abstract: The brain is a fundamental target of the stress response that promotes adaptation and survival but the repeated activation of the stress response has the potential alter cognition, emotion, and motivation, key functions of the limbic system. Three structures of the limbic system in particular, the hippocampus, medial prefrontal cortex (mPFC), and amygdala, are of special interest due to documented structural changes and their implication in post-traumatic stress disorder (PTSD). One of many notable chronic stress-induced changes include dendritic arbor restructuring, which reflect plasticity patterns in parallel with the direction of alterations observed in functional imaging studies in PTSD patients. For instance, chronic stress produces dendritic retraction in the hippocampus and mPFC, but dendritic hypertrophy in the amygdala, consistent with functional imaging in patients with PTSD. Some have hypothesized that these limbic region's modifications contribute to one's susceptibility to develop PTSD following a traumatic event. Consequently, we used a familiar chronic stress procedure in a rat model to create a vulnerable brain that might develop traits consistent with PTSD when presented with a challenge. In adult male rats, chronic stress by wire mesh restraint (6h/d/21d) was followed by a variety of behavioral tasks including radial arm water maze (RAWM), fear conditioning and extinction, and fear memory reconsolidation to determine chronic stress effects on behaviors mediated by these limbic structures. In chapter 2, we corroborated past findings that chronic stress caused hippocampal CA3 dendritic retraction. Importantly, we present new findings that CA3 dendritic retraction corresponded with poor spatial memory in the RAWM and that these outcomes reversed after a recovery period. In chapter 3, we also showed that chronic stress impaired mPFC-mediated extinction memory, findings that others have reported. Using carefully assessed behavior, we present new findings that chronic stress impacted nonassociative fear by enhancing contextual fear during extinction that generalized to a new context. Moreover, the generalization behavior corresponded with enhanced functional activation in the hippocampus and amygdala during fear extinction memory retrieval. In chapter 5, we showed for the first time that chronic stress enhanced amygdala functional activation during fear memory retrieval, i.e., reactivation. Moreover, these enhanced fear memories were resistant to protein synthesis interference to disrupt a previously formed memory, called reconsolidation in a novel attempt to weaken chronic stress enhanced traumatic memory. Collectively, these studies demonstrated the plastic and dynamic effects of chronic stress on limbic neurocircuitry implicated in PTSD. We showed that chronic stress created a structural and functional imbalance across the hippocampus, mPFC, and amygdala, which lead to a PTSD-like phenotype with persistent and exaggerated fear following fear conditioning. These behavioral disruptions in conjunction with morphological and functional imaging data reflect a chronic stress-induced imbalance between hippocampal and mPFC regulation in favor of amygdala function overdrive, and supports a novel approach for traumatic memory processing in PTSD. / Dissertation/Thesis / Ph.D. Psychology 2013

O estresse parece favorecer a hiperalgesia e alodinia, podendo estar associados à alteração da função muscular mastigatória. Alterações morfofisiológicas em músculos da mastigação induzidos pela alteração oclusal associado ao estresse crônico ainda são escassas na literatura. Este estudo investigou os efeitos do estresse crônico repetido em músculo masseter superficial e profundo de ratos submetidos ou não à exodontia unilateral no ganho do peso dos animais, nas alterações morfológicas (HE, MET), histoquímicas (NADH, SDH e ROS), imunoistoquímicas (laminina e CD31), atividade de MMP-2, -9 e infiltração de neutrófilos (MPO). Vinte ratos (machos, 200g) foram alocados em quatro grupos (n=5): controle (GC), exodontia unilateral (GM), estresse crônico repetido (GE), exodontia associado ao estresse crônico repetido (GME). GE e GME foram submetidos a 10 dias de protocolo de estresse crônico repetido (2 horas diárias) a partir do 14º dia após a exodontia. Houve uma diminuição significativa no ganho de peso dos animais GE e GME. Não foram observadas alterações nos níveis de MMPs e na infiltração de neutrófilos no feixe superficial dos diferentes grupos. GE, GM e GME demostraram alterações morfofisiológicas, ultraestruturais e histoquímicas no feixe profundo, com características específicas e distintas de GC; GE apresentou as maiores alterações. Conclui-se que a exodontia e sua associação ao estresse foram responsáveis por discretas alterações morfofisiológicas no músculo masseter de ratos, contudo o estresse crônico repetido causou modificações morfofisiológicas e ultraestruturais significantes, sendo responsável também pela alteração no peso dos animais. / Stress seems to favor the hyperalgesia and allodynia, which may be related with altered masticatory muscle function. Morphological and physiological changes in the masticatory muscles induced by occlusal alteration associated with chronic stress are still scarce in the literature. This study investigated the effects of repeated chronic stress in superficial and deep masseter muscle of rats with or without the extraction unilateral weight gain of animals and morphological changes (HE MET), histochemical (NADH, SDH and ROS), immunohistochemical (laminin and CD31), MMP-2, -9 activities and neutrophil infiltration (MPO). Twenty rats (male, 200g) were allocated into four groups (n=5): control group (CG), unilateral exodontia (MG), repeated chronic stress (EG), extodontia and repeated chronic stress (MEG). EG and MEG were submitted to 10 days of repeated chronic stress protocol, 2 hours daily, from the 14th day after the extraction. There was a significant decrease in weight gain of animals EG and MEG. No changes were observed in the levels of MMPs and neutrophil infiltration among different groups. EG, MG and MEG have shown morphophisyological, ultrastructural and histochemical changes with specific characteristics and distinct GC GE presenting the higher changes. We conclude that the exodontia and its association to stress were responsible for discrete morphophysiological changes in the masseter muscle of rats, however repeated chronic stress caused significant morphophysiological and ultrastructural changes, being also responsible for change in weight of the animals.

L'anthropisation croissante et les changements globaux entrainent de nombreuses perturbations dans l'environnement conduisant à la dégradation, et même à la destruction d'habitat. Le modèle allostatique proposé par McEwen et Wingfield en 2003 permet de mieux appréhender les relations entre physiologie et réponses démographique dans le cadre de la physiologie de la conservation. A travers des approches expérimentales en milieux controlé et semi-naturel nous avons testé l'effet de d'un stress chronique sur les changements des traits d'histoires de vie et les paramétres physiologique chez le lézard vivipare (Zootoca vivipara). Nous discutons de la caractérisation de la charge allostatique et des effets à court terme et long terme d'un stress chronique et l'utilisation de la charge allostatique comme indicateur de la dégradation de l'habitat. Ce travail pourra être utilisé afin de mieux comprendre et prédire la dynamique des populations naturelles soumises aux changements globaux. / Increasing anthropogenic and global changes are causing many disturbances in the environment leading to degradation and even destruction of habitat. The allostatic model proposed by McEwen and Wingfield in 2003 provides a better understanding of the relationships between physiology and demographic responses within the framework of conservation physiology. Experimental approaches in controlled and semi-natural environments have tested the effect of chronic stress on changes in life histories and physiological parameters in the viviparous lizard (Zootoca vivipara). We discuss the characterization of allostatic charge and the short-term and long-term effects of chronic stress and the use of allostatic charge as an indicator of habitat degradation. This work can be used to better understand and predict the dynamics of natural populations subjected to global changes.

Over the last 20 years, there has been increasing research on the negative effects of discrimination on the mental and physical health of people of color. As mental health has an important relationship with the functional connectivity of brain networks, it is vital to further understand this. One way to measure functional brain connectivity is by observing the activity of the brain’s resting state networks (RSN) while a participant is at rest. Previous studies investigating connectivity have demonstrated a relationship between altered connectivity of RSNs and neuropsychiatric disorders, including Alzheimer’s disease, depression, and anxiety. The RSN of interest in this analysis is the salience network (SN). This network, anchored in the anterior insula and dorsal anterior cingulate cortex, is involved in the responses to “salient” stimuli that are infrequent in space or time, compete for an individual’s attention, and are surprising or emotionally engaging, such as an act of discrimination. The aim of this study was to use a seed-based correlation analysis to examine the relationship between perceived discrimination and the functional connectivity of the SN in black and white participants and to evaluate the differences in SN functional connectivity between black and white participants. Resting state functional connectivity was measured by using the functional magnetic resonance imaging (fMRI) data collected from 18 healthy older adults partaking in two different studies investigating aging, cognition, and the accompanying changes in neuroanatomy. The Analysis of Functional NeuroImages (AFNI) software was used to examine the correlations in activation in the primary nodes of the SN with activation in clusters in the other primary nodes. Perceived discrimination was measured using the Experiences of Discrimination Scale (EOD), a self-report measuring the frequency of instances of discrimination and the perceived reason behind the discrimination. Preliminary results from this analysis demonstrated that black participants, when compared to the white participants, demonstrated greater functional connectivity between the left and right insula and decreased functional connectivity between the right anterior cingulate cortex and the right insula. Black participants demonstrated a positive association between perceived overall discrimination and functional connectivity between the right and left insula and a negative association between perceived overall discrimination and functional connectivity between the right anterior cingulate cortex and the left insula. The white participants demonstrated a negative association between perceived overall discrimination and functional connectivity between the left and the right insula. Considering the inability for these results to survive correction for multiple comparisons, a larger sample size is necessary to obtain true statistical significance. Although existing research has implicated functional connectivity changes in the regions of the salience network in populations experiencing social exclusion, anxiety, and depression, further analyses are necessary to expand the limited research available regarding the effects of overall and race-based discrimination on the resting state functional connectivity of neural networks involved in emotional processing.

Orientador: Percília Cardoso Giaquinto / Resumo: CAPÍTULO 1 – Neste estudo avaliamos o efeito do estresse agudo e crônico na memória de aprendizagem de tilápias-do-Nilo com diferentes perfis de personalidade. Inicialmente definimos a personalidade dos peixes através de testes de objeto novo e exposição a um predador, classificando-os em shy (tímido) ou bold (ousado) e em seguida estes indivíduos foram condicionados por um método simples de condicionamento clássico como forma de aprendizagem para posterior avaliação da memória. Os peixes shy foram então divididos em dois grupos, sendo que em um deles os peixes foram diariamente estressados por hipóxia, perseguição com rede ou confinamento (grupo shy-experimental) por 64 dias consecutivos, enquanto que no outro grupo os peixes permaneceram apenas isolados (grupo shy-controle) pelo mesmo período de tempo. O mesmo procedimento foi adotado com os peixes classificados como bold. Nesse mesmo período, testes de memória foram realizados em dias específicos, tanto nos grupos experimental quanto nos grupos controle. Ao final do experimento, reavaliamos se as personalidades se mantiveram. Obtivemos que o estresse agudo afetou a memória de aprendizado em peixes, principalmente em indivíduos com perfil de personalidade shy. CAPÍTULO 2 – Aqui desenvolvemos uma metodologia simples de condicionamento clássico facilmente aplicável em laboratórios de experimentação com peixes, quando comparados aos métodos descritos na literatura atual, onde os estímulos geralmente aplicados para condicioname... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: CHAPTER 1 - In this study we evaluated the effect of acute and chronic stress in learning memory of Nile tilapia with different personality profiles. Initially we defined the personality of the fish through the testo f new object and exposure to a predator, classifying them as shy or bold, and then these individuals were conditioned by a simple method of classical conditioning as a way of learning to evaluation of memory. The shy fish were divided into two groups, and in one group the fish were daily stressed by hypoxia, net chase or confinement (shy-experimental group) for 64 consecutive days, while in the other group the fish remained only isolated (shy-control group) for the same time period. The same procedure was adopted with fish classified as bold. During the same period, memory tests were performed on specific days, in both groups, experimental and control group. At the end of the experiment, we reevaluated whether the personalities held. We found that acute stress affected learning memory in fish, especially in individuals with shy personality profiles. CHAPTER 2 - Here we develop a classical conditioning methodology easily applicable in fish experimentation laboratories when compared to the methods described in the current literature, where the stimuli generally applied for conditioning (sound or light) can interfere with the responses of experimental animals present in the same laboratory. For this conditioning, we isolate the fish in individual aquariums and intro... (Complete abstract click electronic access below) / Doutor

The 21st century world is characterized by globalization, optimization, high performance demands, and continuous acceleration of processes. Not surprisingly, stress has steadily become more prevalent over the past years and has become a permanent challenge for many of us. Still we are always expected to perform at our best, and an impairment of cognitive performance can be devastating, particularly in the professional world. This ubiquity in daily life of chronic stress, cognitive demands, and their potential interactions was the motivation for this dissertation. Among cognitive processes executive functioning (EF) are of particular interest, as they represent set of fundamental cognitive abilities for mastering daily life. More precisely, EF is described as higher-order cognitive processes that control and coordinate complex cognitive tasks (Diamond, 2013; Miyake et al., 2000). The primary aim of this dissertation was to investigate the interplay between chronic stress and EF in detail. A three-year longitudinal cohort, the StressCog cohort, was established for this purpose. In order to understand the longitudinal interplay between chronic stress and EF, methodological foundations and cross-sectional matters had to be investigated first. As a result, this dissertation encompasses the following three studies: With classical laboratory designs, the estimation of generalizable and robust effects on the relationship between chronic stress and EF is impaired. Therefore, the StressCog study was set up to make use of internet-based data assessment within domestic environments. Study 1 addressed the feasibility of internet-based response time data, including the common concern that internet-based response time data collected in domestic environments is subject to increased data variability (Chetverikov & Upravitelev, 2016; Reips, 2002). To this end, performance measures collected in the laboratory were compared with measures collected in domestic environments. We found that a setting-related difference in the variability of conventional performance measures (i.e., response times and error rates), as well as diffusion model-based measures is only of small size. An overall increase of variance of approximately 5% was visible in domestic environments. However, as internet-based assessments allow for the recruitment of larger sample sizes (Reips, 2002) the loss of static power can be easily compensated. Therefore, the findings of Study 1 support the use of internet-based cognitive data collection in domestic environments. This formed a valuable basis regarding the collection and interpretation of the StressCog data used in Study 2 and Study 3. In order to get a broad picture of chronic stress the StressCog study aimed for multimethod assessment. The subjective (i.e., perceived) extent of chronic stress and conceptually related constructs were assessed by multiple self-reported measures. The objective (i.e., physiological) extent of chronic stress was assessed via hair cortisol concentration, which has been established as a widely accepted biological marker of chronic stress (E. Russell et al., 2012; Stalder & Kirschbaum, 2012). Surprisingly, however, multiple studies have shown that hair cortisol concentration is, at best, only weakly correlated with subjective chronic stress (Stalder et al., 2017; Staufenbiel et al., 2013; Weckesser et al., 2019). This lack of psychoendocrine covariance was addressed in Study 2 by investigating the construct validity of commonly used chronic stress instruments. A multidimensional item response theory approach was applied in order to display the overlap between items of commonly used measures of chronic stress, depressiveness, and neuroticism. A common latent scale covered the major amount of variance (40% to 48%). It appeared that the overlap of content is mainly based on fatigue, which is a core symptom of depressiveness. Similar to previously reported findings, the common latent scale displayed only a weak association with hair cortisol concentration. It can therefore be argued that items of self-reported chronic stress do not reflect the physiological (i.e., endocrine) aspect of chronic stress to a satisfactory extent. Thus, the results of Study 2 were a valuable basis for the interpretation of chronic stress data in Study 3. In Study 3, we investigated the cross-sectional association between chronic stress and EF. The study made use of data from the baseline assessment of the StressCog cohort (N = 514). Using structural equation modelling, we found no evidence for a meaningful association between chronic stress (i.e., self-reported measures and hair cortisol concentration) and a common latent EF factor. The results found in Study 3 were further supported by unpublished longitudinal StressCog data and analyses making use of diffusion model performance measures. Considering the mainstream of existing findings, which suggests chronic stress to be negatively associated with EF (e.g., Deligkaris et al., 2014; Sandi, 2013), an absence of an association between chronic stress and EF seems surprising. However, other existing findings support this perspective (Castaneda et al., 2011a; McLennan et al., 2016). Beyond this, the results of Study 1 and 2 help to explain why a lack of an association between chronic stress and EF is quite plausible. As within traditional, laboratory-based settings a recruitment of larger samples sizes is difficult and costly, most existing studies lack large, representative samples. In consequence, many findings are based on narrow sample characteristics. Supported by the findings of Study 1, the StressCog study made use of internet-based data collection, which led to the establishment of one the largest, population-based cohorts in the field. Thus, the results presented in this dissertation can be seen as much more robust and representative than many other studies that suggest opposing results. The findings of Study 2 allow for the assumption that many studies in the field make use of questionable self-report instruments and that subjective (i.e., self-reported) measures of chronic stress are only weakly related to objective (i.e., HCC) measures. In consequence, results always depend on the operationalization of the chronic stress measures being used. Caution is advised when comparing opposing results of different measures. With regard to our daily life demands, it may appear quite promising that no association between chronic stress and EF was found in this dissertation. However, these results should not be misunderstood. It has been demonstrated countless times that chronic stress can severely affect the human organism, causing various negative effects that go far beyond a possible impairment of cognitive abilities. Knowing that chronic stress can impair EF under certain circumstances leads to the central question of what conditions make stress toxic. In order to answer this question further systematic research is needed, in which representative samples and experimental study designs will be of crucial help. As long as these questions are not satisfactorily clarified, it seems best to deal with the challenges of chronic stress in a conscious and responsible manner.

When humans are faced with multiple options, they must decide whether to choose a novel or less certain option (explore) or stick with what they know (exploit). Exploration is a fundamental cognitive process. Importantly, when humans attempt to solve the explore-exploit dilemma, they must effectively incorporate both feedback and uncertainty to guide their actions. While prior work has shown that both acute (short-term) and chronic (long-term) stress can disrupt how humans solve the explore-exploit dilemma, the mechanisms of how this occurs are unclear. For example, does stress disrupt how people integrate feedback to guide their decisions to explore or exploit, or does stress disrupt computations of uncertainty regarding their choices? Importantly, the use of electroencephalography as a tool can help reveal the impact of stress on explore-exploit decision making by measuring neural signals sensitive to feedback learning and uncertainty. In the present dissertation, I provide evidence from a series of experiments where I examined the impact of both acute and chronic stress on the explore-exploit dilemma while electroencephalographic data was collected. In experiment 1, I exposed participants to an acute stressor and then examined their decisions to switch or stay – as a proxy for explore and exploit decisions – in a multi-arm bandit paradigm. I found tentative evidence that the acute stress response disrupted both the feedback learning signal (the reward positivity) and the uncertainty signal (the switch P300). In experiment 2 I adopted a computational neuroscience approach and directly classified participants decisions as explorations or exploitations using reinforcement learning models. There was only an effect of the acute stress response on feedback signals, in this case, the feedback P300. In experiments 1 and 2, I used contextual bandit tasks where the reward probabilities of the options shifted throughout, and there was no behavioural effect of acute stress on task performance or exploration rate. However, in experiment 3, I examined a learnable bandit where one option was preferred. Again, using computational modelling and electroencephalography, I found tentative evidence that the acute stress response disrupted the feedback learning signals (the feedback P300) and stronger evidence that acute stress disrupted the uncertainty signal (the exploration P300). As well, I observed that the acute stress response reduced task performance and increased exploration rate. Lastly, in experiment 4, I examined the impact of chronic stress exposure on explore-exploit decision making and electrophysiology – while I found no effects of chronic stress, I believe future research is necessary. Taken together, these findings provide novel evidence for the neural mechanisms of how the acute stress response impacts the explore-exploit dilemma through disruptions to feedback learning and assessments of uncertainty. These findings also highlight how theories of the P300 signal may not be properly capturing the varied role of the P300 in cognition. / Graduate

This study explores the influence of chronic stress in college students. It focuses on the broader chronic stressors that college students experience related to physical and mental health, financial health and wellbeing, and presence of social supports, then addresses the more specific chronic stressors related to intersecting identities of race, ethnicity, gender, and sexual orientation. This phenomenon is analyzed under the theoretical frameworks of social determinants of health, intersectionality, and systems theory. An online survey with both open and closed-ended questions was conducted with undergraduate social work students from the Bachelors of Social Work program at the University of Central Florida. The results of the study found that there was links between intersecting identities of participants with higher levels of chronic stress based on their chronic stress scores and participant responses on the influence of their identities on barriers to their physical, mental, and financial health.

Parental psychological control has been found to be associated with both internalized and externalized problems for youth and adolescents. Research contributing to an understanding of the possible antecedents of parental psychological control is both limited and of need; specifically regarding parents' psychological attributes. This study sample included 323 two-parent families and an identified target child from each family. Bowen's theory of family systems, [chronic] stress, and differentiation of self and its relation to parental psychological control was examined. Differentiation of self was hypothesized to mediate the relationship between chronic stress and parental psychological control. Differentiation was conceptualized and measured using two subscales assessing emotional reactivity and emotional cutoff. Fathers and mothers were included in the same model to assess for potential partner influences as well possible gender differences. Parental age, parental education, and family income were also included as control variables. Study analyses included bivariate correlations, independent T-tests, and structural path models; all based on study variables constructed in a structural equation measurement model. To test for mediation by differentiation of self, an initial structural model examining the relationship between levels of parental chronic stress and parental psychological control was utilized. Only paternal chronic stress and paternal education predicted child-reported levels of parental psychological control. Parent-reported levels of differentiation of self, when included in a structural path model, did not mediate the relationship between chronic stress and psychological control but did have a significant indirect effect on this relationship. Both maternal and paternal chronic stress significantly predicted individual parental levels of emotional reactivity and emotional cutoff. Systemically, maternal levels of emotional cutoff predicted paternal levels of parental psychological control and paternal levels of emotional reactivity predicted maternal levels of parental psychological control. No control variables other than paternal education had a salient, significant, or interpretable effect on endogenous study variables (differentiation of self and parental psychological control). Paternal and maternal levels of emotional reactivity appeared to partially mediate the relationship between paternal education and maternal psychological control. Interpretation for results, study limitations and future directions, and clinical implications are discussed.

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