Eva H. Telzer, Ph.D - US grants

PROJECT SUMMARY/ABSTRACT OBJECTIVE: Latino adolescents have higher rates of drug use and begin using drugs at an earlier age than other U.S. youth. Given the serious consequences of drug use, it is imperative to identify culturally relevant factors that can enhance the development of efforts to reduce drug use among this population. Familism is a specific type of family connection important to Latino families that implies children[unreadable]s role in the support and assistance of their family. Recent research suggests that familism is a culturally relevant protective factor against drug use among Latinos, but the mechanisms by which it functions are not well understood. Evidence from developmental neuroscience suggests that risk taking behavior increases during adolescence partly due to changes in the brain[unreadable]s neural circuitry. The cognitive control system, which is involved in self-regulation, develops more slowly relative to the socio-emotional system, which is involved in reward evaluation and sensitivity. This neural imbalance may hinder appropriate evaluation of risk and bias youth towards risky decisions. Familism may function by influencing these neural systems and their correlates to real-life risk taking. The proposed research will utilize a multi-method, longitudinal program of research, including daily diaries and functional magnetic resonance imaging (fMRI), to examine the neural mechanisms by which familism buffers Latino youth from drug use. This study will also examine how neural responses to risk taking predict behavioral changes in drug use behaviors over time. No previous studies have examined the role of culture on the neural correlates of risky behavior. METHOD: Thirty-two Mexican origin adolescents who have no history of drug use will complete a daily diary for two weeks examining their family assistance behaviors. Participants will then come in for an fMRI scan, in which they complete a family assistance and risk taking task. One year later, participants will complete measures of their drug use and risk taking behaviors. Analyses will examine the extent to which individual differences in family assistance (as measured during the daily diary) correlate with increased cognitive control and reduced reward system activity when making risky decisions during the risk taking task. In addition, analyses will examine whether the buffering effects of familism on neural sensitivity to risk taking predict changes in adolescents[unreadable] real-life risk behaviors including less drug initiation, association with risky friends, sensation seeking, and externalizing behavior.

? DESCRIPTION (provided by applicant): Risk taking underlies many behavioral and health problems that contribute to the public health burden during the adolescent period. Recent advances in developmental neuroscience have identified key neurobiological underpinnings of adolescent risk taking, but there is little understanding of how these neural processes interact with key social processes in order to promote or prevent risk taking. This is an important limitation given that adolescence is a period marked by increasingly complex social development, and adolescent decision making most often occurs under conditions of socio-emotional arousal. Thus, the time is ripe to examine how social contexts shape the neurobiology of adolescent risk taking. This study will examine how three important social influences - family, peers, and authority - shape neurocognitive development. Adolescents will complete two tasks during a functional magnetic resonance imaging scan during which social influence is manipulated. The data generated should reveal how brain function is modulated by social contexts during this important period of development. In order to understand whether changes in neural activation represent risk or protection for adolescent risk taking, a key aim is of the proposed research is to examine how brain changes co-vary with relevant behavioral changes over time. By connecting key social and developmental processes to the neurobiology of risk taking over time, this project has the potential to challenge and shift current research and unambiguously inform the model of adolescent brain development. A more nuanced understanding of how social contexts differentially modulate neurocognitive development and risk taking will help us to understand the situations that may hinder or promote successful decision-making, creating vulnerabilities or protection for risky behavior. By shedding light on the neural mechanisms supporting these linkages, findings from the proposed study may be useful in intervening with youth at risk for emotional, behavioral, or social difficulties. Relatedy, by investigating such processes as youth transition through puberty, project findings may highlight this developmental period as an effective point of entry for prevention and intervention efforts in deflecting upward trajectories of risk taking and problem behavior.

This project in developmental neuroscience examines the influence parents and peers exert on adolescents' willingness to engage in risky behavior at the neural circuitry level. Adolescent risk seeking behavior presents health and safety risks. This research has to potential to contribute significantly to national health and welfare by informing the design of effective interventions with youth at risk for emotional, behavioral, or social difficulties. This project has the potential to challenge and shift current research, update models of adolescent brain development, and ultimately inform the design of early interventions to prevent the rise in adolescent risk taking.

Risk taking underlies many behavioral and health problems that contribute to the public health burden during the adolescent period, such as substance use and externalizing behavior. Emerging evidence from developmental neuroscience suggests that risk taking behavior increases during adolescence partly due to changes in the brain's neural circuitry. Despite these advances, there currently is little understanding of how neurobiological development interacts with social processes during the adolescent period. This is an important limitation given that adolescence is a period marked by increasingly complex social development, and adolescent decision making most often occurs under conditions of socio-emotional arousal. With support from the National Science Foundation, Dr. Telzer will measure how family and peers differentially impact the neurobiology of adolescent risk taking. Adolescents will be scanned using functional magnetic resonance imaging (fMRI) as they engage in a risk taking task and cognitive control task alone, in the presence of a peer, and in the presence of their parent. Adolescents will be followed for one year to measure self-reported risk taking behaviors in order to examine whether social influence on neuro-cognition predicts longitudinal changes in real-world risk taking. Although self-reported intentions predict some variability in future risk taking behavior, self-reports are not sufficient to capture the multidimensional nature of risk taking, particularly among adolescents. The ability to prospectively predict future engagement in risk taking based on adolescents' current neural sensitivity can have profound effects on our ability to develop early prevention programs.

? DESCRIPTION (provided by applicant): Peer victimization is a salient form of early adversity with long-term costs for youths' mental health. Indeed, research and media coverage place peer victimization on the national agenda as a critical public health issue, given its prevalence and it implications for emotional well-being into adolescence and adulthood. Identifying processes accounting for these enduring effects is critical for informing policy and practice, yet scientists have not yet discovered the processes through which victimization derails youths' development-that is, how victimization gets under the skin in ways that instill long-term risk. Inspired by a growing recognition of the pervasive impact of early life stress on maturing brain systems and associated psychopathology, this research will contribute substantially to scientific knowledge and its application by documenting the adolescent sequelae of victimization, with broader implications for enriching our understanding of the mechanisms through which early adversity shapes stress reactivity and mental health. Integrating ideas across the fields of developmental and social psychology, social affective neuroscience, and developmental psychopathology with the NIMH RDoC framework, this research will examine whether victimization is linked to dysregulated negative valence systems involved in sustained threat/loss, thereby heightening reactivity and compromising regulation and contributing to adolescent depression. Introducing an innovative methodological approach into the field of peer victimization, this research will use a multi-level design, examining reactivity and regulation at both the neural and behavioral levels in the context of an experimental design (laboratory cues of social threat/loss). This study will take advantage of an existing sample of adolescent girls (10th-11th graders), well-characterized on victimization, individual differences in risks and resources, and mental health from 2nd-9th grade, thereby providing the opportunity to leverage a comprehensive longitudinal data set to enrich the proposed short-term (two-year) investigation of neural/behavioral processing and depressive symptoms. Thus, this study is uniquely positioned to examine the link between childhood victimization and subsequent neural and behavioral processing of social cues as well as to determine whether stress reactivity/regulation account for the contribution of victimization to adolescent depression. This research also will provide novel data on individual differences in risk and resilience processes, thereby maximizing the efficiency of prevention/intervention programs. Ultimately, it is anticipated that this researc will serve as a basis for larger longitudinal studies investigating: (a) how early adversity withina variety of contexts influences emerging brain systems in ways that set the stage for adolescent mental health problems; and (b) individual and contextual resources that may buffer youth against these adverse consequences. This line of research can yield clear and compelling implications for policy and practice guidelines aimed at minimizing the threat posed by early social adversity to youths' health and development, with potential implications for long-term adaptation and societal burden.

Early family relationships lay the foundation for children's successful development across the lifespan. One particularly important aspect of early family relationships is child-mother attachment security. A child whose attachment-related bids (e.g., clinging, crying) are consistently met with a timely and sensitive response by the caregiver will likely develop a secure attachment to that caregiver, whereas a child whose bids are met with rejection, hostility, or inconsistent responsiveness will likely form an insecure attachment. Variations in early attachment security play a role in 'sculpting' the brain of the developing child. Yet, we know little about the potential neurobiological mechanisms linking child-mother attachment to children's later adjustment. The goals of this research are twofold: (1) to examine how early child-mother attachment security (measured at age 2.5 years) relates to stress-related neural responses at age 13, and (2) test whether stress-related neural responses are associated with adolescent adjustment at age 14.

To carry out this work, participants will be recruited from an existing longitudinal study, the Children's Social Development Project (CSDP), in which child-mother attachment was assessed at 2.5 years. Ten years later, at age 13, mother-adolescent interactions will be observed and adolescents will be interviewed about current attachment relationships. Adolescents' neural responses in two stress-eliciting tasks will be assessed using functional magnetic resonance imaging (fMRI). At ages 13 and 14, adolescent adjustment in multiple domains will be assessed via self, maternal, and paternal reports. The proposed study will be the first of its kind to assess how child-mother attachment security in early childhood relates to stress-related neural processes and, in turn, adjustment in adolescence. Project findings have the potential to shed light on fundamental questions regarding how early experiences set the stage for later adjustment and will provide a much needed window into the extent to which typical variation in early human attachment predicts brain functioning in later development.

PROJECT SUMMARY Animal and human studies indicate that extreme forms of early life stress are implicated in structural and functional maladaptation in the brain during the early life course. At the same time, research on developmental psychopathology has indicated that early caregiving and development of insecure or disorganized attachment put children at risk for maladaptive behavioral and emotional problems. Thus, the roots of psychopathology likely take shape during this period of development in the context of transactions between the infant, caregiving environment, and developing brain architecture. Yet, we know little about the potential neurobiological mechanisms linking these transactional processes. Leveraging new methods for assessing infant brain via resting state fMRI and diffusion tensor imaging (DTI), this exploratory/ developmental project aims to explore how integration of neural networks over the first year of life vary as a function of caregiving processes and underlie differences in attachment security/insecurity at the end of the first year. In doing so, we will use longitudinal assessments and multimethod techniques to examine how the quality of infant-mother attachment contributes to intra-network and inter-network connectivity from 3 to 12 months using dynamic whole-brain data-driven approaches. At 3 and 12 months of age, infant scans will be conducted during natural sleep, and resting state functional MRI and DTI will assess changes in functional and structural large-scale network connectivity. At 3, 6, and 9 months, infant-mother interactions will be assessed via (a) an established paradigm that provides age-appropriate assessment of infant attachment-related behavior, and (b) new technology that enables collection of the infant's naturalistic home environment on a large-scale using an automated system that is reliable and valid. At 12 months, infant- mother attachment will be assessed via the gold-standard Strange Situation Procedure. By incorporating multiple levels of analysis across multiple time scales, our project will provide novel insight into transactions among maternal caregiving, infant behavior, and neural networks across the first year of life that underlie infants' attachment-related behavior and representations. Such innovation holds promise for conceptual advances in understanding the role of early caregiving environments in the development of early trajectories of brain and behavior, as well as potential applications for preventive intervention.

Project Summary/Abstract An alarming number of adolescents will engage in substance use (including alcohol, tobacco, marijuana and opioids) before they leave high school, a fact that has serious long-term health and societal impacts. Since most adolescents begin using substances with peers, an understanding of the processes that lead to peer influence susceptibility in the context of substance-using peers offers critical avenues for successful intervention in substance use. Our prior research developed a unique performance-based experimental paradigm for measuring peer influence susceptibility and found that individual differences in susceptibility interact with adolescents? perceptions of their peers? substance use to predict their own substance use engagement. However, it remains unclear why some adolescents are more susceptible to peer influence than others, and how development confers increased risk for susceptibility. This work will examine the neural correlates associated with individual differences in peer influence susceptibility. Specifically, we will assess how increased functional connectivity within and between neural networks subserving greater sensitivity to social rewards and punishments, motivation to attain rewards and avoid punishment, and representations of social others is associated with greater peer influence susceptibility. We will also examine a network involved in executive control as a protective factor against later substance use. Using a two-cohort, accelerated longitudinal design including adolescents spanning grades 6-12, we will investigate how individual differences in connectivity within and between candidate neural networks predict prospective substance use initiation in the context of peers. Eight hundred adolescents (age 11-13 years) will complete baseline assessments of substance use, and peer influence susceptibility using an innovative experimental paradigm. A subset (n = 250) of the initial sample will partake in longitudinal task-based functional imaging in year 1 and 3, as well as multi-wave longitudinal assessment occurring at one-year longitudinal intervals in subsequent years 2-5 to obtain extensive data on adolescents? and peers? substance use trajectories across a critical developmental period associated with substance use. By delineating the neurobiological markers of social influence susceptibility, project findings can characterize those individuals at greatest risk for substance use, which can inform interventions by targeting the psychological processes that contribute to peer influence susceptibility.