Women have greater incidence and prevalence of Major Depressive Disorder (MDD) than men during the reproductive life phase when ovarian hormones fluctuate, suggesting that ovarian hormones have a significant role in MDD etiology in women. As the core symptoms of MDD are indicative of alterations in stress responding, emotional processing, and mood regulation, examining the effects of the estrogen on these processes in women may provide a better understanding of the role of estrogen in the sex difference in MDD rates. The general aim of this dissertation was to examine neural, emotional, and attentional processes related to stress response alterations and cognitive bias in MDD in women. To examine menstrual phase and estradiol level effects on the neural and mood response to psychosocial stress, healthy, normally cycling women were examined at either the high or low estradiol phase of the menstrual cycle. Participants were exposed to the Montreal Imaging Stress Task (MIST), with brain activity measured through functional magnetic resonance imaging (fMRI), and behavioral response assessed with subjective mood and stress measures. We found that women during the high estradiol phase showed significantly less hippocampal deactivation during psychosocial stress compared to women during the low estradiol phase. Additionally, women with higher estradiol levels also had less subjective distress in response to the MIST than women with lower estradiol levels. These results suggest that high estradiol may be protective against the shifts in brain system activity and negative mood responses associated with psychosocial stress. Periods of low estradiol may enhance the negative impact of psychosocial stress on neural activity and mood and thus contribute to MDD risk in vulnerable women. The relation of cognitive bias to depression history in women was examined in postmenopausal women with and without a history of major depression using an emotion dot probe task during fMRI. Women with remitted MDD showed greater attentional facilitation for negative images than women with no history of MDD that was directly correlated with amygdala activity for negative images and amygdala-hippocampal connectivity in a resting scan. These findings provide evidence that differences in activity and functional connectivity in emotional processing networks may provide a neurobiological basis for continued cognitive bias in remitted MDD. Preliminary data indicate that estradiol treatment reduces amygdala-hippocampal connectivity specifically in women with a history of MDD and has interactive effects with MDD history on the mood response to psychosocial stress following the MIST such that women with a history of MDD appear to benefit from estradiol treatment while women without such history do not. Women with a history of or vulnerability to MDD may be particularly sensitive to the positive effects of estradiol on brain systems important to regulating emotional responses to psychosocial stress. The findings presented in this dissertation suggest that estrogen fluctuations across the menstrual cycle and at other reproductive events may contribute to depression risk through effects on brain systems integral to emotional evaluation and response with potential cognitive consequences.

La compréhension du fonctionnement cérébral est en constante évolution depuis l’essor des neurosciences.Les nouvelles modalités d’imagerie ont permis de mettre en évidence une architecture de notre cerveau en réseaux complexes. Mon travail a pour but de développer une méthode mettant en évidence les réseaux les plus représentatifs d’un groupe de sujet en IRM fonctionnelle.Dans un premier temps, j’ai développé une méthode de réduction des données basées sur le clustering.J’ai introduit une nouvelle caractérisation de l’information fonctionnelle par le profil de connectivité.Celui-ci permet de réduire le biais induit par le bruit présent au sein des données d’IRM fonctionnelle.De plus ce profil ne nécessite pas d’a priori sur les données contrairement aux méthodesi nférentielles classiques.Dans un deuxième temps, j’ai développé une méthode qui permet l’identification de réseaux communs sur un groupe de sujets tout en prenant en compte les variabilités spatiales et fonctionnelles inter-sujets. Les réseaux obtenus peuvent ensuite être caractérisés par leur distribution spatiale mais également par les liens de connectivités se manisfestant en leur sein.Cette méthode permet également la comparaison des réseaux de différents groupes de sujets et la mise en évidence de l’implication de réseaux différents en fonction de stimulations différentes ou d’un état pathologique. / The comprehension of cerebral operations is in constant evolution since the rise of the neurosciences.New methods of imagery made it possible to highlight an architecture of our brain in complex networks.The purpose of my work is to develop a method to find the most representative networks of a group of subjects in Functional MRI.In the first step, I developed a method to reduce the fMRI data size based on clustering. I introduced a new characterization of functional information by the profile of connectivity. This one makes it possible to reduce the variance induced by the noise present within the data of Functional MRI.Moreover this profile does not require a priori information on the data contrary to the traditional inferential methods.In the second step, I developed a method to identify common networks on a group of subjects while taking into account of spatial and functional inter-subjects variability. The networks obtained can then be characterized by their spatial organization but also by their inner connectivity links.This method also allows the comparison of the networks of various groups of subjects, making it possible to highlight the implications of different networks according to different stimulations or pathological states.

Submitted by PPG Psicologia (psicologia-pg@pucrs.br) on 2018-03-21T13:20:05Z No. of bitstreams: 1 TES_BRENO_SANVICENTE_VIEIRA.pdf: 6222146 bytes, checksum: d1e5e710fc5ec0e52c03bb4ffe92d0f8 (MD5) / Approved for entry into archive by Tatiana Lopes (tatiana.lopes@pucrs.br) on 2018-04-03T20:11:47Z (GMT) No. of bitstreams: 1 TES_BRENO_SANVICENTE_VIEIRA.pdf: 6222146 bytes, checksum: d1e5e710fc5ec0e52c03bb4ffe92d0f8 (MD5) / Made available in DSpace on 2018-04-03T20:22:52Z (GMT). No. of bitstreams: 1 TES_BRENO_SANVICENTE_VIEIRA.pdf: 6222146 bytes, checksum: d1e5e710fc5ec0e52c03bb4ffe92d0f8 (MD5) Previous issue date: 2018-03-07 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / In Brazil, 1.4% of the population reports lifetime use of smoked cocaine (crack). The use of the drug relates to social and economic issues for society and poses serious health problems, including early death. Crack cocaine use disorder (CUD) is the medical condition which refers the pathological use of the drug. CUD relates to several negative outcomes such as higher rates of HIV and HCV infections, familiar problems and crime involvement, in addition to a higher prevalence of concurrent mental disorders. Scientific agendas promote evidence-based studies as a need for better therapeutics. In this regard, some gaps in the field require attention. In this line, distinct factors confer vulnerability for crack cocaine use in males and females: more males use the drug (a 3:1 proportion), but females show a faster transition from initial drug use to CUD. The course of the disease also show differences; females report a higher craving for the drug, while males have more frequent involvement with violent crimes. Thus, scientific commitments highlight a calling for the integration of those biopsychosocial models that consider individual characteristics in addition to those who consider addictive disorders as ?brain diseases.? A more consistent interdisciplinary integration of knowledge from classical theories in combination with advances provided for technologic methods is a promising route. Hence, the aim of this doctoral thesis was to investigate sex differences in crack cocaine users. To address the main objective, the thesis has two studies with groups of participants diagnosed with CUD and hospitalized for drug detoxification. These two groups were one of males (CK-M) and a second of females (CK-F). Study 1 had as its objective to get a picture of sex differences in the psychosocial profile. Study 2 had as its objective the identification of sex differences in brain functioning level. Study 1 had 798 CK-M and 546 CK-F. Results consistently revealed CK-M as having a more severe alcohol use history and higher rates of concurrent alcohol use disorder than CK-F. On the other hand, CK-F showed an earlier crack cocaine use onset, higher drug use severity, and more familiar and work problems along with a higher prevalence for lifetime mental disorders. Particularly, CK-F showed higher rates for trauma and stress. Study 2 had a sample of 80 participants: CK-M (n = 20), CK-F (n = 20), a group of males (HC-M, n = 20), and another of healthy female controls (HC-F, n = 20). Participants did a resting-state functional magnetic resonance imaging (rs-fMRI) scan. The method makes it possible to investigate temporal associations between nonspatially related brain areas by using as a measure fluctuations in the blood oxygen-level dependent (BOLD) level. It is an indirect measure of energy consumption, and by testing those correlations, functional connectivity (FC) can be investigated. Results supported CK-M as having an overall higher intra- and internetwork FC, while CK-F showed an overall lower FC in this regard. Taking both studies, the conclusions of this thesis point toward the existence of sex differences in all biopsychosocial domains. Thus, the interpretation of studies in crack cocaine use, particularly those testing interventions, need to resemble the possible existence of sex differences. Therefore, a hope from studies like this is that sex-specific models for crack cocaine use and CUD emerge and become tested. Similarly, possible interventions, also need to be aware of such backgrounds and consider possible sex differences when developing interventions, researches and public health policies as well. / No Brasil, cerca de 1.4% da popula??o refere j? ter feito uso de coca?na atrav?s de sua forma fumada (crack). O uso da droga gera repercuss?es sociais e econ?micas para a sociedade, al?m de ser um grave problema de sa?de relacionado, inclusive, com a morte precoce. Considerando o Transtorno por Uso de Coca?na (TUC) a manifesta??o patol?gica relacionada ao uso da droga, alguns dos desfechos desfavor?veis incluem: maiores taxas de infec??o por HIV e HCV; problemas judiciais e familiares, al?m maior preval?ncia de transtornos mentais em comorbidade. Iniciativas cient?ficas estimulam que propostas baseadas em evid?ncias sejam realizadas na tentativa de melhores resultados para o tratamento e preven??o do TUC. Neste sentido, maiores aprofundamentos em lacunas do conhecimento na ?rea s?o importantes. Assim, homens e mulheres possuem fatores de vulnerabilidade ao uso da droga distintos: Mais homens usam coca?na (propor??o de 3:1), mas mulheres apresentam uma evolu??o mais r?pida ao TUC ap?s o in?cio do uso. O curso da doen?a tamb?m ? diferente, mulheres sentem mais fissura pela droga, enquanto homens tem mais consequ?ncias relacionadas a crimes violentos. Assim sendo, iniciativas cient?ficas destacam a necessidade de integra??o de modelos biopsicossociais, que levem em conta as caracter?sticas individuais, mas que tamb?m considerem transtornos aditivos ?doen?as do c?rebro?, favorecendo a interdisciplinaridade entre antigas e robustas bases te?ricas e avan?os tecnol?gicos. Neste sentido, o objetivo desta tese foi investigar diferen?as entre homens e mulheres usu?rios de crack. Para tanto, dois estudos foram realizados com grupos de portadores de TUC internados para desintoxica??o do uso de crack, tendo sempre um grupo de homens (TUC-H) e outro de mulheres (TUC-M). No Estudo 1, o objetivo foi tra?ar um claro perfil de diferen?as psicossociais e de gravidade do uso de drogas, enquanto no Estudo 2 o objetivo foi identificar a exist?ncia de diferen?as em um n?vel de funcionamento cerebral. O Estudo 1 teve 798 TUC-H e 546 TUC-M. Resultados identificaram robustas diferen?as, com TUC-H possuindo uma hist?ria mais grave de uso de ?lcool, bem como uma maior preval?ncia para o transtorno por uso de ?lcool. Em contrapartida, TUC-M apresentam uma idade mais precoce do in?cio do uso de crack, maior severidade do uso de drogas em geral, preju?zos mais significativos nas esferas de trabalho e fam?lia, al?m taxas mais altas de preval?ncia de transtornos mentais (em especial transtornos relacionados a trauma e estresse). No Estudo 2, com 80 participantes al?m dos grupos TUC-H (n = 20) e TUC-M (n=20), participaram 20 homens saud?veis e 20 mulheres saud?veis. O m?todo utilizado foi um exame de Resson?ncia Magn?tica funcional (fMRI) em estado de repouso (rs-fMRI). Rs-fMRI permite avaliar associa??es na flutua??o do sinal BOLD (blood oxygen-level dependente, do ingl?s n?vel dependente de oxig?nio no sangue), que ? uma medida indireta de consumo energ?tico, entre ?reas cerebrais anatomicamente distintas, o que ? aceito como um dado de conectividade funcional (CF). Os resultados indicaram que de maneira geral, TUC-H apresentam um aumento na CF entre diferentes redes cerebrais, enquanto TUC-F apresentam redu??o na CF. Com base nos resultados, a tese conclui que homens e mulheres usu?rios de crack apresentam diferen?as em caracter?sticas que permeiam todos os dom?nios biopsicossociais, o que deve ser considerado ao levar em conta interpreta??es de estudos na ?rea e, principalmente, ao planejarem-se poss?veis interven??es no futuro. Portanto, espera-se que modelos sexo-espec?ficos para o uso de coca?na e do TUC sejam formulados, bem como que interven??es, pesquisas e inclusive pol?ticas de sa?de p?blica considerem poss?veis diferen?as em suas fundamenta??es.

Um dos maiores impactos antrópicos aos ecossistemas terrestres é a fragmentação do habitat. Este processo afeta fortemente os padrões de movimentação das espécies, implicando em alterações consideráveis na conectividade entre as manchas de habitat remanescentes. Por sua vez, isso interfere na distribuição espacial e na dinâmica das populações de uma espécie. Nesta dissertação, foram estudados alguns aspectos dos movimentos rotineiros e dispersivo de Pyriglena leucoptera, uma espécie de ave endêmica da Mata Atlântica. Estes dois tipos de movimentação atuam em escalas distintas, afetando diferentemente os parâmetros que regulam a estrutura das populações. Com o uso da técnica de playback, foi verificado se a capacidade desta espécie atravessar áreas abertas, em movimentos rotineiros entre fragmentos, é afetada pela distância entre eles. A partir desta relação, foram obtidas probabilidades de cruzar áreas abertas, as quais foram usadas para parametrizar índices de conectividade funcional (um binário e outro probabilístico) baseados na teoria dos grafos. Em uma abordagem de seleção de modelos, estes dois índices de conectividade mais um outro estrutural (i.e. área do fragmento) foram comparados para se estabelecer qual deles melhor prediz a incidência de P. leucoptera em fragmentos florestais. Quanto aos movimentos dispersivos, foram realizados experimentos de translocação e telemetria para verificar se a dispersão desta espécie em áreas fragmentadas é afetada pela distância entre os fragmentos, assim como para averiguar se este efeito é diferente entre os sexos. Os resultados mostraram que distância entre os fragmentos florestais limita tanto a movimentação rotineira, quanto a dispersiva para esta espécie. Na escala dos movimentos rotineiros, verificou-se que fragmentos distanciados a mais de 45 m estão totalmente isolados. A incidência da espécie foi melhor descrita pelo índice de conectividade funcional probabilístico (PCS), mostrando que a conectividade é fundamental para se compreender a distribuição espacial da espécie, sendo que este atributo da paisagem deve ser visto de forma probabilística. Ademais, a dispersão foi enviesada para fêmeas, as quais possuíram maior propensão a emigrar, assim como foram mais eficientes em sua movimentação pela matriz. As conseqüências deste viés foram discutidas, destacando-se que, em áreas altamente fragmentadas, a probabilidade de colonização de áreas desocupadas diminui, bem como o fluxo gênico entre as populações da espécie pode estar comprometido. Portanto, ambos os tipos de movimento devem ser considerados para que se possa compreender mais precisamente os efeitos da conectividade do habitat para a sobrevivência de uma espécie em paisagens fragmentadas. Por fim, foi sugerido um modelo hierárquico de estrutura populacional, a fim de integrar as informações obtidas pelos dois tipos de movimentação em uma única estrutura conceitual. Esse modelo possui um grande potencial para ser usado no planejamento e manejo ambiental. / Habitat fragmentation is one of the major human impacts on terrestrial ecosystems. This process highly affects the species movement pattern, implying in considerable alterations on the connectivity between the remaining habitat patches. Consequently, it interferes in the spatial distribution and in the population dynamics of species. In this dissertation, some aspects of the routine and dispersal movements of Pyriglena leucoptera, an endemic bird of the Atlantic rainforest, were studied. These two movement types act in distinct scales, affecting, differently, the parameter regulating the structure of the populations. Using the playback technique, we verified if the gap-crossing capacity of this species, by routine movements, is affected by gap width. From this relation, we obtained gap-crossing probabilities, which were used to parameterize functional connectivity indices (one binary and one probabilistic) based on graph theory. In a model selection approach, these two indices plus another structural one (i.e. patch area) were compared to establish which one is the best to predict P. leucopteras incidence in forest fragments. About the dispersal movements, we done translocation and telemetry experiments to investigate if the species dispersal ability in fragmented landscapes is affected by the distance between forest patches, and to verify if there are sexual differences in this effect. The results showed that distance between forest patches limits both the routine movements and the dispersal one to this species. In the routine movements scale, we verified that patches are completely isolated when the gap width is higher than 45 m. The species incidence was better described by the probabilistic connectivity index (PCS), evincing that it is essential to consider connectivity to understand the spatial distribution of P. leucoptera, and this attribute must be viewed in its probabilistic form. Furthermore, dispersal is female-biased, since females are more prone to emigrate and were more efficient in their movement in the matrix. We discussed the consequences of this sex-bias, highlighting that, in severely fragmented landscapes, the colonization probability of empty patches is decreased and the genetic flux between populations should be imperiled. Thus, to comprehend the effects of habitat connectivity on species survival in fragmented landscapes, both movement types must be considered. Finally, we suggested a hierarchically structured population model in order to integrate the two movement type information in one conceptual framework. This model has a great potential to be used in environmental planning and management.

Um dos maiores impactos antrópicos aos ecossistemas terrestres é a fragmentação do habitat. Este processo afeta fortemente os padrões de movimentação das espécies, implicando em alterações consideráveis na conectividade entre as manchas de habitat remanescentes. Por sua vez, isso interfere na distribuição espacial e na dinâmica das populações de uma espécie. Nesta dissertação, foram estudados alguns aspectos dos movimentos rotineiros e dispersivo de Pyriglena leucoptera, uma espécie de ave endêmica da Mata Atlântica. Estes dois tipos de movimentação atuam em escalas distintas, afetando diferentemente os parâmetros que regulam a estrutura das populações. Com o uso da técnica de playback, foi verificado se a capacidade desta espécie atravessar áreas abertas, em movimentos rotineiros entre fragmentos, é afetada pela distância entre eles. A partir desta relação, foram obtidas probabilidades de cruzar áreas abertas, as quais foram usadas para parametrizar índices de conectividade funcional (um binário e outro probabilístico) baseados na teoria dos grafos. Em uma abordagem de seleção de modelos, estes dois índices de conectividade mais um outro estrutural (i.e. área do fragmento) foram comparados para se estabelecer qual deles melhor prediz a incidência de P. leucoptera em fragmentos florestais. Quanto aos movimentos dispersivos, foram realizados experimentos de translocação e telemetria para verificar se a dispersão desta espécie em áreas fragmentadas é afetada pela distância entre os fragmentos, assim como para averiguar se este efeito é diferente entre os sexos. Os resultados mostraram que distância entre os fragmentos florestais limita tanto a movimentação rotineira, quanto a dispersiva para esta espécie. Na escala dos movimentos rotineiros, verificou-se que fragmentos distanciados a mais de 45 m estão totalmente isolados. A incidência da espécie foi melhor descrita pelo índice de conectividade funcional probabilístico (PCS), mostrando que a conectividade é fundamental para se compreender a distribuição espacial da espécie, sendo que este atributo da paisagem deve ser visto de forma probabilística. Ademais, a dispersão foi enviesada para fêmeas, as quais possuíram maior propensão a emigrar, assim como foram mais eficientes em sua movimentação pela matriz. As conseqüências deste viés foram discutidas, destacando-se que, em áreas altamente fragmentadas, a probabilidade de colonização de áreas desocupadas diminui, bem como o fluxo gênico entre as populações da espécie pode estar comprometido. Portanto, ambos os tipos de movimento devem ser considerados para que se possa compreender mais precisamente os efeitos da conectividade do habitat para a sobrevivência de uma espécie em paisagens fragmentadas. Por fim, foi sugerido um modelo hierárquico de estrutura populacional, a fim de integrar as informações obtidas pelos dois tipos de movimentação em uma única estrutura conceitual. Esse modelo possui um grande potencial para ser usado no planejamento e manejo ambiental. / Habitat fragmentation is one of the major human impacts on terrestrial ecosystems. This process highly affects the species movement pattern, implying in considerable alterations on the connectivity between the remaining habitat patches. Consequently, it interferes in the spatial distribution and in the population dynamics of species. In this dissertation, some aspects of the routine and dispersal movements of Pyriglena leucoptera, an endemic bird of the Atlantic rainforest, were studied. These two movement types act in distinct scales, affecting, differently, the parameter regulating the structure of the populations. Using the playback technique, we verified if the gap-crossing capacity of this species, by routine movements, is affected by gap width. From this relation, we obtained gap-crossing probabilities, which were used to parameterize functional connectivity indices (one binary and one probabilistic) based on graph theory. In a model selection approach, these two indices plus another structural one (i.e. patch area) were compared to establish which one is the best to predict P. leucopteras incidence in forest fragments. About the dispersal movements, we done translocation and telemetry experiments to investigate if the species dispersal ability in fragmented landscapes is affected by the distance between forest patches, and to verify if there are sexual differences in this effect. The results showed that distance between forest patches limits both the routine movements and the dispersal one to this species. In the routine movements scale, we verified that patches are completely isolated when the gap width is higher than 45 m. The species incidence was better described by the probabilistic connectivity index (PCS), evincing that it is essential to consider connectivity to understand the spatial distribution of P. leucoptera, and this attribute must be viewed in its probabilistic form. Furthermore, dispersal is female-biased, since females are more prone to emigrate and were more efficient in their movement in the matrix. We discussed the consequences of this sex-bias, highlighting that, in severely fragmented landscapes, the colonization probability of empty patches is decreased and the genetic flux between populations should be imperiled. Thus, to comprehend the effects of habitat connectivity on species survival in fragmented landscapes, both movement types must be considered. Finally, we suggested a hierarchically structured population model in order to integrate the two movement type information in one conceptual framework. This model has a great potential to be used in environmental planning and management.

Previous studies have reported altered glutamate (Glu) concentrations in the blood and brain of individuals with autism spectrum disorder (ASD) compared to neurotypical controls (NC), but the direction (increased or decreased) of metabolite differences is still unclear. Moreover, the relationship between Glu and both brain function and clinical manifestations of the disorder require further investigation. Within this study, we investigated metabolite concentrations within the dorsal anterior cingulate cortex (dACC), a brain region functionally associated with inhibitory executive control tasks and also part of the salience network. There were 19 participants with ASD and 20 NCs between the ages of 23 and 58 years who participated in this study. A study clinician administered the Autism Diagnostic Observation Schedule (ADOS) to individuals with ASD to further confirm their diagnosis. In addition, all participants in this study completed assessments of general intelligence and attention, which included an inhibitory executive control task. Researchers also acquired in vivo single-voxel proton magnetic resonance spectroscopy (1H-MRS) in the dACC to quantify both Glu and combined Glu and glutamine (Glx) concentrations. We hypothesised that these metabolite concentrations would be altered (decreased or increased) in adult participants with ASD compared to NCs and would correlate with inhibitory performance and ASD severity in individuals with ASD. Participants also underwent a resting-state functional magnetic resonance imaging (fMRI) scan to assess the relationship between functional connectivity and Glu and Glx concentrations. We also hypothesised that there would be an altered relationship between local Glu and Glx concentrations and seed-based functional connectivity in adults with ASD compared to NCs. There were no significant group differences in Glu or Glx concentrations between individuals with ASD and NCs. Furthermore, we did not find any relationship between metabolite concentrations and either inhibitory performance or clinical symptoms of the disorder. This evidence suggests that increased or decreased Glu and Glx concentrations were not a core marker of altered brain function in the dACC in this group of adult individuals with ASD. When individuals taking psychotropic medications were excluded from the analysis, there was a significant interaction between age and group for Glx concentrations. This evidence weakly suggests disease-specific variations in Glx concentrations over the lifespan of an individual with ASD. Nevertheless, this result did not survive correction for multiple comparisons and requires further replication. In our final experiment, we reported that Glu concentrations were negatively correlated with right and left dACC seed-based resting-state functional connectivity to the left medial temporal lobe only in individuals with ASD. We also reported an interaction between groups in the association between Glx concentrations and both left and right dACC functional connectivity to other salience network regions including the insular cortex. This evidence suggests that local Glu and Glx concentrations were incongruent with long-distance functional connectivity in individuals with ASD. This analysis was largely exploratory, but further investigation and replication of these relationships may further explain the pathophysiology of the disorder as well as provide a useful marker for therapeutic intervention.

To date, invasive brain-computer interface (BCI) research has largely focused on replacing lost limb functions using signals from hand/arm areas of motor cortex. However, the oculomotor system may be better suited to BCI applications involving rapid serial selection from spatial targets, such as choosing from a set of possible words displayed on a computer screen in an augmentative and alternative communication application. First, we develop an intracortical oculomotor BCI based on the delayed saccade paradigm and demonstrate its feasibility to decode intended saccadic eye movement direction in primates. Using activity from three frontal cortical areas implicated in oculomotor production – dorsolateral prefrontal cortex, supplementary eye field, and frontal eye field – we could decode intended saccade direction in real time with high accuracy, particularly at contralateral locations. In a number of analyses in the decoding context, we investigated the amount of saccade-related information contained in different implant regions and in different neural measures. A novel neural measure using power in the 80-500 Hz band is proposed as the optimal signal for this BCI purpose. In the second part of this thesis, we characterize the interactions between the neural signals recorded from electrodes in these three implant areas. We employ a number of techniques to quantify the spectrotemporal dynamics in this complex network, and we describe the resulting functional connectivity patterns between the three implant regions in the context of eye-movement production. In addition, we compare and contrast the amount of saccade-related information present in the coupling strengths in the network, on both an electrode-to-electrode scale and an area-to-area scale. Different frequency bands stand out during different epochs of the task, and their information contents are distinct between implant regions. For example, the 13-30 Hz band stands out during the delay epoch, and the 8-12 Hz band is relevant during target and response epochs. This work extends the boundary of BCI research into the oculomotor domain, and invites potential applications by showing its feasibility. Furthermore, it elucidates the complex dynamics of the functional coupling underlying oculomotor production across multiple areas of frontal cortex.

Older bilingual adults typically perform better than monolinguals in tasks of executive control, and are diagnosed later with dementia. Studies have also shown structural and functional brain differences between bilinguals and monolinguals. However, it remains poorly understood how language history influences the functional organization of the aging brain. The current study investigated; 1) differences in resting-state functional connectivity between monolinguals and bilinguals in the Default Mode Network (DMN), Frontoparietal Network (FPN), Executive Control Network (ECN), Language Network (LANG), and a network consisting of structures associated with tasks of executive control coined the Bilingual Control Network (BCN); 2) the relationship of cognitive performance with functional connectivity of the BCN; and 3) whether proficiency, age of second language acquisition, degree of second language exposure, and frequency of language use predicts the network’s functional connectivity. Healthy older bilinguals (N=10) were matched pairwise for age, sex and education to healthy older monolinguals (N=10). All participants completed a battery of cognitive tests, a language history questionnaire, and a 6-minute functional scan during rest. Results showed that groups did not differ in cognitive performance, or in the functional connectivity of the FPN, ECN, LANG, or BCN. However, monolinguals had significantly stronger functional connectivity in the DMN compared to bilinguals. Later age of second language acquisition and lower proficiency were also associated with greater DMN functional connectivity. None of these variables predicted BCN’s functional connectivity. However, bilinguals showed stronger functional connectivity with other structures outside of the canonical networks compared to monolinguals. Finally, vocabulary scores, local switch cost accuracy and reaction time were negatively correlated with BCN’s functional connectivity. Overall, these findings illustrate differences in functional brain organization associated with language experience in the DMN, while challenging the “bilingual advantage” hypothesis. The results also suggest a possible neural mechanism by which bilingualism might mediate cognitive reserve.

Complex cognitive functions require interactions within and between different brain regions by direct anatomical connections or synchronous activation. As such, damage to any region involved in a cognitive process has the potential to affect its function. Impulsivity is a multifaceted construct that, when dysfunctional, contributes to many psychiatric conditions. The striatum has been implicated as an integral part of the neural circuitry of impulsivity. The current work aims to contribute to the understanding of neural dysfunction underlying disorders of impulsivity by examining how striatal damage affects impulsive behavior. It also aims to improve our understanding of whether neural processes involved in impulsivity are also involved in maintaining awareness of one's thoughts and actions. No studies have systematically examined the extent to which damage to the striatum correlates with both changes in impulsive behavior and changes in self-awareness of impulsive personality. In the first experiment, I examined the effects of focal unilateral striatal damage on self-awareness of impulsivity and other personality traits. I predicted that participants with striatal damage (SD) would have less self-awareness of changes in impulsivity and other personality traits after brain damage, as compared to brain damage comparisons (BDC), due to indirect disruption of neural networks responsible for self-referential processing. I tested this prediction using self and collateral versions of the Barratt Impulsiveness scale (BIS) and the Iowa Scales of Personality Change. In partial support of my hypothesis, there were mean differences in self- and collateral-reported impulsivity on the BIS, with self ratings higher than collateral ratings in the SD group. There were no significant differences in the correlations between self- and collateral-reports for current impulsivity, change in impulsivity, or change in other personality traits. In the second experiment, I examined the effects of focal unilateral striatal damage on laboratory measures of impulsivity. I predicted that participants with striatal damage would exhibit lower levels impulsivity than brain damaged comparisons due to structural loss of regions involved in reward/motivation and motor activity. I tested this using impulsive action tasks (Go/NoGo and Stop Signal Tasks) and impulsive choice tasks (Delay and Probability Discounting). In contrast to my hypothesis, SD participants did not exhibit less impulsive action or impulsive choice than BDC participants. In the third experiment, I examined the effects of focal unilateral striatal damage on the integrity of frontostriatal resting state functional connectivity. I predicted that participants with striatal damage would exhibit alterations in functional connectivity between the remaining regions of the frontostriatal network. I tested this by comparing the strength of functional connectivity of the caudate head and ventromedial prefrontal cortex. While my hypothesis was not directly supported, the data showed interesting trends that warrant further exploration. These included stronger caudate-vmPFC resting state functional connectivity on the lesion side, and weaker functional connectivity on the non-lesioned side in striatal participants compared to brain damaged comparisons. Together, these experiments suggest that although unilateral striatal damage does not appear to affect subjective reports or laboratory measures of impulsivity, it may affect the underlying neural networks utilized by the striatum, as evidenced by changes in frontostriatal resting state functional connectivity. This work extends our understanding of the neurobiology of impulsive behavior and self-awareness, at systems level, and may help pave the way for treatments of those with brain injury, such as traumatic brain injury and stroke patients, or psychiatric disorders involving impulsivity.

My dissertation focused on understanding how different areas of the brain coordinate in networks to drive higher cognitive functions, and how damage, changes the brain’s synchronized activity (or functional connectivity) in the short and long term. In this dissertation, I studied the functional connectivity of brain networks that are thought to underlie emotion and decision-making, and how these networks change in the face of neurological injury. In my first set of experiments, I studied participants with chronic focal brain damage to determine how damage to brain areas which have been identified as important in emotion and decision-making behaviors (amygdala, ventromedial prefrontal cortex, & insula), affected connectivity of brain networks, and how changes in connectivity following damage to these areas related to emotion and decision-making behavior. Supporting my predictions, I found evidence that damage to the amygdala, ventromedial prefrontal cortex, and insula all result in significantly weaker connections between a network of areas important for assigning value to stimuli. Additionally, I found that stronger connectivity in this valuation network was significantly positively associated with performance on ratings of disgusted faces, while stronger connectivity in a network important for processing emotional salience was significantly positively correlated with decision-making performance. In the second set of studies in this dissertation, I utilized a population of epilepsy patients who were undergoing brain surgery to treat their seizures to investigate how a brain network related to emotional salience changed from before to after surgery. This approach allowed me to study how the connectivity and associated behavior of this network changed from preoperative baseline, to the weeks and months after part of this network was removed. While I expected a decline in this network in the weeks following surgery, instead I found a significant positive correlation between preoperative and acute postoperative connectivity in a subset of this network. However, my hypothesis that there would be a significant increase in the connectivity of this network between acute and chronic postoperative epochs was supported. I only have partial evidence for a significant correlation between the change in salience network connectivity between preoperative and acute postoperative assessments and the associated change in decision-making behavior. This correlation was in the opposite direction of my hypothesis, with increased change in connectivity being positively associated with change in risk-taking behavior. I did not observe a significant correlation between the change in network connectivity and change in behavior across acute and chronic measurements. These findings provide important insight on how measures of network connectivity can inform theories of neuroplasticity and reorganization following brain damage. Understanding how these networks change over time, and how changes in these networks relate to behavioral outcomes, are critical for the development and effective deployment of therapeutic interventions. Together, these studies provide a foundation for further study, demonstrating that these networks change over time with damage, and the residual network strength is associated with performance on measures of emotion and decision-making.