perceived the body (subjective task) or how others perceived it (intersubjective task). In keeping with previous reports, at baseline, we found an overall underestimation of body size. Crucially, EBA-rTMS increased the underestimation bias when participants adjusted the images according to how others perceived their own or the other woman's body, suggesting a specific role of EBA in allocentric body representations. Conversely, TPJ-rTMS increased the underestimation bias when participants adjusted the body of another person, either a familiar other or a close friend, in both subjective and intersubjective tasks, suggesting an involvement of TPJ in representing others' bodies. These effects were body-specific, since no TMS-induced modulation was observed when participants judged a familiar object. The results suggest that right EBA and TPJ play active and complementary roles in the complex interaction between the perceptions of one's own and other people's body.

Chan Yu-leung. / "Nov 2003." / Thesis (M.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 179-193). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web.

Use of time-compressed speech stimuli has been found to be clinically effective in differential diagnosis of lesions of the temporal lobe. However, notably absent from the literature is information concerning performance of adults on time-compressed closed-set speech discrimination tasks. The goal of this study mas to compare performance of 12 males and 12 females between age 50 and age 70 on a time-compressed closed-set speech discrimination test against the performance of 12 males and 12 females between age 10 and age 28 on the same task. The Word Intelligibility by Picture Identification test (WPI) was presented in both non-compressed and time-compressed conditions to all subjects. Previous research suggests that a difference in performance between age groups and between males and females in the older age group should be expected. Average results indicated negligible differences between age or gender groups under any of the conditions tested. Additionally, the test yielded perfect or near perfect scores for all subjects in the non-compressed condition. Lack of differentiation of results suggests that the Word Intelligibility by Picture Identification CUIPI) may be insensitive to the discrimination disorders expected in older adults, that the subjects included in the study were atypical of older adults in general and therefore such discrimination disorders did not exist in the sample, or that the subjects in the study uiere able to apply some type of compensatory strategies which resulted in the unexpected performance.

A epilepsia do lobo temporal (ELT), além de ser o tipo de epilepsia focal mais comum, também é a que tem maior refratariedade à farmacoterapia, correspondendo à 30% dos casos. Se não tratada pode levar à piora da qualidade de vida, déficits cognitivos e risco de morte (ENGEL, 1998). O tratamento padrão para ELT farmacorresistente é a remoção cirúrgica das estruturas envolvidas (ENGEL, 1996), com taxas de cura que podem chegar a 80% (ENGEL, 2001a). Os benefícios da cirurgia são: diminuição da frequência e severidade das crises, diminuição da mortalidade, melhores índices de qualidade de vida. Recomenda-se que pacientes com ELT farmacorresistentes sejam referenciados a um centro de cirurgia de epilepsia para avaliar a possibilidade de intervenção cirúrgica (ENGEL et al., 2003). Em nosso estudo, avaliamos 621 pacientes com epilepsia mesial do lobo temporal, com confirmação histopatológica de esclerose hipocampal, que realizaram ressecção do lobo temporal no Centro de Cirurgia de Epilepsia de Ribeirão Preto (CIREP) entre os anos de 1994 até 2011. Avaliamos os principais fatores preditores que influenciam no sucesso cirúrgico relacionados ao controle das crises epilépticas, através de um estudo longitudinal e retrospectivo. Realizamos o acompanhamento clínico desses pacientes por até 23 anos, com média de 11,6 anos (± 5,3) e encontramos que 73,6% dos pacientes ficaram livres de crises com alteração da consciência (Engel I) e 84,7% tiveram um bom prognóstico cirúrgico (Engel I + II). Esse prognóstico foi relativamente mantido ao longo do tempo em 65 % dos pacientes, após 20 a 23 anos da cirurgia. Encontramos que a história de crise febril foi um fator de bom prognóstico, enquanto que a aura dismnésica e olfatória foram fatores de mau prognóstico. Em relação ao tipo de técnica cirúrgica, a lobectomia temporal anteromesial (com ressecção do polo temporal), obteve significativo melhor prognóstico (78,6% Engel I) em relação à cirurgia que poupa o polo temporal (67,2% Engel I), p=0,002*, sugerindo que as conexões neurais envolvidas na zona epileptogênica podem estar além das estruturas mesiais. Concluímos que a cirurgia para epilepsia é um procedimento seguro, com baixos índices de complicações pós-operatórias e bons resultados em longo prazo. / Temporal lobe epilepsy (TLE) is the most common type of focal epilepsy and the one that has greater refractoriness to pharmacotherapy, corresponding to 30% of the cases. If untreated, it can lead to worsening of quality of life, cognitive deficits and risk of death (ENGEL, 1998). The standard treatment for medically refractory TLE is the surgical removal of the structures involved (ENGEL, 1996), with good outcomes rates that can reach to 80% (ENGEL, 2001a). The benefits of the surgery are: decrease in frequency and severity of seizures, decrease in mortality, better indexes of quality of life and higher rates of return to school and work. It is recommended that medically refractory TLE patients should be referred to an epilepsy surgery center to evaluate the possibility of surgical intervention (ENGEL et al., 2003). In our study, we evaluated 621 patients with mesial temporal lobe epilepsy secondary to hippocampal sclerosis (MTLE-HS), who underwent a temporal lobectomy at our epilepsy surgery center (CIREP) between the years 1994 to 2011. We evaluated the main predictive factors that influence the surgical outcome, through a longitudinal and retrospective study. We performed the clinical follow-up for up to 23 years and the mean follow-up was 11,6 years (± 5,3). We found that 73,6 % of the patients were free of disabling seizures and 84,7% had a good surgical outcome (Engel I + II). This prognosis was relatively maintained over the time in 65% of patients after 20 to 23 years of surgery. We found that history of febrile seizure was a good prognostic factor, whereas the dysmnesic and olfactory aura were factors of poor outcome. Regarding the type of surgical technique, the anteromesial temporal lobe resection obtained significant better outcomes (78,6% Engel I) in relation to the surgery who preserve the temporal pole (67,2% Engel I), p value = 0,002*, suggesting that the neuronal networks involved in the epileptogenic zone may be beyond mesial structures. We conclude that epilepsy surgery is a safe procedure, with low rates of postoperative complications and good long-term results.

Alta prevalência, farmacorresistência e bom prognóstico cirúrgico são algumas das características clínicas que tornam a epilepsia do lobo temporal mesial com esclerose hipocampal (ELTM-EH) uma das mais importantes formas de epilepsia. Ela é o modelo da epilepsia cirurgicamente curável. Infelizmente, cerca de 10% dos pacientes evoluem com resultado cirúrgico insatisfatório. A ELTM-EH está associada a alterações amplas do perfil de expressão dos microRNAs (miRNAs) do hipocampo. Recentemente, constatou-se a existência de miRNAs estáveis no sangue periférico e em outros fluidos corporais, comprovadamente aplicáveis como biomarcadores, cuja abrangência vai do diagnóstico à resposta terapêutica. Tendo isso em vista, a pesquisa partiu do seguinte questionamento: é possível a identificação, no sangue periférico, de assinaturas moleculares por miRNAs que predigam o resultado do tratamento cirúrgico da ELTM-EH? Por meio de técnicas de biologia molecular, avaliaram-se amostras de sangue e hipocampo de pacientes submetidos à lobectomia temporal anterior em consequência de ELTMEH farmacorresistente. As amostras eram representativas de indivíduos com resultado cirúrgico favorável (Engel IA) e desfavorável (Engel III e IV). Com a técnica de microarray obteve-se o perfil de expressão de miRNAs das amostras triadas e chegou-se a um conjunto de seis miRNAs candidatos a biomarcadores de prognóstico cirúrgico: miR-92b-3p; miR-1238-3p; miR-1181; miR-636; miR- 1229-3p e miR-486-5p. Em seguida, com a técnica de PCR em tempo real, quantificou-se a expressão destes seis miRNAs e, a partir da otimização de um ponto de corte na escala de expressão, cada miRNA circulante foi apreciado como preditor de resultado cirúrgico. Assim, constatou-se hiperexpressão sanguínea dos seis miRNAs, sem distinção estatística entre os grupos Engel IA e Engel III-IV, hiperexpressão hipocampal do miR-486-5p no grupo Engel IA e hipoexpressão hipocampal do miR-636 nos grupos Engel IA e Engel III-IV. Na análise dos miRNAs circulantes como preditores de sucesso cirúrgico, o miR- 1238-3p exibiu uma sensibilidade de 40,00%, especificidade de 92,86% e acurácia de 65,52%. O conjunto miR-1238/miR1181 mostrou sensibilidade de 46,67%, especificidade de 85,71% e acurácia de 65,52%. O único miRNA circulante sondado como preditor de insucesso cirúrgico, o miR-636, revelou sensibilidade de 21,43%, especificidade de 93,33% e acurácia de 58,62% / A high prevalence, drug resistance and good surgical prognosis are some of the clinical characteristics that cause mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) to be one of the most important forms of epilepsy. This condition is the model of surgically curable epilepsy, although unfortunately about 10% of the patients exhibit an unsatisfactory surgical outcome. MTLE-HS is associated with extensive changes in the expression profile of hippocampal microRNAs (miRNAs). It has been recently observed that stable miRNAs exist in peripheral blood and in other body fluids which have been proved to be applicable as biomarkers from diagnosis to therapeutic response. On this basis, the present investigation was based on the following question: is it possible to identify molecular signatures by peripheral blood miRNAS that predict the outcome of surgical treatment of MTLE-HS? Molecular biology techniques were used to evaluate blood and hippocampal samples of patients submitted to anterior temporal lobectomy as a consequence of drug-resistant MTLE-HS. The samples were representative of patients with a favorable (Engel IA) and unfavorable (Engel III and IV) surgical outcome. The microarray technique was used to obtain the expression profile of miRNAs in the samples, with a set of six miRNAs being reached as candidate biomarkers for surgical prognosis: miR-92b-3p, miR-1238- 3p, miR-1181, miR-636, miR-1229-3p, and miR-486-5p. Next, real-time PCR was used to quantitate the expression of these six miRNAs and, based on the optimization of a cut-off point on the expression scale, each circulating miRNA was evaluated as surgical outcome predictor. We observed blood hyperexpression of the six miRNAs with no significant difference between the Engel IA and Engel IIIIV groups, hippocampal hyperexpression of miR-486-5p in the Engel IA group, and hippocampal hypoexpression of miR-636 in the Engel IA and Engel III-IV groups. Analysis of circulating miRNAs as predictors of surgical success revealed that miR-1238-3p exhibited 40.00% sensitivity, 92.86% specificity and 65.52% accuracy. The miR-1238/miR1181 set showed 46.67% sensitivity, 85.71% specificity and 65.52% accuracy. The only circulating miRNA evaluated as a predictor of surgical failure, miR-636, showed 21.43% sensitiviy, 93.33% specificity, and 58.62% accuracy

No final do século 19, o neurônio foi descrito como a unidade funcional básica do sistema nervoso e sua formação era considerada inexistente na fase adulta, explicando a ausência de recuperação significativa em doenças neurológicas. Evidências de geração de neurônios em mamíferos adultos surgiram na década de 1960 e foram confirmadas três décadas depois. Atualmente, predomina a visão de que mamíferos adultos possuem dois nichos neurogênicos independentes: a zona subventricular (ZSV) e a zona subgranular (ZSG) do giro denteado. No entanto, a existência de nichos neurogênicos em humanos adultos é controversa. Nossa hipótese foi de que o mapeamento de nichos neurogênicos no lobo temporal humano poderia esclarecer aspectos sobre a neurogênese adulta. A detecção destes nichos foi buscada em 28 lobos temporais através de imuno-histoquímica para nestina, o marcador mais comum de células-tronco neurais, que são aquelas capazes de se autorrenovar e de gerar novas células neurais. A neurogênese foi pesquisada no hipocampo pelo uso de DCX (do inglês \"doublecortin\"), o principal marcador de neuroblastos e neurônios imaturos. Nestina foi observada em uma camada contínua formada pela ZSV, zona subpial do lobo temporal medial e ZSG, terminando no subículo. A partir do subículo, uma intensa expressão de DCX ocorreu através da principal via eferente do hipocampo até a fímbria. A visão panorâmica das marcações por nestina e DCX mostrava em conjunto uma linha que circundava as estruturas límbicas do lobo temporal. Por isto, foi denominada linha externa de células do sistema límbico (LECEL). Uma possível explicação para os resultados é que a LECEL seja um nicho neurogênico no qual a ZSV, a zona subpial do lobo temporal medial e a ZSG formam uma unidade contendo células-tronco neurais que se diferenciam em neurônios no subículo. Curiosamente, a área identificada previamente como sendo a corrente migratória rostral humana (formada por células neurais imaturas migrando a partir da ZSV do corno frontal) pode ser na verdade o fórnix, que contém axônios originados no subículo. A implicação mais intrigante dos resultados é que se as características da LECEL seguirem além do lobo temporal, então o encéfalo humano pode conter um anel neurogênico límbico, em que a neurogênese ocorreria principalmente no subículo e seria modulada pelas estruturas relacionadas à fissura coroideia. Este estudo sugere que a neurogênese ocorre de maneira orquestrada em uma área ampla do lobo temporal humano / At the end of the 19th century, the neuron was described as the basic functional unit of the nervous system. The formation of neurons was thought to be absent in adulthood, thus explaining the lack of significant recovery from neurological diseases. Evidence for the generation of neurons in adult mammals was reported in the 1960s and confirmed three decades later. Currently, the prevailing view is that adult mammals harbour two neurogenic niches: the subgranular zone (SGZ) of the dentate gyrus and the subventricular zone (SVZ). Nonetheless, the existence of these niches in adult humans is controversial. We hypothesised that mapping neurogenic niches in the human temporal lobe could clarify this issue. The presence of neurogenic niches was examined in 28 temporal lobes via immunostaining for nestin, the most common marker for neural stem cells, which are cells with the capacities of self-renewal and the generation of neural cells. The presence of neurogenesis was examined in the hippocampus with doublecortin (DCX), a prominent marker for neuroblasts and immature neurons. Nestin was observed in a continuous layer that was formed by the SVZ, the subpial zone of the medial temporal lobe and the SGZ, terminating in the subiculum. In the subiculum, remarkable DCX expression was observed through the principal efferent pathway of the hippocampus to the fimbria. A panoramic view of nestin and DCX staining collectively displayed a line that surrounded the limbic structures of the temporal lobe. Hence, we termed it the external line of cells of the limbic system (EXCEL). A possible explanation for the results is that the EXCEL is a neurogenic niche, in which the SVZ, the subpial zone of the medial temporal lobe and the SGZ form a unit containing neural stem cells that differentiate into neurons in the subiculum. Curiously, the area previously identified as the human rostral migratory stream (formed by immature neural cells that migrate from the SVZ of the frontal horn) may in truth be the fornix, which contains axons that originate in the subiculum. Perhaps most intriguingly, if the EXCEL acts as a neurogenic niche beyond the boundaries of the temporal lobe, the human brain may contain a limbic neurogenic ring, in which neurogenesis would occur in the subiculum through the modulation of choroid fissure-related structures. This study suggests that neurogenesis may occur in an orchestrated manner in a broad area of the human temporal lobe

Este estudo teve como objetivo avaliar a expressão hipocampal de proteínas e de RNAm das Cx43 e Cx36 no modelo de epilepsia do lobo temporal (ELT) induzido por pilocarpina. Além disso, os efeitos do bloqueador de canais de junções comunicantes (CJC), carbenoxolona (CBX), foram avaliados por eletrofisiologia durante o período de status epilepticus. Os dados referentes à Cx43 demonstraram redução dos níveis proteicos no período latente (p<0,05) e aumento no período crônico do modelo (p<0,01). Os níveis de RNAm de Cx43 não sofreram alterações. Tanto os níveis proteicos quanto os de RNAm de Cx36 não se alteraram. Os dados eletrofisiológicos mostraram redução da potência na banda de frequência entre 15 e 30 Hz no eletrocortigrama, além de redução da amplitude relativa dos potenciais epileptiformes. Foi observado ainda que o grupo tratado com CBX passou a apresentar períodos flat antecipadamente. Os dados deste estudo sugerem um importante papel dos CJC na ELT induzida por pilocarpina, contribuindo para o conhecimento da regulação destes canais na epilepsia. / In this study, the hippocampal protein and mRNA levels of Cx43 and Cx36 were investigated in the pilocarpine model of temporal lobe epilepsy (TLE). In addition, the effects of a gap junction (GJ) blocker (carbenoxolone-CBX) on pilocarpine-induced status epilepticus (SE) were also evaluated by electrophysiological recordings. Our results on Cx43 showed reduction of protein levels in the latent period (p<0.05) and increase in the chronic period of the model (p<0.01), whereas no changes were observed in the mRNA levels. Both protein and mRNA levels of Cx36 showed no changes. The electrophysiological recordings indicated that CBX promoted a marked reduction of power in the 15-30 Hz electrocorticographic frequency. Decrease in the amplitude of the epileptiform potentials was also seen, in addition to anticipation of occurrence of flat periods in the group treated with CBX. Data obtained from this study suggest an important role for GJ channels in the pilocarpine-induced TLE, contributing to a greater understanding of the regulation of these channels in the epilepsy.

1. Interaktion zwischen entorhinalem Kortex und Hippokampus Lernen und Gedächtnis sind auf das engste mit dem Hippokampus und dem entorhinalen Kortex (EC) verbunden. Allerdings sind diese Hirnstrukturen auch an einer der häufigsten und medikamentös oftmals nur schwer therapierbaren fokalen Epilepsien beteiligt: der mesialen Temporallappenepilepsie (TLE). Der EC scheint eine wesentliche Bedeutung in der Generierung extrahippokampaler Temporallappenanfälle zu besitzen. Unsere bisherigen Untersuchungen zur Interaktion zwischen dem EC und dem Hippokampus haben gezeigt, daß unter physiologischen Bedingungen die Area dentata eine Filterfunktion übernimmt und die Übertragung epileptiformer Aktivität vom EC zum Hippokampus unterbindet. Im chronisch epileptischen Tier (Kindling-Modell) kommt es allerdings zu einer Aufhebung dieser Filterfunktion und somit zu einer ungehinderten Ausbreitung epileptiformer Aktivität in den Hippokampus. Da der glutamaterge NMDA-Rezeptor eine zentrale Rolle in der Induktion nutzungsabhängiger Plastizität spielt, ist er von wesentlicher Bedeutung in der Epileptogenese. Untersuchungen an Körnerzellen der Area dentata zeigten wenige Stunden nach dem letzten epileptischen Anfall eine Zunahme der über NMDA-Rezeptoren vermittelten Ströme. Diese führte zu einer Faszilitierung hochfrequenter reizevozierter Potentiale. Dieser Befund zeigt, daß im epileptischen Gewebe hochfrequente Entladungen die Area dentata überwinden können und in den Hippokampus weitergeleitet werden. Vier Wochen nach dem letzten Anfallsereignis waren die beschriebenen Veränderungen allerdings nicht mehr nachweisbar. Diese kurzzeitig veränderte synaptische Transmission der NMDA-Rezeptorkanäle scheint demzufolge eher für die Epileptogenese als für die Ictogenese verantwortlich zu sein. Die Bedeutung der Kainat-Rezeptoren im chronisch epileptischen Gewebe ist aufgrund der bis vor wenigen Jahren fehlenden selektiven Agonisten und Antagonisten kaum untersucht worden. Wir haben gezeigt, daß in der Area dentata des chronisch epileptischen Tieres (Kindling-Modell) die Aktivierung von präsynaptischen Kainat-Rezeptoren inhibitorischer Interneurone sowohl die spontane als auch die reizevozierte GABA-Freisetzung reduziert. Über diesen Mechanismus scheint der während eines epileptischen Anfalls vermehrt freigesetzte exzitatorische Neurotransmitter Glutamat die GABAerge Inhibition zu vermindern und somit die Erregbarkeit der Area dentata zu steigern. 2. Die Rolle des Subikulums in der Temporallappenepilepsie Eine wesentliche Aufgabe des Subikulums ist es, hippokampale Informationen zu verarbeiten und in verschiedene kortikale und subkortikale Hirnregionen weiterzuleiten. Zudem scheint es von besonderer Bedeutung für die Generierung und Ausbreitung hippokampaler Anfälle zu sein. Gestützt wird diese Annahme durch folgende Befunde: Zunächst besitzt das Subikulum Netzwerkeigenschaften, die es ihm im in vitro Epilepsiemodell ermöglichen, spontane epileptiforme Aktivität zu generieren. Darüber hinaus verfügt es über einen hohen Anteil sogenannter burst-spiking Zellen. Deren intrinsische Eigenschaften tragen erheblich zu dem epileptogenen Verhalten des Subikulums bei. Weiterhin erhalten subikuläre Pyramidenzellen exzitatorische Eingänge sowohl aus der Area CA1 als auch aus dem EC, welche bereits bei Ruhemembranpotential aktivierbare NMDA-Rezeptorströme zeigen. Schließlich zeigen burst-spiking Zellen im Vergleich zu regular-spiking Zellen eine ausgeprägte über NMDA-Rezeptoren vermittelte synaptische Plastizität (Langzeit-Potenzierung; LTP). Untersuchungen am chronisch epileptischen Tier (Kindling-Modell) ergaben einen unverändert hohen Anteil an burst-spiking Zellen im Subikulum. Wenige Stunden nach dem letzten epileptischen Anfall fällt bei diesen Neuronen eine fehlende, durch Aktionspotentiale induzierte Nachhyperpolarisation auf. Diese supprimierte intrinsische Hemmung ist jedoch 28 Tage nach dem letzten epileptischen Anfall nicht mehr nachzuweisen und spielt demzufolge insbesondere in der Genese, weniger im chronischen Verlauf der Erkrankung eine Rolle. Neben den exzitatorischen und inhibitorischen Neurotransmittern Glutamat und GABA bestimmen auch körpereigene Amine wie Serotonin und Dopamin über subkortikale Afferenzen das funktionelle Gleichgewicht aus Erregung und Hemmung wesentlich mit. Da die TLE nicht selten mit neurologischen und psychiatrischen Erkrankungen einhergeht, die mit in das Dopamin- und Serotoninsystem eingreifenden Pharmaka therapiert werden, haben wir uns in einigen Arbeiten mit deren modulatorischen Wirkungen auf die Membraneigenschaften und die synaptische Transmission befaßt. Die Wirkungen von Dopamin auf die Neurotransmission sind vielfältig, abhängig von den beteiligten Rezeptoren in der entsprechenden Hirnregion. Das Subikulum, das eine ausgeprägte mesenzephale, dopaminerge Projektion vom ventralen Tegmentum erhält, expremiert sowohl D1- als auch D2-Rezeptoren. Wir konnten zeigen, daß Dopamin primär die glutamaterge synaptische Transmission über einen präsynaptisch lokalisierten D1-Dopaminrezeptor unterdrückt und sekundär über die verminderte Erregung inhibitorischer Interneurone die polysynaptische GABAerge Hemmung reduziert. / 1. Interaction between the entorhinal cortex and the hippocampus The hippocampus and the entorhinal cortex are crucially involved in the acquisition, consolidation and retrieval of long-term memory traces. However, both structures play a critical role in pharmacologically intractable temporal lobe epilepsy. The entorhinal cortex provides the main input to the hippocampus. We have shown that kindling facilitates the propagation of epileptiform activity through the dentate gyrus. Our data are consistent with the normal function of the dentate gyrus as a filter limiting the spread of epileptiform activity within the entorhinal-hippocampal complex. This gating mechanism breaks down after chronic epilepsy induced by kindling. In the mammalian brain, the NMDA subclass of glutamate receptors plays a central role in the induction of several forms of use-dependent plasticity. However, synaptic plasticity can potentially underlie pathological situations, notably in animal and human forms of epilepsy. The enhanced excitability of the kindled dentate gyrus several hours after the last seizure, as well as the breakdown of its gating function, appear to result from transiently enhanced NMDA receptor activation that provides significantly slower EPSC kinetics than those observed in control slices and in slices from kindled animals with a four weeks seizure-free interval. Therefore, NMDA receptors seem to play a critical role in the acute throughput of seizure activity and in the induction of the kindled state but not in the persistence of enhanced seizure susceptibility. The functional involvement of kainate receptors in epileptogenesis gets more and more elucidated. We found that in chronic epileptic rats (kindling-model), activation of presynaptic kainate receptors of inhibitory interneurons depresses spontaneous and stimulus-induced GABA release. The kindling-induced sensitivity of GABA release to kainate receptor activation may produce a use-dependent hyperexcitability in the epileptic dentate gyrus facilitating the spread of limbic seizures through the entorhinal-hippocampal complex in temporal lobe epilepsy. 2. The role of the subiculum in temporal lobe epilepsy The subiculum controls most of the entorhinal-hippocampal output. It receives strong excitatory input from area CA1 and the entorhinal cortex and relays information to a variety of distant cortical and subcortical structures. The subiculum seems to be crucially involved in the generation and propagation of hippocampal seizures. The seizure susceptibility of the subiculum relies (a) on a high fraction of burst-firing principle cells that a capable to undergo synaptic plasticity and (b) on an epilepsy-prone network to generate spontaneous seizures. In both, control and kindled preparations the subiculum contains an extensive sub-population of bursting cells expressing amplifying membrane characteristics. Subicular cells showed a transient depression of the fast and slow afterhyperpolarization in the course of kindling that may contribute to the induction but not permanence of the kindled state. Apart from the excitatory and inhibitory neurotransmission physiological amines like 5-HT and dopamine (DA) may offset the frail balance between excitation and inhibition in the hippocampus. As temporal lobe epilepsy is often associated with diseases that are treated with drugs affecting the 5-HT and DA system, we investigated the effect of these transmitters on intrinsic and synaptic properties of subicular principle cells. The subiculum receives a dense mesencepahalic dopaminergic projection from the ventral tegmental area and expresses high levels of D1- and D2-like DA receptors. Our results indicate that DA strongly suppresses glutamatergic hippocampal and entorhinal neurotransmission onto subicuar neurons by activation of presynaptic D1-like DA receptors. In addition, DA decreases polysynaptic inhibition by attenuating the glutamatergic drive onto subicular interneurons.

Le lobe temporal est classiquement divisé en deux systèmes fonctionnels: la voie visuelle ventrale et le système mnésique temporal médial. Cependant, cette séparation fonctionnelle a été remise en question par plusieurs études suggérant que le lobe temporal médial serait mieux compris comme une extension de la voie visuelle ventrale hiérarchiquement organisée. Le but de cette thèse était d’étudier le rôle perceptivo-mnésique du lobe temporal médial. Nous avons ainsi voulu tester à l’aide d’enregistrement électro-encéphalographiques intracérébraux (SEEG) si : (i) les régions médiale, ventrale et latérale du lobe temporal pouvaient être regroupées dans des ensembles fonctionnellement distincts et, (ii) quelles régions étaient à l’interface de ces ensembles fonctionnels. Pour répondre à ces questions, nous avons étudié la connectivité effective dérivée de potentiels évoqués cortico-corticaux issus de stimulations électriques de faible intensité et de basse fréquence (0.5mA, 1Hz, 4ms) réalisées chez 16 patients atteints d’épilepsies pharmaco-résistantes temporale ou temporo-occipitale, lors de leur évaluation pré-chirurgicale par la surveillance à long terme des activités intracérebrales électro-encéphalographiques. Onze régions d'intérêt ont été délimitées au sein du lobe temporal en fonction de repères anatomiques tels que les gyri et sulci. Un modèle de connectivité effective au sein du lobe temporal a été extrait, basé sur les caractéristiques électrophysiologiques des potentiels évoqués cortico-corticaux, telles que les occurrences, amplitudes et latences des pics de la première composante du potentiel évoqué. Le modèle a été discuté du point de vue d’une organisation fonctionnelle globale du fait de la non-indépendance de ses caractéristiques électrophysiologiques. L’amplitude et la latence des potentiels évoqués ont montré des distributions de probabilité cohérente avec les observations de transfert d'informations cognitive. La théorie des graphes nous a fourni des algorithmes pouvant extraire les caractéristiques pertinentes du réseau, telles que la centralité des régions, leur ségrégation fonctionnelle ou les voies d’interaction entre les sous-ensembles fonctionnels des régions du lobe temporal. En particulier, le cortex rhinal est apparu comme la structure la plus centrale du lobe temporal alors que le gyrus temporal supérieur était la moins centrale. Le lobe temporal médial a pu être ségrégué en un ensemble fonctionnel à part entière. Le pôle temporal est apparu comme une zone de convergence et de transfert de l’information provenant des structures du lobe temporal latéral vers les structures médiales. Le gyrus fusiforme antérieur a montré des caractéristiques d’interface duale de convergence d’afférences néocorticales et de rétrocontrôle issu des structures médiales. Par ailleurs, l'hippocampe a montré un rôle d’amplificateur du signal des afférences néocorticales passant par l’amygdale et le cortex rhinal, pour être redistribuée vers les structures limbiques. L’hippocampe postérieur se comportait comme une voie de sortie des structures médiales modulant le gyrus parahippocampique postérieur de manière quasi-unidirectionnelle. Notre étude fournit un modèle régional ou macroscopique du transfert de l’information électro-physiologique au sein du lobe temporal humain. Nos résultats ont été discutés à la lumière des modèles cognitifs actuels de ‘complétion de l’information’ et du ‘binding temporel’ / The temporal lobe is conventionally divided into two functional systems: the ventral visual pathway and the medial temporal mnemonic system. However, this functional separation has been questioned by several studies suggesting that the medial temporal lobe would be better understood as an extension of the ventral visual pathway hierarchically organized. The aim of this thesis was to study the perceptive-mnestic role of the medial temporal lobe. We have tested using intracerebral EEG recordings (SEEG) if (i) the medial, lateral and ventral regions of the temporal lobe could be grouped into functionally distinct modules and, (ii) which areas were at the interface of these functional modules. To answer these questions, we studied the effective connectivity derived from cortico-cortical evoked potentials elicited by electrical stimulations from low intensity, low frequency (0.5mA, 1Hz, 4ms) conducted in 16 patients with drug-resistant temporal or temporo-occipital epilepsies at their pre-surgical long-term monitoring of intracerebral electroencephalographic activity. Eleven regions of interest were defined within the temporal lobe based on anatomical landmarks such as gyri and sulci. We built an effective connectivity model within the temporal lobe, based on the electrophysiological characteristics of cortico-cortical evoked potentials, such as the occurences, latencies and amplitudes of the peaks of the first component of the evoked potential. The model was discussed from the perspective of a global functional organization due to the non-independence of its electrophysiological characteristics. The amplitude and latency of the evoked potentials showed consistent probability distributions with the information transfer in cognitive observations. Graph theory has provided algorithms that can extract the relevant characteristics of the network, such as the centrality of the regions, their functional segregations or the ways of interaction between functional subsets of the regions within the temporal lobe. In particular, the rhinal cortex appeared as the most central structure of the temporal lobe whereas the superior temporal gyrus appeared as the less central. The medial temporal lobe could be segregated as a functional module by itself. The temporal pole appeared as a convergence area of the information transfer from the lateral temporal lobe structures to the medial structures. Anterior fusiform gyrus acted as a dual interface of convergence of neocortical afferences and feedback from medial structures. Furthermore, the hippocampus behaved as an amplifier of neocortical afferent signal passing through the amygdala and the rhinal cortex, and redistributed this amplification to the limbic structures. The posterior hippocampus acted as a way out of the medial structures modulating the posterior parahippocampal gyrus in a almost unidirectional manner. Our study provides a regional or macroscopic model of the transfer of electro-physiological information within the human temporal lobe. Our results were discussed in line with current cognitive models of 'pattern completion' and 'temporal binding'

Introdução: A exploração cirúrgica do como temporal do ventrículo lateral (CTVL) é realizada para o tratamento de lesões neoplásica, vasculares e, principalmente, para o tratamento cirúrgico da epilepsia do lobo temporal. As abordagens cirúrgicas a esta cavidade são realizadas, a partir da superficie cortical e através de suas paredes, pelos acessos laterais, transsilvianos e inferiores. A escolha do acesso cirúrgico se baseia na exposição adequada e nas alterações neurológicas que possam advir do trauma ao parênquima cerebral. A secção dos diferentes feixes de fibras brancas pode resultar em déficits neurológicos mais duradouros do que a lesão ao córtex cerebral. Os déficits visuais oriundos da interrupção das fibras da radiação óptica são os mais estudados. A identificação das interrupções dos demais conjuntos de fibras e as correlações dos déficits neurológicos originados têm sido subestimadas na literatura Objetivo: Avaliar a interrupção dos feixes de fibras brancas nos diferentes acessos cirúrgicos ao como temporal do ventrículo lateral, utilizando a técnica de dissecção de fibras brancas de Klinger. Métodos: Para o estudo, foram utilizados 40 hemisférios cerebrais cadavéricos adultos (20 encéfalos) preparados no Laboratório de Anatomia da UFMS de acordo com a descrição do método de preparação de Klinger. As aberturas da cavidade ventricular, mimetizando os acessos cirúrgicos lateral (através do giro temporal médio), inferior (através do giro parahipocampal), transsilviano e transuncal foram realizados por meio de incisões de l5 mm a partir das superficies corticais. Resultados: A introdução dos instrumentos de dissecção, de 15 mm de largura por 2 mm de espessura, garantiu a uniformidade das transecções das fibras da superficie cortical à cavidade ventricular. Como resultado obteve­se o acesso que causou menor comprometimento de fibras brancas foi o acesso transucal, esse que atingiu apenas 8,3% das fibras analisadas, sendo as fibras em \"U\" situadas no córtex piriforme. Em seguida, os acessos inferior e transsilviano causaram lesões em 25% das fibras brancas. O acesso que acometeu o maior número de fibras, sendo considerado o mais lesivo para a substância branca foi o acesso lateral, esse que acometeu 75% das fibras analisadas durante a pesquisa. Conclusão: O acesso lateral através do giro temporal médio ocasiona lesões da porção inferior do fascículo longitudinal superior (segmento arqueado e vertical), do fascículo uncinado (segmento dorso lateral da porção temporal), do fascículo occipitofrontal (segmento ventral da porção posterior), da comissura anterior (segmento posterior da extensão lateral), das fibras temporopontinas, do pedúnculo talârnico posterior (alça temporal), do pedúnculo talâmico inferior (fibras posteriores) e do tapete. O acesso transsilviano ocasiona lesões do fascículo uncinado (segmento ventromedial da porção temporal), da comissura anterior (segmento anterior da extensão lateral) e da substância cinzenta da amígdala. O acesso inferior, através do giro parahipocampal, ocasiona lesões do segmento inferior do cíngulo e da formação hipocampal. O acesso transuncallesa apenas a substância cinzenta da amígdala . / Introduction: Surgical access to the temporal hom of lateral ventric1e is performed to treat tumoral and vascular lesions, but mainly to the surgi cal treatment of temporal epilepsy. The surgi cal exploration of this cavity is realized from the cortical surface towards the ventricular walls, through the lateral, transsylvian and inferior approaches, based on the adequate exposure of the cavity and on the postoperative deficits that might be originated from the brain parenchymal trauma. Lesions to the fibers bundles often result in more severe and prolonged deficits than corticallesions. The most common recognized deficits are the visual fields defects secondary to injuries to the optic radiation. Identification of the interruption of other fibers bundles involved and their correlated c1inical manifestation have been underestimated on the literature. Objective: To identify the interruption of the fiber bundles originated from the different approaches to the temporal hom utilizing the Klinger\'s fiber dissection technique. Methods: We studied 40 cerebral hemispheres of 20 brains, prepared according to Klingers method, at the UFMS Laboratory of Anatomy. The surgical access of the temporal hom was performed simulating the lateral (middle temporal gyrus), inferior (parahippocampal gyrus), transsylvian and transuncal approaches, through 15 mm cortical incisions, followed by stepwise dissection of the fibers. Results: Introduction ofthe dissector (15 mm width, 2 mm height) warranted an uniform transection of the fibers from the cortical surface to the ventricular cavity. The least destructive access encountered was the transuncal access, interrupting 8,3% of the studied fibers. Following it, the inferior and the transsylvian approaches interrupted 25% of the fibers. The most destructive, interrupting 75% of the studied fibers was the lateral approach. Conclusion: The lateral approach through the middle temporal gyrus caused interruptions on the inferior portion (vertical and arcuate segments) of the superior longitudinal fasciculus; on the dorso lateral segment of the temporal portion from the uncinate fasciculus; on the ventral segment of the posterior portion from the occipitofrontal fasciculus; on the posterior segrnent of the lateral extension from the posterior commissure; on the temporopontine fibers; on the anterior loop of the posterior thalamic pedunc1e, on the posterior fibers of the inferior thalamic pedunc1e and the tapetum fibers. The transsylvian approach caused interruptions on the ventromedial segrnent of the temporal portion from the uncinate fasciculus; on the anterior segrnent of the lateral extension from the anterior commissure and transected the amygdala on its anterosuperior surface. The inferior approach through the parahippocampal gyrus caused interruptions on the inferior segment of the cingulum and on the fimbria, due to the transection of the hipocampal formation. The transuncal approach only transected the amygdala