Executive Dysfunction after Moderate and Severe Pediatric Traumatic Brain Injury

Executive Dysfunction after Moderate and Severe Pediatric Traumatic Brain Injury Predicts Clinical Dysfunction on the Child and Adolescent Functional Assessment Scale A thesis submitted to the Graduate School of the University of Cincinnati in partial fulfillment of the requirements for the degree of Master of Science in Clinical & Translational Research In the Department of Environmental Health Division of Epidemiology & Biostatistics of the College of Medicine July, 2012 by Brad Kurowski MD, Case Western Reserve University School of Medicine, May 2004 MS, University of Massachusetts at Amherst, September 2000 BS, University of Massachusetts at Amherst, September 1999 Committee Chair: Kim Dietrich, PhD Committee Member: Shari Wade, PhD Committee Member: Amy E. Cassedy, PhD

Abstract Objective: To identify neurobehavioral and neurocognitive predictors of impaired behavioral functioning after adolescent traumatic brain injury (TBI). Design: Multicenter crosssectional study. Setting: Outpatient. Participants: 132 primary caregivers and children age 12-17 years who sustained a moderate or severe TBI within the past 1-6 months. Primary Measures: Self and parent ratings of executive function (EF), tests of memory and processing speed (PS), and a structured clinical interview of behavioral functioning. Analysis: Logistic regression was used to examine associations of behavioral functioning with ratings of EF and tests of memory and PS. Results: Caregiver ratings of problems in EF were associated with global behavioral functional impairment (OR 1.11 [95% CI: 1.05, 1.17], p<0.01) as well as impairments in the domains of school (OR 1.09 [95% CI: 1.04, 1.15], p <0.01), home (OR 1.10 [95% CI: 1.04, 1.16], p<0.01), community (OR = 1.13 [95% CI: 1.04, 1.22], p = 0.01), behavior towards others (OR = 1.13 [95% CI: 1.07, 1.20], p<0.01), and moods and emotions (OR =1.06 [95% CI: 1.01, 1.11], p=0.02). Slower PS (OR 0.97 [95% CI: 0.95, 1.00], p = 0.03) and lower memory scores (OR 0.96 [95% CI: 0.93, 1.00], p=0.03) were also associated with global behavioral impairment. Conclusions: Caregiver ratings of EF and measures of PS and memory are associated with behavioral impairment after adolescent TBI. Understanding the ability of neuropsychological measures to predict clinical impairment will potentially help hone assessment batteries and focus treatments where they are needed most. Key words: traumatic brain injury, adolescent, executive function, memory, processing speed ii

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Acknowledgments This work was supported in part by 1) NIH grant R01-MH073764 from the National Institute of Mental Health; 2) a grant from the Colorado Traumatic Brain Injury Trust Fund Research Program, Colorado Department of Human Services, Division of Vocational Rehabilitation, Traumatic Brain Injury Program; and 3) Rehabilitation Medicine Scientist Training Program K-12 grant (NIH/NICHD/NCMRR/AAP). Data analyzed in this study were originally collected from four sites, Cincinnati, OH, Cleveland, OH, Rochester, MN, and Denver, CO from 3/22/2007 1/18/2011. Data collection was performed under guidance of the site principle investigators, Shari Wade, PhD, Gerry H. Taylor, PhD, Terry Stancin, PhD, Tanya Brown, PhD, and Michael Kirkwood, PhD. Data cleaning was performed by the data management team at Cincinnati Children s Hospital under the guidance of Amy Cassedy, PhD. All data analysis, interpretation, and write-up of findings specific to this study were performed by Brad Kurowski, MD, MS. iv

Table of Contents Title page... i Abstract.. ii Acknowledgements.. iv Table of Contents. v List of Tables and Figures.. vi Body of Text.. 1-13 Introduction. 1-3 Methods.. 3-6 Results.... 7-9 Discussion.... 9-12 Conclusion. 13 Bibliography.... 14-18 Appendix A: Figures.. 19 Appendix B: Table. 20-23 v

List of Tables and Figures Figure 1. Distribution of Child and Adolescent Functional Assessment Scale (CAFAS) domain scores in study population Table 1. Comparison of Outcome Measures for Individuals with Non-severe and Severe Traumatic Brain Injuries Table 2. Final logistic regression models for Child and Adolescent Functional Assessment Scale (CAFAS) domain and total scores with Behavioral Rating Inventory of Executive Function (BRIEF) scores as primary predictor variables Table 3. Final logistic regression models for Child and Adolescent Functional Assessment Scale (CAFAS) domain and total scores with California Verbal Learning Test (CVLT) and processing speed scores as primary predictor variables Table 4. Final logistic regression model for Child and Adolescent Functional Assessment Scale (CAFAS) total scores with Behavioral Rating Inventory of Executive Function (BRIEF) scores, California Verbal Learning Test (CVLT) and processing speed scores as primary predictors vi

Introduction Pediatric traumatic brain injury (TBI) is one of the most common causes of acquired morbidity and mortality in children. 1,2 TBI in children results in 2,685 deaths, 37,000 hospitalizations, and 435,000 emergency department visits in the United States. 2,3 Cognitive and behavioral deficits are common after pediatric TBI 4,5, with problems in executive function (EF) being particularly common and persisting long-term after injury. 6-10 EF is a complex construct and involves multiple overlapping domains including attentional control, goal setting, cognitive flexibility, working memory, inhibition, decision making, and information processing. 11-13 Difficulties in EF may lead to social and behavioral problems. Various aspects of EF are affected after TBI in children. 13 Anderson and Catroppa (2005) found a dose response relationship between TBI severity and four components of EF, attentional control; planning, goal setting, and problem solving; cognitive flexibility; and abstract reasoning 24 months after injury in children. 6 Other studies have also demonstrated longer term deficits in components of EF after TBI in children. Ten years after TBI in adolescents, individuals who sustained a severe TBI had poorer performance on goal setting and processing speed tasks compared to those with mild and moderate TBI and typically developing participants. 14 Additionally, deficits in EF, memory, and verbal IQ can persist 6 to 13 years after neurosurgically treated childhood TBI. 15 These studies demonstrate that various components of EF are affected after TBI in children; however, the extent to which EF and cognitive processes that subserve (i.e., memory and processing speed) EF skills relate to behavioral, emotional, and psychosocial difficulties after TBI in children is less clear. Several recent studies have begun to evaluate the relationships of EF and cognitive measures with behavioral and social outcomes after TBI in children. In a small study of 28 children age 8-16 years with TBI, Tonks et al. demonstrated that a psychometric measure of EF (Delis-Kaplan Executive Function System battery) and processing speed correlated with socio- 1

behavioral difficulties assessed by the Strength and Difficulties Questionnaire. 16 Similarly, in a study of children age 3-6 years with TBI (n=87) and orthopedic injuries (n=119), Ganesalingam et al. found that neuropsychological measures of EF (Delayed Alternation task and Shape School) and behavioral ratings of EF (Behavior Rating Inventory of Executive Function and Child Behavior Questionnaire) were correlated with social competence (Adaptive Behavior Assessment System, Pre-school Kindergarten Behavior Scales, and Home and Community Social Behavior Scales). 17 Behavioral ratings were more strongly correlated with social competence than neuropsychological measures of EF. 17 Furthermore, in a study of 36 adolescents age 16-22 years who sustained a TBI between age 8-12 years, problems in psychometric measures of EF predicted less sophisticated problem solving skills and poorer social outcomes in young adulthood. 18 Problem solving skills also mediated the relationship between poor EF with adverse social outcomes. 18 In other studies, reaction time and resistance to interference on a flanker task were correlated with long-term social outcomes 12 and processing speed was associated with socioemotional difficulties after TBI in children and adolescents. 19 After TBI in adults, lab-measures of EF and measures of memory have been associated with occupational and psychosocial outcomes. Lab-based EF measures explained 13.3% of the variance in occupational functioning and 16.0% in social integration in a large cohort of adolescents and adults after TBI. 20 Wood and Rutterford found that working memory predicted long-term employment status, community integration, and life satisfaction after adult brain injury. 21 These previous studies demonstrated that both behavioral and cognitive aspects of EF are associated with behavioral, psychosocial, and occupational outcomes after TBI in children. However, many studies have included relatively small sample sizes and further research is needed to improve our understanding of the relationship of behavioral and cognitive aspects of EF with behavioral and social functioning after TBI in children. 2

The goal of this paper is to build on these previous findings and better elucidate the association of functional impairments in behavior after TBI in adolescents with ratings of problems in executive function and psychometric measures of memory and processing speed. We hypothesized that higher levels of self- and parent-rated deficits in executive function, greater memory impairment, and slower processing speed would be associated with impaired behavioral functioning across multiple settings. A better understanding of the relationship of formal neurobehavioral and neurocognitive assessments with impairments in behavioral functioning after pediatric TBI would help in targeting interventions to individuals at increased risk for these problems. METHODS Participants The current study is part of a larger randomized clinical trial comparing the efficacy of two internet-based interventions: Counselor Assisted Problem Solving (CAPS), a 6-month webbased, family-centered intervention that focuses on problem solving, communication, and selfregulation. Study sites included 4 tertiary pediatric hospitals, 2 tertiary general medical centers, and 1 specialized children s hospital. Prior to initiation of the study, institutional review board approval was obtained from all participating institutions. Only baseline data collected as part of the initial assessment are presented here. Participants included adolescents age 12-17 years who sustained a moderate or severe TBI. We used the Glasgow Coma Scale (GCS) to characterize TBI severity. 22 Moderate TBI was defined as a GCS score of 9-12 or a higher score accompanied by evidence of neurological insult on neuroimaging. Severe TBI was defined as a GCS score below 9. Exclusion criteria included non-blunt trauma (e.g. penetrating head injury), primary language other than English, history of moderate or severe mental retardation prior to injury, history of child abuse as documented in the medical record or reported by parents, 3

insufficient recovery to allow participation in the study, and history of participant or parental psychiatric hospitalization one year previous to enrollment. Participants were enrolled 1-6 months after initial injury into the multi-center cross-sectional study. Of the 308 families initially identified as potential participants in the study, 52 did not meet inclusion criteria, 52 refused participation, 5 were unable to be contacted, and 67 were unable to be recruited during the initial 6 months post-injury. The final study population evaluated consisted of 132 participants, 65.15% males, 19.7% non-whites, and 38.63% severe TBIs. The mean age of injury was 14.54 years (SD = 1.74) and mean time since injury was 3.56 months (SD = 1.74). Age at injury, injury severity, and race were compared between participating and non-participating families. There were no differences in regard to age at injury between participants [mean age = 14.54 (SD=1.74)] and non-participants [mean age = 14.68 (SD=1.74)]. Non-participants were significantly more likely than participants to be non-white (24.4 % to 19.7%, respectively). There was also a significant difference in injury severity as measured by GCS between non-participants [mean GCS = 11.94 (3.89)] and participants [mean GCS = 10.03 (4.56)]. Measures Measures were collect during home visits by trained research coordinators. Impairments in behavioral functioning were assessed using the Child and Adolescent Functional Assessment Scale (CAFAS). The CAFAS is a structured clinical interview of adolescent functioning and has been used widely to assess clinical outcomes in children with serious emotional disturbances. 23,24 The CAFAS generates a total score as well as clinical ratings in eight domains: school, home, community, behavior toward others, moods/emotions, self-harmful behaviors, substance abuse, and thinking. 25 The rating is ordinal: 0 - no impairment, 10 - mild impairment, 20 - moderate impairment, and 30 - severe impairment. Additionally, a total score 4

(range: 0-240) is generated by adding the scores for each of the eight domains. The CAFAS has been well validated and has excellent inter-rater reliability with correlation coefficients ranging from 0.74-0.99. 23 To insure high inter-rater reliability for administration of the CAFAS for this study, a PhD level psychologist and Master s level counselor attended a 2-day training session provided by the creator of the CAFAS that certified them as CAFAS trainers. The certified trainers then provided subsequent training to site raters until they were able to pass the necessary tests to achieve 80% inter-rater reliability as recommended by the creator of the CAFAS. Trainers and raters participated in monthly reliability calls throughout the course of the study to discuss recently administered CAFAS interviews, answer questions that had arisen, and ensure that each site continued to rate the CAFAS in a standard manner. Each rater taped 10% of their CAFAS interviews, which were sent off to a certified trainer to be double rated for reliability. Inter-rater reliability was 90% in this study. The Behavior Rating Inventory of Executive Function (BRIEF) includes parent-rated and self-rated measures of everyday problems in executive function. 26-30 The measure has good internal consistency, inter-rater reliability, and test-retest reliability and has been validated in pediatric TBI. 26,30 The global executive composite (GEC) score was used to measure global executive functioning in this study. Higher scores indicate more problems in executive function, with a score of 65 or greater indicating clinical impairment. The California Verbal Learning Test (CVLT) was used to assess verbal learning and memory. 31,32 The CVLT child version 32 was used in participants up to age 17 and the adult version 31 was used in children 17 years and older. The CVLT has been used previously in pediatric TBI and has sound psychometric properties. 33-35 The T-score for trials 1-5 on the CVLT was used in the analysis with lower scores indicating greater verbal learning and memory impairment. The Wechsler processing speed index was used to assess processing speed. 36,37 The Wechsler intelligence scale for children, 4 th edition processing speed index (WISC-IV-PS) 36 was used in participants up to age 17 years 5

and the Wechsler adult intelligence scale, 4 th edition processing speed index (WAIS-IV-PS) 37 was used in participants older than age 17 years. The processing speed index is sensitive to effects of TBI. 34,38,39 The composite processing speed score was used in the analysis with lower scores indicating greater deficits in processing speed. Data analysis All data analysis was performed using SAS enterprise guide version 4.3 (SAS Institute, Inc., Cary, NC) or JMP genomics 5.0 (SAS Institute, Inc., Cary, NC). Pearson correlations were performed to determine the association among BRIEF self-report ratings, BRIEF primary caregiver ratings, CVLT scores, and processing speed scores. The CAFAS domain scores were dichotomized into no impairment versus any impairment for the analysis. For the CAFAS total score, consistent with previous studies 40,41 adolescents were classified into two levels of impairment: no/mild (n=87, score range:0-50) and at risk (n=45, score range: > 50). The severe and non-severe TBI groups were compared using t-tests for continuous scores and Chi-square for dichotomous outcomes. Logistic regression was performed for the dichotomized CAFAS total score and each domain score. GEC scores for the self and caregiver versions of the BRIEF and standardized scores for the CVLT and processing speed were each included as continuous independent variables in separate analyses. Covariates considered for each model included age at injury, months since injury, gender, caregiver education (less than high school or high school or greater), race (white or non-white), and injury severity (severe or non-severe TBI). Bivariate associations of dependent variables with each potential covariate were examined. If the bivariate analysis indicated that the covariate was associated with the dependent variable of interest at a p-value < 0.15, then it was included in the final models. Covariates not associated with the dependent variable at a p-value < 0.15 were excluded from the final models. 6

Results Correlation of Executive Function Ratings, Memory, and Processing Speed Measures GEC scores for the self-report and caregiver forms of the BRIEF were positively correlated (r=0.51, p< 0.0001) and the caregiver GEC score was negatively correlated with CVLT (r= -0.22, P=0.003) and processing speed (r=-0.26, P=0.02). The CVLT and processing speed were also correlated (r=0.41, P<0.0001). The GEC score for the BRIEF self-report form was not correlated significantly with either the CVLT or processing speed. Distribution of CAFAS Scores in the Study Sample The distributions of the CAFAS domain scores for the study participants were as follows: school (median = 0, mean = 7.12), home (median = 10, mean = 9.51), community (median = 0, mean = 1.36), behavior towards others (median = 0, mean = 6.06), moods and emotions (median = 10, mean = 9.02), self-harm (median = 0, mean = 0.68), substance abuse (median = 0, mean = 0.91), and thinking (median = 10, mean = 9.92) (Figure 1). The total CAFAS score median was 40 and mean (SD) was 45.76 (35.02). Thirty four percent of the study population scored in the at risk range (CAFAS total score > 50). The mean CAFAS total score (SD) for this group was 85.56 (26.25). Comparison of Severe and Non-severe TBI Groups (Table 1) Adolescents with severe TBI had significantly lower processing speed and CVLT scores (p < 0.05) than those with non-severe TBI. The groups did not differ significantly on the selfreport or caregiver GEC scores or on the CAFAS total or domain scores. However, a high proportion of individuals in both groups (non-severe and severe) had some impairment in the school (45.68% non-severe, 39.22% severe), home (67.90% non-severe, 70.59% severe), 7

behavior toward others (40.74% non-severe, 47.06% severe), moods and emotions (53.09% non-severe, 68.63% severe), and thinking (54.32% non-severe, 70.59% severe) domains. A relatively low proportion of individuals in both groups had some impairment in the community (8.64% non-severe, 9.80% severe), self-harm (2.47% non-severe, 5.90% severe), and substance abuse (3.70% non-severe, 9.80% severe) domains. Logistic Regression Models Examining GEC Scores as Predictors of the CAFAS (Table 2). Higher caregiver GEC scores were associated with impairments in the following CAFAS domains: school, odds ratio (95% confidence interval) [OR (CI)] = 1.09 (1.04,1.15), p < 0.01; home, OR (CI) = 1.10 (1.04,1.16), p < 0.01; community, OR (CI) = 1.13 (1.04,1.22), p = 0.01; behavior towards others, OR (CI) = 1.13 (1.07,`1.20), p < 0.01; and moods and emotions, OR (CI) = 1.06 (1.01,1.11), p=0.02). Boys had more dysfunction at school than girls, OR (CI) = 2.64 (1.08,6.44), p=.03. Shorter time since injury and severe TBI were associated with more dysfunction in moods and emotion, OR (CI) = 0.64 (0.50,0.82), p<0.01 and OR (CI) = 0.41 (0.17,0.96), p=0.04, respectively. Non-white race and severe TBI was associated with more thinking dysfunction, OR (CI) = 4.16 (1.22,14.23), p=0.02, OR (CI) = 0.43 (0.19,0.98), p=0.04, respectively. A higher caregiver GEC score was also associated with a higher level of impairment on the CAFAS total score, OR (CI) = 1.11 (1.05,1.17), p<0.01. The self-report GEC score was not significantly associated with any of the CAFAS domain scores or the total score. Logistic Regression Models for CAFAS Domain and Total Scores with CVLT and Processing Speed Scores as Primary Predictor Variables (Table 3). CVLT and processing speed scores did not significantly predict dysfunction on any of the CAFAS domain scores. Slower processing speed and lower CVLT scores were significantly 8

associated with higher levels of impairment on the total CAFAS score, OR (CI) = 0.97 (0.95, 1.00), p = 0.03 and 0.96 (0.93, 1.00), p= 0.03, respectively. Logistic Regression Models for CAFAS Total Score with BRIEF, CVLT, and Processing Speed in the Model as Primary Predictor Variables (Table 4). A higher caregiver GEC score was associated with more impairment on the CAFAS total school, OR (CI) = 1.09 (1.03,1.15), p <0.01. CVLT, processing speed and self-report GEC scores were not significantly associated with impairments on the total CAFAS score. Discussion Overall, this study demonstrated that primary caregiver ratings of problems in executive function after adolescent TBI were associated with functional impairment across multiple domains (school, home, community, behavior towards others, and moods and emotion), as well as with global behavioral functioning as assessed on the CAFAS. Verbal memory (CVLT) and processing speed were not associated with impairments in any of the CAFAS domain scores; however, slower processing speed and lower memory scores were associated with a greater likelihood of impaired global behavioral functioning. When considering behavioral ratings of executive function, memory, and processing speed together, behavioral ratings of problems in executive function (BRIEF) were associated with a greater likelihood of impaired global functioning. These findings suggest that primary caregiver ratings of problems in executive function and psychometric measures of processing speed and memory may all be predictive of behavioral impairment; however, the magnitude of the effects is small. This study adds to the literature by better elucidating the association of behavioral ratings of executive function and psychometric measures of memory and processing speed with impairment in behavioral functioning assessed using the CAFAS in a relatively large cohort of 9

adolescents who sustained a moderate or severe TBI. Previous studies have demonstrated an association between neuropsychological measures of executive functioning and occupational, social, and cognitive outcomes. 12,18-21,42 To our knowledge, this is the first study to evaluate the association of behavioral ratings of executive function, memory, and processing speed with functional outcomes as measured by the CAFAS. The CAFAS reliably determines the need for intensive services, assesses clinical changes, and can be used to monitor response to interventions for children with serious emotional disturbances. 24 It also predicts utilization of services better than either the Child Behavior Checklist (CBCL) or psychiatric diagnoses. 23,24 Understanding the ability of neuropsychological measures to predict behavioral impairments is important because it will potentially help hone screening and assessment batteries to include tests that are more sensitive to identification of adolescents at risk for functional impairments. Moreover, it may also allow clinicians to focus treatments where they are needed most. Despite moderate correlations between primary caregiver ratings of executive function and the CVLT (r=-0.26) and processing speed (r=-0.22), caregiver ratings of executive function were most often associated with behavioral impairments globally and across multiple domains in this study. These correlations indicate that behavioral ratings of executive function and measures of memory and processing speed measure overlapping but distinct constructs related to executive function. This finding is in agreement with previous work that describes the ecological validity of the BRIEF in the assessment of problems in executive function after pediatric TBI. 26 Interestingly, memory and processing speed scores were significantly different between individuals with severe and non-severe TBIs, indicating that these measures reflect injury severity, but may be less predictive of clinical functioning than the behavioral ratings. This could also reflect common method variance since both the BRIEF and CAFAS are based on parent report. Furthermore, memory and processing speed are commonly considered cool executive functions and risk taking behavior is considered hot executive function. 43,44 The hot 10

or behavioral components of executive function may be more associated with clinical functioning while the cool components may be more associated with cognitive tasks. Future research should continue to better define the relationship of behavioral and neurocognitive measures with clinical functioning after adolescent TBI. In the final regression models, several covariates assessed in this study were also predictive of clinical functioning. In the BRIEF models (Table 2), male gender was significantly associated with greater school dysfunction; less time since injury and severe injuries were associated with greater mood and emotion problems; and non-white race and severe injuries were associated with greater thinking impairment. Although parental education was associated with functioning in several of the bivariate models, it was not significantly associated with behavioral impairment on the CAFAS when BRIEF primary caregiver ratings were evaluated as the primary independent variable. Covariate effects also indicate that individual and injury related factors should be considered as potential modifiers of clinical functioning after adolescent TBI. In the processing speed and CVLT final models, several covariates were significantly associated with behavioral functioning on the CAFAS (Table 3). Socioeconomic status was significantly associated with school functioning and gender and time since injury were associated with moods and emotion behavioral functioning. This suggests that these variables may be important to consider when evaluating behavioral functioning after injury. Further research is needed to define the interaction among injury related variables, demographic variables, and performance-based cognitive measures to better identify individuals potentially at risk for poorer behavioral outcomes after injury. Self-report ratings of executive function were not associated with injury severity or clinical functioning on the CAFAS domain or total scores. This finding is in agreement with another study that found adolescents with TBI underestimated the degree of their executive function deficits. 45 Therefore, it is important to obtain behavioral information from sources other 11

than the adolescent when evaluating behavioral deficits in executive function and associated risk for behavioral impairment after TBI in this age group. In this study, 34% of adolescents with moderate and severe TBI scored in the at risk range on the total CAFAS score (> 50). The mean score for the at risk group was 85.56 (SD: 26.25), which is similar to scores for individuals with severe emotional disturbances receiving community mental health services (mean: 89.35, SD: 32.35). 40 Additionally, a high proportion of the study population had some impairment in the school, home, behavior toward others, moods and emotions, and thinking domains. A low proportion of the study population had some impairment in the community, self-harm, and substance abuse domains. Given that behavioral and emotional problems are common after pediatric TBI, further elucidation of the role of the CAFAS in the evaluation of clinical functioning after injury is needed. Limitations One of the primary limitations for this study is the lack of a non-tbi control group. However, the primary findings that caregiver ratings of executive function and psychometric measures of processing speed and verbal memory are associated with behavioral functioning on the CAFAS remain valid. The CAFAS is a well validated measure; however, this is the first study to our knowledge that utilized the scale to assess clinical functioning after adolescent TBI. In the future it will be important to examine the properties of the CAFAS as they relate to the assessment of outcomes after pediatric TBI. Another limitation is our focus on cross-sectional differences between TBI severity groups rather than on the effect of severity on longitudinal changes post-injury. Our failure to assess pre-injury functioning also precludes assessment of changes relative to premorbid levels of functioning. A final concern is that information on the child was obtained from parents, which may have artificially increased the association of primary caregiver ratings of executive function with our clinical ratings based on the CAFAS. Collection 12

of ratings from teachers would be useful in obtaining less biased estimates of associations of behavioral indications of poor executive function with findings from the CAFAS. Conclusions Our study demonstrated that primary caregiver behavioral ratings of executive function and performance-based measures of processing speed and verbal memory are significantly associated with functioning assessed using the CAFAS. Self-report ratings of executive function did not significantly predict functioning measured by the CAFAS. Larger longitudinal studies would better elucidate the association of behavioral and neuropsychological measures of executive functioning with clinical function after pediatric TBI. Understanding the ability of neuropsychological measures to predict clinical impairment is important because it will potentially help hone screening and assessment batteries and allow clinicians to focus treatments where they are needed most. The findings from this study suggest that cognitive and behavioral interventions that attempt to improve neurocognitive and neurobehavioral aspects of executive functioning may lead to improved clinical functioning after adolescent TBI. 13

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Appendix A: Figures Figure 1. Distribution of Child and Adolescent Functional Assessment Scale (CAFAS) domain scores in study population 19

Appendix B: Tables Table 1. Comparison of Outcome Measures for Individuals with Non-severe and Severe Traumatic Brain Injuries Measure Non-severe Mean (SD) Severe Mean (SD) BRIEF-PR 59.33 (10.70) 60.88 (9.44) BRIEF-SR 52.94 (13.10) 52.47 (12.20) Processing Speed* 95.57 (14.62) 82.84 (15.76) CVLT Score* 46.50 (12.84) 40.78 (11.53) CAFAS Total Score 42.35 +/- 34.03 51.18 +/- 36.20 CAFAS Domains Non-severe (% any impairment) Severe (% any impairment) School 45.68 39.22 Home 67.90 70.59 Community 8.64 9.80 Behavior Towards Others 40.74 47.06 Moods and Emotions 53.09 68.63 Self-Harm 2.47 5.88 Substance Use 3.70 9.80 Thinking 54.32 70.59 BRIEF-PR = Behavioral Rating Inventory of Executive Function primary caregiver report; BRIEF-SR = Behavioral Rating Inventor of Executive Function self-report; CVLT = California Verbal Learning Test; CAFAS = Child and Adolescent Functional Assessment Scale *indicates significant difference between groups at p-value < 0.05 20

Table 2. Final logistic regression models for Child and Adolescent Functional Assessment Scale (CAFAS) domain and total scores with Behavioral Rating Inventory of Executive Function (BRIEF) scores as primary predictor variables CAFAS domain Independent variables Odds Ratio (95% CI) p-value School Home Community Behavior towards others Moods and Emotions Thinking Total Score SES 1.19 (0.53,2.67) 0.68 Gender 2.64(1.08,6.44) 0.03 BRIEF-SR 1.00 (0.96,1.04) 0.98 BRIEF-PR 1.09 (1.04,1.15) < 0.01 SES 1.08 (0.45,2.62) 0.86 Age at injury 0.79 (0.60,1.04) 0.09 Gender 1.58 (0.63,4.00) 0.33 BRIEF-SR 1.00 (0.96, 1.04) 0.99 BRIEF-PR 1.10 (1.04,1.16) <0.01 BRIEF-SR 0.98 (0.92,1.03) 0.39 BRIEF-PR 1.13 (1.04,1.22) 0.01 SES 1.17 (0.48,2.83) 0.73 Race 2.52 (0.83,7.60) 0.10 BRIEF-SR 1.00 (0.96,1.04) 0.91 BRIEF-PR 1.13 (1.07,1.20) <0.01 Gender 0.49 (0.21,1.19) 0.11 Time since injury 0.64 (0.50,0.82) <0.01 Injury severity 0.41 (0.17,0.96) 0.04 BRIEF-SR 1.00 (0.96,1.04) 0.99 BRIEF-PR 1.06 (1.01,1.11) 0.02 SES 1.30 (0.56,3.04) 0.54 Race 4.16 (1.22,14.23) 0.02 Injury severity 0.43 (0.19,0.98) 0.04 BRIEF-SR 1.03 (1.00,1.07) 0.09 BRIEF-PR 1.03 (0.99,1.08) 0.17 BRIEF-SR 1.01 (0.97,1.04) 0.80 BRIEF-PR 1.11 (1.05,1.17) <0.01 CAFAS = Child and Adolescent Functional Assessment Scale; SES = socioeconomic status estimated by primary care giver education; BRIEF-SR = Behavioral Rating Inventor of Executive Function self-report; BRIEF-PR = Behavioral Rating Inventory of Executive Function primary caregiver report 21

Table 3. Final logistic regression models for Child and Adolescent Functional Assessment Scale (CAFAS) domain and total scores with California Verbal Learning Test (CVLT) and processing speed scores as primary predictor variables CAFAS domain Independent variables Odds Ratio (95% CI) p-value School Home Community Behavior towards others Moods and Emotions Thinking Total Score SES 2.36 (1.08,5.16) 0.03 Gender 2.22 (1.00,4.94) 0.05 CVLT 1.01 (0.98,1.05) 0.43 Processing Speed 1.01 (0.98,1.03) 0.67 SES 1.89 (0.81,4.41) 0.14 Age at injury 0.84 (0.66,1.08) 0.17 Gender 1.56 (0.66,3.74) 0.31 CVLT 1.02 (0.98,1.06) 0.28 Processing Speed 0.98 (0.95,1.00) 0.08 CVLT 1.02 (0.97,1.08) 0.41 Processing Speed 1.01 (0.97,1.05) 0.78 SES 1.90 (0.87,4.13) 0.11 Race 1.79 (0.69,4.62) 0.23 CVLT 0.99 (0.96,1.02) 0.54 Processing Speed 0.98 (0.96,1.01) 0.15 Gender 0.39 (0.17,0.93) 0.03 Time since injury 0.67 (0.53,0.85) <0.01 Injury severity 0.46 (0.19,1.09) 0.08 CVLT 0.99 (0.96,1.02) 0.54 Processing Speed 0.99 (0.96,1.02) 0.40 SES 1.35 (0.60,3.05) 0.47 Race 2.30 (0.78,6.76) 0.13 Injury severity 0.59 (0.25,1.39) 0.23 CVLT 0.98 (0.95,1.02) 0.28 Processing Speed 0.98 (0.95,1.00) 0.07 CVLT 0.96 (0.93,1.00) 0.03 Processing Speed 0.97 (0.95,1.00) 0.03 CAFAS = Child and Adolescent Functional Assessment Scale; SES = socioeconomic status estimated by primary care giver education; CVLT = California Verbal Learning Test 22

Table 4. Final logistic regression model for Child and Adolescent Functional Assessment Scale (CAFAS) total scores with Behavioral Rating Inventory of Executive Function (BRIEF) scores, California Verbal Learning Test (CVLT) and processing speed scores as primary predictors CAFAS domain Independent variables Odds Ratio (95% p-value CI) Total Score CVLT 0.97 (0.93,1.01) 0.11 Processing Speed 0.98 (0.95,1.01) 0.10 BRIEF-SR 1.01 (0.97,1.06) 0.50 BRIEF-PR 1.09 (1.03,1.15) <0.01 CAFAS = Child and Adolescent Functional Assessment Scale; SES = socioeconomic status estimated by primary care giver education; CVLT = California Verbal Learning Test; BRIEF-SR = Behavioral Rating Inventor of Executive Function self-report; BRIEF-PR = Behavioral Rating Inventory of Executive Function primary caregiver report 23