This study investigated the associations between (1) handedness (demonstrated preference of one hand for the performance of most unimanual tasks) and neuroanatomical asymmetry (measurable differences in width between the cerebral hemispheres) and (2) familial history of handedness (the presence of a left-handed sibling or parent of a right-handed subject) as an intervening factor in the relation between handedness and neuroanatomical asymmetry. Width measurements of the brain were derived from computerized tomographic ( CT) films and grouped in to categories by hand preference (measured by the Edinburgh Handedness Inventory) and family history. The measurements of right (n=68), right with left-· handed relatives (n=24), and left-handed (n=16) groups were then compared by width and other transformations of the brain measurements. Subjects were adults of both sexes who had been referred for neurologic examination and were diagnosed as free of major distorting brain pathology. Hemispheric widths were compared by group, as ratios (left÷right) and as differences (left-right). Analysis of variance revealed significant differences between right-hemisphere widths at three percentages of brain length in the posterior occipital and temporal-parietal portion of the right hemisphere. The two right-handed groups had significantly smaller right-hemisphere measurements than the left group at 80% (p=.03), 75% (p= .012), and 60% (p= .029) of brain length. There were no significant left-hemisphere differences between the groups. In terms of ratios of sides and differences between sides in the same brain region, the left - handed group was different from the right-handed group at the p Handedness appears to be moderately associated with neuroanatomical asymmetry. The differences in sizes of brain structures and their relation to functionally lateralized abilities may shed light on the processes by which each hemisphere becomes specialized to perform specific tasks and other aspects of individual differences.

Submitted by Ronildo Prado (ronisp@ufscar.br) on 2017-08-23T19:35:48Z No. of bitstreams: 1 DissNSC.pdf: 1757369 bytes, checksum: 8c5c3122b8536a2aa61fd673039785e3 (MD5) / Approved for entry into archive by Ronildo Prado (ronisp@ufscar.br) on 2017-08-23T19:35:55Z (GMT) No. of bitstreams: 1 DissNSC.pdf: 1757369 bytes, checksum: 8c5c3122b8536a2aa61fd673039785e3 (MD5) / Approved for entry into archive by Ronildo Prado (ronisp@ufscar.br) on 2017-08-23T19:36:03Z (GMT) No. of bitstreams: 1 DissNSC.pdf: 1757369 bytes, checksum: 8c5c3122b8536a2aa61fd673039785e3 (MD5) / Made available in DSpace on 2017-08-23T19:36:10Z (GMT). No. of bitstreams: 1 DissNSC.pdf: 1757369 bytes, checksum: 8c5c3122b8536a2aa61fd673039785e3 (MD5) Previous issue date: 2017-04-13 / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Stressful situations are risk factors to the development of neuropsychiatric diseases, as anxiety disorders. However, not everyone who experiences stressful events develops stress-related illness. That is due to the existence of differences in the ability to adapt to stress, that is, the manifestation of susceptibility or resilience phenotypes. The search for understanding neural systems involved to these differences has evidenced an important role of the medial Prefrontal Cortex (mPFC), and, recently, its functional lateralization has been highlighted. In this sense, the right mPFC (RmPFC) seems to modulate anxiogenic-like responses, while the left mPFC (LmPFC) would attenuate such responses, thereby facilitating animals to cope with threatening situations. If so, LmPFC inhibition would intensify ansiogenic-like behavior front to aversive stimuli. Under this hypothesis, one of the goals of the present study was to investigate whether the inhibition of the LmPFC could modulate the effect of two types of stress (the restraint and the social defeat) on anxiety. Yet, we also aimed to investigate whether NMDA-glutamate receptor would be involved to the anxiogenic-like effect induced by nitrergic activation of the RmPFC, given the anxiogenic potential of glutamate and the interaction already known between these neurotransmissions. To reach that, experiments were carried out (1) to characterize the effects of social defeat and restraint stress on animals exposed to elevated plus maze (EPM) 5 minutes or 24 hours later; (2) to evaluate the effects of restraint or social defeat combined to the synaptic inactivation (through nonspecific inhibitor, CoCl2) of the LmPFC on the defensive behavior of mice exposed to EPM 24 h after stress; (3) to investigate the effects of NMDA receptor antagonism and (4) the effect of that antagonism on anxiogenic-like effects induced by NO donor. The results showed that both restraint and defeat stress are anxiogenic at 5 minutes, but defeated mice do not display anxiety 24 h after stress. Furthermore, the synaptic inhibition produced a clear anxiogenic-like effect in defeated (but not restrained) mice. In addition, the blockade of NMDA receptors produced anxiolytic-like effects and reversed the anxiogenic effect induced by NO injection into the RmPFC. Taken together, these results corroborate previous studies demonstrating the functional lateralization of the mPFC, in which the right and left hemispheres seem to have distinct roles in the modulation of aversive events. / O estresse, que pode ser definido como uma condição que perturba o equilíbrio fisiológico e psicológico de um indivíduo, é fator de risco para o desenvolvimento de doenças neuropsiquiáticas, como transtornos de ansiedade. No entanto, nem todos os indivíduos que vivenciam um evento estressor desenvolvem doenças relacionadas a ele. Isto se deve à existência de diferenças na habilidade de se adaptar ao estresse, ou seja, a manifestação dos fenótipos de susceptibilidade ou resiliência. A busca pelo entendimento dos sistemas neurais envolvidos nessas diferenças tem evidenciado um papel importante do Córtex Pré-Frontal medial (CPFm) e, mais recentemente, a sua lateralização funcional vem ganhando especial destaque. Neste sentido, o CPFm Direito (D) parece modular respostas ansiogênicas, enquanto o CPFm Esquerdo (E) atenuaria essas respostas, ajudando o animal a lidar com eventos aversivos. Neste caso, a inibição do CPFmE intensificaria as respostas geradas por situações ameaçadoras. Sob essa hipótese, um dos objetivos do presente trabalho foi investigar se a inibição do CPFmE poderia modular o efeito de dois tipos de estresse (a contenção e a derrota social) sobre a ansiedade. Ainda, esse estudo também investigou se os receptores glutamatérgicos do tipo NMDA (N-metil-D-aspartato) estariam envolvidos no efeito ansiogênico provocado pela ativação nitrérgica [com injeção local do doador de óxido nítrico (NO), o NOC-9] no CPFmD, haja vista o potencial ansiogênico do glutamato e as interações já conhecidas entre essas neurotransmissões. Para tanto, foram feitos experimentos para (1) caracterizar os efeitos imediatos (após 5 minutos) ou tardios (após 24 horas) do estresse de derrota social e de contenção sobre o comportamento de animais expostos ao labirinto em cruz elevado (LCE); (2) avaliar os efeitos da combinação do estresse de contenção ou de derrota social com a inativação sináptica (através do inibidor inespecífico, CoCl2) do CPFm E no comportamento defensivo de camundongos expostos ao LCE 24h após o evento estressor; (3) investigar os efeitos do antagonismo per se de receptores NMDA e (4) o efeito desse antagonismo sobre a ansiogênese provocada pelo doador de NO sobre o comportamento de animais expostos ao LCE. Os resultados obtidos demonstram que ambos os estressores são ansiogênicos aos 5 minutos, mas a derrota social não provoca aumento de ansiedade 24 h após o estresse. Ainda, a inbição sináptica do CPFmE produz efeito ansiogênico 24 h depois quando associada ao estresse de derrota social (mas não à contenção). Além disso, o bloqueio de receptores NMDA por si provoca efeito ansiolítico e reverte o efeito ansiogênico provocado pelo NO em animais expostos ao LCE. Tomados em conjunto, esses resultados substanciam as evidências sobre a lateralização funcional do CPFm, em que os hemisférios direito e esquerdo parecem possuir diferentes participações na modulação de eventos aversivos.