Richard J. Davidson - US grants

The research proposed in this application is designed to continue our studies of cerebral asymmetry and its relation to emotion and depression. Studies will be conducted on the relation between facial signs of emotion elicited by brief film clips and patterns of concurrently recorded brain activity. A methodological experiment will be performed during the first year of this project period which is designed to validate a procedure for removing muscle tension artifact from the ongoing EEG. The experiments which examine EEG during facial signs of emotion will broaden the range of emotions which have been studied. We will compare a negative emotion associated with withdrawal and one more commonly associated with approach (anger) in order to shed light on whether the basis for affective lateralization is hedonic tone or approach/avoidance. The role of facial expression in contributing to the EEG asymmetries associated with affect will be studied in order to more precisely specify which components of emotion are most directly reflected in scalp recorded brain activity. This will be accomplished by comparing EEG asymmetry in situations where facial signs of emotion and a measure of real-time self-report are consistent versus inconsistent. Asymmetries which differentiate between depressed patients and controls will also be explored. Differences between these groups in patterns of EEG asymmetry will be examined during resting conditions as well as in response to both cognitive and affective challenges. Relations between activation asymmetries in anterior and posterior cortical regions will be compared in these groups to replicate and extend our recent findings which suggest that depressed subjects show inverse relations between activation asymmetries in these regions. Differences between these groups in emotional response will be explored to determine whether elicitors which produce a range of different emotions in controls are more likely to produce sadness in depressed subjects. The groups will also be compared on EEG and self-report when facial behavior indicates that the same emotion is present, in order to determine, once an emotion is elicited, whether the pattern of EEG asymmetry and self-report is the same in these groups. The proposed studies will directly contribute to understanding emotion and affective disorders.

The major objectives of the research proposed in this application are: 1. to examine electrophysiological indices of cerebral asymmetry in subjects with several subtypes of depressive disorder and in bipolar patients when symptomatic and during remission; and 2. to determine whether resting measures of frontal and anterior temporal activation asymmetry predict vulnerability to drepressive disorders in a large unselected sample followed longitudinally for four years. In one experiment, Major Depressives and controls will be assessed initially on EEG measures of regional activation during rest and in response to short emotional film clips designed to elicit different discrete emotions. Self-report measures of emotional responsivity and measures of facial expressions of emotion will also be obtained in response to the film clips. Following this initial session, subjects will be tested at weekly intervals on resting measures of asymmetry and at an 8 and 16 week time point on EEG and behavioral responses to the film clips. Relations between changes in symptomatology over the course of the study and patterns of regional brain asymmetry at rest and in response to affective challenge will be examined. A second experiment calls for the study of depressive subtypes. Endogenous Major Depressives, Non-endogenous Major Depressives, Biploar depressed and Intermittent Depressed subjects will be tested in an experiment which examines resting EEG, EEG in response to emotional film clips and EEG in response to verbal and spatial cognitive tasks. Subjects will be tested at two points--when acutely depressed and 16 weeks later. The final experiment calls for the initial assessment of 300 unselected subjects on measures of resting activation asymmetry. Those falling at the upper and lower extremes, and those at the mid-point of the distribution on measures of frontal and anterior temporal asymmetry will be followed for four years. A diathesis/stress model of anterior activation asymmetries is proposed which argues that right-sided frontal and/or anterior temporal activation is assoicated with increased vulnerability to depressive symptomatology. Accordingly, depressive symptomatology in the extreme asymmetry groups will be assessed over the course of the study. Overall, the research proposed will advance our understanding of cerebral asymmetries related to depression and will provide important new information on the use of electrophysiological measures of regional activation asymmetries as markers of vulnerability to depressive disorders.

mood disorders; mental disorder diagnosis; behavior disorders; brain electrical activity; cerebral dominance; personality disorders; psychobiology; problem solving; emotions; neuropsychological tests; electroencephalography;

The research to be performed during the project period is designed to extend our studies on cerebral asymmetry, emotion and affective disorders. The research is based upon findings which indicate that l. the anterior regions of the two hemispheres are differentially activated during the experience/expression of positive and negative emotions associated with approach and withdrawal behavior respectively; and 2. individual differences in baseline anterior activation asymmetry predict emotional reactivity to affective challenges and are associated with affective and anxiety disorders. The proposed research will examine: brain electrical asymmetries associated with a range of different positive and negative emotions; individual differences in anterior asymmetries in normals and their relation to affective reactivity, personality and mood; anterior and posterior train electrical asymmetries in different sub-types of depressive disorders during the acute stage of illness and in remission; asymmetries in simple phobics prior to and after exposure therapy treatment; the effects of an opiate blocker on brain electrical asymmetries and behavioral manifestations of fear in phobics over the course of exposure therapy; and baseline and task-related asymmetries in young children selected at 30 months of age to be extremely wary and fearful or extremely uninhibited in a longitudinal study. The research proposed offers considerable promise in the identification of patterns of brain activity which index emotions associated with approach and withdrawal and vulnerability to affective and anxiety disorders.

emotions; startle reaction; cerebral dominance; brain electrical activity; neural information processing; conditioning; glucose metabolism; psychobiology; face expression; brain metabolism; amygdala; brain mapping; bioimaging /biomedical imaging; behavioral /social science research tag; clinical research; young adult human (21-34); electroencephalography; human subject; positron emission tomography; neuropsychological tests;

biomedical equipment purchase;

This is a request to establish a Center for Behavioral Sciences Research (CBSR) focused on social and psychobiological contributions to affective style at the University of Wisconsin-Madison. Affective style refers to the broad range of individual differences in emotion-related processes. We will approach the issue of affective style from a myriad of perspectives in four projects, supported by three cores. Project 1, will examine relations among patterns of regional brain electrical activity, regional glucose metabolism (assessed with positron emission tomography) and emotion-modulated startle in subjects selected on the basis of extreme left or right or symmetrical prefrontal or anterior temporal brain electrical activity measures. Another experiment will assess electrophysiological measures of regional brain activity and autonomic indices in the mothers and fathers of the twins to be tested in Project II. In Project II monozygotic and dizygotic twins will be assessed at 6 and 12 months of age on behavioral measurements of temperament. In addition, they will be assessed on electrophysiological measures of regional brain function, measures of heartrate and respiratory sinus arrthymia and activity in the hypothalamic-pituitary- adrenal (HPA) system via measures of salivary cortisol. In Project III the physiological correlates and biological substrates of behavioral inhibition will be examined in rhesus monkeys. Differences between extremely inhibited and less inhibited monkeys in activity in the HPA axis, autonomic activity and regional brain electrical activity will be examined. Differences in the acquisition and extinction of learned fearful responses will also be studied in the different groups. Autoradiography will be used to examine the density and distribution of benzodiazepine receptors and c-Fos techniques will be used to characterize the specific neural circuits that participate in responses to fearful stimuli. In Project IV data will be analyzed from an existing corpus available from the NIMH- funded Wisconsin Maternity Leave and Health Project. Videotaped interactions between mothers and infants at ages four and twelve months will be coded for quality of affective communication. The influence of maternal affective style on the affective quality of the exchange will be studied and the social mediators of this relationship (such as demographic characteristics, personal resources, social support) will be examined. A second study will investigate the impact of individual differences in infant temperament on the course of personality and depressive symptoms in the mothers. Social mediators of this relation will also be examined. These projects will be supported by Administrative, Behavioral Assessment and Biological Measures Cores. This Center will significantly advance our understanding of the social, psychological and biological bases of individual differences in affective style and yield important new information that will facilitate our understanding of disorders of emotion.

Project Summary/Abstract This application seeks five additional years of support for the training grant on emotion research at the University of Wisconsin-Madison. This training program continues to focus on four specific themes: 1. Personality, temperament and individual differences: Lifespan developmental, genetic, cognitive and biological approaches; 2. Affective neuroscience; 3. Emotion and health; and 4. Emotion and psychopathology. In this renewal, funds are requested for 5 pre-doctoral and 3 post-doctoral stipends/year, the same as our current funding. At the time of the last competing continuation, this training grant provided support for 7 pre-doctoral and 3 post-doctoral stipends/year. Since the time of the last competitive renewal, several additional faculty with research interests centrally in emotion have been added; the brain imaging facility has been strengthened?the Waisman Center Laboratory for Brain Imaging and Behavior?that is focused principally on affective neuroscience; the innovative Center for Healthy Minds has dramatically expanded, which focuses on contemplative neuroscience and its impact on positive affect; novel new data and research strategies have emerged from the NIMH-sponsored Conte Center here at Wisconsin; and several major collaborative projects focused on emotion in aging, various areas of affective neuroscience, and affective development have begun. There are now 17 program faculty, drawn from three academic units, with Psychology as the lead department. Pre-doctoral trainees will be supported for two years and post-doctoral trainees will be offered up to three years of support but will be encouraged to write their own post-doctoral training proposals during their initial year in the program to help leverage the funds we request from this T32. Major elements of the training program include: two 8-week course modules devoted to different aspects of emotion theory and research, focusing primarily on the four themes upon which the program is based, with Davidson and Goldsmith each teaching one module on a rotating basis; a Spring seminar each year associated with the Wisconsin Symposium on Emotion, an annual event at the University of Wisconsin-Madison that brings 5-6 outside speakers to campus for a meeting on a specific topic in emotion research; participation in a seminar series devoted to ethical issues in research; participation in periodic meetings of our NIMH-funded Conte Center that focus on the neural bases of individual differences in emotion regulation in adolescents; and participation in monthly emotion groups held in informal off-campus locations (e.g., restaurants) each month. We believe this program is unique and provides an extraordinary opportunity for interdisciplinary training in emotion research.

emotional adjustment; psychophysiology; brain electrical activity; injury /disease stressor; neuroendocrine system; electrophysiology; psychoneuroimmunology; longitudinal human study; rheumatoid arthritis; fibromyalgia; hippocampus; brain mapping; bioimaging /biomedical imaging; functional magnetic resonance imaging; female; behavioral /social science research tag; human subject; clinical research; women's health;

This Center will focus on mechanisms of mind-body interaction with an emphasis on emotion as a core intermediary level through which psychosocial influences and interventions exert their effects and thereby influence health. The Center builds upon the strength in research on emotion at Wisconsin. We conceptualize emotion as the key mediating variable through which social influences get transduced and impact upon the organism to influence autonomic, endocrine and immune function and thus effect health. Emotion is instantiated in elements of brain circuitry that have now been characterized. We highlight three regions-the prefrontal cortex, amygdala, and hippocampus-that play an important role in subserving emotion and in influencing other biological systems that have health-relevance. Project 1 will focus on later life resilience and vulnerability and will study psychosocial and biological processes in older women who have been followed through the major life transition of relocation. Project 2 will focus on well-being, symptom expression, endocrine and immune function in women with two musculoskeletal conditions, fibromyalgia (FMS) and rheumatoid arthritis (RA). In addition, this study will evaluate the impact of mindfulness meditation on emotion, symptom expression and immune and endocrine function in these patients. Project 3 will use samples from Projects 1 and 2 to study the functional neural circuitry of emotion (with fMRI), structural integrity of the hippocampus and peripheral psychophysiology of resilient and vulnerable individuals. In a second study, this project will also collect these measures in patients from Project 2 before and after they participate in the mindfulness meditation intervention, Project 4 will study the biology and behavior of free-ranging rhesus monkeys to predict their reactivity to the naturally occurring stress of leaving their natal group. Project 5 will evaluate the efficacy of a group exercise program in older women with breast cancer and will assess emotion-related constructs as well as endocrine and immune function to examine the mechanisms by which this intervention may have salubrious effects. Project 6 will investigate linkages among life course social inequities, emotion-related variables and adult physical health in the context of several large epidemiological surveys and longitudinal studies. These projects will be supported by Administrative; Statistics; Mind-self-report and interviews; and Body-biological measures, cores. We are ideally positioned to significantly advance our scientific understanding of the mechanisms of mind-body interaction.

DESCRIPTION: (Applicant's Description) Specific brain regions, such as the nucleus accumbens and ventral tegmentum, are implicated in drug motivation. However, little is known about the role of these regions in human smoking motivation and relapse. This pilot study will recruit 10 smokers (5 male) to participate in 4 experimental functional magnetic resonance imaging (fMRI) assessment sessions. The sessions will manipulate both withdrawal status (24 hr withdrawal or ad lib smoking) and motivational state (neutral vs. anticipation of smoking). The results will reveal the extent to which incentive brain system structures such as the nucleus accumbens are influenced by manipulations of smoking motivation. In addition, smokers will receive nicotine replacement therapy (NRT-combined nicotine patch and nicotine nasal spray) prior to one of the sessions. This will indicate whether common smoking cessation treatments actually reduce activity of incentive system structures when smokers anticipate smoking. Finally, smokers will be exposed to non- pharmacologic incentive stimuli. This is one test of the notion that nicotine withdrawal reduces incentive system activity and thus, reduces pleasurable anticipation in response to non-drug incentives. These findings will make an important contribution to scientific understanding of the mechanisms of effective smoking cessation treatments and contribute to basic scientific understanding of motivation and addictive processes. Finally, they may provide clues to the vital clinical problem of preventing relapse following smoking cessation treatment.

This project builds upon previous work by the PI and others indicating that asymmetrical prefrontal activation derivedfrom brain electrical activity recordings is associated with both psychological and biological indices that reflect affective style. We have found that subjects with greater left prefrontal activation report more dispositional positive affect, have lower levels of basal cortisol, recover more quickly from a laboratory stressor and show higher levels of antibody titer following vaccination with influenza vaccine. During this grant period, we propose to test 400 MIDUS respondents on measuresof brain electrical activity under both baseline conditions and in response to affective stimuli. In addition, using emotion-modulated startle, we will assess startle modulation before, during and after the presentation of positive, negative and neutral pictures to derive indices of affective chronometry, or the time course of emotional responding. Brain electrical activity measures will be analyzed using both conventional spectral power estimates as well as source localization procedures. We predict that subjects with greater left prefrontal activation will show faster recovery following negative challenge. These individuals are also predicted to have lower cortisol (both basal and in response to challenge), lower levels of IL-6 and higher levels of psychological well-being. Analyses will also be conducted to ascertain the impact of cumulative adversity on these biological indices and to determine the extent to which measures of adversity account for variance in brain function and emotion-modulatedstartle over and beyond variance accounted for by contemporary measures of mood and well-being. The data from this project will provide significant clues to understanding the central mechanisms through which cumulative adversity and psychological well-being are instantiated in the brain and affect peripheral biology in ways that may be consequential for health.

DESCRIPTION (provided by applicant): This project will use magnetic resonance imaging (MRD to obtain high resolution information about the morphometry of particular brain regions implicated in emotion and emotion regulation and their levels of functional activation in a biological subsample of WLS respondents. Respondents will undergo functional and structural MR imaging, along with brain electrical activity measures. The circuitry that will be featured will include the amygdala, hippocampus and different territories of the prefrontal cortex (PFC). Each of these structures has been implicated in different aspects of emotion and emotion regulation and is part of the central circuitry that is likely crucial for understanding how cumulative psychosocial burden can have deleterious effects upon health. For example, the hippocampus plays a crucial role in the regulation of the hypothalamicpituitary-adrenal axis and high levels of glucocorticoids have been implicated in hippocampal atropy. The failure to modulate emotion in a context-appropriate fashion is likely a consequence of hippocampal dysfunction. In addition to the hippocampus, the amygdala and prefrontal cortices are other key structures in the circuitry of emotion regulation and also play an important role in regulating peripheral biology that may be consequential for health. This project will utilize functional and structural MRI along with high-density electrophysiological measures to makes inferences about the structure and function of this circuitry in a subsample of WLS respondents. These measures of brain function and structure will be related to indices of advantage and adversity as well as measures of affect, mental health and physical health. The data will provide the most comprehensive examination to date of the relations between the central circuitry of emotion in the aging brain and physical and mental health.

The broad goal of this project is to examine the brain circuitry underling emotion in autistic and comparison subjects. In response to previous reviews, we now restrict data collect to the Wisconsin site. All studies will involve functional magnetic resonance imaging (fMRI) during tasks designed to probe different aspects of affective function. In addition, all studies will also use eye tracking in the scanner to ascertain precisely where subjects are fixating during stimulus presentation since some of the extant neuroimaging data in autistic subjects are assumed to be a function of the fact that autistic subjects are exhibiting gaze aversion and not foveating the stimuli to the same degree as controls. Since the last submission, we have collected pilot data on 8 participants with autism and 10 controls illustrating our capability for measuring gaze patterns in the scanner, recording electrodermal activity in the scanner and successfully collecting fMRI data. In each of the proposed studies, analyses will be conducted on all trials, as well as restricted to only those trials during which subjects are fixating on the stimuli. Aim 1 is to test the hypothesis that when fixating on social stimuli (e.g., faces) autistic subjects will show increased activation in the amygdala and increased electrodermal activity. Aim 2 will test the hypothesis that autistic subjects will show more fixation to non-social positive stimuli while controls will show more fixation to social positive stimuli. In circuitry associated with positive affective responding such as the ventral striatum, we predict that autistic subjects will show the greatest activation in response to ideographic non-social stimuli while controls will show the greatest activation to ideographic social stimuli. We predict that autistic subjects will show greater activation in the amygdala and other regions associated with negative affect in response to social vs non-social stimuli while controls will not show amygdala activation in this contrast. Aim 3 will use a task that involves the presentation of congruent and incongruent faces and voices. We predict that autistic subjects will show less activation in the anterior cingulate cortex in response to the incongruent conditions compared with the congruent conditions relative to controls. We will also test a sample of children with social phobia to use a second comparison group to ascertain the extent to which the deficits observed for autistic subjects are specific to this population.

brain morphology; functional magnetic resonance imaging; emotions; brain imaging /visualization /scanning; brain mapping; magnetic resonance imaging; psychological aspect of aging; hippocampus; amygdala; prefrontal lobe /cortex; longitudinal human study; bioimaging /biomedical imaging; behavioral /social science research tag; human subject; clinical research;

Budgets; Communication; Ethics Committees, Research; Faculty; Funding; Human Resources; IRBs; Institutional Review Boards; Manpower; Postdoc; Postdoctoral Fellow; Protocol; Protocols documentation; Records; Reporting; Research Associate; Research Ethics Committees; SCHED; Schedule; Students; Training; Travel; personnel; post-doc; post-doctoral

The overarching purpose of this project is to further our understanding of the neural circuitry underlying the regulation of negative affect, with a focus on prefrontal cortex (PFC), anterior cingulate cortex (ACC) and amygdala. Variations in affective style are assumed to be based in large part on variations in the capacity or skill to regulate emotion. A series of functional magnetic resonance imaging (fMRI) studies are proposed to examine basic neural mechanisms of voluntary emotion regulation in response to both emotional picture viewing as well as to a paradigm that elicits anticipatory anxiety. Individual differences in the functional neuroanatomical substrates of emotion regulation will be examined and relations with electrophysiological measures of prefrontal activation asymmetry and with startle probe measures of emotion regulation will be determined. We will also examine the extent to which regulatory skill evidenced in response to phasic stimuli in an acute laboratory paradigm are related to regulation of cortisol in response to the Trier Social Stress Test administered on two occasions. Finally two experiments with samples derived from Project V (adolescents are varying risk for internalizing disorders) and Project IV (MZ and DZ 7-9 year old twin pairs) will be conducted. One of these studies will utilize the same emotion regulation to determine whether adolescents selected to be at risk for internalizing disorders differ in their patterns of PFC, ACC and amygdala activation and other study will continue our psychophysiological analysis of temperament in MZ and DZ twins. The experiments in this project will collectively advance our knowledge of the neural basis and physiological concomitants of affective styles that are associated with vulnerability to psychopathology and will facilitate the early detection of risk for mood and anxiety disorders.

DESCRIPTION (provided by applicant): This application requests five years of funding to establish an Interdisciplinary Behavioral Science Center for Mental Health (IBSC). Our Center builds upon our previous Center for Behavioral Sciences Research and is focused on affective style--consistent individual differences in particular parameters of emotional reactivity and affect regulation. Why some individuals respond especially intensely and persistently to negative events while others appear considerably more resilient, is a question of profound significance to understanding vulnerability to psychopathology. Each of the projects in this Center is focused on different, but related aspects of affective style. Each of the projects converge toward an understanding of the behavioral, neural and hormonal substrates of vulnerability toward mood and anxiety disorders, with a focus on understanding the interconnected roles of different territories of prefrontal cortex, anterior cingulate cortex, amygdala and the hypothalamic-pituitary-adrenal axis (HPA) in these processes. The Center is comprised of five projects and three cores. The projects are focused on different populations including normal adults, adults at putative risk for mood and anxiety disorders based upon biological indices that reflect emotion regulation, adolescents at risk for internalizing disorders, MZ and DZ twin children well-characterized with behavioral and other measures of temperament, and rhesus monkeys also selected to differ on temperamental features that are likely to confer risk for psychopathology. The twin and adolescent samples are tested across multiple projects in both behavioral and MR imaging protocols. There are many common behavioral (supported by a Behavioral Assessment/Clinical Diagnosis Core) and biological measures (supported by a Biological Measures Core that includes MR and microPET imaging, neuroendocrine measures and psychophysiological measures) across the projects. The science proposed will significantly advance our understanding of the neural and behavioral substrates of affective style and this new knowledge will aid in the prediction, prevention and treatment of mood and anxiety disorders.

[unreadable] DESCRIPTION (provided by applicant): This is a competing continuation of R37-MH-43454 which received a MERIT award at the time of its last competitive renewal. This application seeks five additional years of support to continue the PI's research program on the neural substrates of affective style and emotion regulation. Individual differences in affective style and emotion regulation determine variation in stress responsivity and vulnerability to mood and anxiety disorders. The broad goal of this application is to further understand the neural circuitry that underlies individual differences in emotion regulation and to determine the nomological network of associations with these individual differences. Work is proposed that also extends this work to patients with major depression to further our understanding of the nature of emotion regulation abnormalities in this disorder. In the first study, a large sample of community volunteers will be tested using peripheral psychophysiological measures (startle and corrugator EMG) to characterize relations between individual differences in emotional reactivity and emotion regulation and to select individuals showing stable and extreme profiles on these measures for subsequent intensive study. In follow-up studies with these selected extreme groups, fMRI studies of neural circuitry underlying voluntary regulation of emotion in response to both negative and positive emotional pictures and to thermal pain will be evaluated. In addition, these individuals will undergo two Trier Social Stress Tests (TSST) to examine cortisol response and habituation to psychosocial stress. In addition, behavioral measures of cognitive and affective conflict processing will be obtained. Structured clinical interviews will be conducted on parents of probands to examine family history of psychopathology in the extreme groups. Finally, an independent sample of patients with major depression and matched controls will be scanned using the identical paradigms for the assessment of the voluntary regulation of affect to examine how abnormalities in the circuitry of emotion regulation are related to heterogeneity of symptoms in depression. This work will provide critical new information on the neurobiology of affective style. These new data will further our understanding of endophenotypes of affective processing that are associated with vulnerability to psychopathology. [unreadable] [unreadable] [unreadable]

[unreadable] DESCRIPTION (provided by applicant): This is a competing continuation of R37-MH-43454 which received a MERIT award at the time of its last competitive renewal. This application seeks five additional years of support to continue the PI's research program on the neural substrates of affective style and emotion regulation. Individual differences in affective style and emotion regulation determine variation in stress responsivity and vulnerability to mood and anxiety disorders. The broad goal of this application is to further understand the neural circuitry that underlies individual differences in emotion regulation and to determine the nomological network of associations with these individual differences. Work is proposed that also extends this work to patients with major depression to further our understanding of the nature of emotion regulation abnormalities in this disorder. In the first study, a large sample of community volunteers will be tested using peripheral psychophysiological measures (startle and corrugator EMG) to characterize relations between individual differences in emotional reactivity and emotion regulation and to select individuals showing stable and extreme profiles on these measures for subsequent intensive study. In follow-up studies with these selected extreme groups, fMRI studies of neural circuitry underlying voluntary regulation of emotion in response to both negative and positive emotional pictures and to thermal pain will be evaluated. In addition, these individuals will undergo two Trier Social Stress Tests (TSST) to examine cortisol response and habituation to psychosocial stress. In addition, behavioral measures of cognitive and affective conflict processing will be obtained. Structured clinical interviews will be conducted on parents of probands to examine family history of psychopathology in the extreme groups. Finally, an independent sample of patients with major depression and matched controls will be scanned using the identical paradigms for the assessment of the voluntary regulation of affect to examine how abnormalities in the circuitry of emotion regulation are related to heterogeneity of symptoms in depression. This work will provide critical new information on the neurobiology of affective style. These new data will further our understanding of endophenotypes of affective processing that are associated with vulnerability to psychopathology. [unreadable] [unreadable] [unreadable]

[unreadable] DESCRIPTION (provided by applicant): This project will examine the impact of two different forms of meditation training on aspects of emotion regulation. One form of meditation is specifically designed to prime and enhance qualities of compassion and loving kindness. Another form of meditation-mindfulness meditation-is said to alter an individual's relationship with his/her emotions so that the individual is less identified with them and they are less likely to perseverate. A major goal of this project is to investigate the impact of these forms of mental training on emotional reactivity and regulation. This goal will be realized by the investigation of two primary samples: 1. Individuals undergoing a standardized program of 8 weeks of mindfulness-based stress reduction (MBSR) that includes training in loving-kindness and compassion; and 2. individuals who are expert meditators with daily meditation practices of at least 30 minutes/day for 10 years that include both lovingkindness/ compassion and mindfulness meditation. Among this latter group of participants, we will conduct assessments on three occasions: an initial testing session without preceding meditation; after an intensive day of 10 hours of practice of compassion/loving-kindness meditation; and after an intensive day of 10 hours of practice of mindfulness meditation. Assessment of the MBSR group will be longitudinal since we can obtain assessments before and after the training is presented. A four-month follow-up period will also be included for the MBSR group. We will also use a highly structured, very well-matched comparison group for the MBSR group, one that we have termed the Health Enhancement Program (HEP) that is matched on hours of contact, daily practice, class structure etc., but that does not include a mindfulness or lovingkindness/compassion component. Participants from each of these samples will be tested in laboratorysessions conducted over the course of two days to assess the impact of loving-kindness/compassion meditation and mindfulness meditation on reactivity to and recovery from emotional pictures that depict human suffering. Peripheral physiological reactivity and recovery will be measured with startle and facial electromyography and the neural circuitry associated with reactivity and recovery will be assessed with functional magnetic resonance imaging (fMRI). We will also investigate the impact of these different forms of meditation on cortisol reactivity to the Trier Social Stress Task (TSST) and examine relations between changes in the brain produced by the meditation practices and changes in response to the TSST. Finally, relations between measures obtained in this project and in Projects 2 and 3 will also be assessed. [unreadable] [unreadable] [unreadable]

This project will examine the neural bases of emotion regulation and dysregulation in samples of adolescents selected on the basis of their risk status for internalizing disorder. Adolescent is a period during which risk for anxiety and mood disorders increases substantially and little is known about the brain mechanisms responsible for vulnerability to these disorders. We will take advantage of extensive data collected within two longitudinal cohorts that will be a central feature of this Center. From these cohorts, three samples will be tested. One sample consists of 85 individuals from Project 2 who underwent fMRI scanning using virtually the identical tasks when they were 14 years of age. A second sample, also derived from Project 2 (Essex), will include participants who will be selected to vary in levels of basal cortisol early in life (age 4.5 years) and later in early adolescence. In another cohort derived from Project 3 (Goldsmith) monozygotic and dizygotic twin pairs will be selected in which one member of the pair has high levels of internalizing symptoms. Both concordant and discordant pairs will be selected in this manner. All participants will undergo a scanning session during which functional MRI will be obtained while participants engage in two tasks. One task will assess the neural correlates of both voluntary and automatic emotion regulation while the other task will be a face go-no-go task that assesses sensitivity to different facial expressions of emotion and inhibitory control in the face of emotional distracters. During scanning, electrodermal and pupillary measures will be obtained, in addition to eye tracking. In addition, participants will be administered an automated version of a task designed to assess working memory capacity (O-span) to ascertain the relation between individual differences in working memory capacity and emotion regulation. We will test the hypothesis that adolescents selected to be vulnerability to internalizing disorders (either because of cortisol profiles or symptoms of anxiety) will exhibit evidence of the poor emotion regulation expressed as high levels of amygdala activation and low levels of activation in ventromedial prefrontal cortex during instructions to down-regulate negative affect. A similar pattern is expected during the task phase designed to assess automatic emotion regulation. The face go-no-go task will allow us to test the hypothesis that adolescents at increased risk for internalizing disorders will show increased sensitivity to fear and angry faces and show a more conservative response bias (inhibiting their response to faces other than the target);moreover these individuals are predicted to show increased activation in the right inferior frontal gyrus, a region in which we have previously found to correlated with social anxiety. The findings from this project will provide novel new evidence on the neural bases of emotion regulation and dysregulation in adolescence and will showcase the role of these processes in vulnerability to anxiety and mood disorders.

This Center seeks support for a major program of highly interdisciplinary research at the University of Wisconsin-Madison that uses an affective neuroscience perspective to further our understanding of the underlying neural and behavioral bases of risk for anxiety and mood disorders (internalizing disorders), with a specific focus on the adolescent period. Adolescence is a period of extraordinarily increased risk for these disorders and it is also a period during which dramatic maturational and experience-induced alterations in brain function and structure take place. Moreover, epidemiological evidence indicates a 2-3 fold increased risk in adulthood for these disorders if an individual had a diagnosis as an adolescent. Through a highly integrated and collaborative program of research in non-human primates and humans that involves five PI's all on the faculty at UW-Madison, this Center will produce novel new data over the next five years on the brain mechanisms and behavioral, endocrine and autonomic correlates of individual differences in emotion regulation and emotional reactivity. A major focus will be on early life predictors of adolescent brain circuits that underlie the regulation of emotion and abnormalities in these circuits in individuals vulnerable to internalizing disorders. The research strategies will also permit the examination of relations between early diatheses and later vulnerability in adolescence since longitudinal data are available in both human cohorts. In the non-human cohort, an explicit manipulation of early stress will be performed. The Center will also provide new strategies for parsing the heterogeneity of anxiety and mood disorders using profiles of brain function and structure. Each of the PIs involved in this Center have a long history of collaboration. There are many two, three and four way collaborations among the PIs. All have published with at least one other PI and many have published with many of the Center PIs. Each of the projects involves the collaborative involvement of all of the PIs. This overall program of work is critically dependent upon this entire team and the scope of the work and the multiple levels of analysis would only be possible within a Center. This team is highly experienced, has a demonstrated record of working well together, has been extraordinarily productive in the past, and promises to produce novel insights about the neural and behavioral bases of adolescent internalizing disorders that will directly inform diagnosis and treatment.

The Administration Core will serve all Center projects. The core will coordinate and facilitate the work of each project and core through monthly meetings, PI administrative meetings and meetings with individual Pis. In addition, the Core will coordinate public outreach and dissemination activities of the Center by creating a Center website and maintaining the site. The Administration Core will also coordinate training activities within the Center and will interface with four existing T32's from which trainees will be drawn to work on Center-related research. The Administration Core will also plan and implement the Undergraduate Summer Research Program and the Summer Workshop to be held in conjunction with the Summer Research Program. The Administration Core will coordinate meetings of the Scientific Advisory Board of the Center. Finally the Administration Core will provide advice and support to Pis of the Center for all administrative issues including budgeting, personnel and IRB issues. The most important method to be used by the Administration Core to accomplish these aims is excellent and frequent communication with all Center Pis and staff, and with University offices and extramural entities of relevance to the Center. We have outstanding staff to insure that these goals can be effectively accomplished.

The IDDRC Brain Imaging Core was established in 2001, is central to the integration of behavioral and neuroscience research at the Waisman IDDRC, and is a key component of our translational research efforts. The Core is housed on the first and second floors of the Waisman Center North Tower. Since the Core was established, it has grown significantly. Among the major infrastructure improvements during the past five years has been the acquisition of a new 3T MRI scanner (GE MR 750) to replace our original GE 3T system. In addition, during the past five-year project period, we replaced our PET scanner with a Siemens ECAT EXACT HR+ PET scanner for human PET studies (now a research-only dedicated PET scanner), and expanded our capacity for image analysis and training. The Core was rated as outstanding in the most recent competitive review. One unique feature is that the Brain Imaging Core is housed in the Waisman Center building and is an integral component of the IDDRC. The Core gives priority to IDDRC investigators, who do not have to share scanner time with clinical use, as the Brain Imaging Core scanners (MRI, PET) are devoted 100% to research. As a result, there have been significant scientific accomplishments during the past five years.

The primary goal of Project V of the MIDUS Refresher is to add to our sample size so that we can examine the neural bases and psychophysiological expression of individual differences in emotional reactivity and regulation and determine how these processes vary with age, SES, gender, ethnicity and economic adversity. Fundamental mechanisms of emotional reactivity and emotion regulation underlie a substantial portion of the variance in both vulnerability to psychopathology and resilience. For the first time, with the additional sample size afforded by the MIDUS refresher cohort, we can determine age, SES, gender and ethnicity differences in these processes using psychophysiological and imaging measures. The protocol to be utilized is based upon our MIDUS II procedures and involves two laboratory sessions, one during which psychophysiological measures are obtained and the second during which structural and functional MRI measures are collected. A number of extremely promising findings have emerged in the MIDUS II data, including new findings on relations between measures obtained in this project and every other project in MIDUS 11, but limitations of sample size preclude a systematic examination of age, SES, gender and ethnicity as contributing factors in modulating these critical features of brain function and structure. We propose to add 200 respondents from the MIDUS refresher cohort in the Wisconsin region, approximately 67 of whom will be African-Americans from the Milwaukee area. Based upon our currently available data, we hypothesize that age, gender and ethnicity will contribute importantly to variation in mechanisms of emotional reactivity and emotion regulation. These new data will add highly novel information to our understanding of the brain bases of emotional reactivity and emotion regulation and will help to provide mechanistic insights concerning how psychosocial factors might actually modulate brain function in ways that affect peripheral biology and ultimately health.

The impact of meditation on the regulation of emotion is perhaps the most salient effect of meditation for the average practitioner. Yet the mechanisms responsible for these alterations are pooriy understood and the consequences of these changes have not been characterized. The purpose of this project is to examine the impact of these two forms of meditation on the neural, biobehavioral and hormonal correlates of emotion regulation among naive practitioners who learn Mindfulness-Based Stress Reduction (MBSR) and among Long-Term Meditators (LTMs). The MBSR group will be compared with our rigorous comparison intervention, the Health Enhancement Program (HEP) and to Wait List (WL) controls. Both of the active groups will be administered booster training following the completion of the 8-week course to maximize consolidation of learning and increase the amount of practice. These groups will be tested before and after training. The LTMs will be studied on three occasions: once with no practice period prior to testing, once after an intensive day of MM practice and once after an intensive day of LKM-CO practice. Participants will be tested on an emotion regulation task in the scanner during which four conditions will be randomly interspersed across blocks: MM, LKM-CO, relaxation and listening to music. The task will consist of the presentation of pictures depicting human suffering (negative) or human flourishing (positive) while participants engage in one of the four regulatory conditions. Facial electromyography (fEMG) will be recorded from corrugator and zygomatic muscle regions in the scanner to provide real-time online objective measures of emotion during the regulation conditions. Saliva will be collected for three consecutive days, three times/day just prior to each lab visit to provide measures of Cortisol and total Cortisol output to relate to the fMRI measures. We predict that MM will primarily impact fronto-amgydala circutiry and LKM-CO will impact fronto-striatal circuitry and that these neural changes will have downstream biobehavioral effects on reports of daily mood, Cortisol and immune measures collected in this and the other two CERC projects. RELEVANCE (See instructions): This project will provide unique new information on the mechanisms by which two of the most commonly taught meditation practices work. The downstream biobehavioral consequences of these practices will be examined and relations between practice time, changes in brain function and alterations in behavior and peripheral biology will be explored in analyses examining relations among measures across projects.

There is growing interest in the effects of meditation practices on health. Meditation targets the practitioner's brain/mind, with subsequent positive effects on bodily functions. However, there is great need for rigorous studies that establish if meditation does indeed produce long-lasting changes in the brain, what these changes may be, and their functional significance for healthy subjects in daily life as well as in clinical populations. Project 1 of the Center Proposal aims at demonstrating effects of meditation training on behavior as well as on neurobiological markers related to emotion and emotion regulation. Project 2 will evaluate the effects of meditation training on inflammatory markers and its potential benefits in a clinical population with asthma, a typical inflammatory disease. This project (Project 3) aims at establishing the functional significance of our previous observation of meditation-induced changes in electroencephalographic (EEG) activity during sleep for brain activity and cognitive functioning during wakefulness. In the previous NCCAM project we found that long term meditators had an increase in EEG gamma activity during non rapid eye movement sleep as compared to meditation naive individuals. This increase was specific for the gamma range, and correlated with the length of meditation practice. We will evaluate if this increased gamma activity during sleep in long term meditators is associated with changes in sleep mentation (a change in the occurrence and cognitive aspects of dream reports). We will also evaluate if meditation-induced changes in brain activity during sleep are associated with changes in brain activity and cognitive function during wakefulness. We will then assess whether the differences in brain activity patterns and cognitive function observed in long term meditators can be induced in meditation naive individuals after intense 8 week meditation training, enhanced by post-training meditation boosters. Finally, we will assess the general significance of our findings for health, by correlating meditation-induced brain activity changes with inflammatory markers in a population of asthmatic patients.

This Center consists of three highly coordinated projects, conducted on the identical participants (Ps) and supported by a Recruitment and Phenotyping Core. Pis have substantial neuroscientific expertise, enjoy historical and current research collaborations, and direct major laboratories with substantial infrastructure. These will be harnessed to make significant progress on a neuroscientific understanding of meditation by collecting measures allowing the synthesis of neuroimaging, behavioral (emotion regulation, stroop, breath counting, working memory, affective Go/No-go, attentional blink), immune (white blood cell counts and inflammatory cell differentials), autonomic nervous system functioning, sleep (PSG with high-density EEG, EMG, EOG, leg EMG, EKG, pulse oximetry, airflow, respiratory effort, position and video, dream reports, and Mismatch Negativity paradigm given during non-REM sleep), questionnaire (including mental health symptoms, compassion, mindfulness, medical symptoms, sustainable well-being, and ecological footprint), and interview data (interviews with study Ps' significant others will provide third-person reports on compassion and mindfulness). The Core will recruit, screen and schedule Ps for all three projects, including: (1) Long-term meditators (LTM; n=40); (2) Meditation naive Ps (MNP) diagnosed with asthma (MNP-A; n=80), a clinical sample with relevance for inflammatory processes as well as mental health risks; and (3) Meditation naive Ps without asthma (MNP-NA; n=120). After completion of T l measures, all MNPs will be randomized to either MBSR, HEP (an active comparison group that we pioneered), or a wait-list control group (WL). The WL group will serve as a control for MNPs in HEP and MBSR as well as LTMs. MNP-As will be randomized to either MBSR or WL. All Ps will be assessed on measures for all three projects at two time points, pre- (Tl) and post-intervention (T2) for MNPs with a third time point (T3) for LTMs and WL. Instead of being assigned an intervention, LTMs will be randomized to 3 days (23 hours total) of either mindfulness or loving-kindness-compassion practice at T2 (with the alternate practice type at T3).

DESCRIPTION (provided by applicant): Childhood anxious temperament (AT) is a key risk factor for developing anxiety and co- morbid depression. In primates, AT is evident early in life, stable, and associated with increased threat reactivity. Early adversity is known to increase the risk of developing extreme AT. While adversity is common, the neural mechanisms linking it to AT are not understood. This understanding would permit identification of novel therapeutic targets with the potential for developing neuroscientifically-informed interventions. This proposal builds on work validating the AT phenotype and identifying the neural circuit underlying AT. Recent microarray and RNA sequencing (RNA-seq) work suggests the hypothesis that extreme AT reflects neuroplasticity deficits in the lateral division of the central nucleus of the amygdala (CeL), a key regulator of amygdalar outflow to regions that give rise to signs of anxiety, and the region most predictive of AT in our imaging work. This proposal aims to understand how peer rearing (PR), a controlled early adversity manipulation, causes extreme AT in primates, something not possible in human studies. The use of primates increases the likelihood that discoveries will translate to at-risk children. PR and maternally- reared (MR) animals will be longitudinally assessed, testing adversity's impact on the development of AT. Repeated multimodal imaging will assess adversity's impact on the development of amygdala reactivity and prefrontal-amygdala anxiety regulation circuits. Importantly, the primate model affords an opportunity to test whether adversity's harmful effects on AT are mediated by alterations in CeL neuroplasticity pathways. Immunohistochemical and RNA-seq analyses will be performed on CeL microdissected neurons. This novel synthesis of tools promises new insights into how adversity-induced molecular alterations manifest in brain function, connectivity, and structure, and how these macroscopic changes contribute to extreme AT- insights not readily available from molecular-level rodent or systems-level human studies. Further, a stem cell model of CeL GABAergic neurons will be created and compared to neurons from CeL. A valid stem cell model would enhance understanding of AT's molecular bases and accelerate the screening of new therapeutics.

In previous research we found that early adversity and early measures of anxious temperament predict adolescent brain function and structure. Since our scans were obtained in adolescence, we do not know whether the brains of our participants were similar early on and then only through repeated exposure to adverse life events were altered to express the functional and structural changes we have observed, or whether neural differences are present early in life. The answer to this question will have critical import for the development of early interventions and in understanding the neurodevelopmental origins of psychopathology. To address this question we will conduct a longitudinal imaging study of participants from birth through age 2 years. Families will be identified during the third trimester of pregnancy. We will begin with a total of 180 participants and infants will be scanned at age one month and at two years. At one month of age we will obtain anatomical, DTI and resting state scans. Between these ages, extensive behavioral assessment of the families will be conducted. At 2 years of age, we will add a short functional task consisting of the presentation of emotional sounds to assess reactivity to and recovery from emotional stimuli. The functional and structural measures at 1 and 24 months of age will be related to behavioral and clinical measures obtained at one, six, 12 and 24 months of age. In addition, we will examine relations with maternal symptoms and psychopathology and with measures of Cortisol at one month and two years of age. Our general prediction is that less connectivity between ventromedial prefrontal cortex and amygdala, greater amygdala volume and less fractional anisotropy in cortico-limbic tracts at one month of age will be associated with increased behavioral measures of AT at later ages. In addition, higher levels of adversity between 1 and 24 months will be associated with more extreme deviations in these measures. These findings will shed new light on neurodevelopmental origins of childhood anxiety and can lead to the development of new preventative interventions that are focused on these neurodevelopmental targets.

This project will investigate the efferent pathways, from brain to periphery, through which psychological factors contribute to the expression, severity and management of inflammation in asthma. In addition, it will establish the efficacy of mindfulness-based stress reduction (MBSR) training in reducing the lung function impairment and inflammation associated with exposure the allergen in asthmatic individuals by reducing the reactivity of emotion-related neural circuitry. We will recruit asthmatic individuals with a dual response to allergen exposure, who will be randomized to either MBSR training or to a wait-list control group. Participants will undergo an inhaled allergen challenge and provide measures of pulmonary function and asthma-relevant inflammation pre- and post-intervention. In addition, fMRI data will be collected during the hour preceding the onset of the late-phase response. This timing was designed to detect neural signals that may influence the development inflammation that underiies the late-phase fall in lung function. During fMRI data collection, participants perform a variant of the Stroop Task, where they identify the color of letters spelling asthma- related (e.g. wheeze), generally negative (e.g. loneliness), or neutral (e.g. curtains) words. This design is based on our prior work showing increased activation in affective neural circuitry, specifically to disease- related cues, in the context of allergen challenge. This increased responsivity predicted the lung function decline and inflammation associated with the late-phase response that would occur several hours later. The current design allows up to specifically target the efferent pathways in this bi-directional relationship, by employing an intervention focused on cognitive and emotional processes. In so doing, we have the potential to identify an entirely new domain of disease management strategies, such as neurofeedback, geared at reducing responsivity in specific neural circuits to impact the function of peripheral disease processes. Thus, our proposed project represents a new paradigm in asthma and holds the promise to better understand the complexity of this disease, its regulation, and ultimately to provide for more effective treatment. RELEVANCE (See instructions): Asthma currently represents and enormous public health burden, affecting more than 10% of the population in the U.S., and costing tens of billions of dollars in healthcare and leading to tens of millions of missed days of work. Current treatment strategies are expensive and not fully effective in some individuals. Given the evidence suggesting that psychological factors contribute substantially to asthma symptom expression, an intervention that addresses this influence on asthma exacerbation is missing from the current toolbox.

PROJECT SUMMARY (See instructions): The Administration Core will serve all Center projects. The core will coordinate and facilitate the work of each project and core through monthly meetings, PI administrative meetings and meetings with individual Pis. In addition, the Core will coordinate communication with UNC colleagues who are part of the Imaging Core. This Core will also coordinate the public outreach and dissemination activities of the Center by creating a Center website and maintaining the site. The Administration Core will also coordinate training activities within the Center and will interface with three existing T32's from which trainees will be drawn to work on Center-related research. The Administration Core will also plan and implement the Undergraduate Summer Research Program and the Summer Workshop to be held in conjunction with the Summer Research Program. The Administration Core will coordinate meetings ofthe Scientific Advisory Board ofthe Center. Finally the Administration Core will provide advice and support to Pis of the Center for all administrative issues including budgeting, personnel and IRB issues. The most important method to be used by the Administration Core to accomplish these aims is excellent and frequent communication with all Center Pis and staff, and with University offices and extramural entities of relevance to the Center. We have outstanding staff to insure that these goals can be effectively accomplished.

Abstract ? Project 3 ? Neuroscience Project The Neuroscience project will collect psychophysiological and MRI data from 300 MIDUS 3 respondents to derive measures of emotional reactivity and recovery in response to standardized positive and negative emotional stimuli. In addition, measures of resting state connectivity, structural MRI, and white matter connectivity measured with diffusion tensor imaging will provide additional indices of brain function and structure. Collectively these neuroscientifically-based measures will provide a unique opportunity to examine the neural pathways through which psychosocial factors are transduced and impact psychological function, health and well-being as we age. Among the several innovative features of this project, facial EMG will be acquired in the scanner to provide real-time, continuous, objective measures of emotional reactivity and recovery that will be used in conjunction with the imaging measures. Based upon findings from MIDUS 2, we predict that prolonged responding in the ventral striatum in response to positive incentives will be associated with higher levels of well-being and with lower levels of cortisol and with a biomarker and gene expression profile indicative of increased resilience. Functional connectivity between the different sectors of the prefrontal cortex and the amygdala and ventral striatum in resting state functional MRI are predicted to be associated with individual differences in well-being and with peripheral measures of stress biology. Increased functional connectivity between prefrontal cortex and these subcortical zones is predicted to be associated with a more resilient profile. Structural variations in key circuits will also be examined in relation to psychosocial factors and peripheral biology. The neuroscience project provides key measures of the neural bases and correlates of key emotion-related processes that are central to well-being and health and will enable MIDUS to provide a mechanistic account of how psychosocial factors are transduced and in turn impact neural circuits and peripheral biology in ways that modulate mental and physical health.

Waisman Center investigators study intellectual and developmental disabilities (IDD) through investigating the brain structure and function of individuals exhibiting these conditions or at risk for these conditions, or in animal models of these conditions. The Waisman Brain Imaging Core (BIC) provides all of the tools and services required for these types of investigations and includes facilities for magnetic resonance imaging (MRI), human positron emission tomography (PET), high-resolution PET for animal imaging, ancillary physiological recordings during imaging, and extensive software tools and training for image analysis. This facility occupies a key role in providing systems level neuroscience that lies at the interface between the behavioral and molecular levels of analysis. We propose the following specific aims for the next project period. Aim 1 is to develop and translate hardware and software technologies for magnetic resonance imaging (MRI) neuroimaging studies of normal development, atypical development, and neurodegeneration in both humans and animal models. The objectives of this aim encompass all of the major modalities of MRI and include structural MRI, diffusion weighted imaging to examine white matter connectivity, and functional MRI. We also provide access to a highly realistic MRI simulator to enable participants to acclimate to the procedures and rehearse the behavioral protocols that are used in scanning. Aim 2 is to develop and translate radiotracers and methodologies for using positron emission tomography (PET) neuroimaging to study normal development, atypical development and neurodegeneration in humans. The objectives of this aim include radio- pharmaceutical development to translate the use of novel radiotracers for the study of molecules relevant to understanding IDD. The BIC provides access to expertise in radiotracer development and PET physics expertise to characterize the kinetics and quantification of novel PET neuroligands. The BIC also performs regular maintenance and quality control for the Siemens PET scanner. Aim 3 is to provide high quality macaque and rodent PET neuroimaging services. The objectives of this aim include the maintenance of two microPET scanners and the development of protocols with PIs to use high resolution microPET imaging to characterize the neurochemistry of IDD in non-human primates and rodents. Aim 4 is to provide training and technical support for investigators and their staffs in the use of all of the imaging modalities in the BIC. The objectives of this aim include the conduct of courses and training workshops, regular technical updates at BIC monthly meetings and lab meetings of the participating PIs, specialized consultation with the staff and students of PIs, development of specialized scanning sequences and data acquisition protocols for novel applications and consultation, and support in statistical analysis of imaging data.

The Cyberlearning and Future Learning Technologies Program funds efforts that support envisioning the future of learning technologies and advance what we know about how people learn in technology-rich environments. Cyberlearning Exploration (EXP) Projects explore the viability of new kinds of learning technologies by designing and building new kinds of learning technologies and studying their possibilities for fostering learning and challenges to using them effectively. So-called 'non-cognitive' factors such as grit, tenacity, and perseverance have drawn renewed attention from researchers, policy makers, and the public. Cutting across all three concepts is the fundamental idea of 'self-regulation,' or the ability to monitor and appropriately regulate one's attention. Self-regulation skills are critical for success in today's era of rapid technological and social change. Luckily, evidence is accumulating that such skills can be taught. New technologies for collecting, tracking, and reporting data offer great promise for developing and scaffolding students' ability to self-regulate. One such tool is the touch tablet application entitled Tenacity. Tenacity is a tablet based application for middle schoolers designed to train and track the user's attentional self-regulation. Prior research found that, after using the tool for roughly 20 minutes per day for a period of two weeks, students showed significant improvements in self-regulation skills. In this project, researchers will adapt the existing prototype application for more accessible use on wearable devices, add a data dashboard for monitoring one's skill development over time, and then assess its use and effectiveness in the natural environment both inside and outside the classroom. The results will be a market ready application for wearable technologies (smart watches) for self-regulating attention, empirical results assessing its use and impact among everyday users, and the public release on iTunes of the software for dissemination and assessment at mass scale.

Specifically, the research team will adapt the current prototype for use on the Apple iWatch, debug and polish its ability to train and track breath-counting accuracy intermittently throughout the day, and implement data visualization tools for use by users and their parents and teachers. They will then assess its effectiveness in an 8-week experimental study using a pretest/posttest control group design with teens (13-15 years old). Finally, they will release the tool to the public via the Apple App Store to examine its use and effectiveness at mass scale. The hypothesis is that systematic use of Tenacity will result in behavior change on standard measures for attention, foster a more productive conceptual understanding of self-regulation, increase self-regulation skills on first order tasks (i.e., direct skill improvement measures within the application) and second order variables, such as school grades and social wellbeing, and increase school affiliation.

PROJECT SUMMARY/ABSTRACT This U24 application is written in response to RFA-AT-20-003 to establish a high-priority research network on emotional well-being (EWB). While psychological research on well-being has dramatically increased over the past 15 years, virtually all of this work has been descriptive and has not emphasized the ?how? of well-being: How might well-being be cultivated? In addition, virtually all of the extant work on the correlates of individual differences in well-being has used responses on retrospective questionnaires as the primary tool to assess well-being. While there have been exciting findings, particularly relating individual differences in well-being to various indices of physical health, many questions remain and methodological limitations plague the validity of this work. This U24 network will assemble a highly multi-disciplinary group of 10 investigators across 3 (or more in the future) institutions to significantly advance our understanding of the ?how? of EWB, identify the core plastic constituents of EWB, specify and/or develop robust measures of these constituents at biological, behavioral and experiential levels of analysis and characterize the plasticity of these constituents. The measurement strategy will ultimately focus on the development of technology-based passive measures of EWB that require no explicit user input and are highly scalable. The network will also focus its efforts on the development and evaluation of programs to train EWB and will assess whether such programs might serve as prevention strategies. The network will consist of scientists and scholars from a broad range of fields including psychology, neuroscience, electrical and computer engineering, population health and biology, computer science and the humanities. These scientists and scholars will focus on the following major aims: Aim 1: To arrive at a core consensus of the minimal set of constituents that can be described and measured at biological, behavioral and experiential levels that constitute the plastic elements of EWB and to specify already existing measures and /or develop novel measures of each of these constructs at each level of analysis. Aim 2: Using the active measures described in Aim 1, to develop passive measures using digital technologies of at least two of the core constituents of well-being. Aim 3: To develop pilot projects specifically focusing on prevention strategies for learning well-being in various samples. The network will train new investigators and bring established investigators into this new field, disseminate a framework for understanding the plasticity of well- being, a toolbox of measures for assessing the plasticity of components of well-being, and several pilot datasets that showcase the novel passive and field-friendly biological measures. In these ways, the network will dramatically accelerate progress in the nascent field of EWB.