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«by Amy Lynn Byrd, Ph.D. B.S. in Psychology, College of Charleston, 2006 M.S. in Clinical Psychology, University of Pittsburgh, 2010 Submitted to the ...»

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REWARD AND PUNISHMENT PROCESSING IN SUBGROUPS OF YOUTH WITH

CONDUCT PROBLEMS: CHARACTERIZATION OF THE NEURAL RESPONSE

AND IMPLICATIONS FOR INTERVENTION

by

Amy Lynn Byrd, Ph.D.

B.S. in Psychology, College of Charleston, 2006

M.S. in Clinical Psychology, University of Pittsburgh, 2010

Submitted to the Graduate Faculty of

The Kenneth P. Dietrich School of Arts and Sciences in partial fulfillment of the requirements for the degree of Doctor of Philosophy University of Pittsburgh 2015

UNIVERSITY OF PITTSBURGH

DIETRICH SCHOOL OF ARTS AND SCIENCES

This dissertation was presented by Amy L. Byrd It was defended on October 10, 2014 and approved by Susan B. Campbell, Ph.D., Department of Psychology Daniel S. Shaw, Ph.D., Department of Psychology Stephen B. Manuck, Ph.D., Department of Psychology Dissertation Co-Director: Rolf Loeber, Ph.D., Department of Psychology and Psychiatry Dissertation Director: Dustin A. Pardini, Ph.D., Department of Psychology and Psychiatry ii Copyright © by Amy L. Byrd 2015 iii

REWARD AND PUNISHMENT PROCESSING IN SUBGROUPS OF YOUTH WITH

CONDUCT PROBLEMS: CHARACTERIZATION OF THE NEURAL RESPONSE

AND IMPLICATIONS FOR INTERVENTION

Amy L. Byrd, Ph.D.

University of Pittsburgh, 2015 Extensive research has focused on abnormalities in reward and punishment processing as a mechanism underlying childhood-onset conduct problems (CP), particularly among CP youth with callous-unemotional (CU) traits. However, there is still debate about the neural underpinnings of this mechanism. Moreover, while researchers suggest that these youth may be resistant to social learning based interventions due to deficits in reward and punishment processing, this has not been empirically investigated. This dissertation expands on previous research by 1) examining neural abnormalities in reward and punishment processing among CP youth with and without CU traits relative to healthy controls (HC); and 2) assessing whether individual differences in reward and punishment processing are associated with CP following intervention. Prior to treatment, neural responsivity to reward and punishment was assessed in key regions of interest among a sample of boys (ages 8-11; n=64) using an event-related fMRI task. CP youth were then randomly assigned to an empirically supported treatment (Stop-NowAnd-Plan (SNAP) or treatment as usual, and were re-evaluated following intervention. Baseline differences in brain function were examined as a predictor of post-intervention CP. Results demonstrated differences in neural reactivity to be most reliable and robust with regard to amygdala responsivity to punishment. Specifically, boys with CP demonstrated reduced amygdala reactivity to punishment relative to HC; however, there was no difference in responsivity between subgroups of children with CP, suggesting that reduced punishment

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reward, CP youth with low levels of CU exhibited reduced reactivity to reward across several key regions of interest (e.g., caudate, amygdala) while CP youth with CU were characterized by significant activation to reward that did not differ from HC; notably, this was reduced to nonsignificance after controlling for co-occurring internalizing problems. Finally, although random assignment to SNAP resulted in significant reductions in CP at post-treatment follow-up, responsivity to reward and punishment was unrelated to post-treatment levels of CP. Findings highlight the importance continuing to investigate the role of reward and punishment processing in the development of early-onset CP and point to potential implications for intervention.

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PREFACE

1.0 INTRODUCTION

2.0 BACKGROUND AND SIGNIFICANCE

2.1 CONDUCT PROBLEMS IN YOUTH AND SUBTYPES

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THEORETCIAL BACKGROUND

2.3.1 Developmental Considerations

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BEHAVIORAL EVIDENCE

2.4.1 Primary Abnormality in Reward Processing

2.4.2 Primary Abnormality in Punishment Processing

2.4.3 Abnormalities in Reward and Punishment Processing

2.4.4 Limitations

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PROCESSING

2.5.1 Reward/Approach System

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2.5.3 Regulatory System

2.5.4 Summary

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FMRI EVIDENCE

2.6.1 Summary

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ROLE OF REWARD AND PUNISHMENT PROCESSING

2.7.1 Overview of Treatment Literature

2.7.2 Stop-Now-And-Plan Intervention

2.8 RATIONALE

2.9 HYPOTHESES

3.0 RESEARCH DESIGN AND METHOD

3.1 PARTICIPANTS

3.2 RECRUITMENT

3.3 PROCEDURE

3.4 TREATMENT CONDITIONS

3.5 MEASURES

3.6 GROUP CLASSIFICATION

3.7 FMRI CARD GUESSING TASK

3.8 IMAGING METHODS

3.9 DATA ANALYSIS PLAN

4.0 RESULTS

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THE RECEIPT OF REWARD AND PUNISHMENT AMONG BOYS WITH CP

AND CU?

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THE RECEIPT OF REWARD AND PUNISHMENT AMONG BOYS WITH CP

AND PSYCHOPATHIC FEATURES?

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PROCESSING ASSOCIATED WITH RESPONSIVENESS TO TREATMENT?..... 93 5.0 GENERAL DISCUSSION

5.1 NEURAL ABNORMALITIES IN REWARD PROCESSING

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5.3 CLINICAL IMPLICATIONS FOR INTERVENTION

5.4 LIMITATIONS AND FUTURE DIRECTIONS

BIBLIOGRAPHY

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Table 1. Crosstab of overlap between CPCU and CP PSY group classifications

Table 2. Correlations between all study variables

Table 3. Means and standard deviations for all study variables by CPCU group

Table 4. Means and standard deviations for all study variables by CP PSY group

Table 5. Suprathreshold clusters associated with combined effects of large and small reward relative to baseline

Table 6. Suprathreshold clusters associated with combined effects of large and small punishment relative to baseline

Table 7. Suprathreshold clusters for CPCU group differences: 3x4 ANOVA

Table 8. Suprathreshold clusters for CP and CU severity: Univariate and multivariate regressions

Table 9. Suprathreshold clusters for CP PSY group differences: 3x4 ANOVA

Table 10. Suprathreshold clusters for CP and PSY severity: Uunivariate and multivariate regressions

Table 11. Means and standard deviations for all study variables by treatment group.

................ 96 Table 12. Effect of treatment, brain function and the interaction between treatment and brain function: Repeated measures ANOVAs

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Figure 1. Diagram of hypotheses for Aim 1

Figure 2. Flow diagram of attrition and exclusions among participants with conduct problems recruited from SNAP treatment study

Figure 3. Flow diagram of attrition and exclusions among healthy control participants.

........... 43 Figure 4. Schematic of events within each trial of the fMRI reward/punishment task................ 55 Figure 5. Combined effects of large and small reward reveal robust task-related activation throughout reward-related circuitry

Figure 6. Combined effects of large and small punishment reveal task-related activation throughout punishment-related circuitry

Figure 7. Activation in left BA10 is associated with main effect of CPCU group

Figure 8. Activation in the left amygdala is association with CPCU

Figure 9. Activation in the left caudate is associated with CPCU

Figure 10. Exploratory whole brain analyses revealed CPCU group X task condition interaction within the bilateral cingulate gyrus and left postcentral gyrus

Figure 11. Activation in the bilateral amygdala is negatively associated with conduct problems, even after controlling for variance associated with CU traits

Figure 12. Activation in the bilateral amygdala is associated with CP PSY group X task condition interaction

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Figure 14. Interaction between time and treatment group reveal effectiveness of SNAP intervention relative to TAU

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I will be forever indebted to the many that have helped to make the completion of this journey possible. Thank you to my committee members for all of their feedback and guidance throughout my dissertation and the many milestones that preceded it. A special thank you to Steve Manuck, who has gone above and beyond to facilitate and support my growth. To my advisor, Dustin Pardini, thank you for taking a chance on me as your first graduate student. You have continually challenged me to be a better thinker, a better writer and a better researcher. This would not have been possible without you.

Thank you to all of my family and friends who have been, and continue to be, the most awesome people on the planet. To my parents who have unconditionally offered their steadfast belief in me and unwavering love and support. Thank you to my dad who has instilled a fierce drive and determination to always push myself to be better. Thank you to my mom who exudes a genuine, non-judgmental compassion that I strive to emulate in all that I do. To my brothers, Michael and Sam, thank you for keeping me grounded, smiling and laughing. And finally, to my Luke, the most patient and understanding person I know. I am so grateful to have had you by my side through this journey. You are truly the best.

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Longitudinal research has consistently shown the presence of childhood-onset conduct problems (CP) to be an important risk factor for the development of severe and protracted trajectories of antisocial behavior and delinquency. Improving our understanding of the mechanisms that underlie the manifestation and persistence of early CP has significant implications for prevention and intervention efforts. Extensive research has focused on abnormalities in reward and punishment processing as one potential mechanism contributing to the development of CP in youth, particularly in CP youth with callous-unemotional (CU) traits or psychopathic features.

Historically, reward and punishment processing has been conceptualized in terms of two neurobiological systems and considerable behavioral work has focused on potential associations between CP and deficits in one or both of these systems. While behavioral work documents fairly consistent performance deficits on tasks targeting reward/punishment responsivity, these studies are limited in their ability to completely disentangle the neural mechanisms underlying aberrant reward and punishment processing. Recent advances in neuroscience have the ability to address these limitations by examining the implicated neural circuitry; however, a dearth of research remains. Moreover, there are no known investigations that examine whether potential abnormalities may be specific to or most pronounced within subgroups of CP youth, particularly among those characterized by high levels of CU traits or psychopathic features. Lastly, preliminary research in this area has focused on these mechanisms in adolescence, a

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underlying reward and punishment processing. As such, it may be particularly important to evaluate potential abnormalities in this circuitry during pre-adolescence, prior to a period of heightened neural maturation. Therefore, a primary aim of this dissertation is to characterize the neural response to the receipt of reward and punishment among subgroups of CP youth (age 8relative to healthy controls (HC).

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Decades of research have identified multiple causal factors that underlie the development and persistence of chronic trajectories of CP in youth. Theories on the etiology of CP have emphasized a wide variety of biological and environmental factors, recognizing that the development of these behaviors is likely the result of a complex interplay between child, family, and broader social factors. Given the active role individuals play in shaping their social environments (Patterson, Reid, & Dishion, 1992; Plomin, DeFries, & Loehlin, 1977), one prominent area of research has focused on further elucidating child-specific mechanisms. As described above, research has emphasized further exploring abnormalities in reward and punishment processing, as deficits within this realm have been conceptualized as one potential causal mechanism underlying chronic and severe CP (e.g., Fowles, 1980; Newman & Wallace, 1993; Quay, 1993). Along these lines, the current dissertation attempts to take a more nuanced approach in testing this theory and in doing so, also seeks to expand on the literature by exploring how aberrant reward/punishment processing may impact responsiveness to intervention.

The current chapter begins by presenting a detailed description of CP in youth and subtyping schemes that have attempted to delineate a more homogenous, etiologically unique group of at-risk youth. Next, an overview of the theoretical and behavioral evidence for abnormalities in reward/punishment processing among youth with CP as well as subgroups of

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