Greg Hajcak - US grants

DESCRIPTION (provided by applicant): This research will integrate developmental psychophysiology and psychopathology by investigating error-related brain activity in pediatric obsessive-compulsive disorder (OCD) and trichotillomania (TTM) both before and after cognitive-behavioral intervention. The error-related negativity (ERN) is an event-related brain potential (ERP) that has been associated with response monitoring and error detection. The ERN has been source-localized to the anterior cingulate cortex (ACC), which is part of the hyperactive fronto-striatal-thamalic circuitry in OCD (Stein, 2000). Thus, an enhanced ERN may serve as a marker of ACC hyperactivity relevant to the pathophysiology of OCD. Previous research has found ERN magnitude to be significantly correlated with symptom severity in a group of adult patients with OCD (Gerhing et al., 2000). The current research extends previous studies to pediatric populations, and includes pediatric TTM and pediatric controls. There is controversy about whether or not TTM is part of the OCD spectrum disorders, and the current study will provide psychophysiological data that may help differentiate these disorders. It is hypothesized that pediatric OCD patients will show enhanced error-related brain activity at protreatment, relative to both pediatric TTM patients and pediatric controls. Pediatric TTM patients are not expected to differ from pediatric controls with respect to error-related brain activity, supporting the notion that TTM is not simply a variant of OCD. Finally, the current study will also investigate the ERN after pediatric patients with OCD and TTM complete a course of CBT. It is hypothesized that only the error-related brain activity in pediatric OCD will change over the course of CBT reflecting the post-treatment alteration in the fronto-striatal-thalamic circuitry that underlies OCD.

[unreadable] DESCRIPTION (provided by applicant): Anxiety disorders are one of the most common forms of psychopathology. Fortunately, despite their daunting prevalence rates, a large treatment-outcome literature indicates that anxiety disorders are extremely amenable to empirically-based psychological treatments. However, the availability of effective and efficacious treatments for psychological disorders depends upon access to effective training in evidence-based treatments (Nathan & Gorman, 2002). The goal of the present proposal is to develop a scientifically-informed clinical training program in exposure based therapy for anxiety disorders that would integrate research and practice at all stages of training, and would serve as a model for how exposure-based therapy for anxiety disorders can be disseminated both within clinical psychology graduate programs and in the larger clinical psychology community. This will be accomplished by developing and refining a curriculum that provides clinical psychology graduate students with a broad training that focuses on the conceptual and empirical bases of exposure-based therapy for anxiety disorders and that provides them with skills necessary for effective dissemination of evidence-based approaches. [unreadable] [unreadable] [unreadable]

DESCRIPTION (provided by applicant): The error-related negativity (ERN) is an electrocortical response observed at the scalp that is maximal approximately 50 ms after an erroneous response. A number of studies have reported increased ERNs in anxious and depressed participants, and recently, a similar pattern of results has been reported in anxious pediatric patients both before and after successful therapy. Other studies have reported increased error- related brain activity in subjects who report high levels of negative emotionality and punishment sensitivity personality traits that are elevated across both anxiety disorders and depression. Collectively, these results suggest that an increased ERN may reflect information-processing abnormalities during self-monitoring that reflect a shared risk factor for anxiety and depressive disorders. To address this possibility, the present study will examine the ERN in relation to two well-known risk factors related to the development of anxiety and depressive disorders: familial psychopathology and temperamental measures of negative emotionality and behavioral inhibition. The overall goal of this study is to evaluate the relationship between error-related brain activity and the development of anxiety and depression, and to assess the utility of error-related brain activity as a potential endophenotype for affective psychopathologies. Additionally, the present study will contribute to the literature on the developmental neurobiology of individual differences in temperament and personality. PUBLIC HEALTH RELEVANCE: This study explores the relationship between error-related brain activity, and parental psychopathology and laboratory measures of behavioral inhibition and negative emotionality in a sample of 300 6-year olds. The present study aims to examine whether variation in error- related brain activity relates to these well-known risk factors for developing both anxiety and depressive disorders.

DESCRIPTION (provided by applicant): The feedback-related negativity (FRN) is an electrocortical response observed at the scalp as an apparent negativity approximately 300 ms following feedback indicating monetary loss compared to gain. Our work suggests that the neural differentiation between gains and losses is being driven by a reward-related positive potential that is generated in the ventral striatum-part of the basal ganglia that has been implicated in reward- related neural circuits. In a series of studies, we have found that the FRN is reduced in individuals who are more depressed-and have recently extended this work to middle childhood in pilot studies. This work is consistent with a growing body of data that indicates is characterized by attenuated reward-related brain activity in the ventral striatum. In the current proposal, we extend this work to a large (N=300) sample of 9 year-olds who have been followed as part of a large NIMH-funded study since age 3, to determine whether the FRN is related to depressive symptoms in middle childhood (Aim 1); based on our pilot data, we hypothesize that increasing depressive symptoms in middle childhood will be associated with reduced differentiation between rewards and non-rewards (i.e., a reduced FRN). Moreover, we want to examine whether the FRN is related not only the current depressive symptoms, but to increased risk for MDD in the sample. To address this possibility, the present study will examine the FRN in relation to two well-known risk factors related to the development of MDD: temperamental measures of positive emotionality and familial history of MDD. We predict that children low in temperamental positive emotionality (assessed at age 6) will be characterized by a reduced FRN (Aim 2); further, that children who have a parent who have had MDD will be characterized by a reduced FRN (Aim 3). If Aim 2 and 3 are confirmed, these data would suggest that the FRN may be a risk marker for MDD. The overall goal of this study is to evaluate the relationship between reward-related brain activity and depressive symptoms and risk for MDD in middle childhood. Additionally, the present study will contribute to the literature on the developmental neurobiology of individual differences in temperament and personality.

DESCRIPTION (provided by applicant): Anxiety disorders are one of the most common forms of psychopathology. Fortunately, despite their daunting prevalence rates, a large treatment-outcome literature indicates that anxiety disorders are extremely amenable to empirically-based psychological treatments. However, the availability of effective and efficacious treatments for psychological disorders depends upon access to effective training in evidence-based treatments (Nathan & Gorman, 2002). The goal of the present proposal is to develop a scientifically-informed clinical training program in exposure based therapy for anxiety disorders that would integrate research and practice at all stages of training, and would serve as a model for how exposure-based therapy for anxiety disorders can be disseminated both within clinical psychology graduate programs and in the larger clinical psychology community. This will be accomplished by developing and refining a curriculum that provides clinical psychology graduate students with a broad training that focuses on the conceptual and empirical bases of exposure-based therapy for anxiety disorders and that provides them with skills necessary for effective dissemination of evidence-based approaches.

DESCRIPTION (provided by applicant): There is increasing focus on changes in reward sensitivity that take place across adolescence; in particular, puberty appears to be a time characterized by increased sensitivity to rewards. At the same time, puberty is a time characterized by a significant increase in depressive symptoms, and depression is characterized by reductions in sensitivity to rewards. The current project examines reward sensitivity as a latent trait, capitalizing on a combination of EEG, functional neuroimaging (fMRI), behavioral, and self-report measures. Along the same lines, we consider multiple assessments of depressive symptoms (e.g., parent and child reports) so that depressive symptoms can also be modeled as a latent trait. The current proposal examines both reward sensitivity and depression in a large (N=300) sample of girls, ranging from 9 to 14 years of age; moreover, this sample will be examined two years after the initial visit, so that both cross-sectional and longitudinal relationships can be examined. In our pilot data, we have focused extensively on the feedback-related negativity (FRN), an electrocortical response observed at the scalp as an apparent negativity approximately 300 ms following feedback indicating monetary loss compared to gain. Our work suggests that the neural differentiation between gains and losses is being driven by a reward-related positive potential that is generated in the ventral striatum-part of the basal ganglia that has been implicated in reward-related neural circuits. We have found that the FRN relates to fMRI-based measures of striatal response to rewards, as well as behavioral metrics of reward sensitivity. Moreover, we have found that the FRN is reduced in both adults and adolescents who are more depressed-and have recently found that reduced reward-related brain activity can predict changes in depressive symptoms over the course of two years among adolescents. The current proposal extends this work into a much larger and longitudinal sample, and incorporates multiple measures of reward sensitivity, depressive symptoms, and puberty. We will assess: a) the relationship between multiple measures of reward sensitivity and depressive symptoms in a large sample that spans adolescence at two time points, separated by 2 years (Aim 1); b) normative developmental increases in both reward sensitivity and depressive symptoms, especially as a function of pubertal stage (Aim 2); c) prospective relations between reward sensitivity and depressive symptoms over time, and whether reward sensitivity at the first assessment can predict changes in depression two years later (Aim 3); finally, if pubertal changes predicts a stronger link between reward sensitivity and later depressive symptoms (Aim 3). A number of secondary aims are also evaluated (e.g., specificity to depressive symptoms and not anxious symptoms; utility of salivary testosterone as a marker of pubertal stage; role of stressful life events). The present study will contribute to the literature on the developmental neurobiology of reward, as well as the neurobiological changes related to individual differences in depression and risk for depression across adolescence. PUBLIC HEALTH RELEVANCE: We examine the role of pubertal stage and change on reward sensitivity (RS; measured using behavioral, ERP, fMRI, and self-report methods) and depressive symptoms among 300 females (aged 9 to 14) in a time-sequential design-and evaluate if low RS can predicts depression.

? DESCRIPTION (provided by applicant): Increased error-related brain activity, as indexed by the error-related negativity (ERN) component of the event-related brain potential, has been proposed as an inherited risk factor for anxiety. Both the ERN and anxiety symptoms increase dramatically during adolescence-our data suggest this is especially true between the ages of 11 and 14. The current study aims to examine whether increased ERN is a mechanism of risk for the development of increased anxiety, and whether the ERN is a modifiable biomarker of risk among a large (N=600) and prospective sample of adolescents recruited at Stony Brook University and San Diego State University. At each site, 300 adolescents aged 11 to 14 will be recruited. Based on our pilot data, we examine whether ERN can be altered using adaptive attentional bias modification (AABM). AABM is a computer-based approach to train individuals to attend away from threat in their environments, and our pilot data suggests AABM reduces the ERN. High-ERN participants (N=300) will be randomized to AABM (N=150) or a control condition (CC; N=150). We target increased ERN precisely because this is the proposed neural biomarker we wish to reduce with AABM. We will examine the impact of AABM on ERN, and the relationship between ERN and anxiety, both in the short term (i.e., after AABM/CC) and at two year follow-up. All participants (i.e., even low-ERN participants not randomized to AABM/CC) will return to the lab to have ERN and anxiety assessed at two year follow-up. Across the entire sample, we predict that baseline ERN will relate to anxiety; we expect anxiety to increase from baseline to two year follow-up; we predict that a larger ERN at baseline will predict increased anxiety prospectively, and that changes in anxiety will relate to changes in ERN (Aim 1). Crucially, we predict that AABM will reduce the ERN (Aim 2), and that the degree to which ERN is reduced will relate to AABM-related reductions in anxiety (Aim 3). Overall, we will test whether the ERN is a modifiable biomarker of risk. Although all adolescents randomized to AABM will be characterized by a relatively large ERN, we will also be able to examine whether a larger ERN at baseline will predict change in anxiety following AABM. Finally, we conduct exploratory analyses to examine the impact of gender on all hypotheses, and determine whether age moderates the strength of the proposed relationships tested in our primary aims-which would suggest critical information about the best timing to assess and modify ERN to inform and impact anxious trajectories of risk.

? DESCRIPTION (provided by applicant): Depression and anxiety represent urgent public health problems, as these disorders are highly prevalent, chronically impairing for the affected individuals and their families, and very costly to society at large. Impaired functioning of core neural systems involved in reward processing and error monitoring may confer specific risk for depression and anxiety, respectively. In children, a reduced feedback negativity (FN), an ERP component sensitive to monetary rewards versus losses, predicts the first-onset of depressive disorders, whereas an increased error-related negativity (ERN), reflecting over-activation of an error-monitoring system, predicts the first-onset of anxiety disorders. Further, these biomarkers of risk for depression (i.e., FN) and anxiety (i.e., ERN) appear to be influenced by positive parenting and harsh parenting, respectively. The current proposal leverages a well-developed evidence-based parenting intervention to experimentally manipulate positive and harsh parenting in order to examine whether the FN and ERN can be altered in children and assess the specificity of these associations. This mechanism-focused approach has the potential to inform neurobiological models of developmental psychopathology and offer novel targets for intervention.

Cognitive representational flexibility is the ability to use multiple external representations, switch flexibly between them, and select or generate appropriate representations for particular tasks. This cognitive capability is critical for the practices of computational thinking and problem solving across STEM and computing domains. However, the development and enactment of representational flexibility in cognitive processes is effortful and demanding for most learners, but particularly so for students with autism spectrum disorder (ASD). Evidence suggests that students with ASD enrolling in colleges are more likely than members of the general population or other disability groups to gravitate toward STEM-related majors, but their need for training in representational flexibility has been identified as a barrier to their college enrollment. This project aims to study individualized training of representational flexibility for STEM and computational reasoning and problem solving among adolescents with ASD, hence addressing a significant barrier to college enrollment of this learner group who otherwise have the potential to become future sources of STEM talent. Researchers will utilize 3D virtual reality (VR) with body sensory technologies to create an adaptive, representational flexibility training program that helps participants learn how to design and code simulations and games in a 3D virtual-reality context. This program, called Force and Motion-Adaptive Representation (FM-AR), will facilitate participants' ability to select, connect, convert, and construct multimodal representations of physics and mathematics problems while practicing and experimenting with computational concepts during VR-based simulation design and programming. As a result of the powerful innovation and application of computing in STEM disciplines, the STEM+C program supports research and development of interdisciplinary and transdisciplinary approaches to the integration of computing within STEM teaching and learning for preK-12 students in both formal and informal settings. This interdisciplinary project will advance the research and practice of STEM+Computing education by investigating representational flexibility as the critical threshold for integrating computational thinking in and across STEM domains, and specifying the conditions that lead to the development and manifestation of representational flexibility, especially for learners with special needs.

Via a design-based, mixed-method research of the computational behaviors of adolescents with ASD and their learning outcomes in the FM-AR program, the following research questions will be investigated: 1. What representational practices will adolescents with ASD implement during FM-AR-supported simulation design and programming? 2. How and under what circumstances will adolescents with ASD demonstrate representational flexibility for computational reasoning and scientific/mathematical problem solving? 3. How will adolescents with ASD interact with adaptive representational-practice support in FM-AR? What is the effect of the adaptive support on participants? development of representational flexibility during physics- and math-related computational practices? Researchers will study the above research questions with (a) individualized selection and presentation of representational-practice tasks in variant types and flexibility demands; (b) representational performance assessment via real-time learner data mining and modeling; and (c) assessment-driven cues and prompts to scaffold representation interpretation, comparison, coordination, and adaptation during physics- and mathematics-related computational practices. This project aims to generate a conceptual and design framework governing the design and research of a STEM+Computing learning environment that scaffolds representational flexibility for a heterogeneous learner group.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

Postpartum depression (PPD) affects 10-15% of women ? and is associated with a range of severe negative outcomes that impact both the mother's and child's well-being. Even elevated depressive symptoms not meeting full MDD criteria have a debilitating effect on the mother and infant. Therefore, there is a critical opportunity and need to validate markers of risk during the prenatal period that could be used to guide early identification of the highest risk women; these markers might then be leveraged for prevention efforts and serve as targets of novel intervention strategies. Because women regularly access health care during pregnancy, this period presents an ideal opportunity to test and improve identification of risk. There is an emerging consensus that anhedonia ? insensitivity to reward ? is a core deficit in MDD. However, biological markers of anhedonia have not been studied in the perinatal period. The present proposal focuses on reward-related neural activity reflected in an event-related potential referred to as the reward positivity (RewP). The RewP is blunted among both adults and children with diagnosed MDD?and we have found that a reduced RewP prospectively predicts increases in depressive symptomatology and first onset of major depressive episodes?even when accounting for other known measures of risk. This proposal aims to extend our previous work to PPD?and test the novel hypothesis that a blunted RewP obtained during pregnancy will prospectively predict increased depressive symptoms and new depressive episodes in the postpartum period. We will record EEG during a reward task in 300 pregnant women in conjunction with prenatal care visits at an OB/GYN office between 16 and 32 weeks gestation. Depressive symptoms and disorders will be assessed both at baseline and six weeks following delivery?so that the predictive ability of the RewP can be examined when controlling for other known risk factors (e.g., history of MDD and baseline symptoms). This sample size was chosen to assure adequate variability in postpartum depressive outcomes and sufficient cases of PPD. Aim 1 is to examine the relationship between the RewP and current depressive symptoms and diagnoses at 16 weeks gestation. Aim 2 assesses whether a smaller RewP at baseline will prospectively predict increases in depression during the postpartum period. Aim 3 will determine whether blunted reward-related neural activity (i.e., the RewP) during pregnancy predicts depressive outcomes even after controlling for other baseline predictors of postpartum depression. We will also examine time-frequency based measures of reward (i.e., reward-related delta band activity), and examine positive and negative predictive value of reward-related neural activity in predicting depressive outcomes in the postpartum period?both alone and in conjunction with baseline risk factors. This R21 will provide the first evidence that hypoactive reward-related neural activity, assessed using EEG during pregnancy at a routine OB/GYN visit, could be used to improve the prediction of increased depression during the postpartum period.