The research presented in this thesis addresses the neural mechanisms of auditory motion processing and the impact of early visual deprivation on motion-responsive brain regions, by using functional magnetic resonance imaging. Visual motion, and in particular direction selectivity, is one of the most investigated aspects of mammalian brain function. In comparison, little is known about how the brain processes moving sounds. More precisely, we have a poor understanding of how the human brain codes for the direction of auditory motion and how this process differs from auditory sound-source localization. In the first study, we characterized the neural representations of auditory motion within the Planum Temporale (PT), and how motion direction and sound source location are represented within this auditory motion responsive region. We further explore if the distribution of orientation responsive neurons (topographic representations) within the PT shares similar organizational features to what is observed within the visual motion area MT/V5. The spatial representations would, therefore, be more systematic for axis of motion/space, rather than for within-axis direction/location. Despite the shared representations between auditory spatial conditions, we show that motion directions and sound source locations generate highly distinct patterns of activity. The second study focused on the impact of early visual deprivation on auditory motion processing. Studying visual deprivation-induced plasticity sheds light on how sensory experience alters the functional organization of motion processing areas, and exploits intrinsic computational bias implemented in cortical regions. In addition to enhanced auditory motion responses within the hMT+/V5, we demonstrate that this region maintains direction selectivity tuning, but enhances its modality preference to auditory input in case of early blindness. Crucially, the enhanced computational role of hMT+/V5 is followed by a reduced role of PT for processing both motion direction and sound source location. These results suggest that early blindness triggers interplay between visual and auditory motion areas, and their computational roles could be re-distributed for effective processing of auditory spatial tasks. Overall, our findings suggest (1) auditory motion-specific processing in the typically developed auditory cortex, and (2) interplay between cross- and intra-modal plasticity to compute auditory motion and space in early blind individuals.

Awake surgery is a surgical procedure applied to people with brain tumors. Patients are kept awake during surgery to perform language tasks during electrical stimulation of cortico-subcortical brain structures. When the application of electrical pulses to the brain repeatedly triggers errors, this is taken as an indication that the area is critically involved in the language skills probed by the task, and therefore should not be removed, as this would result in postoperative language deficits. In this thesis, we focused on the role of production tasks using finite verbs and the evaluation of their ability to assess language processing in comparison with the current gold standard (i.e., object naming). As a preliminary step in the development of novel, controlled object and verb production tasks, we critically reviewed the literature. We discussed published studies that proposed intraoperative tasks requiring the production of verbs in isolation and in sentences, and we graphically represented the stimulation sites and error types that were reported in each study. Subsequently, we discussed the advantages and disadvantages of each from a cognitive neuroscience and neurolinguistic perspective. With this information in mind, we constructed and validated two naming tasks for native speakers of Italian undergoing awake surgery – an object naming task and a finite verb production task. We administered the finite verb production task and other picture naming tasks to subjects with post-stroke aphasia, and established that a task that uses finite verbs shows a strong correlation with communicative abilities in daily life. Also, we introduced and compared our standardized finite verb task in the operating theater and compared it with an object naming task. Our tests are currently and successfully used in different surgery wards in Italy and overseas. This work can be extended to other neurological populations such as stroke, dementias, and epilepsy.

Human mental life is accompanied by oscillatory signals that send information across distributed neural networks. Whether a stimulus reaches or escapes our conscious experience is influenced by the state of the brain in that moment, reflected in cerebral electrophysiology. Our understanding of this brain activity has grown vastly in recent years, thanks to leading advances in electro- and magneto-encephalography (EEG and MEG, or M-EEG, which enable us to monitor the electric brain signal) and recent developments allowing the direct modulation of endogenous oscillatory components that underlie cortical functions. Transcranial current stimulation, particularly the variant with alternating current (tACS), putatively lets us assess and gauge the role of oscillations on cognition. Several studies have confirmed that tACS can influence neural mechanisms and behavior, even conscious access. Until recently, cerebral activity during stimulation could not be assessed and observations were limited to the aftereffects. The aim of the project described in this dissertation is to investigate the validity of a pioneering procedure that can recover brain signal during simultaneous MEG and tACS. Then, exploiting this approach, we furthered our grasp of how the neural system is altered by transcranial stimulation and the complex relationship between the external current and the internal mechanisms of the brain. The overall goal is to explore our ability to manipulate neural signatures in ongoing activity and the conscious perception of an upcoming stimulus. Chapter 1 provides the reader with a general introduction of current studies and theories behind tACS influence on cognition and behavior. After a description of what tACS is and what it does, the focus is mostly on cutting-edge methods combining tACS and M-EEG, network connectivity and graph theoretical frameworks to study cognitive processes. At the end of the introductory chapter, we indulge on applications and consequences of these approaches, as well as open questions about our understanding of the prerequisites of conscious perception that drove the experiments described in the following chapters. Chapter 2 reports the first study in which we addressed the feasibility of concurrent tACS and MEG, the prerequisite for the rest of the project. Chapter 3 and 4 present studies that better delineated what happens in the brain in terms of oscillatory phase, connectivity and the dependency of tACS effects with the ongoing brain state during electrical stimulation. We addressed some key issues on the mechanisms of action of tACS and its sensitivity to in-vivo brain networks. Chapter 5 provides preliminary results of a study employing a near-threshold task paired with tACS and MEG in the context of conscious perception. We stimulated prestimulus brain rhythms in sensory cortices to see if their strength and connectedness with the rest of the brain could determine whether a stimulus will be perceived or not. Chapter 6, after a recapitulation of the main results in a broader perspective, discusses the meaning and the limitations of the experimental findings and how these extend our current knowledge.

Cross-modal processing and multisensory integration (MSI) can be observed at early stages of sensory processing in the cortex. However, the neurophysiological mechanisms underlying these processes and how they vary across sensory systems remain elusive. The aim of this study was to investigate how cross-modal processing and MSI are reflected in power and phase of oscillatory neuronal activity at different temporal scales in different sensory cortices. To this goal, we recorded stereo-electroencephalographic (SEEG) responses from early visual (calcarine and pericalcarine) and auditory (Heschl’s gyrus and planum temporale) regions in patients with drug-resistant epilepsy while performing an audio-visual oddball task. To Investigate crossmodal processing and MSI in the power domain of oscillatory activity, we explored a wide range of frequency bands (theta/alpha band: 5-13Hz; beta band: 13-30 Hz; gamma band: 30-80 Hz; high-gamma band: 80-200 Hz) during the first 150 ms post-stimulus onset. Differently, to investigate crossmodal processing and MSI in the phase domain of oscillatory activity, we explored a narrow range of frequency bands (theta/alpha band: 5-13Hz; beta band: 13-30 Hz; gamma band: 30-80 Hz) during the first 300 ms post-stimulus onset. In the power domain, we showed that cross-modal processing occurs mainly in the high-gamma band (80-200Hz) in both cortices. However, we evidenced that the way MSI is expressed across modalities differs considerably: in the visual cortex, MSI relies mainly on the beta band, however it is also evident, to a lesser extent, in the gamma and high-gamma band, while the auditory cortex reveals widespread MSI in the high-gamma band and, to a lesser extent, across the gamma band and the other investigated frequency bands. In the phase domain, we showed that cross-modal processing is differently expressed across modalities: in the auditory cortex it induces an increased phase concentration index (PCI) in ongoing oscillatory activity across all the investigated frequency bands, while, in the visual cortex, it induces an increased PCI particularly evident in the theta/alpha band with few or no effect respectively in the gamma and beta band. Importantly in both cortices, the most part of the COIs showing increased PCI, were not accompanied by a concomitant increase in power. These results indicate that in both auditory and visual cortex, cross-modal processing induces a pure phase resetting of the oscillatory activity. During MSI processing we observed, in both cortices, a stronger increase in PCI, in comparison to the intramodal processing, in the theta/alpha band and in the gamma band. Our results confirm the presence of cross-modal information representations at neuronal populations level and conform to a model where the cross-modal input induces phase-locked modulation of the ongoing oscillations. Importantly, our data showed that the way MSI is expressed in power modulations differs between the investigated sensory cortices suggesting the presence of different types of neurophysiological interactions during this process. These results are discussed in the framework of the current literature.

In literature there are large discrepancies about methods to assess cerebral lateralization in both human and nonhuman primate populations. This study aimed to allow valid comparisons across different primate species by employing a quantitative Multidimensional Method. A comprehensive range of interactions with both social and non-social targets were considered to verify which aspects might elicit the manifestation of lateralized behaviours underpinned by asymmetrical neuronal functions. Spontaneous activities were observed in two groups of zoo great apes, chimpanzees (Pan troglodytes) and gorillas (Gorilla gorilla gorilla), and a group of 3-4 year-old typical pre-school children. Results demonstrated a strong consistency in both human and non-human species for a right-hand/left hemisphere dominance during contact with inanimate targets (i.e. objects and environmental items), suggesting a evolutionary hemispheric specialization influenced by object animacy. Additionally, both great ape species significantly preferred to keep conspecifics closer than 3 metres to their left during manual activities, suggesting a right hemisphere specialization for emotion processing. Only the silverback gorilla (alpha male) manifested the opposite pattern, potentially related to his hierarchical role within the gorilla society. No side preference was found in typical children however, their young age may indicate that they are still undergoing hemispheric development for emotion processing. This study supports an evolutionary origin of hemispheric specialization underling manipulative and social asymmetric behaviours that occurred prior to the split of humans from great apes.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-10-11T22:03:58Z No. of bitstreams: 1 VivianeDaSilvaMedeiros_TESE.pdf: 1371501 bytes, checksum: a315d90a24e3c18fd1b8fb7298920bca (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-10-17T21:48:53Z (GMT) No. of bitstreams: 1 VivianeDaSilvaMedeiros_TESE.pdf: 1371501 bytes, checksum: a315d90a24e3c18fd1b8fb7298920bca (MD5) / Made available in DSpace on 2016-10-17T21:48:53Z (GMT). No. of bitstreams: 1 VivianeDaSilvaMedeiros_TESE.pdf: 1371501 bytes, checksum: a315d90a24e3c18fd1b8fb7298920bca (MD5) Previous issue date: 2015-11-13 / A carcinicultura mundial sofre grandes perdas econ?micas por enfermidades virais e bacterianas, sendo importante que sejam incentivados estudos e a??es que minimizem os danos provocados por estas doen?as em todas as ?reas, desde os econ?micos, sa?de animal e humana at? ambientais. Diante destes fatos, foram avaliados: a) o efeito da presen?a de areia como substrato sobre o comportamento de camar?es juvenis Litopenaeus vannamei em laborat?rio (manuscrito I); b) as atividades comportamentais de camar?es juvenis L. vannamei infectados por Vibrio parahaemolyticus (ATCC 17802) e submetidos a tratamentos veterin?rios em laborat?rio (manuscrito II); c) identifica??o dos agentes envolvidos em enfermidades com altas mortalidades em fazendas de carcinicultura (manuscrito III). O estudo foi realizado em tr?s etapas. Na primeira etapa (manuscrito I), os animais foram submetidos a tratamentos com aus?ncia ou presen?a de areia como substrato, divididos em dois grupos, cujos animais foram colocados em 30 aqu?rios de material pl?stico com capacidade para quatro litros, 15 deles com areia como substrato e 15 sem areia. Foram avaliados os comportamentos de enterramento somente para o grupo com areia e inatividade, nata??o, ingest?o de alimento, limpeza e rastejamento; sobreviv?ncia e ganho de peso para ambos os grupos. Na segunda etapa (manuscrito II), os animais foram divididos em cinco grupos: 1) Controle 1, 2) Controle 2 -animais infectados e sem tratamento veterin?rio; 3) Animais infectados, tratados com medicamento isop?tico ISO; 4) Animais infectados, tratados com medicamento antibi?tico (florfenicol) ANTIB; 5) Animais infectados, tratados com medicamentos isop?tico e antibi?tico (florfenicol) simultaneamente ISO+ANTIB. Foram ent?o analisados os comportamentos desses animais, a sobreviv?ncia e o ganho de peso. Na terceira etapa (manuscrito III), foi visitada uma fazenda de carcinicultura com altos ?ndices de mortalidade na cidade de Obreg?n, em Sonora, no M?xico. Foram coletados 30 animais dessa fazenda, os quais foram levados para an?lises presuntivas (an?lise a fresco e bacteriologia) e confirmat?rias (bioqu?mica e qPCR) para identifica??o de agentes patog?nicos virais e/ou bacterianos. Os resultados obtidos no manuscrito 1 mostram que n?o houve diferen?a significativa entre os comportamentos observados, tamb?m n?o houve diferen?a entre crescimento e ganho de peso, indicando que a aus?ncia de areia n?o interferiu na express?o de comportamento dos animais. Isto possibilita que os experimentos seguintes n?o usem areia como substrato. No manuscrito 2, os camar?es infectados e tratados com isopatia e antibi?tico simultaneamente apresentaram desempenho comportamental semelhante ao grupo controle 1, indicando que apresentam comportamento compat?vel com animais saud?veis. No Manuscrito 3, ficou evidente que a alta mortalidade identificada em viveiros com camar?es juvenis, al?m da cepa pat?gena causadora da AHPND, Vibrio parahaemolyticus, outras esp?cies de bact?rias dos g?neros Vibrio e Aeromonas estavam associadas. / World shrimp culture suffers large economic losses for viral and bacterial diseases, so it is important that studies and actions be encouraged to minimise the damage caused by these diseases in all areas - economy, animal and human health and environment. The present study evaluated the effect of a) presence of the substrate on the behaviour of juvenile shrimp Litopenaeus vannamei in the laboratory (manuscript I); b) behavioral activities of juvenile shrimp L. vannamei infected by Vibrio parahaemolyticus (ATCC 17802) and subjected to veterinary treatments in laboratory (manuscript II); c) identified the pathogenic agents associated to diseases with high mortality in shrimp culture farms (manuscript III). The study was conducted in three stages. In the first stage (manuscript I), the animals were subjected to two treatments, the absence or presence of sand as substrate, and were divided into two groups, placed in 30 plastic aquariums with capacity for four liters, half of them with sand on the bottom as substrate and the other half without sand. Burying behavior was evaluated only for the group whose aquariums had sand as substrate; inactivity, swimming, food intake, cleaning and crawling, survival and weight gain were measured in both groups. In the second stage (manuscript II), the animals were divided into five groups: 1) control, 2) infected animals with no veterinary treatment; 3) infected animals treated with isopathic medicine; 4) infected animals treated with antibiotics (florfenicol); 5) infected animals treated with isopathic medicine plus antibiotics (florfenicol). Then, the behaviors and survival and weight gain of the animals were analysed. In the third stage, we visited a shrimp farm with high rates of mortality in Obreg?n city, Sonora, Mexico. Thirty animals collected in the ponds were taken to presumptive (fresh smear analysis and bacteriology) and confirmatory (Biochemistry and qPCR) analyses for identification of viral and/or bacterial pathogens. The results in Manuscript 1 showed that for juvenile prawns maintained in aquariums with or without sand as substrate for up to three weeks, behavior, survival and weight gain were not significantly different, which demonstrates that lack of sand on the substrate did not modify behavioral responses of the animals. So, in the next stage, sand was not used as substrate anymore. In Manuscript 2, the infected prawns that were treated with isopathy plus antibiotics showed behavioral performance similar to the control group, indicating that their behavior is compatible with healthy individuals. And in Manuscript 3, concerning the high mortality of juvenile prawns in the ponds, besides the pathogenous that causes AHPND, Vibrio parahaemolyticus, other species of bacteria of the genus Vibrio and Aeromonas were associated to the pathology of the prawns.

Submitted by Automação e Estatística (sst@bczm.ufrn.br) on 2018-08-01T23:06:14Z No. of bitstreams: 1 JaddeEmmylleSilvaDeMoura_DISSERT.pdf: 1612798 bytes, checksum: aef54b5521355bd929dc0d8a6b6f8771 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2018-08-03T22:39:41Z (GMT) No. of bitstreams: 1 JaddeEmmylleSilvaDeMoura_DISSERT.pdf: 1612798 bytes, checksum: aef54b5521355bd929dc0d8a6b6f8771 (MD5) / Made available in DSpace on 2018-08-03T22:39:41Z (GMT). No. of bitstreams: 1 JaddeEmmylleSilvaDeMoura_DISSERT.pdf: 1612798 bytes, checksum: aef54b5521355bd929dc0d8a6b6f8771 (MD5) Previous issue date: 2018-04-17 / Conselho Nacional de Desenvolvimento Científico e Tecnológico - CNPq / As cores não são apenas um estímulo estético, elas também afetam diretamente a cognição e o comportamento humano. Estudos denominados de psicodinâmica e psicologia das cores, por exemplo, indicam que as cores de um objeto, ou de um local, podem induzir emoções. As emoções, por sua vez, também interferem na visão e percepção das cores, devido à capacidade de determinados estados emocionais induzirem alterações em importantes neurotransmissores, afetando diretamente a excitação que por sua vez provoca contrações ou dilatações na pupila, alterando a quantidade de luz que chega até a retina. Emoções negativas como a tristeza, por exemplo, prejudicariam a percepção visual da cor por desencadear reações que promovem quedas nos níveis de dopamina, e interromperem a contração da pupila, consequentemente prejudicando a sensibilidade ao contraste cromático. Já estados emocionais positivos, como a alegria, poderiam ser responsáveis por ampliar a atenção visual. A presente pesquisa objetivou observar a influência dos estados emocionais de alegria ou tristeza sobre a percepção de cores da visão humana. Investigamos tal influência em indivíduos com visão em cores normal e em indivíduos daltônicos. A pesquisa contou com a participação de 74 homens com idades entre 18 e 35 anos, daltônicos e não daltônicos. Todos os participantes foram submetidos ao Inventário de Depressão de Beck (BDI), ao Teste de Ishihara, e ao teste de percepção de cores de Lanthonny D-40 Hue, e assistiram a um vídeo de aproximadamente 3 minutos de estímulo emocional durante o qual houve monitoramento da contração pupilar. Após a exibição dos vídeos os participantes realizaram novamente o teste de percepção de cores e foi avaliado se houve ou não mudança significativa no desempenho da capacidade de sua percepção cromática. Os dados resultantes deste trabalho sugerem que há influência significativa da emoção tanto sobre a percepção de cores quanto para o tamanho da pupila. Sendo assim, como hipotetizado inicialmente, não apenas informações semânticas, mas também aspectos emocionais parecem estar envolvidos na cognição visual e consequentemente na percepção de cores da visão humana. / Colors are not just an aesthetic stimulus, they also directly affect human cognition and behavior. Studies of psychodynamics and color psychology, for example, indicate that the colors of an object, or a place, can induce emotions. Emotions, in turn, also interfere with color vision and perception, due to the ability of certain emotional states to induce changes in important neurotransmitters, directly affecting the excitation, which in turn causes contractions or dilations in the pupil, altering the amount of light that reaches the retina. Negative emotions such as sadness, for example, would impair the visual perception of color by triggering reactions that promote falls in dopamine levels, and disrupt pupil contraction, consequently impairing sensitivity to chromatic contrast. Already positive emotional states, such as joy, could be responsible for expanding visual attention. The present research observed the occurrence of the influence of the emotional states of joy or sadness on the perception of colors of the human vision. We investigate how that influence affects individuals with normal color vision and colorblind individuals, who in turn can no longer distinguish certain colors, the research had the participation of 74 men between the ages of 18 and 35, colorblind and non-colorblind. All participants were submitted to the Beck Depression Inventory (BDI), the Ishihara Test, and the Lanthonny D-40 Hue color perception test and watched a video of approximately 3 minutes of emotional stimulation. After the videos were taken, the participants again performed the color perception test. We evaluated whether there was a significant change in the performance of the ability of their color perception. The data resulting from this work suggest that there is significant influence of emotion on both color perception and pupil size. Thus, as hypothesized initially, not only semantic information, but also emotional aspects seem to be involved in visual cognition and consequently in color perception of human vision.

Made available in DSpace on 2014-06-11T19:29:00Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-03-14Bitstream added on 2014-06-13T19:17:01Z : No. of bitstreams: 1 gazzola_ra_me_bauru.pdf: 248528 bytes, checksum: 218a7bda6ba9d6f0a378ed3514a7906f (MD5) / Universidade Estadual Paulista (UNESP) / O objetivo do presente estudo foi avaliar o comportamento de preferência por escuridão em peixes da espécie C. auratus. No primeiro experimento avaliamos os efeitos das condições de alojamento sobre o comportamento de preferência, comparando posteriormente a situações onde foi inserido um substrato de cor intermediária (cinza). No segundo experimento avaliamos se a preferência por escuridão alterava-se após expor os sujeitos a variados regimes de luz. No primeiro experimento utilizamos 48 peixes (c. auratus), medindo entre cinco e sete centímetros, alojados em grupo (n = 24) em aquários de vidro (30 x 45 x 35 cm), com água filtrada e tamponada ph = 7,5 ± 5, sob temperatura de 27 ± 2ºc, ciclo de luz alternados em 12:12 h, controle de luz externa e alimentados uma vez ao dia. O aparato utilizado constituiu-se por seis aquários (15 x 10 x 45 cm) nas cores: preto, branco, cinza, branco-preto, cinza-branco e cinza-preto, com coluna d'água de 10 cm. No segundo experimento utilizamos 32 peixes da mesma espécie e com as mesmas características, mantidos em grupo (n = 11) em condições similares (4h, 8h, 12h, 16h ou 20h de luz). Foi utilizado aparato com medida similar ao experimento anterior e nas cores preto-branco. Após 5 minutos de habituação no centro do aquário as comportas eram removidas. As sessões tiveram duração de quinze 15 min. O procedimento foi o mesmo nos 2 experimentos. Os resultados indicaram maior preferência dos animais pelo substrato preto quando em contraste com o substrato branco, e do cinza, em relação ao preto e ao branco. O segundo experimento indicou que a exposição a regimes de luz diferenciados altera a preferência dos animais fazendo com que no regime de 20 h a preferência por substrato escuro desapareça, desta forma, alguns regimes luminosos, em específico os mais longos,... / The aim of the present study was to evaluate the darkeness preference behavior in fish . The first experiment evaluated the preference among three substratum (dark, white and ash) . The second experiment evaluated the preference by darkness after exposition to differentes light regimes. In the first experiment 48 fish (c. auratus), five to seven centimeters of body size, were housed in group (n = 24) with light cycle alternated in 12:12 h, light control expresses and they were fedded once a day. The apparatus was constituted by six aquariums (15 x 10 x 45 cm) in colors (black, white, ash, white-black, ash-white and ash-black) and column of water of 10 cm. In the second experiment 32 fish of the same species and with the same characteristics, under similar conditions, were exposed to inverted and alternated light cycles (4 h, 8 h, 12 h, 16 h or 20h). The apparatus had similar measures and black-white colors to the previous experiment. After 5 minutes of habituation in the center of the aquarium the floodgates were removed. The sessions finished at 15 minutes. The procedure was the same in two experiments. The data of teh first experiment shows that the subjects prefer black substract than white and they o prefer ash than blak or white. The second experiment suggested that the kind of exposure of light regime effects the preferency in fishes. Twenty hours lighting regime faded out the darkeness preferency. Some luminous regimes, in specific the longest, altered the preference for darkness in the fish. There is preference for the intermediate substratum (ash) when available.

Made available in DSpace on 2015-06-06T02:06:15Z (GMT). No. of bitstreams: 1 000470034-Texto+Parcial-0.pdf: 704188 bytes, checksum: 0b6ee2369c382001ce0912a4980343b5 (MD5) Previous issue date: 2015 / Introduction : Although the impact of childhood maltreatment (CM) are known, not only regarding clinical but psychosocial outcomes, an extensive field of study is still open to understanding the neurophysiological mechanisms mediating cause and outcome. Systems somehow connected to stress response, as the hypothalamic-pituitary-adrenal axis (HPA) and the immune system, are strong candidates to play an important role in this association. Objective : To investigate peripheral cytokines and hormonal measures in healthy adolescents exposed to CM. Method : This thesis consists of three studies. The first one aims to understand the immune activation state by measuring six cytokines (IFN-Υ, IL-2, IL-4, IL-6, IL-10 and IL-17A) in adolescentes exposed and not exposed to CM. In the second study, we used hair and plasma cortisol measures to compare both groups. The third study investigated plasma copeptina in these groups. Results : The first trial has showed decreased levels of IFN-Υ, IL-2, IL-4, IL-6 and IL-10 in CM adolescents. The second study an increased hair cortisol in adolescent victims of CM. This elevation was not confirmed with plasma cortisol. The third study found no correlation between plasma levels of copeptin and history of CM in these adolescents. Conclusions : These were the first studies to examine cytokines, hair cortisol and copeptin in healthy adolescent victims of CM. The results of this thesis seems to confirm a distinct immunological pattern in adolescent victims of CM. The decreased levels of cytokines found in this group may be due to a mechanism of immunosuppression secondary to HPA axis activation, confirmed by hair cortisol. The use of hair cortisol proved to be interesting for getting over the numerous biases contained in cortisol cross sampling, indicating an excellent measure of medium-term neuroendocrinologic response. Although there was no difference between groups in plasma copeptin, we consider important the emphasis in the studies with this biomarker in non-clinical populations, searching for a better understanding of the mechanisms involved in this association. / Introdução : Embora sejam conhecidos os impactos dos maus-tratos na infância (MTI) não somente em relação a desfechos clínicos como também psicossociais, um extenso campo de estudo ainda está aberto visando a compreensão sobre os mecanismos neurofisiológicos que mediam a causa e o desfecho. Sistemas que, de alguma forma, estão conectados à resposta ao estresse, como o Eixo Hipotálamo-Hipófise-Adrenal (HPA) e o sistema imunológico são fortes candidatos a desempenharem um importante papel nessa associação. Objetivo : Investigar a concentração de citocinas periféricas e medidas hormonais em adolescentes hígidos expostos a MTI.Método : A presente tese é composta por três estudos. O primeiro estudo procura entender o estado de ativação imunológica através da mensuração de seis citocinas (IFN-ϒ, IL-2, IL-4, IL-6, IL-10 e IL-17A) em um grupo de adolescentes expostos e não expostos a MTI. O segundo estudo comprarou a concentração de cortisol capilar e cortisol plasmático entre ambos grupos. O terceiro estudo investigou níveis plasmáticos de copeptina nas duas amostras investigadas. Resultados : O primeiro estudo mostrou uma diminuição nos níveis de IFN-ϒ, IL-2, IL-4, IL-6 e IL-10 em adolescentes vítimas de MTI em relação aos não expostos. O segundo estudo mostrou medidas elevedas de cortisol capilar nos adolescentes vítimas de MTI. Tal elevação não se confirmou através da medida do cortisol plasmático. O terceiro estudo não encontrou associação entre níveis plasmáticos de copeptina e história de MTI nesses adolescentes. Considerações finais : Esses foram os primeiros trabalhos a analisar citocinas, cortisol capilar e copeptina em adolescentes sadios vítimas de MTI. Os resultados dessa tese confirmam um padrão imunoendócrino alterado em adolescentes vítimas de MTI. Os níveis diminuídos de citocinas encontrados nesse grupo podem ser consequência de um mecanismo de supressão imunológica secundário a ativação do Eixo HPA, confirmado através do cortisol capilar. O uso da medida de cortisol capilar mostrou-se interessante por conseguir superar os inúmeros vieses contidos nas amostragens transversais de cortisol, indicando uma excelente medida de médio prazo de resposta neuroendocrinológica. Embora não tenhamos encontrado diferença entre os grupos nos níveis de copeptina sérica, consideramos importante a insistência nos estudos com esse biomarcador em populações não-clínicas, na busca de um melhor entendimento sobre os mecanismos intervenientes nessa associação.

Made available in DSpace on 2013-08-07T19:08:28Z (GMT). No. of bitstreams: 1 000401825-Texto+Completo-0.pdf: 1382109 bytes, checksum: f74c6f908d10490fb30a927b02c207b2 (MD5) Previous issue date: 2007 / INTRODUCTION: Developmental traumatology is a model of De Bellis (2001), it consists of systematic investigation of psychological and psychobiological impact on adverse events to child development. The majority of animal studies use maternal deprivation as a method to investigate the effect of early stress on behavioral and neurobiological responses of adults, but interesting the psychobiological impact of neglect forms of maltreatment are very few studied in humans. OBJECTIVE: The main goal is to investigate the effects of history of childhood neglect on memory performance of females with Major Depressive Disorder (MDD), In addition, this work tries to search for associations between memory performance and neurobiological and psychosocial variables. METHOD: The current thesis includes three studies. In the first study, the last 18 years literature on neurobiology and psychobiology of child maltreatment was carefully reviewed in journals with impact factor higher than 1. The second study proposes a multiple regression model where the impact of childhood physical neglect (CPN) and the plasmatic level of Brain Derived Neurotrophic Factor (BDNF) on verbal memory performance of adult females with MDD were investigated. The third study consists in a experiment where females with MDD who reported childhood emotional neglect (EN+) were compared to females with MDD but without EN (EN-) and healthy controls on recognition test performance for semantic related words. RESULTS: The first study “Psychobiology of Childhood Maltreatment: Effects of Allostatic Load?” selected 75 articles (JCR IF range: 1 - 31. 4, median: 5. 88) to the review. The results of second study “Low Plasma Brain Derived Neurotrophic Factor and Childhood Physical Neglect Are Associated with Memory Impairment in Major Depression” suggest significant correlations between immediate verbal recall and severity of depression, posttraumatic stress disorder symptoms, CPN and plasma BDNF.The delayed verbal recall showed associations with the same variables plus years of education. In addition, the MDD+CPN group showed impairment on immediate and delayed recall when compared to other groups, but the same pattern was not observed to memory retention rate. It was observed that the severity of CPN and low plasma BDNF predicted immediate verbal recall impairment and CPN was related with the both immediate and delayed recall, corroborating with previous childhood sexual abuse studies. The third study “Gist Memory Impairment in Depressed Women with Childhood Emotional Neglect Reduce False Recognition” indicates that EN+ group has lower rates of false recognition when compared to EN- and control groups. In regard to true recognition of previous studied words (correct targets recognition) there aren’t significant differences between groups. Signal detection methods show significant differences between groups in regard sensitivity to verbatim memory. Corroborating with the beginning analyses, EN+ group is less affected by semantic effect, indicating a semantic association deficit, reflected by gist memory impairment. CONCLUSION: This thesis coming up with brand new results until now not published in literature. All studies suggest that childhood neglect may have an important role on memory systems and this could be modulated thorough neurotrophins actions. Considering that developmental traumatology model proposed a network of complex interactions between individual genetic constitutions, unique environmental experiences, critical periods of developmental vulnerability, and resilience to the 13 understanding on how these factors can influence changes in stress biological systems and brain development, it is highlighted the importance of such results replication to a more definitive conclusions. / INTRODUÇÃO: A traumatologia desenvolvimental é um termo proposto por De Bellis, (2001) e consiste na investigação sistemática do impacto psiquiátrico e psicobiológico de eventos adversos ao desenvolvimento infantil. A maioria dos estudos com animais utilizam modelos de privação materna para investigar o efeito do estresse precoce na resposta comportamental e neurobiológica de adultos, mas surpreendentemente o impacto psicobiológico das formas de negligência infantil são muito poucos investigados em humanos. OBJETIVO: Estudar o efeito da história de negligência na infância em relação à performance em testes de memória de mulheres com Depressão Maior (MDD), além de investigar associações com variáveis neurobiológicas e psicossociais. MÉTODO: A presente tese é composta por três estudos. O primeiro estudo, de cunho teórico, revisa os últimos 18 anos da literatura científica no que tange a artigos sobre psicobiologia dos maus-tratos infantis, publicados em revistas com fator de impacto maior que 1. O segundo estudo propõe um modelo de regressão múltipla, onde se investigou o papel da negligência física na infância (CPN) e do nível plasmático do Fator Neurotrófico Derivado do Cérebro (BDNF) no desempenho da memória verbal de mulheres adultas com MDD. Por fim, o terceiro estudo consistiu em um experimento onde mulheres com MDD e que relatavam ter sofrido negligência emocional na infância (CEN) foram comparadas com mulheres com MDD sem CEN e controles saudáveis em relação ao desempenho em um teste de reconhecimento para palavras semanticamente associadas.RESULTADOS: No primeiro estudo “Psicobiologia dos Maus-tratos na Infância: Efeito de Peso Alostático?” foram selecionados 75 artigos (Fator de Impacto JCR: 1 - 31. 4, mediana: 5. 88) para essa revisão. Os resultados do segundo estudo “Negligência Física na Infância, Baixo Fator Neurotrófico Derivado do Cérebro (BDNF) no Plasma e Prejuízo da Memória Verbal em Adultos” sugerem a existência de correlações significativas entre recordação verbal imediata e severidade da depressão, sintomas do transtorno de estresse pós-traumático, negligência física na infância (CPN) e BDNF plasmático. A recordação verbal posterior mostrou-se associada às mesmas variáveis, além de estar associada com a quantidade de anos de instrução. Ainda, o grupo com depressão maior e histórico de negligência física na infância (MDD + CPN) mostrou maior prejuízo na recordação imediata e posterior quando comparado aos demais grupos, mas o mesmo padrão não é observado para o percentual de retenção da memória. Foi observado que a severidade da CPN e o baixo BDNF plasmático predizem o prejuízo na recordação verbal imediata. Além disso, a CPN foi relacionada com o grau de comprometimento da memória verbal imediata e posterior, corroborando diversos estudos que investigaram essa relação com exposição na infância ao abuso sexual. O terceiro estudo “O Comprometimento da Memória de Essência em Mulheres com Negligência Emocional na Infância Reduz o Falso Reconhecimento” indica que o grupo com negligência emocional (EN+) teve menores porcentagens de reconhecimento falso quando comparado com os grupos sem negligência emocional (EN-) e o controle. No que diz respeito ao reconhecimento correto de palavras que foram mostradas anteriormente (taxas de acerto), os grupos não mostraram diferenças significativas entre si.Métodos de detecção de sinal apontam para diferenças significativas entre grupos na sensibilidade para memória literal. Condizente com as análises iniciais, o grupo EN+ foi menos afetado pelo efeito semântico, indicando um comprometimento da capacidade de associação semântica, refletido pelo prejuízo na memória de essência. CONCLUSÃO: A presente tese traz resultados até então não encontrados na literatura. Os estudos sugerem um efeito das formas de negligência na infância sobre a memória que poderia ser modulado pela ação de neurotrofinas. Considerando que o modelo da traumatologia desenvolvimental consiste em uma rede de complexas interações entre genética, experiências ambientais, períodos críticos de vulnerabilidade desenvolvimental e características de resiliência, na tentativa de entender como tais fatores poderiam influenciar mudanças nos sistemas biológicos de estresse e no desenvolvimento cerebral, ressalta-se a necessidade de replicação dos resultados para conclusões mais definitivas.