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Self-rated health (SRH) is a robust indicator of mortality, morbidity, and health behaviors. Despite consisting of a single item, SRH is a comprehensive measure that captures overall health status and encompasses biological, social, and psychological factors that influence health. Predictors of SRH across these domains are not well understood, particularly among young healthy individuals. Using a biopsychosocial approach, this dissertation explored in three separate studies biological markers of systems implicated in stress physiology (i.e., immune, autonomic, and endocrine), social determinants of health, and psychological factors that are relevant to SRH. Study 1 (N = 99) showed that higher levels of salivary (p = .011) and serum (p = .013) inflammatory markers predicted higher odds of reporting poor SRH, highlighting that inflammation is associated with worse SRH. Study 2 (N = 148) explored whether cardiovascular reactivity to stress, indexing activity of the sympathetic nervous system, and discrimination, a social determinant of health, were related to SRH. The study showed that increases in pre-ejection period (PEP) reactivity were associated with a 2% greater chance of reporting better SRH. Findings for the association between discrimination and SRH differed based on the participants’ ethnicity. Study 3 (N = 50) investigated endocrine markers in relation to SRH and documented that higher levels of placental corticotropin releasing hormone (pCRH) were associated with increased odds of poor SRH (p = .046) among a sample of pregnant Latinas. Everyday discrimination (p = .005), familism (p = .021) and positive trait emotion (p = .003) predicted lower odds of poor SRH. Findings from this dissertation provide direction for further examining SRH through a biopsychosocial lens. Implications for understanding the utility of SRH as a screening tool to identify individuals at risk for poor health outcomes are discussed.

Negative emotional states are frequently associated with declines in cognitive performance. However, the mechanisms and pathways underlying the relationship between emotion and cognition are not well understood. In a three-study series, this dissertation examined associations between affect, perceived stress, and cognitive functioning and how unconstructive repetitive thinking (URT), and inflammatory markers may underlie the association between emotion and cognition. The first two studies focused on the association between fluctuations in momentary affective experiences and cognitive functioning. Study 1 examined how high arousal negative and positive emotional states relate to working memory across different age groups. Findings indicated that both high negative and positive affect were linked to poorer working memory performance, with younger adults experiencing more pronounced negative effects when positive affect increased. Study 2 explored the impact of momentary unconstructive repetitive thinking (URT), such as worry and rumination, on cognitive function throughout the day. Contrary to expectations, greater URT was associated with improved working memory, especially in younger adults, although this relationship was moderated by negative affect, which suppressed the cognitive benefits of URT. Study 3 investigated the effects of chronic perceived stress on cognitive performance and its potential mediation by inflammatory cytokines among adults in midlife. Results revealed that higher perceived stress was directly related to poorer cognitive function and elevated levels of certain inflammatory markers; however, inflammation did not mediate the perceived stress–cognition link. These studies underscore the nuanced interactions between affective states, stress, and cognitive performance, highlighting age-related differences and the complex role of physiological stress responses in cognitive aging. Overall, in moments when positive and negative affect were heightened

Ethnic disparities in physical health outcomes have been a pressing public health concern for decades, with African Americans (AAs) displaying disproportionately higher rates of morbidity and mortality from prominent communicable (e.g., infectious) and chronic (e.g., cardiovascular) diseases compared to European Americans (EAs). Importantly, higher levels of emotional (e.g., positive affect) and social (e.g., social support) well-being factors have generally been linked with better physical functioning and health, but there remains a lack of research exploring if their psychological and physiological downstream effects on health may vary based on ethnicity. Thus, the current dissertation sought to explore AA and EA differences in physiological pathways implicated in health as well as determine if emotional and social well-being factors were differentially linked with physical health measures and outcomes. Study 1 is a systematic review and meta-analysis that examined differences in baseline levels of common inflammatory measures between AAs and EAs. Study 2 is a secondary data analysis of viral exposure studies that explored whether common emotional well-being factors were equally protective against upper respiratory infections in a localized sample of AAs and EAs. Study 3 built on Study 2 by investigating potential differences in the benefits of social well-being factors on physiological measures of cardiovascular functioning and diagnosed cardiovascular health outcomes in a nationally representative sample of AAs and EAs. Results from Study 1 indicated that AAs generally had higher resting levels of pro-inflammatory factors (e.g., C-reactive protein), while EAs generally had higher resting levels of anti-inflammatory factors (e.g., Interleukin-10). Results from Study 2 revealed that emotional well-being factors (e.g., positive affect, self-esteem) were associated with a reduced risk of infection after experimental virus exposure for EAs, but for AAs the same facto

The process of spoken word recognition is influenced by both bottom-up sensory information and topdowncognitive information. These cues are used to process the phonological and semantic representations of speech. Several studies have used EEG/ERPs to study the neural mechanisms of children’s spoken word recognition, but less is known about the role of visual speech information (facial and lip cues) on this process. It is also unclear if populations with different early sensory experiences (e.g. deaf children who receive cochlear implants; CIs) show the same pattern of neural responses during audiovisual (AV) spoken word recognition. Here we investigate ERP components corresponding to typical hearing (TH) and CI-using school age children’s sensory, phonological, and semantic neural responses during a picture-audiovisual word matching task. Children (TH n = 22; CI n = 13; ages 8 – 13 years) were asked to match picture primes and AV video targets of speakers naming the pictures. ERPs were time-locked to the onset of the target’s meaningful visual and auditory speech information. The results suggest that while CI and TH children may not differ in their sensory (Visual P1, Auditory N1) or semantic (N400, Late N400) responses, there may be differences in the intermediary components associated with either phonological or strategic processing. Specifically, we find an N280 response for the CI group and a P300 component in the TH group. Subjects’ ERPs are correlated with their age, hearing experience, task performance, and language measures. We interpret these findings in light of the unique strategies that may be employed by these two groups of children based on the utilization of different speech cues or task-level predictions. These findings better inform our understanding of the neural bases of AV speech processing in children, specifically where differences may emerge between groups of children with differential sensory experiences; the results have implications for imp

Comparative studies provide important insights into the evolution of general features of brain organization as well as features that are unique across species. These unique differences in brain organization are thought to reflect specialized adaptations in body morphology, behavior and lifestyle. While there is a great diversity of mammalian behavioral and morphological specializations, we know little about evolutionary changes in the neocortical structures that support these differences. Using histological collections from the Krubitzer lab, a comparative dataset was created in order to measure the sizes of cortical fields across evolution. In this analysis we focus on 4 cortical fields, the primary somatosensory (S1), visual (V1) and auditory (A1) areas, as well as the motor cortex (M1). These areas were examined in 18 species representing 6 different mammalian lineages: 7 species of Rodentia (rodents), 5 species of Marsupialia (marsupials), 2 species of Chiropotera (bats), 2 species of Eulipotyphla (water shrews and hedgehogs), 1 from Scandentia (tree shrews) and 1 from Afrosoricida (tenrecs). We quantify the lineage-specific changes and general properties of the sizes of primary motor and primary sensory cortical fields using allometric analysis, and discuss several outliers from the trends. We found that larger brains with a larger neocortex devote less space to M1, A1 and S1, whereas V1 becomes exceptionally larger, or alternatively exceptionally smaller in mammals with a small neocortex. We also found several examples of mosaic evolution in S1 and one example in A1. The neocortex is the underlying substrate that supports adaptive sensorimotor specializations, yet this varies across species. We found that not all convergent sensorimotor specializations share the same underlying expansions and contractions of cortical fields, suggesting that there are multiple ways the neocortex can organize to “solve” for the same specialization in different species.

People often seek out experiences that increase negative emotions. Doing so often serves instrumental purposes, even though it may come at a hedonic cost. The fact that many people consume contra-hedonic media such as forensic (true crime) media, seemingly without an instrumental payoff, poses a problem for affective science. The experience of flow, a self-reinforcing and enjoyable state, may explain the tendency for some people to approach hedonically unpleasant experiences. Here, I introduce the novel concept of emotion regulation (ER) flow, proposing that ER flow may be achieved when one meets an emotional demand with a well-matched set of emotion regulatory skills. In the pilot study (N = 283), participants completed self-report questionnaires to assess their enjoyment of forensic media in relation to traditional flow, exploratory ER flow items, and socio-emotional aspects of well-being. Further, they (retrospectively) reported their emotional experiences before, during, and after consuming forensic media. In the primary study (N = 278), I experimentally manipulated flow as part of a pretest-posttest design and used self-report and physiological indices of autonomic functioning to characterize ER flow. Results from both studies show that a) ER flow is associated with enjoying forensic media and fandom, in spite of the hedonically unpleasant experience, b) ER flow is positively associated with aspects of socio-emotional well-being, c) ER flow can be achieved from an emotional challenge, and d) ER flow is likely characterized by parasympathetic dominance at rest and during the activity, although not reactively to the activity. Overall, results support ER flow as a novel concept with many benefits worthy of further exploration.

Microbes were the first organisms to evolve on Earth, and inhabit every known environment, including the human gut. Diverse microbial ecosystems are involved in a number of crucial bodily processes including educating the immune system. Interestingly, human microbiome composition and function is also linked to central nervous system activity, specifically, the stress response. Extant literature exploring the stress-microbiome connection in healthy, human adult samples is sparse and primarily tests these links in non-human animals or in clinical human samples, particularly those with depression and anxiety. This dissertation is among the first to explore stress-microbiome links across three stress domains in two samples of healthy adults, specifically, perceived stress, stressful life events, and cardiovascular function surrounding stress as indexed by Respiratory Sinus Arrhythmia (RSA). This vital next step will help researchers better understand the nuanced, dynamic connections between stress types and microbial composition.We carried out two main studies: Study 1 includes 62 healthy adults, 68% female with a mean age of 37.3 years and Study 2 includes 74 healthy women with a mean age of 41.6 years. Participants completed surveys assessing stressful life events, perceived stress and completed a laboratory stressor. RSA was collected prior to, during, and following a laboratory stressor. Following the laboratory visit, participants were given fecal collection kits to collect microbiome samples that were assayed for microbial composition. In Study 1, the low perceived stress group was higher in alpha diversity than the high perceived stress group. Both Study 1 and Study 2 revealed differences in beta diversity between stressful life events groups and Study 1 revealed differences in beta diversity between RSA stress reactivity groups. Differentially abundant microbes between groups are discussed. Further, levels of Clostridium were negatively associated with RSA stres

Communication reinforces vital social bonds across the animal kingdom. Some of the most rare and specialized social systems require similarly specialized communication. One of the rarest social organizations in the animal kingdom, especially amongst mammals, is monogamy. Monogamous mates rely on a variety of communication modalities to find and initiate a bond, maintain their bond, coordinate daily activity, raise offspring, avoid predation, and defend shared resources, among other behaviors . Understanding these communication signals, both their structure and function, is of utmost importance in order to fully understand closely bonded social species. Coppery titi monkeys (Plecturocebus cupreus) are monogamous, South American monkeys who form selective, enduring psychosocial emotion attachments, referred to as pair bonds. Titi monkeys must form and maintain long term relationships, coordinate biparental care, and maintain control over a shared territory. These pair-bonded monkeys provide the perfect model system in which to investigate a variety of communication modalities in relationship to the unique pair bond. At the California National Primate Research Center, I investigated three aspects of titi monkey communication. First, I assessed patterns of individual identity in the morning adult duet contributions and infant trill vocalizations of this species. Strong patterns of individuality exist in adult duets, such that individuals are identifiable based on vocalizations alone. Second, I assessed female titi monkey responses to a variety of vocal stimuli in a playback experiment. Female titi monkey responses depended more on their own pairing status and reproductive status than the content of the social vocalization, suggesting titi monkeys respond generally to any unfamiliar acoustic signal. Finally, I presented titi monkeys with paired faces of their mate and a stranger in order to test for a partner preference in looking behavior. I found little evidence of vis

For social animals, social relationships are massively important to an individual’s ability to survive and thrive. Some relationships, like pair bonds, involve a high degree of attachment and interact with physiological processes like stress, sleep, and reproduction. The projects in this dissertation represent a cross-section of influential life events and processes throughout a pair-bonding primate’s life and examine the impact of those events on the pair relationship and individual psychophysiology of captive coppery titi monkeys (Plecturocebus cupreus). In the first study, we observed nighttime activity as a behavioral proxy for sleep in newly formed pairs of titis to assess how they habituated to a new social and physical environment across their first week with a new mate. We also compared the frequency of nighttime and daytime affiliative behaviors between pair mates to assess the comparative frequency and role of such behaviors at different times of day in a diurnal species. In the second study, we examined the impact of hormonal contraceptive use on reproductive cycling and affiliation within pairs. The effects of physiological interventions are particularly important to understand in a laboratory setting where breeding is selectively managed, and relationships are studied in neuropsychological research. Finally, in the third study, we assessed the role of pregnancy and infant rearing on the relationship between co-parents and pair mates. Together, this work represents the first studies that quantify nighttime behavior, assess the impact of contraception, and consider the changing relationship between parenting partners in this diurnal, pair-bonding species.

Psychologist career satisfaction and burnout, particularly in those populations who do heavy assessment work, is largely understudied. Given mixed feelings throughout the field regarding assessment practices and gaps between supply of practitioners and increasing demand, it is important to understand how assessment practices can be improved for those who use them and undergo them. The collaborative/ therapeutic assessment model, developed by Finn and colleagues, challenges practitioners to frame assessment with a more empathetic and fair perspective that allows psychologists to share power with their clients. This qualitative study explored, with eight participants through semi structured interviews, the process of adopting the c/ta method into practice in hopes to understand whether the model provides benefits to assessors and clients alike. Five themes were drawn from the interviews using phenomenological methods and validity checks. The conclusions that the c/ta model can provide positive personal and professional benefits to assessors, increase equity and fairness of assessment, and subsequently, buffer against feelings of burnout or lack of job satisfaction were made. Study limitations and suggestions for further research were also discussed.

In this dissertation I consider the role of psychosocial stress in mental and physical health, and investigate the role of a month-long Buddhist meditation retreat in altering the pathways between our biochemical makeup and our experience of the world. As living beings, we possess a tremendous capacity for adaptation, and yet we are deeply conditioned by circumstance and bound by certain truths. We inhabit bodies that deteriorate, yet the rate and form of this degradation varies wildly depending on our environments and prior experiences. Stress research considers how our experiences become embedded in our bodies in ways that contribute to illness and disease, while also considering the protective factors that mitigate these outcomes. Importantly, decades of research indicate that one of the most potent modulators of health and well-being are our relationships and psychosocial environment. Buddhist philosophy and meditation practices offer another framework for understanding our interdependence with others, and for investigating the intricate system of causes and conditions that govern our existence. Much of our conditioning and adaptation happens outside of our awareness and conscious intent, and meditation practices are often designed to bring some of this content into conscious awareness, so that we can learn to differentiate between the aspects of our lives we have agency in and those that are inevitable. In the Insight meditation tradition studied here, primary practices include directing one’s attention to the coming and going of bodily sensations and observing thoughts as transient phenomena without grasping or over-identification. These practices are taught in combination with practices designed to support the four immeasurables: loving-kindness, compassion, empathetic joy, and equanimity. Together, these practices aim to cultivate beneficial qualities of mind and positive aspirations for oneself and others that allow practitioners to live in greater harmony

The locus coeruleus (LC) exerts its neuromodulatory effects via two distinct modes of activity: tonic and phasic. Tonic activity refers to extended periods of low to moderate firing (1-10Hz) that are thought to mediate relatively long-lasting changes in brain state by setting brain-wide noradrenergic tone. This type of activity is particularly important for regulating the overall level of arousal, which can, in turn, affect many psychological and physiological processes. Phasic activity refers to brief bouts of elevated firing rate (10-20Hz), usually in response to a specific environmental event. Phasic LC responses to task-related events are generally associated with improved performance across a variety of cognitive domains including perception, attention, and decision making. However, the role of precisely timed phasic LC responses in memory formation is relatively understudied. In particular, the role of phasic LC activity in hippocampus-dependent memory formation is unknown. In Part 1 of this dissertation, we characterize a trace fear conditioning task that requires mice to associate a tone and shock that are separated in time by 20 seconds. Using optogenetics, we show that this task requires intact hippocampal activity during both learning and memory retrieval. In Part 2, we characterize the phasic responses of the LC and its projections to the dorsal hippocampus during trace fear conditioning. We find learning related changes in these responses that are consistent with a role for LC in signaling the learned salience of environmental stimuli. We go on to show that amplifying these phasic responses can lead to enhancements in long-term memory. We also demonstrate that LC stimulation increases both norepinephrine and dopamine content in the dorsal hippocampus. Somewhat unexpectedly, we find that only the release of dopamine is needed to enhance memory formation. The implications of these findings for LC function and dopamine release in the hippocampus during ave

Social interactions regulate our behavior and physiology (Uchino, 2006), and connections between social well-being and health may be one reason why individuals who are happy with their relationships live longer (Diener & Chan, 2011). A pair bond is a selective, enduring, relationship that is regulated by physiology and behavior (Bales et al., 2021). Understanding mechanisms underlying social bonds is especially critical now because the COVID-19 pandemic has detrimentally impacted human social relationships (Evans et al., 2020; Luetke et al., 2020), which may result in adverse health outcomes (Saggiorio de Figueiredo et al., 2021). Despite the importance of social bonds for well-being, little is known about their underlying neurobiology. Much of what we know about the neurobiology of attachment comes from research conducted on males (Bales et al., 2017), despite studies finding opposite behavioral responses to neuroendocrine manipulations in males and females (Carter et al., 2008). Women are more likely to develop affective disorders like depression, which may be linked to social risk factors. Research on female attachment, particularly studies on daughters’ relationships with fathers, is incredibly limited and therefore warrants further investigation. Nonhuman primates are excellent models for understanding the effects of social bonds on human health due to their similar social dynamics, cognitive functioning, and immune systems (Phillips et al., 2014). Coppery titi monkeys (Plecturocebus cupreus) are socially monogamous South American monkeys that live in small family groups. They display classic attachment behaviors (Fuentes, 1998), including proximity maintenance with (Carp & Rothwell et al., 2015), distress upon separation from (Mendoza & Mason, 1986a), and stress buffering by (Mendoza et al., 2000) the attachment figure. Partners are each other’s primary attachment figures, while infants form selective bonds with their fathers (Mendoza & Mason

Older adults (> 65 years old) make up an ever-growing percentage of the global human population. This demographic shift is among the most pressing public health concerns of our time due to the unique health challenges that older adults face. Although aging is clearly detrimental to some aspects of physical health and mental ability, relatively less work has evaluated how aging impacts social and affective (socioaffective) processing, despite the important role these two fundamental aspects of our lives play in determining our health and wellbeing. The existing literature shows the somewhat paradoxical finding that aspects of people’s socioaffective processing improve with age—though in whom and for what reasons remain an open question. Understanding sources of variation in socioaffective aging trajectories will help promote wellbeing for those who are most in need. Although most research on socioaffective aging to date has taken place in humans, adopting a comparative approach will illuminate novel psychological, physiological, and social mechanisms through which changes to socioaffective processing occur and speak to the evolutionary origins of such changes. Here, I investigate how aspects of socioaffective processing differs across the lifespan in rhesus monkeys (Macaca mulatta), which share key features of human developmental neurobiology, physiology, and social behaviors. In Chapter 1, I evaluate age-related differences in visual attention towards faces of conspecifics ranging in affective content to test the hypothesis that aging influences how monkeys process affective stimuli. Consistent with work in humans, I find that while middle-aged animals display robust biases in visual attention towards threatening faces, aged animals show no such bias, suggesting phylogenetically conserved mechanisms of age-related threat avoidance. Chapter 2 evaluates age-related differences in monkeys’ autonomic nervous system responsivity towards social stimuli and finds age-re

This dissertation introduces a biologically-detailed computational model of how rule-guided behaviors become automatic. The model assumes that initially, rule-guided behaviors are controlled by a distributed neural network centered in the prefrontal cortex, and that in addition to initiating behavior, this network also trains a faster and more direct network that includes projections from sensory association cortex directly to rule-sensitive neurons in premotor cortex. After much practice, the direct network is sufficient to control the behavior, without prefrontal involvement. The model is implemented as a biologically-detailed neural network constructed from spiking neurons and displaying a biologically plausible form of Hebbian learning. The model successfully accounts for single-unit recordings and human behavioral data that are problematic for other models of automaticity.The dissertation also presents the results from two experiments investigating the nature of what is automatized after lengthy practice with a rule-guided behavior. The results of both experiments suggest that an abstract rule, if interpreted as a verbal-based strategy, was not automatized during training, but rather the automatization linked a set of stimuli with similar values on one visual dimension to a common motor response. The experiments were designed to test the Cortex Automatizes Rules Model. The present results support this model and suggest that the projections from visual cortex to prefrontal and premotor cortex are restricted to visual representations of the relevant stimulus dimension only.

Older adults (> 65 years old) make up an ever-growing percentage of the global human population. This demographic shift is among the most pressing public health concerns of our time due to the unique health challenges that older adults face. Although aging is clearly detrimental to some aspects of physical health and mental ability, relatively less work has evaluated how aging impacts social and affective (socioaffective) processing, despite the important role these two fundamental aspects of our lives play in determining our health and wellbeing. The existing literature shows the somewhat paradoxical finding that aspects of people’s socioaffective processing improve with age—though in whom and for what reasons remain an open question. Understanding sources of variation in socioaffective aging trajectories will help promote wellbeing for those who are most in need. Although most research on socioaffective aging to date has taken place in humans, adopting a comparative approach will illuminate novel psychological, physiological, and social mechanisms through which changes to socioaffective processing occur and speak to the evolutionary origins of such changes. Here, I investigate how aspects of socioaffective processing differs across the lifespan in rhesus monkeys (Macaca mulatta), which share key features of human developmental neurobiology, physiology, and social behaviors. In Chapter 1, I evaluate age-related differences in visual attention towards faces of conspecifics ranging in affective content to test the hypothesis that aging influences how monkeys process affective stimuli. Consistent with work in humans, I find that while middle-aged animals display robust biases in visual attention towards threatening faces, aged animals show no such bias, suggesting phylogenetically conserved mechanisms of age-related threat avoidance. Chapter 2 evaluates age-related differences in monkeys’ autonomic nervous system responsivity towards social stimuli and finds age-re

This dissertation introduces a biologically-detailed computational model of how rule-guided behaviors become automatic. The model assumes that initially, rule-guided behaviors are controlled by a distributed neural network centered in the prefrontal cortex, and that in addition to initiating behavior, this network also trains a faster and more direct network that includes projections from sensory association cortex directly to rule-sensitive neurons in premotor cortex. After much practice, the direct network is sufficient to control the behavior, without prefrontal involvement. The model is implemented as a biologically-detailed neural network constructed from spiking neurons and displaying a biologically plausible form of Hebbian learning. The model successfully accounts for single-unit recordings and human behavioral data that are problematic for other models of automaticity.The dissertation also presents the results from two experiments investigating the nature of what is automatized after lengthy practice with a rule-guided behavior. The results of both experiments suggest that an abstract rule, if interpreted as a verbal-based strategy, was not automatized during training, but rather the automatization linked a set of stimuli with similar values on one visual dimension to a common motor response. The experiments were designed to test the Cortex Automatizes Rules Model. The present results support this model and suggest that the projections from visual cortex to prefrontal and premotor cortex are restricted to visual representations of the relevant stimulus dimension only.

Social interactions regulate our behavior and physiology (Uchino, 2006), and connections between social well-being and health may be one reason why individuals who are happy with their relationships live longer (Diener & Chan, 2011). A pair bond is a selective, enduring, relationship that is regulated by physiology and behavior (Bales et al., 2021). Understanding mechanisms underlying social bonds is especially critical now because the COVID-19 pandemic has detrimentally impacted human social relationships (Evans et al., 2020; Luetke et al., 2020), which may result in adverse health outcomes (Saggiorio de Figueiredo et al., 2021). Despite the importance of social bonds for well-being, little is known about their underlying neurobiology. Much of what we know about the neurobiology of attachment comes from research conducted on males (Bales et al., 2017), despite studies finding opposite behavioral responses to neuroendocrine manipulations in males and females (Carter et al., 2008). Women are more likely to develop affective disorders like depression, which may be linked to social risk factors. Research on female attachment, particularly studies on daughters’ relationships with fathers, is incredibly limited and therefore warrants further investigation. Nonhuman primates are excellent models for understanding the effects of social bonds on human health due to their similar social dynamics, cognitive functioning, and immune systems (Phillips et al., 2014). Coppery titi monkeys (Plecturocebus cupreus) are socially monogamous South American monkeys that live in small family groups. They display classic attachment behaviors (Fuentes, 1998), including proximity maintenance with (Carp & Rothwell et al., 2015), distress upon separation from (Mendoza & Mason, 1986a), and stress buffering by (Mendoza et al., 2000) the attachment figure. Partners are each other’s primary attachment figures, while infants form selective bonds with their fathers (Mendoza & Mason

The locus coeruleus (LC) exerts its neuromodulatory effects via two distinct modes of activity: tonic and phasic. Tonic activity refers to extended periods of low to moderate firing (1-10Hz) that are thought to mediate relatively long-lasting changes in brain state by setting brain-wide noradrenergic tone. This type of activity is particularly important for regulating the overall level of arousal, which can, in turn, affect many psychological and physiological processes. Phasic activity refers to brief bouts of elevated firing rate (10-20Hz), usually in response to a specific environmental event. Phasic LC responses to task-related events are generally associated with improved performance across a variety of cognitive domains including perception, attention, and decision making. However, the role of precisely timed phasic LC responses in memory formation is relatively understudied. In particular, the role of phasic LC activity in hippocampus-dependent memory formation is unknown. In Part 1 of this dissertation, we characterize a trace fear conditioning task that requires mice to associate a tone and shock that are separated in time by 20 seconds. Using optogenetics, we show that this task requires intact hippocampal activity during both learning and memory retrieval. In Part 2, we characterize the phasic responses of the LC and its projections to the dorsal hippocampus during trace fear conditioning. We find learning related changes in these responses that are consistent with a role for LC in signaling the learned salience of environmental stimuli. We go on to show that amplifying these phasic responses can lead to enhancements in long-term memory. We also demonstrate that LC stimulation increases both norepinephrine and dopamine content in the dorsal hippocampus. Somewhat unexpectedly, we find that only the release of dopamine is needed to enhance memory formation. The implications of these findings for LC function and dopamine release in the hippocampus during ave

Rationale: Over half of people with HIV (PWH) report loneliness (i.e., perceived social isolation) in their lifetime. PWH may be at increased risk of loneliness compared to people without HIV (PWoH) due to stigma, discrimination, and objective social isolation. Depression can be a consequence of loneliness, which is problematic given its high prevalence in PWH. This dissertation aimed to address gaps in the literature related to loneliness in PWH by examining: 1) the prevalence of loneliness and psychosocial factors that may mitigate it, 2) associations between loneliness and systemic inflammatory biomarkers, and 3) cross-sectional and longitudinal impacts of loneliness on depression. Design: Retrospective data from the Multi-Dimensional Successful Aging Among HIV-Infected Adults Study were extracted. Participants with UCLA Loneliness Scale-Version 3 data were included in analyses (N=202; PWH n=120, PWoH n=82). Studies 1 and 2 used multivariable regressions, and Study 3 used multilevel modeling. Results: Study 1 (cross-sectional; N=202) 41.7% of PWH reported clinically significant loneliness, exceeding rates for PWoH (29.3%; p=.049). Resilience, personal mastery, and affective wisdom were negatively associated with loneliness (ps<.05). PWH were more vulnerable to loneliness than PWoH when cognitive wisdom and emotional support were lower. Loneliness explained significant variance in depressive scores after accounting for demographic, psychological, and social variables. Study 2 (cross-sectional; N=82) In PWH, specific biomarkers of inflammation (D-dimer, CCL2/MCP-1, and sCD14) predicted loneliness after accounting for relevant covariates (ps<.05). There was also a combined association of loneliness and inflammation with depressive symptoms whereby higher D-dimer was associated with increased depressive symptoms only when loneliness was higher (p=.0497). Study 3 (longitudinal; N=139) Individuals who experienced more loneliness than their typical average reporte

In this dissertation I consider the role of psychosocial stress in mental and physical health, and investigate the role of a month-long Buddhist meditation retreat in altering the pathways between our biochemical makeup and our experience of the world. As living beings, we possess a tremendous capacity for adaptation, and yet we are deeply conditioned by circumstance and bound by certain truths. We inhabit bodies that deteriorate, yet the rate and form of this degradation varies wildly depending on our environments and prior experiences. Stress research considers how our experiences become embedded in our bodies in ways that contribute to illness and disease, while also considering the protective factors that mitigate these outcomes. Importantly, decades of research indicate that one of the most potent modulators of health and well-being are our relationships and psychosocial environment. Buddhist philosophy and meditation practices offer another framework for understanding our interdependence with others, and for investigating the intricate system of causes and conditions that govern our existence. Much of our conditioning and adaptation happens outside of our awareness and conscious intent, and meditation practices are often designed to bring some of this content into conscious awareness, so that we can learn to differentiate between the aspects of our lives we have agency in and those that are inevitable. In the Insight meditation tradition studied here, primary practices include directing one’s attention to the coming and going of bodily sensations and observing thoughts as transient phenomena without grasping or over-identification. These practices are taught in combination with practices designed to support the four immeasurables: loving-kindness, compassion, empathetic joy, and equanimity. Together, these practices aim to cultivate beneficial qualities of mind and positive aspirations for oneself and others that allow practitioners to live in greater harmony

Trace fear conditioning (TFC) is a variant of Pavlovian conditioning in which the CS and US are separated by a temporal gap (aka trace interval). The hippocampus is commonly assumed to facilitate this type of learning by maintaining a memory of the CS until the US occurs. Prior work from our lab and others has demonstrated that optogenetic inhibition of CA1 during the tone and trace interval impairs the acquisition of TFC. However, there is currently little to no evidence that individual hippocampal neurons reliably maintain a memory of the CS during the trace interval. Here, we used fiber photometry to record bulk calcium activity in CA1 as mice underwent TFC. Similar to previous work, we found that the footshock US produced a large and prolonged increase in CA1 activity. To determine if this activity was important for learning, we optogenetically silenced CA1 after footshock and found that trace fear memory was significantly impaired. In contrast, silencing CA1 for an equivalent period during the intertrial interval had no effect, indicating that immediate, but not delayed post-shock activity is essential for memory formation. However, this was only true for new learning, as post-shock silencing on the second day of training did not disrupt a previously formed trace fear memory. Similar patterns of activity in CA1 have been observed in spatial studies when a reward US is encountered on a maze. In that case, reward induces replay during sharp wave-ripples that travel backwards in time to reactivate the path leading to food. We hypothesize that something similar may happen during TFC: the aversive US activates CA1 and causes it to replay the sequence of events that lead to footshock. This allows the animal to associate the aversive outcome with predictive stimuli that occurred tens of seconds earlier. Implications for models of trace conditioning and hippocampal function are discussed.

This study assessed whether different types of childhood maltreatment (CM) (i.e., abuse vs. neglect) had differential relationships with heart rate variability (HRV) and baroreflex sensitivity (BRS), two established markers of autonomic functioning. Additionally, this study used a moderated mediation model to investigate the potentially mediating role of HRV in the relationship between CM subtypes and adult psychopathology, and whether these relationships differed in those with high vs. low resting HRV. Secondary analysis was performed using the MIDUS II Biomarker Project dataset. Structural equation modeling was used to assess the relationships between key variables at baseline, as well as reactivity and recovery to stressor tasks. Baseline pathways from abuse and neglect to BRS were nonsignificant, as was the pathway from HRV to psychopathology. Notably, greater abuse was significantly predictive of lower HRV (standardized ß = -.42, p<.01) while greater neglect was significantly predictive of higher HRV (standardized ß = .32, p<.05). Additionally, higher childhood abuse was significantly predictive of greater adult psychopathology (standardized ß = .39, p<.001), but childhood neglect was not found to be related to adult psychopathology in this sample. Significant relationships between target variables were only found in those with low HRV. Our findings suggest that greater differentiation between abuse and neglect are appropriate in investigations of the impact of CM on adult physical and mental health outcomes. Additionally, our findings contribute further evidence that low HRV may be a transdiagnostic endophenotype for mood-related pathology.

Anxiety disorders are among the most common psychiatric diagnoses worldwide and rank prominently among the World Health Organization’s leading causes of disability. Existing treatments for anxiety disorders are inconsistently effective and often cause adverse side effects, underscoring the need to develop clinical entry points that lead to new intervention strategies. In the past decade, clinical and basic research efforts have identified uncertain threat anticipation as causal in anxiogenesis and have established sensitivity to uncertain-threat anticipation as a transdiagnostic marker of anxiety disorders. Across a range of temporally “certain-vs-uncertain” threat paradigms in nonhuman animals and human participants alike, uncertain-threat contexts consistently elicit heightened behavioral, physiological, neurobiological, and (in the case of humans) emotional measures of anxiety. However, the research community has no compelling explanation as to why individuals become more anxious in uncertain-threat contexts—possibly because the term “uncertainty” is sufficiently imprecise as to allow for many operationalizations. This dissertation builds toward a higher-acuity operationalization of “uncertainty” that enables sophisticated manipulations of its tractable features. Chapter 1 details our replication and extension of nonhuman-primate research into the neural substrates of threat processing. We used a novel machine-learning approach to uncover a new link between infant temperament and adolescent behavioral and neurobiological response to uncertain threat (N=18). In Chapter 2, we argue that the extended amygdala has evolved as an arbiter of risk-vs-reward tradeoffs for survival optimization, propose a novel “feature-space” model to explain how distinct pathophysiologies can promote a common clinical phenotype, and discuss the implications of our model in the context of psychiatric disorder. In Chapter 3, we recount our development of a computational model of uncertain

The current investigation documented how individuals of different socioeconomic backgrounds differ in their judgments of the severity of economic inequality. Seven empirical studies provide robust support for the central hypothesis that those of higher (vs. lower) socioeconomic backgrounds will judge wealth distributions as less severely unequal. Further analyses suggested that these differences (in economic inequality judgments) can, in part, be explained by differences in economic system justification (i.e., stronger among those of higher socioeconomic backgrounds). Toward the end, I demonstrated how such differences can lead to, and explain, diverging reactions (in emotions and attributions) toward other societal issues – in current data, the unhousedness problem.

Empathy has gained prominence within Evolutionary Psychology. It consists of sharing emotions and understanding the other's point of view and tends to differ between men and women. However, it is still unclear what are its evolutionary advantages. Clinical and mental health factors may also influence the expression of empathy. Therefore, the aim of this study was to compare empathy between male and female undergraduate students, as well as the clinical and mental health profiles in individuals with low and high empathy scores. We applied online the “Escala Multidimensional de Reatividade Interpessoal” (EMRI), to measure empathy, and the "ConVid - Pesquisa de Comportamentos'' to assess the emotional states and clinical profile of 155 students from the Federal University of Goiás. In total, there were 69 male participants (23.85 ± 3.72 years) and 86 female participants (24.29 ± 5.55 years). The scores of the empathy subscales were compared between genders using Student's t-test (p<0.05). Higher scores of Empathic Concern (p<0.0001), Personal Distress (p=0.0051) and Global Empathy Score (p=0.0002) were found for women compared to men. Moreover, more empathic people have higher levels of self-perception of their emotional states (p=0.0026). The results confirm the findings in the literature, which indicate that women tend to be more empathic than men. The study of the subject in other contexts are still important for a more precise understanding of the evolutionary phenomenon of empathy., La empatía ha cobrado protagonismo dentro de la Psicología Evolutiva. Ella consiste en compartir las emociones y comprender el punto de vista del otro, y suele ser diferente entre hombres y mujeres. Sin embargo, aún no está claro cuáles son sus ventajas evolutivas. Los factores clínicos y de salud mental también pueden influir en la expresión de la empatía. Por lo tanto, el objetivo de este estudio fue comparar la empatía entre estudiantes universitarios de los sexos masculino y feminino, así como el perfil clínico y de salud mental en individuos con puntuaciones de empatía bajas y altas. Aplicamos en línea la “Escala Multidimensional de Reatividade Interpessoal” (EMRI), para medir la empatía, y el "ConVid - Pesquisa de Comportamentos" para evaluar los estados emocionales y el perfil clínico de 155 estudiantes de la Universidad Federal de Goiás. En total había 69 participantes masculinos (23,85 ± 3,72 años) y 86 femeninos (24,29 ± 5,55 años). Las puntuaciones de las subescalas de empatía se compararon entre los sexos mediante la Prueba t de Student (p<0,05). Las puntuaciones de Consideración Empática (p<0,0001), Angustia Personal (p=0,0051) y Score Global (p=0,0002) fueron mayores en las mujeres que en los hombres. Además, las personas más empáticas tienen mayores niveles de autopercepción de sus estados emocionales (p=0,0026). Los resultados confirman los hallazgos de la literatura, que indican que las mujeres tienden a ser más empáticas que los hombres. El estudio del tema en otros contextos sigue siendo importante para una comprensión más precisa del fenómeno evolutivo de la empatía., A empatia vem ganhando destaque dentro da Psicologia Evolucionista. Ela consiste no compartilhamento de emoções e compreensão do ponto de vista do outro, e tende a diferir entre homens e mulheres. Entretanto, ainda não está claro quais as vantagens evolutivas dela. Fatores clínicos e de saúde mental também podem influenciar a expressão da empatia. Portanto, o objetivo deste estudo foi comparar a empatia entre estudantes universitários dos sexos masculino e feminino, assim como o perfil clínico e de saúde mental em indivíduos com baixos e altos escores de empatia. Aplicamos online a Escala Multidimensional de Reatividade Interpessoal (EMRI), para mensurar a empatia, e o “ConVid - Pesquisa de Comportamentos" para avaliar os estados emocionais e perfil clínico de 155 estudantes da Universidade Federal de Goiás. No total foram 69 participantes do sexo masculino (23,85 ± 3,72 anos) e 86 do sexo feminino (24,29 ± 5,55 anos). Os escores das subescalas de empatia foram comparados entre os sexos por meio do Teste t de Student (p<0,05). Foram encontrados maiores escores de Consideração Empática (p<0,0001), Angústia Pessoal (p=0,0051) e Escore Global de Empatia (p=0,0002) para as mulheres em comparação com os homens. Ademais, pessoas mais empáticas têm maiores níveis de autopercepção dos seus estados emocionais (p=0,0026). Os resultados confirmam os achados da literatura, que apontam que as mulheres tendem a ser mais empáticas do que os homens. O estudo do tema em outros contextos é ainda importante para a compreensão mais precisa do fenômeno evolutivo da empatia.

Empathy has gained prominence within Evolutionary Psychology. It consists of sharing emotions and understanding the other's point of view and tends to differ between men and women. However, it is still unclear what are its evolutionary advantages. Clinical and mental health factors may also influence the expression of empathy. Therefore, the aim of this study was to compare empathy between male and female undergraduate students, as well as the clinical and mental health profiles in individuals with low and high empathy scores. We applied online the “Escala Multidimensional de Reatividade Interpessoal” (EMRI), to measure empathy, and the "ConVid - Pesquisa de Comportamentos'' to assess the emotional states and clinical profile of 155 students from the Federal University of Goiás. In total, there were 69 male participants (23.85 ± 3.72 years) and 86 female participants (24.29 ± 5.55 years). The scores of the empathy subscales were compared between genders using Student's t-test (p<0.05). Higher scores of Empathic Concern (p<0.0001), Personal Distress (p=0.0051) and Global Empathy Score (p=0.0002) were found for women compared to men. Moreover, more empathic people have higher levels of self-perception of their emotional states (p=0.0026). The results confirm the findings in the literature, which indicate that women tend to be more empathic than men. The study of the subject in other contexts are still important for a more precise understanding of the evolutionary phenomenon of empathy., La empatía ha cobrado protagonismo dentro de la Psicología Evolutiva. Ella consiste en compartir las emociones y comprender el punto de vista del otro, y suele ser diferente entre hombres y mujeres. Sin embargo, aún no está claro cuáles son sus ventajas evolutivas. Los factores clínicos y de salud mental también pueden influir en la expresión de la empatía. Por lo tanto, el objetivo de este estudio fue comparar la empatía entre estudiantes universitarios de los sexos masculino y feminino, así como el perfil clínico y de salud mental en individuos con puntuaciones de empatía bajas y altas. Aplicamos en línea la “Escala Multidimensional de Reatividade Interpessoal” (EMRI), para medir la empatía, y el "ConVid - Pesquisa de Comportamentos" para evaluar los estados emocionales y el perfil clínico de 155 estudiantes de la Universidad Federal de Goiás. En total había 69 participantes masculinos (23,85 ± 3,72 años) y 86 femeninos (24,29 ± 5,55 años). Las puntuaciones de las subescalas de empatía se compararon entre los sexos mediante la Prueba t de Student (p<0,05). Las puntuaciones de Consideración Empática (p<0,0001), Angustia Personal (p=0,0051) y Score Global (p=0,0002) fueron mayores en las mujeres que en los hombres. Además, las personas más empáticas tienen mayores niveles de autopercepción de sus estados emocionales (p=0,0026). Los resultados confirman los hallazgos de la literatura, que indican que las mujeres tienden a ser más empáticas que los hombres. El estudio del tema en otros contextos sigue siendo importante para una comprensión más precisa del fenómeno evolutivo de la empatía., A empatia vem ganhando destaque dentro da Psicologia Evolucionista. Ela consiste no compartilhamento de emoções e compreensão do ponto de vista do outro, e tende a diferir entre homens e mulheres. Entretanto, ainda não está claro quais as vantagens evolutivas dela. Fatores clínicos e de saúde mental também podem influenciar a expressão da empatia. Portanto, o objetivo deste estudo foi comparar a empatia entre estudantes universitários dos sexos masculino e feminino, assim como o perfil clínico e de saúde mental em indivíduos com baixos e altos escores de empatia. Aplicamos online a Escala Multidimensional de Reatividade Interpessoal (EMRI), para mensurar a empatia, e o “ConVid - Pesquisa de Comportamentos" para avaliar os estados emocionais e perfil clínico de 155 estudantes da Universidade Federal de Goiás. No total foram 69 participantes do sexo masculino (23,85 ± 3,72 anos) e 86 do sexo feminino (24,29 ± 5,55 anos). Os escores das subescalas de empatia foram comparados entre os sexos por meio do Teste t de Student (p<0,05). Foram encontrados maiores escores de Consideração Empática (p<0,0001), Angústia Pessoal (p=0,0051) e Escore Global de Empatia (p=0,0002) para as mulheres em comparação com os homens. Ademais, pessoas mais empáticas têm maiores níveis de autopercepção dos seus estados emocionais (p=0,0026). Os resultados confirmam os achados da literatura, que apontam que as mulheres tendem a ser mais empáticas do que os homens. O estudo do tema em outros contextos é ainda importante para a compreensão mais precisa do fenômeno evolutivo da empatia.

Prenatal ethanol exposure (PrEE) is a leading cause of preventable birth defects and neurobehavioral disorders; PrEE can lead to Fetal Alcohol Spectrum Disorders (FASD). Clinical profiles of patients with FASD indicate damage to the central nervous system (CNS), including the neocortex, may underlie the varied, cognitive deficits associated with FASD. Recent preclinical evidence has suggested that PrEE may induce epigenetic dysregulation in offspring, producing adverse heritable, transgenerational behavioral effects, however the neurobiological underpinnings remain unclear. Preventive or therapeutic treatments for FASD have not yet been discovered and need to reflect the neurobiological damage inflicted by PrEE as well as the abstinence-resistant population. Additionally, although much research has focused on maternal PrEE, much less is known about the impact of paternal ethanol exposure (PatEE) and how development of the neocortex may be disrupted by preconception alcohol use by fathers. The research presented within this dissertation attempts to fill these gaps in knowledge using three, distinct research designs and multi-level neurobiological and behavioral approaches. First, in Chapter 1, we assessed the full extent of behavioral disruptions that are passed several generations following PrEE and attempted to find novel mechanistic links within the CNS using a transgenerational mouse model of FASD. We found multi-modality behavioral abnormalities that extend several generations and novel CNS anomalies in directly exposed offspring. Second, in Chapter 2, we investigated how co-administration of choline could prevent PrEE-induced neurobehavioral deficits. We found choline has a robust protective effect on several parameters of neocortical development and behaviors that are normally disrupted by PrEE in a mouse model. Lastly, in Chapter 3, we described the impact of preconception ethanol exposure on early postnatal development of the neocortex in an novel PatEE mous

Dysregulated diurnal secretion patterns of the hormone cortisol are implicated in mediating associations between stress exposure and health outcomes (Chrousos & Gold, 1992; Davis & Sandman, 2010; Lupien et al., 2009), including the onset and progression of mental and physical health disorders (Heim et al., 2008). Physical activity participation has been associated with lower levels of cortisol secretion during times of stress and may contribute to effective regulation of cortisol secretion over time. Adequate HPA-axis regulation is one potential mechanism by which physical activity participation may impact stress-related outcomes and quantifying the effect across studies will demonstrate the degree to which physical activity participation is associated with effective HPA-axis regulation and help to identify the potential conditions or factors that may affect it. We synthesized research examining the association between physical activity participation and two distinct indices of effective HPA-axis regulation; the diurnal cortisol slope and the cortisol awakening response, as well as factors that moderate this relationship across existent literature. The three-level meta-analysis revealed a small, non-zero negative correlation between physical activity and the diurnal cortisol slope with high heterogeneity. Moderator analyses examining effects of sample sociodemographic differences, study design characteristics, cortisol measurement methods, and physical activity-related differences indicated few differences in the averaged physical activity-diurnal cortisol slope relationship across studies at different levels of each moderator. There were observed differences effect in some isolated cases, for example, the correlation was slightly larger and non-zero in experimental studies compared to observational studies in which the correlation was smaller and no different from zero. However, overall, evidence for the effect of moderators on the physical activity-diurnal

The possibility of directed improvement of perceptual ability is the main force behind this work. In contrast to the majority of perceptual studies that focus on vision, this work centers on the mechanical senses of touch and hearing. In the case of touch perception, aspects of vibratory stimulation that would promote perceptual learning that transfers to untrained features were explored. This line of inquiry has the long-term goal of building useful training for prosthetic limb control. In the case of hearing, a much more nuanced depiction of relevant dimensions of perceptual ability is provided based on research from the fields of psychophysics and auditory neuroscience. We identify and begin to address the need for translation of this scientific laboratory work into a clinical domain. To this end, a number of central auditory processes assessments with potential clinical relevance was validated in a portable automatic rapid testing (PART) platform. We present robust results across different external noise conditions as well as variations of portable device, headphones, and testing settings (lab vs home). Our results suggest PART may be used to start collecting large enough datasets to create performance norms and ultimately translate these laboratory assessments into clinical practice. Finally, we use PART as the assessment element to evaluate perceptual improvement after an auditory training video-game intervention called Listen that incorporates a body of findings in perceptual learning (PL) to promote learning that would generalize to the ability to perceive speech in noise. We present promising preliminary results with a young normal hearing sample and suggest a potential application for people in need. Such application could serve to improve people’s lives in meaningful ways through the preservation or improvement of hearing. In conclusion, the work compiled here portrays a somewhat broad picture of conducting PL research across the mechanical senses (touch

Executive function (EF) is an umbrella term for a collection of important cognitive skills, including working memory, cognitive flexibility, and inhibitory control. These skills are important for both short-term and long-term outcomes such as peer relations, mental and physical health, and academic achievement. Numerous factors influence performance on each of these skills, one of which is experiencing stress. However, how different stressors impact EF across the life span, and how stress-induced impacts on EF are related to other outcomes, is not fully understood. For example, while there is a large body of literature examining the effects of acute stress on adult EF, the literature on this relation in childhood is sparse. The aim of the following studies was to examine how different stressors impact EF and how this process relates to other outcomes, such as academic achievement and mental health. First, longitudinal analyses of the mediating role of executive function in middle childhood (age 7-11) in the relation between early-life family income (age 0-5) and academic achievement in late adolescence (16-18) were examined. These analyses indicated that executive function serves as a mediator in this relation. Second, the effects of an acute experimental stressor on EF performance in 9-11-year-old children were examined, as well as the potential moderating roles of child characteristics such as physiological reactivity and emotional and behavioral problems. There was no overall effect of stress on EF performance but there was a moderating effect of parasympathetic nervous system reactivity in the relation between stress condition and inhibitory control performance. Lastly, the association between COVID-19-related economic stress and both EF and mental health in 9-17-year-old children and their parents was examined. There were no effects of either parental job loss or family financial stress on EF, but family financial stress did predict worse mental health in paren

Neurodevelopmental disorders (NDDs) are a broad group of conditions characterized by abnormal development of the nervous system that includes intellectual disability and autism spectrum disorders. NDDs are pervasive, lifelong, and increasing in prevalence, yet neither targeted pharmacological nor precision medicine therapies are currently available. This unmet need is in large part due to the complex and relatively unknown etiology of many NDDs. Multiple genetic loci, in combination with exposure to environmental risk factors during critical periods of development, contribute to both NDD susceptibility and symptom severity. In an effort to improve our understanding of NDD etiology, as well as help develop effective treatments, we used Sprague Dawley rats to examine the effects of two environmental risk factors and one causal genetic mutation on behaviors and neurobiological outcomes relevant to NDDs. While the mouse has predominated in recent decades as the species of choice for modeling NDDs, we sought to take advantage of the broader and more nuanced social communication repertoire of the rat. Therefore, we measured effects on a variety of behavioral domains including motor and cognition and gave particular focus to social and communication behaviors. Chapter 1 serves as an introduction to the study of social communication in rodent models of NDDs and provides detailed rationales behind many of the assays utilized in subsequent chapters. Chapters 2 and 3 investigate environmental factors that have been associated with increased risk for NDDs: air pollution and pesticides, respectively. Our findings support the hypothesis that developmental exposure to heavily trafficked roadways, or to the commonly used pesticide chlorpyrifos, increases NDD risk. Then, Chapters 4 and 5 characterize a novel genetic rat model of the NDD Angelman Syndrome, which is caused by dysfunction of the gene UBE3A (ubiquitin protein ligase E3A). We discovered that the Ube3a deletion rat model

There is recognized comorbidity of obesity and depression, and research suggests chronic low-grade inflammation as a potential shared mechanism connecting these two health conditions. However, this hypothesis is mainly based on cross-sectional studies with adult clinical samples, which limits understanding of the developmental nature of these constructs. Furthermore, there is a debate on the directionality of these associations. Recent research also suggests that there are sex differences not only in the individual developmental trajectories of depression, obesity and inflammation across adolescence, but also in the associations among them. Examining the co-development of these constructs in adolescence is particularly important given the high prevalence of first onset-depression during adolescence. Biological mechanisms are critical to consider because obesity and inflammation are associated with endocrine processes which are salient during puberty, and sex differences may be especially apparent during this period. However, few studies have examined these questions in a prospective longitudinal manner throughout adolescent development. Thus, the current study aimed to examine the co-development of adiposity, inflammation and depressive symptoms in the period from pre-adolescence to early adulthood, and to examine whether these associations differ between boys and girls. These questions were explored in a subset of data from the Avon Longitudinal Studies of Parents and Children (ALSPAC; N=6,525). Fat Mass Index (FMI) was used as a measure of general adiposity. C-reactive protein (CRP) was used as a marker of systemic inflammation. Depressive symptoms were assessed by the Short Mood and Feelings Questionnaire (SMFQ; Angold et al., 1995). Each was measured at 4 time points between 9 and 24 years. A combination of both cross-lagged panel analyses and parallel-processes latent growth curve models were used to examine their associations. The most robust and consistent fi

Dysregulated diurnal secretion patterns of the hormone cortisol are implicated in mediating associations between stress exposure and health outcomes (Chrousos & Gold, 1992; Davis & Sandman, 2010; Lupien et al., 2009), including the onset and progression of mental and physical health disorders (Heim et al., 2008). Physical activity participation has been associated with lower levels of cortisol secretion during times of stress and may contribute to effective regulation of cortisol secretion over time. Adequate HPA-axis regulation is one potential mechanism by which physical activity participation may impact stress-related outcomes and quantifying the effect across studies will demonstrate the degree to which physical activity participation is associated with effective HPA-axis regulation and help to identify the potential conditions or factors that may affect it. We synthesized research examining the association between physical activity participation and two distinct indices of effective HPA-axis regulation; the diurnal cortisol slope and the cortisol awakening response, as well as factors that moderate this relationship across existent literature. The three-level meta-analysis revealed a small, non-zero negative correlation between physical activity and the diurnal cortisol slope with high heterogeneity. Moderator analyses examining effects of sample sociodemographic differences, study design characteristics, cortisol measurement methods, and physical activity-related differences indicated few differences in the averaged physical activity-diurnal cortisol slope relationship across studies at different levels of each moderator. There were observed differences effect in some isolated cases, for example, the correlation was slightly larger and non-zero in experimental studies compared to observational studies in which the correlation was smaller and no different from zero. However, overall, evidence for the effect of moderators on the physical activity-diurnal

The possibility of directed improvement of perceptual ability is the main force behind this work. In contrast to the majority of perceptual studies that focus on vision, this work centers on the mechanical senses of touch and hearing. In the case of touch perception, aspects of vibratory stimulation that would promote perceptual learning that transfers to untrained features were explored. This line of inquiry has the long-term goal of building useful training for prosthetic limb control. In the case of hearing, a much more nuanced depiction of relevant dimensions of perceptual ability is provided based on research from the fields of psychophysics and auditory neuroscience. We identify and begin to address the need for translation of this scientific laboratory work into a clinical domain. To this end, a number of central auditory processes assessments with potential clinical relevance was validated in a portable automatic rapid testing (PART) platform. We present robust results across different external noise conditions as well as variations of portable device, headphones, and testing settings (lab vs home). Our results suggest PART may be used to start collecting large enough datasets to create performance norms and ultimately translate these laboratory assessments into clinical practice. Finally, we use PART as the assessment element to evaluate perceptual improvement after an auditory training video-game intervention called Listen that incorporates a body of findings in perceptual learning (PL) to promote learning that would generalize to the ability to perceive speech in noise. We present promising preliminary results with a young normal hearing sample and suggest a potential application for people in need. Such application could serve to improve people’s lives in meaningful ways through the preservation or improvement of hearing. In conclusion, the work compiled here portrays a somewhat broad picture of conducting PL research across the mechanical senses (touch

Prenatal ethanol exposure (PrEE) is a leading cause of preventable birth defects and neurobehavioral disorders; PrEE can lead to Fetal Alcohol Spectrum Disorders (FASD). Clinical profiles of patients with FASD indicate damage to the central nervous system (CNS), including the neocortex, may underlie the varied, cognitive deficits associated with FASD. Recent preclinical evidence has suggested that PrEE may induce epigenetic dysregulation in offspring, producing adverse heritable, transgenerational behavioral effects, however the neurobiological underpinnings remain unclear. Preventive or therapeutic treatments for FASD have not yet been discovered and need to reflect the neurobiological damage inflicted by PrEE as well as the abstinence-resistant population. Additionally, although much research has focused on maternal PrEE, much less is known about the impact of paternal ethanol exposure (PatEE) and how development of the neocortex may be disrupted by preconception alcohol use by fathers. The research presented within this dissertation attempts to fill these gaps in knowledge using three, distinct research designs and multi-level neurobiological and behavioral approaches. First, in Chapter 1, we assessed the full extent of behavioral disruptions that are passed several generations following PrEE and attempted to find novel mechanistic links within the CNS using a transgenerational mouse model of FASD. We found multi-modality behavioral abnormalities that extend several generations and novel CNS anomalies in directly exposed offspring. Second, in Chapter 2, we investigated how co-administration of choline could prevent PrEE-induced neurobehavioral deficits. We found choline has a robust protective effect on several parameters of neocortical development and behaviors that are normally disrupted by PrEE in a mouse model. Lastly, in Chapter 3, we described the impact of preconception ethanol exposure on early postnatal development of the neocortex in an novel PatEE mous

Neurodevelopmental disorders (NDDs) are a broad group of conditions characterized by abnormal development of the nervous system that includes intellectual disability and autism spectrum disorders. NDDs are pervasive, lifelong, and increasing in prevalence, yet neither targeted pharmacological nor precision medicine therapies are currently available. This unmet need is in large part due to the complex and relatively unknown etiology of many NDDs. Multiple genetic loci, in combination with exposure to environmental risk factors during critical periods of development, contribute to both NDD susceptibility and symptom severity. In an effort to improve our understanding of NDD etiology, as well as help develop effective treatments, we used Sprague Dawley rats to examine the effects of two environmental risk factors and one causal genetic mutation on behaviors and neurobiological outcomes relevant to NDDs. While the mouse has predominated in recent decades as the species of choice for modeling NDDs, we sought to take advantage of the broader and more nuanced social communication repertoire of the rat. Therefore, we measured effects on a variety of behavioral domains including motor and cognition and gave particular focus to social and communication behaviors. Chapter 1 serves as an introduction to the study of social communication in rodent models of NDDs and provides detailed rationales behind many of the assays utilized in subsequent chapters. Chapters 2 and 3 investigate environmental factors that have been associated with increased risk for NDDs: air pollution and pesticides, respectively. Our findings support the hypothesis that developmental exposure to heavily trafficked roadways, or to the commonly used pesticide chlorpyrifos, increases NDD risk. Then, Chapters 4 and 5 characterize a novel genetic rat model of the NDD Angelman Syndrome, which is caused by dysfunction of the gene UBE3A (ubiquitin protein ligase E3A). We discovered that the Ube3a deletion rat model

There is recognized comorbidity of obesity and depression, and research suggests chronic low-grade inflammation as a potential shared mechanism connecting these two health conditions. However, this hypothesis is mainly based on cross-sectional studies with adult clinical samples, which limits understanding of the developmental nature of these constructs. Furthermore, there is a debate on the directionality of these associations. Recent research also suggests that there are sex differences not only in the individual developmental trajectories of depression, obesity and inflammation across adolescence, but also in the associations among them. Examining the co-development of these constructs in adolescence is particularly important given the high prevalence of first onset-depression during adolescence. Biological mechanisms are critical to consider because obesity and inflammation are associated with endocrine processes which are salient during puberty, and sex differences may be especially apparent during this period. However, few studies have examined these questions in a prospective longitudinal manner throughout adolescent development. Thus, the current study aimed to examine the co-development of adiposity, inflammation and depressive symptoms in the period from pre-adolescence to early adulthood, and to examine whether these associations differ between boys and girls. These questions were explored in a subset of data from the Avon Longitudinal Studies of Parents and Children (ALSPAC; N=6,525). Fat Mass Index (FMI) was used as a measure of general adiposity. C-reactive protein (CRP) was used as a marker of systemic inflammation. Depressive symptoms were assessed by the Short Mood and Feelings Questionnaire (SMFQ; Angold et al., 1995). Each was measured at 4 time points between 9 and 24 years. A combination of both cross-lagged panel analyses and parallel-processes latent growth curve models were used to examine their associations. The most robust and consistent fi

Executive function (EF) is an umbrella term for a collection of important cognitive skills, including working memory, cognitive flexibility, and inhibitory control. These skills are important for both short-term and long-term outcomes such as peer relations, mental and physical health, and academic achievement. Numerous factors influence performance on each of these skills, one of which is experiencing stress. However, how different stressors impact EF across the life span, and how stress-induced impacts on EF are related to other outcomes, is not fully understood. For example, while there is a large body of literature examining the effects of acute stress on adult EF, the literature on this relation in childhood is sparse. The aim of the following studies was to examine how different stressors impact EF and how this process relates to other outcomes, such as academic achievement and mental health. First, longitudinal analyses of the mediating role of executive function in middle childhood (age 7-11) in the relation between early-life family income (age 0-5) and academic achievement in late adolescence (16-18) were examined. These analyses indicated that executive function serves as a mediator in this relation. Second, the effects of an acute experimental stressor on EF performance in 9-11-year-old children were examined, as well as the potential moderating roles of child characteristics such as physiological reactivity and emotional and behavioral problems. There was no overall effect of stress on EF performance but there was a moderating effect of parasympathetic nervous system reactivity in the relation between stress condition and inhibitory control performance. Lastly, the association between COVID-19-related economic stress and both EF and mental health in 9-17-year-old children and their parents was examined. There were no effects of either parental job loss or family financial stress on EF, but family financial stress did predict worse mental health in paren

In the first chapter, I investigate the role of prefrontal cortex activity in working memory. Here, I am motivated by inconsistencies in the neural substrates for working memory across studies, species, and recording techniques. For instance, non-human primate electrophysiology research finds that prefrontal circuitry maintains working memory representations, while human neuroimaging suggests that working memory content is instead stored in sensory cortices. These seemingly incompatible accounts for working memory are often confounded by differences in the amount of task training and stimulus exposure across studies, suggesting that long-term learning may influence the role of prefrontal function in working memory maintenance. To answer these questions, we longitudinally trained and scanned participants on a working memory task with complex stimuli. Then, we used multivariate analyses of functional neuroimaging (fMRI) data to test how representational structures of working memory activity patterns in prefrontal cortex change across intensive learning. We show that human prefrontal cortex develops stimulus- selective working memory responses with learning, more akin to results from electrophysiology studies. This approach uses a unique training and analysis framework to establish novel evidence for long-term memory influences on working memory maintenance.In the second chapter, we investigate how working memory is constantly used to guide our moment to moment behaviors. This reliance on working memory can lead us to make mistakes, like saying aloud the wrong word in a conversation. Such “action slips” are common occurrences but especially pronounced in individuals with prefrontal lesions, who may often pour salt instead of sugar into one’s coffee, or mistakenly type “pizza” in an immediate texting conversation when thinking about your upcoming lunch (Lhermitte et al. 1986). To study this interaction between working memory and ongoing behavior, I implemented a dual-ta

Research in performance optimization aims to improve cognitive-motor performance under arduous conditions. From a kinesiology perspective, effectiveness in performance optimization can be quantified through the neurophysiological economy of goal-directed motor behavior. Derived from the psychomotor efficiency hypothesis, the cognitive-affective-motor (CAM) model discusses the brain's complex intersections of cognitive-motor and cognitive-affective processes. The CAM model subscribes to the principle that superior performance is achieved by minimizing nonessential motoric processes, such as mental stress management. When stress response becomes unmanageable, there will be an elevation in nonessential motoric processes and negatively impact motor preparation. The resulting disfluency within the central nervous system will ultimately manifest in the motor and autonomic sections of the peripheral nervous system. To combat the disruptive effects of mental stress, employing autonomic regulation techniques such as Vagus nerve neuromodulation can remedy the inefficiencies of the nervous systems and promote an adaptive state for performance. This dissertation aimed to assess the CAM model empirically by investigating the integrative model of the cortical, autonomic, and motor nervous systems during a precision motor task (i.e., dart-throwing). A thorough examination was conducted on preserving the nervous system’s efficiency and positive impacts on the quality of motor performance through Vagus nerve neuromodulations. Specifically, the study focused on varying levels of mental stress to determine inoculation capabilities. Twenty-three participants were enrolled in a repeated-measures within-subjects design. Neurophysiological measures of nervous system activity were captured before motor execution to determine the amalgamated influence of Vagus nerve neuromodulation and mental stress. The observed results revealed an elevation in psychomotor efficiency through the Vagus nerv

Autism spectrum disorder (ASD) has been identified as a heterogeneous disorder with multiple syndromes and etiologies (Tordjman et al., 2017). The current literature has yet to identify valid subgroups with key distinct features in the ASD population that can contribute further insights into the disorder. By taking a bottom-up approach in observing trait differences within ASD through the lens of personality profiles, it is possible that homogeneous subgroups may be identified. Thus, the present study aimed to identify possible personality subgroups within school-aged children in the ASD population, and to evaluate potential differences in treatment outcomes between these subgroups as one mechanism for assessing the predictive validity of the subgroups. Data from a CBT treatment multi-site RCT with school-aged children (N=213; ages 7 – 13 years old) were used. Latent profile analysis of the participants’ personality measure scores revealed a 5-class solution that best fit the data. Omnibus ANCOVAs identified significant differences between the five identified personality subgroups on the Child Anxiety Impact Scale (CAIS; Langley et al., 2014) treatment outcome scores, after controlling for pre-treatment scores. Furthermore, specific contrasts revealed that personality subgroup response to CBT treatment for anxiety was also contingent on the type of treatment each individual received. One subgroup (Group 1) responded better to a particular treatment condition (Standard-of-Practice CBT), while another subgroup (Group 2) responded better to the other treatment condition (Adapted CBT). Exploratory analyses and implications are discussed.

Callous-unemotional (CU) traits (e.g., lack of empathy, deficient guilt/remorse, and shallow affect) are a risk factor for delinquent behavior. Youth high in CU traits exhibit a range of cognitive and emotional deficits, such as fearlessness, insensitivity to punishment, and reward dependency, that predispose them to antisocial behavior and justice system involvement. This two-part dissertation study sought to better understand how CU traits predispose youth to delinquent behavior by examining the hormones thought to underlie these emotional and cognitive deficits. Employing a sample of 55 justice-involved male youth recruited from an ongoing longitudinal study of first-time juvenile offenders, Study One examined the association between CU traits, adverse experiences (prior exposure to violence and hostile parent-child relationships), and cortisol and alpha-amylase reactivity. The results indicate that individuals with elevated levels of CU traits exhibit lower cortisol reactivity than their counterparts. However, they exhibited the same pattern of alpha-amylase reactivity. In addition, prior adversity did not moderate the association between CU traits and either indicator of stress reactivity. Study Two tested whether cortisol and testosterone mediated the association between CU traits, reward and punishment sensitivity, and risk taking. Unfortunately, the study was underpowered and could not determine whether there was a direct or indirect association between CU traits, risk taking, or reward/punishment sensitivity. However, the study provided evidence that individuals with high CU traits exhibited the same pattern of testosterone reactivity as their counterparts. Taken together, the results of the two studies suggest youth with elevated levels of CU traits exhibit a pattern of stress reactivity that may contribute to their behavior. Future research should continue to explore the relation between stress reactivity, CU traits, and other aspects of antisocial behavi

Morphine, a µ opioid agonist, elicits eating in rats when injected into multiple brain regions related to feeding and reward including the ventral tegmental area (VTA), nucleus accumbens shell and multiple regions of the hypothalamus (Castro & Berridge, 2014). It produces a particularly large feeding effect when injected into the lateral septum (LS) (Stanley et al., 1988), an area previously linked to several motivational and affective behaviors. The LS has connections to cortical and subcortical regions associated with motivation, and emotion, which makes it a potentially important integrative site for control and modulation of feeding-related behaviors. In this dissertation, I sought to establish receptor specificity, site-specificity and behavioral specificity of opioid-stimulation induced feeding in the LS.I replicated the robust feeding effects found by Stanley et al. (1988) at a lower morphine dose of 5 µg and found that this effect was reliable across days. I found that naloxone (a competitive opioid receptor antagonist) attenuated the feeding effect of morphine without changing baseline food intake, suggesting that the elicited feeding is likely specific to opioid receptors. I found that both the mu specific receptor agonist DAMGO and the GABA agonist muscimol increased feeding behavior when injected into the lateral septum. The effects of morphine were blocked at high doses by the mu specific receptor antagonist CTAP, suggesting that both mu opioid and GABA receptors may play a similar role in the modulation of feeding behaviors by the lateral septum.Although there are many sites in the brain in which stimulation of opioid receptors might stimulate feeding there are differences in feeding response to mu opioid and GABA agonists within the lateral septum. Specifically, muscimol was effective in the ventral and rostral lateral septum, while opioids are more effective in the medial septum, even more than the lateral septum. This interesting finding could r

Discrimination predicts several negative health outcomes, including all-cause mortality, cardiovascular disease, and immune response. Mechanisms such as the development of hypertension and biological aging via telomere attrition are plausible pathways from discrimination to these health outcomes, as evidenced by past research linking them to discrimination. Recent evidence suggests that cultural and psychosocial factors such as Afro-centric world view and social support protect individuals from the harmful health outcomes associated with discrimination. The current study had two main aims addressed with secondary data analyses of longitudinal data from a study conducted by researchers and community partners in five sites across the United States. The objectives were: (1) To test the effect of two forms of discrimination (lifetime and everyday) reported by Black mothers on blood pressure eleven months later (Study 1) and to test effects of the same two types of discrimination among a multi-ethnic (Latina, White, Black) sample of mothers on telomere length eight years later (Study 2); (2) To determine if racial identity, a construct representing one’s beliefs about their race, modifies the effect that discrimination has on the aforementioned outcomes. Results of Study 1 indicated that lifetime discrimination was significantly associated with systolic blood pressure but not diastolic for Black mothers, while everyday discrimination was not associated with either. However, further analyses revealed that everyday and lifetime discrimination attributed to one’s ancestry or accent were significantly associated with systolic blood pressure for Black mothers but not diastolic. Racial identity did not significantly modify the effect of either lifetime or everyday discrimination on resting blood pressure. In Study 2, results indicated that mothers with higher lifetime discrimination had shorter telomere length. Additionally, mothers with higher everyday discrimination based on

Interest has grown in understanding the connection between the state of mind of an individual and its effect on the body at the molecular level. Studies suggest that mental stress can alter the biochemical functions of the body (Juster, 2010). Depression is an example of a condition associated with mental stress. Exposure to environmental stresses is essential to the development of major depression, which in turn has been shown to affect the body systems in several ways. These effects are exerted at three main levels: genetic, molecular and neural. (Kupfer, 2016). Evidence is beginning to emerge that depression can lead to epigenetic changes in the human genome. Studies have also shown that epigenetic changes are critical to the development of many human malignancies including prostate cancer. It is therefore possible that these two processes may be linked, and that the presence of depression could predispose the individual to the development of cancers. Epigenetic mechanisms include DNA methylation, histone acetylation or methylation and post-translational effects of non-coding RNAs. The Decipher genomic classifier (GC) uses coding and noncoding RNA to predict men with prostate cancer who are at risk for aggressive disease or disease progression. Using the Decipher genomic classifier as a surrogate for coding and noncoding RNA, we seek to demonstrate a possible association between depression and a tendency for developing aggressive prostate cancer. A multivariable logistic regression comparing Decipher scores in depressed subjects will first be done using depression as a continuous variable adjusting for age, SES and total illness burden index and again after dichotomizing subjects into depressed vs. non-depressed with the same adjustments. We will also seek to demonstrate that high levels of resilience attenuate this association. A limitation of this study is that a correlation is not proof of direct causation. However, a positive association between depre

Autism spectrum disorder (ASD) has been identified as a heterogeneous disorder with multiple syndromes and etiologies (Tordjman et al., 2017). The current literature has yet to identify valid subgroups with key distinct features in the ASD population that can contribute further insights into the disorder. By taking a bottom-up approach in observing trait differences within ASD through the lens of personality profiles, it is possible that homogeneous subgroups may be identified. Thus, the present study aimed to identify possible personality subgroups within school-aged children in the ASD population, and to evaluate potential differences in treatment outcomes between these subgroups as one mechanism for assessing the predictive validity of the subgroups. Data from a CBT treatment multi-site RCT with school-aged children (N=213; ages 7 – 13 years old) were used. Latent profile analysis of the participants’ personality measure scores revealed a 5-class solution that best fit the data. Omnibus ANCOVAs identified significant differences between the five identified personality subgroups on the Child Anxiety Impact Scale (CAIS; Langley et al., 2014) treatment outcome scores, after controlling for pre-treatment scores. Furthermore, specific contrasts revealed that personality subgroup response to CBT treatment for anxiety was also contingent on the type of treatment each individual received. One subgroup (Group 1) responded better to a particular treatment condition (Standard-of-Practice CBT), while another subgroup (Group 2) responded better to the other treatment condition (Adapted CBT). Exploratory analyses and implications are discussed.

Callous-unemotional (CU) traits (e.g., lack of empathy, deficient guilt/remorse, and shallow affect) are a risk factor for delinquent behavior. Youth high in CU traits exhibit a range of cognitive and emotional deficits, such as fearlessness, insensitivity to punishment, and reward dependency, that predispose them to antisocial behavior and justice system involvement. This two-part dissertation study sought to better understand how CU traits predispose youth to delinquent behavior by examining the hormones thought to underlie these emotional and cognitive deficits. Employing a sample of 55 justice-involved male youth recruited from an ongoing longitudinal study of first-time juvenile offenders, Study One examined the association between CU traits, adverse experiences (prior exposure to violence and hostile parent-child relationships), and cortisol and alpha-amylase reactivity. The results indicate that individuals with elevated levels of CU traits exhibit lower cortisol reactivity than their counterparts. However, they exhibited the same pattern of alpha-amylase reactivity. In addition, prior adversity did not moderate the association between CU traits and either indicator of stress reactivity. Study Two tested whether cortisol and testosterone mediated the association between CU traits, reward and punishment sensitivity, and risk taking. Unfortunately, the study was underpowered and could not determine whether there was a direct or indirect association between CU traits, risk taking, or reward/punishment sensitivity. However, the study provided evidence that individuals with high CU traits exhibited the same pattern of testosterone reactivity as their counterparts. Taken together, the results of the two studies suggest youth with elevated levels of CU traits exhibit a pattern of stress reactivity that may contribute to their behavior. Future research should continue to explore the relation between stress reactivity, CU traits, and other aspects of antisocial behavi