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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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Abnormalities in reward and punishment processing have been conceptualized as a causal mechanism underlying the development of persistent CP in boys. However, there is still some debate about the neural underpinnings of this proposed mechanism. Specifically, some researchers have hypothesized that CP stems from an overactive reward system, characterized by heightened neural reactivity to reward and in turn, hypersensitivity to reward, while others have posited that CP reflects an inherently underactive reward system that necessitates excessive reward seeking to achieve adequate stimulation. Researchers have also suggested that a primary deficit in punishment processing, characterized by a hypoactive neural response and

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indication that these abnormalities may be most pronounced in a more homogenous sub-group of boys with elevated CP and CU traits (or psychopathic features) who are thought to be at heightened risk for severe and protracted CP. Although extensive theoretical and behavioral work as well as burgeoning neuroimaging literature provides some support for abnormalities in reward/punishment processing in CP youth, several questions remain. First, past research has often utilized complex behavioral paradigms that incorporate multiple aspects of reward and punishment processing, making it difficult to clearly delineate the strength and direction of associations between abnormalities in reward and/or punishment responsivity and CP in boys.

Moreover, these studies often focus on adolescents and rarely examine potential differences in these neural processing systems within subgroups of CP youth relative to healthy controls.

Lastly, we have a limited understanding of how abnormalities in processing reward/punishment may influence response to intervention, as child-focused cognitive-behavioral therapies (CBT) and parent management training (PMT) rely heavily on behavioral strategies associated with reward and punishment. While abnormal reward and punishment processing may help to drive early and chronic engagement in CP, child-focused CBT and skills training interventions coupled with PMT have demonstrated positive effects in reducing CP in samples of youth. Specifically, these interventions, which emphasize reward/punishment contingencies, may help to modify problem behaviors in youth characterized by aberrant reward/punishment processing who are atrisk for more chronic forms of CP. However, it is also possible that these interventions are insufficient to overcome the behavioral impairments associated with deficient reward and/or punishment responsivity in youth.

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in processing reward and punishment among subgroups of youth with CP relative to HC and 2) to assess the extent to which differences in neural processing of reward and punishment are associated with levels of CP following treatment and whether these differences serve to moderate treatment effectiveness. Neural responsivity to reward and punishment was examined using an event-related fMRI task prior to treatment initiation. BOLD response was assessed as a marker of neural activation in key regions associated with reward and punishment processing in subgroups of CP youth and HC. In addition, all CP youth were re-evaluated post-treatment and baseline differences in brain function were examined as predictors of post-treatment CP following random assignment to an empirically supported multi-modal intervention (i.e., SNAP) vs. TAU.

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Based on the theory and empirical findings described above, the following aims were examined and hypotheses were tested (see Figure 1).

Aim 1: Characterize differences in the BOLD response to the receipt of reward and punishment among boys with CP and low CU traits (CPCU-), boys with CP and high CU traits (CPCU+) and matched HC.

Hypothesis 1a: Reward. It was hypothesized that both CPCU- and CPCU+ youth would be characterized by increased BOLD response in the ventral striatum (VS) to reward relative to HC. However, no differences were expected in BOLD activation to reward between CPCU+ and

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with reward activation in the VS, while CU was hypothesized to show little to no relationship.

Hypothesis 1b: Punishment. It was hypothesized that relative to HC, CPCU- and CPCU+ youth would be characterized by increased BOLD activation in the dorsal striatum (DS) to the receipt of punishment. Additionally, it was predicted that both CP groups would evidence decreased BOLD activation in the amygdala, ACC, mPFC and OFC to punishment relative to HC. Moreover, these differences are expected to be most pronounced in CPCU+ youth relative to CPCU-. Finally, both CP and CU constructs were expected to show a positive association with BOLD response to punishment in the DS, while demonstrating negative associations with BOLD activation in all other regions. These associations were hypothesized to be driven by CU.

Aim 1b: Given that prior fMRI studies have subtyped CP youth based on overall psychopathy scores rather than CU traits per se, the current dissertation will examine whether the findings from Aim1a change when CP youth are subdivided based on high and low psychopathic features. Specifically, BOLD response to the receipt of reward and punishment was evaluated among boys with CP and low levels of psychopathic features (CP PSY-), boys with CP and high levels of psychopathic features (CP PSY+) and matched HC.





Hypothesis 1c: Reward. Hypotheses regarding responsivity to reward were identical to those stated above. It was predicted that both CP PSY- and CP PSY+ youth would be characterized by increased BOLD response in the VS to reward conditions relative to HC, though no differences were expected between CP PSY+ and CP PSY- youth. Continuous measures of CP were expected to show a positive association with reward activation in the VS, while PSY was hypothesized to show little to no relationship.

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PSY+ youth were expected to demonstrate increased BOLD activation in the DS to the receipt of punishment. Both CP groups were expected to show decreased BOLD activation in the amygdala, ACC, mPFC and OFC to punishment relative to HC and these differences were expected to be most pronounced in CP PSY+ youth. Finally, both CP and PSY constructs were expected to show a positive association with BOLD response to punishment in the DS, while demonstrating negative associations with BOLD activation in all other regions. These associations were hypothesized to be driven by PSY.

Aim 2: Evaluate the extent to which individual differences in reward and/or punishment processing are associated with responsiveness to a multi-modal intervention that emphasizes behavioral principles associated with reward and punishment contingencies. Responsivity to reward and punishment was examined as a predictor only within those regions exhibiting significant group differences.

Hypothesis 2a: Treatment Effectiveness. It was predicted that youth participating in SNAP would show greater reductions in CP at the 3-month follow-up relative to youth in TAU.

Hypothesis 2b: Main effect of brain function. Collapsed across treatment group, abnormalities in reward/punishment processing were expected to be positively associated with CP at post-treatment follow-up. With regard to reward, it was hypothesized that BOLD response in the VS would be significantly associated with increased levels of CP at post-treatment followup, even after controlling for pre-treatment CP severity. With regard to punishment, it was hypothesized that BOLD response in the amygdala, DS, ACC, mPFC and OFC would be associated with heightened levels of CP at post-treatment follow-up, even after controlling for pre-treatment CP severity.

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exploratory in nature, associations between brain function and post-treatment CP were expected to be strongest among youth participating in TAU relative to those youth assigned to SNAP.

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The previous chapter summarizes the extant literature relevant to the current dissertation and briefly overviews the proposed hypotheses. The following section presents a more detailed description of the study design, procedures and analytic strategies. As depicted in Figures 2 and 3, following recruitment and initial screening, both CP youth (Figure 2) and matched HC (Figure

3) underwent two study phases, including a baseline assessment and a scan day assessment.

Then, CP youth, as a part of a larger treatment study (Burke & Loeber, 2014), completed one of two treatment conditions for approximately 3 months and received a follow-up assessment immediately following the completion of treatment. The subsequent section provides a description of all participants, including inclusion and exclusion criteria, procedures for each phase of the study, and a detailed description of all measures used. This section also discusses the fMRI task, methods for fMRI data acquisition and processing, and the statistical model for single-subject and group level analyses.

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Participants were recruited from a larger treatment study aimed to evaluate the effectiveness of SNAP (Burke & Loeber, 2014). The sample for the current dissertation consisted of 64 boys

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northeastern United States, including 37 boys with CP and 27 matched HC. The majority of the participants were African-American (n=49, 76.6%), with the remainder being Caucasian (n=10, 15.6%) and mixed race (n=5, 7.9%). Nearly all of the boys lived with their biological mother (91%) and 28% of the boys had a biological father living in the home. Over half of the families reported receiving governmental financial assistance (63%) and the majority of families reported a total annual income of less than $20,000 per year (54%). Procedures were reviewed and approved by the Institution Review Board. Written informed consent was obtained from parents/guardians and youth provided assent prior to each assessment. Participants and youth were compensated at the completion of each assessment phase.

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Conduct Problem Youth CP youth who participated in the current fMRI study represent a subset of youth recruited from a larger treatment study aimed to evaluate the effectiveness of SNAP (Burke & Loeber, 2014), an evidence based intervention program designed to reduce CP in children between the ages of 6 and 11 (see description below). All participants were recruited from new referrals to one of two SNAP treatment agencies in the area. Caregivers of boys between the ages of 6 and 11 calling to inquire about the SNAP program at either agency were told about the treatment study and informed that study participation would involve a random assignment to SNAP or treatment as usual (TAU) in the community. Approximately thirty percent of caregivers declined further contact regarding the study and the most common reasons for refusal was unwillingness to be randomly assigned or being involved in other services at the time. Caregivers requesting further information were contacted by research team staff and completed the screening phase of the treatment study (n=364). Youth from the larger treatment study were determined to be eligible if they: 1) had an estimated IQ 70 and 2) were rated by parents as having clinically significant behavior problems, as indexed by an age-based T-score 70 on the aggressive behavior, rule breaking, or conduct problems subscales of the Child-Behavior Checklist (CBC-L) or a T-score 64 on the externalizing behavior composite of the CBCL. All participants eligible for the larger treatment study were scheduled for a baseline assessment (n=252; see details below). At this time those between the ages of 8 and 11 were informed of the fMRI study (see details below).

Healthy Controls

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recruited for the fMRI substudy predominately from local pediatricians’ offices in the community. Participants were also recruited via flyers, brochures, and magazine ads placed in buses, churches and local community centers. Caregivers were informed of the study and those expressing interest completed a preliminary screener administered by local health care providers or trained research assistants (n=89). Youth were determined eligible if they had no history of services or medications for emotional/behavioral problems, no police contacts and had not received special education services for learning problems. Additionally, to provide an initial screen for CP, caregivers answered several questions from the CBCL. Eligible participants were scheduled for an in-office baseline assessment (n=81; see details below).

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Baseline Assessment All CP youth in the larger treatment study completed a baseline assessment prior to treatment initiation. This was conducted by research staff in the participant’s home and both caregivers and youth completed a variety of questionnaires. At the completion of the assessment, caregivers of boys between the ages of 8-11 were informed of an additional fMRI study (n=155) and those that expressed interest (61%; n=95) were contacted by research staff to complete an additional screening. Any participants with a history of claustrophobia, irremovable metal (i.e., surgical implants, braces, bullets, etc.), serious medical conditions affecting brain function (i.e., meningitis) or history of concussion within the past year were excluded (n=12). An additional 9 participants were unable to be re-contacted or indicated that they were no longer interested

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weeks of their treatment start date (n=74) and any youth taking stimulant medications were asked not to take their medications for 24 hours prior to the study visit.

The comparison group of HC also completed a baseline assessment identical to that of CP youth. This was conducted by research staff in the office and served as a more comprehensive screening procedure. Inclusion criteria necessitated that caregivers’ and youth report behavior problems below the at-risk threshold on all externalizing and internalizing scales as indexed by an age-based T-score below 60 on the CBCL. Additionally, participants with an IQ 70, a history of claustrophobia, irremovable metal, a history of neurological disease or structural brain injury or a concussion within the past year were excluded (n=24). Eligible participants were scheduled for an fMRI scan (n=57).



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