Relationships Among Structural Neuroimaging and Neurocognitive Outcomes in Adolescents and Young Adults with Congenital Heart Disease: A Systematic Review.

Congenital heart disease (CHD) is the most common cause of major congenital anomalies in the world. Disruptions to brain development in this population may impact cognitive outcomes. As individuals with CHD age, understanding of long-term neurocognitive and brain outcomes is essential. Synthesis of the current literature of brain-behavior relationships in adolescents and young adults with CHD is needed to understand long-term outcomes and identify literature gaps. This systematic review summarizes and integrates the current literature on the relationship between structural neuroimaging and neurocognitive outcomes in adolescents and young adults with CHD. Included papers were published through August 2, 2021. Searches were conducted on Pubmed and APA PsycInfo. Studies were eligible for inclusion if they evaluated adolescents or young adults (ages 10-35) with CHD, and without genetic comorbidity. Studies explored relationships among structural neuroimaging and neurocognitive outcomes, were in English, and were an empirical research study. A total of 22 papers were included in the current review. Data from each study was extracted and included in a table for comparison along with a systematic assessment of study quality. Results suggest worse brain outcomes (i.e., brain abnormality, reduced volume, lower fractional anisotropy, and brain topology) are related to poorer performance in neuropsychological domains of intelligence, memory, and executive functioning. Consistently, poorer memory performance was related to lower hippocampal and temporal region volumes. Statistically significant brain-behavior relationships in adolescents and young adults with CHD are generally observed across studies but there is a lack of consistency in investigated neuropsychological constructs and brain regions to be able to make specific conclusions. Further research with adult samples of CHD is needed to better understand the long-term impacts of early neurological insult.

Within-Individual BOLD Signal Variability and its Implications for Task-Based Cognition: A Systematic Review.

Within-individual blood oxygen level-dependent (BOLD) signal variability, intrinsic moment-to-moment signal fluctuations within a single individual in specific voxels across a given time course, is a relatively new metric recognized in the neuroimaging literature. Within-individual BOLD signal variability has been postulated to provide information beyond that provided by mean-based analysis. Synthesis of the literature using within-individual BOLD signal variability methodology to examine various cognitive domains is needed to understand how intrinsic signal fluctuations contribute to optimal performance. This systematic review summarizes and integrates this literature to assess task-based cognitive performance in healthy groups and few clinical groups. Included papers were published through October 17, 2022. Searches were conducted on PubMed and APA PsycInfo. Studies eligible for inclusion used within-individual BOLD signal variability methodology to examine BOLD signal fluctuations during task-based functional magnetic resonance imaging (fMRI) and/or examined relationships between task-based BOLD signal variability and out-of-scanner behavioral measure performance, were in English, and were empirical research studies. Data from each of the included 19 studies were extracted and study quality was systematically assessed. Results suggest that variability patterns for different cognitive domains across the lifespan (ages 7-85) may depend on task demands, measures, variability quantification method used, and age. As neuroimaging methods explore individual-level contributions to cognition, within-individual BOLD signal variability may be a meaningful metric that can inform understanding of neurocognitive performance. Further research in understudied domains/populations, and with consistent quantification methods/cognitive measures, will help conceptualize how intrinsic BOLD variability impacts cognitive abilities in healthy and clinical groups.

A Systematic Review of Host Genomic Variation and Neuropsychological Outcomes for Pediatric Cancer Survivors.

Pediatric survivors of brain tumors and acute lymphoblastic leukemia (ALL) are at risk for long-term deficits in their neuropsychological functioning. Researchers have begun examining associations between germline single nucleotide polymorphisms (SNPs), which interact with cancer treatment, and neuropsychological outcomes. This review synthesizes the impact of treatment-related toxicity from germline SNPs by neuropsychological domain (i.e., working memory, processing speed, psychological functioning) in pediatric survivors. By focusing on specific neuropsychological domains, this review will examine outcome measurement and critique methodology. Fourteen studies were identified and included in this review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). All studies were published in peer-reviewed journals in English by November 24th, 2021. Reviewed studies were not of sufficient quality for a meta-analysis due to varying measurement strategies, gaps in reported descriptive variables, and low power. All neuropsychological domains evaluated in this review had associations with SNPs, except fine motor and visual integration abilities. Only five SNPs had consistent neuropsychological findings in more than one study or cohort. Future research and replication studies should use validated measures of discrete skills that are central to empirically validated models of survivors' long-term outcomes (i.e., attention, working memory, processing speed). Researchers should examine SNPs across pathophysiological pathways to investigate additive genetic risk in pediatric cancer survivors. Two SNPs were identified that confer resiliency in neuropsychological functioning, and future work should investigate resiliency genotypes and their underlying biological mechanisms.

A systematic review of pediatric neuropsychological outcomes with proton versus photon radiation therapy: A call for equity in access to treatment.

OBJECTIVE: There is increasing interest in the utilization of proton beam radiation therapy (PRT) to treat pediatric brain tumors based upon presumed advantages over traditional photon radiation therapy (XRT). PRT provides more conformal radiation to the tumor with reduced dose to healthy brain parenchyma. Less radiation exposure to brain tissue beyond the tumor is thought to reduce neuropsychological sequelae. This systematic review aimed to provide an overview of published studies comparing neuropsychological outcomes between PRT and XRT. METHOD: PubMed, PsychINFO, Embase, Web of Science, Scopus, and Cochrane were systematically searched for peer-reviewed published studies that compared neuropsychological outcomes between PRT and XRT in pediatric brain tumor patients. RESULTS: Eight studies were included. Six of the studies utilized retrospective neuropsychological data; the majority were longitudinal studies (n = 5). XRT was found to result in lower neuropsychological functioning across time. PRT was associated with generally stable neuropsychological functioning across time, with the exception of working memory and processing speed, which showed variable outcomes across studies. However, studies inconsistently included or considered medical and sociodemographic differences between treatment groups, which may have impacted neuropsychological outcomes. CONCLUSIONS: Despite methodological limitations, including limited baseline neuropsychological evaluations, temporal variability between radiation treatment and first evaluation or initial and follow-up evaluations, and heterogenous samples, there is emerging evidence of sociodemographic inequities in access to PRT. With more institutions dedicating funding towards PRT, there may be the opportunity to objectively evaluate the neuropsychological benefits of patients matched on medical and sociodemographic variables.

Graph Theoretical Analysis of Brain Network Characteristics in Brain Tumor Patients: A Systematic Review.

Graph theory is a branch of mathematics that allows for the characterization of complex networks, and has rapidly grown in popularity in network neuroscience in recent years. Researchers have begun to use graph theory to describe the brain networks of individuals with brain tumors to shed light on disrupted networks. This systematic review summarizes the current literature on graph theoretical analysis of magnetic resonance imaging data in the brain tumor population with particular attention paid to treatment effects and other clinical factors. Included papers were published through June 24th, 2020. Searches were conducted on Pubmed, PsycInfo, and Web of Science using the search terms (graph theory OR graph analysis) AND (brain tumor OR brain tumour OR brain neoplasm) AND (MRI OR EEG OR MEG). Studies were eligible for inclusion if they: evaluated participants with a primary brain tumor, used graph theoretical analyses on structural or functional MRI data, MEG, or EEG, were in English, and were an empirical research study. Seventeen papers met criteria for inclusion. Results suggest alterations in network properties are often found in people with brain tumors, although the directions of differences are inconsistent and few studies reported effect sizes. The most consistent finding suggests increased network segregation. Changes are most prominent with more intense treatment, in hub regions, and with factors such as faster tumor growth. The use of graph theory to study brain tumor patients is in its infancy, though some conclusions can be drawn. Future studies should focus on treatment factors, changes over time, and correlations with functional outcomes to better identify those in need of early intervention.

White matter pathways associated with empathy in females: A DTI investigation.

Empathy is a component of social cognition that allows us to understand, perceive, experience, and respond to the emotional state of others. In this study, we seek to build on previous research that suggests that sex and hormone levels may impact white matter microstructure. These white matter microstructural differences may influence social cognition. We examine the fractional anisotropy (FA) of white matter pathways associated with the complex human process of empathy in healthy young adult females during the self-reported luteal phase of their menstrual cycle. We used tract-based spatial statistics to perform statistical comparisons of FA and conducted multiple linear regression analysis to examine the strength of association between white matter FA and scores on the Empathy Quotient (EQ), a self-report questionnaire in which individuals report how much they agree or disagree with 60 statements pertaining to their empathic tendencies. Results identified a significant negative relationship between EQ scores and FA within five clusters of white matter: in the left forceps minor/body of the corpus callosum, left corticospinal tract, intraparietal sulcus/primary somatosensory cortex, superior longitudinal fasciculus, and right inferior fronto-occipital fasciculus/forceps minor. These consistent findings across clusters suggest that lower self-reported empathy is related to higher FA across healthy young females in specific white matter regions during the menstrual luteal phase. Future research should seek to examine if self-reported empathy varies across the menstrual cycle, using blood samples to confirm cycle phase and hormone levels.

Cerebellar-Subcortical-Cortical Systems as Modulators of Cognitive Functions.

Over the past few decades, research has established that the cerebellum is involved in executive functions; however, its specific role remains unclear. There are numerous theories of cerebellar function and numerous cognitive processes falling under the umbrella of executive function, making investigations of the cerebellum's role in executive functioning challenging. In this review, we explored the role of the cerebellum in executive functioning through clinical and cognitive neuroscience frameworks. We reviewed the neuroanatomical systems and theoretical models of cerebellar functions and the multifaceted nature of executive functions. Using attention deficit hyperactivity disorder and cerebellar tumor as clinical developmental models of cerebellar dysfunction, and the functional magnetic resonance imaging literature, we reviewed evidence for cerebellar involvement in specific components of executive function in childhood, adolescence, and adulthood. There is evidence for posterior cerebellar contributions to working memory, planning, inhibition, and flexibility, but the heterogeneous literature that largely was not designed to study the cerebellum makes it difficult to determine specific functions of the cerebellum or cerebellar regions. In addition, while it is clear that cerebellar insult in childhood affects executive function performance later in life, more work is needed to elucidate the mechanisms by which executive dysfunction occurs and its developmental course. The limitations of the current literature are discussed and potential directions for future research are provided.

White matter hyperintensity volumes are related to processing speed in long-term survivors of childhood cerebellar tumors.

PURPOSE: Across several clinical populations, higher white matter hyperintensity (WMH) burden is consistently associated with decreases in cognitive performance, especially processing speed. Research of childhood cancer survivors has not utilized WMH quantification methodology to better understand the impact of WMH burden and its relationship with core cognitive skills. The present study aimed to quantify WMH volumes in a sample of long-term survivors of childhood cerebellar tumor and investigate the relationships with performance on a measure of oral processing speed. To further explore brain-behavior relationships, multivariate sparse canonical correlations was employed to identify WMH areas that predict processing speed performance. METHODS: Thirty-five survivors and 56 healthy controls underwent neuroimaging and completed a measure of oral processing speed. The survivor group was further divided based on treatment (i.e., chemoradiation therapy (n = 20) vs. surgery only (n = 15)) to better understand the impact of treatment. RESULTS: Survivors, and especially those treated with chemoradiation therapy, showed higher total WMH volumes and slower processing speed. Higher total WMH volumes were significantly associated with poorer processing speed (r = - 0.492, p = 0.003). Multivariate brain-behavior relationships revealed that periventricular WMHs were significantly associated with slower processing speed performance (p < 0.05). CONCLUSION: Results exemplify that long-term survivors treated with and without chemoradiation therapy are at increased risk of developing higher WMH volumes compared to healthy peers. In addition, processing speed was robustly shown to be related to periventricular WMHs using an automated neuroimaging pipeline. This methodology to monitor WMH burden has the potential to be implemented efficiently with routine clinical neuroimaging of cancer survivors.

The Neurological Predictor Scale Predicts Adaptive Functioning via Executive Dysfunction in Young Adult Survivors of Childhood Brain Tumor.

OBJECTIVES: Survivors of childhood brain tumors experience neurological sequelae that disrupt everyday adaptive functioning (AF) skills. The Neurological Predictor Scale (NPS), a cumulative measure of tumor treatments and sequelae, predicts cognitive outcomes, but findings on its relation to informant-reported executive dysfunction (ED) and AF are mixed. Given known effects of frontal-subcortical system disruptions on AF, this study assessed the NPS' relationship with AF as mediated by frontal systems dysfunction, measured by the Frontal Systems Behavior Scale (FrSBe). METHODS: 75 participants (Mage = 23.5, SDage = 4.5) were young adult survivors of childhood brain tumors at least 5 years past diagnosis. FrSBe and Scales of Independent Behavior-Revised (SIB-R), a measure of AF, were administered to informants. Parallel multiple mediator models included Apathy and ED as mediators, and age at diagnosis and time between diagnosis and assessment as covariates. RESULTS: More complex treatment and sequelae were correlated with poorer functioning. Mediation models were significant for all subscales: Motor Skills (MS), p = .0001; Social Communication (SC), p = .002; Personal Living (PL), p = .004; Community Living (CL), p = .007. The indirect effect of ED on SC and CL was significant; the indirect effect of Apathy was not significant for any subscales. CONCLUSIONS: More complex tumor treatment and sequelae were associated with poorer long-term AF via increased ED. Cognitive rehabilitation programs may focus on the role of executive function and initiation that contribute to AF, particularly SC and CL skills, to help survivors achieve comparable levels of independence in everyday function as their peers.

Distinct neural networks for detecting violations of adjacent versus nonadjacent sequential dependencies: An fMRI study.

The ability to learn and process sequential dependencies is essential for language acquisition and other cognitive domains. Recent studies suggest that the learning of adjacent (e.g., "A-B") versus nonadjacent (e.g., "A-X-B") dependencies have different cognitive demands, but the neural correlates accompanying such processing are currently underspecified. We developed a sequential learning task in which sequences of printed nonsense syllables containing both adjacent and nonadjacent dependencies were presented. After incidentally learning these grammatical sequences, twenty-one healthy adults (age M = 22.1, 12 females) made familiarity judgments about novel grammatical sequences and ungrammatical sequences containing violations of the adjacent or nonadjacent structure while in a 3T MRI scanner. Violations of adjacent dependencies were associated with increased BOLD activation in both posterior (lateral occipital and angular gyrus) as well as frontal regions (e.g., medial frontal gyrus, inferior frontal gyrus). Initial results indicated no regions showing significant BOLD activations for the violations of nonadjacent dependencies. However, when using a less stringent cluster threshold, exploratory analyses revealed that violations of nonadjacent dependencies were associated with increased activation in subcallosal cortex, paracingulate cortex, and anterior cingulate cortex (ACC). Finally, when directly comparing the adjacent condition to the nonadjacent condition, we found significantly greater levels of activation for the right superior lateral occipital cortex (BA 19) for the adjacent relative to nonadjacent condition. In sum, the detection of violations of adjacent and nonadjacent dependencies appear to involve distinct neural networks, with perceptual brain regions mediating the processing of adjacent but not nonadjacent dependencies. These results are consistent with recent proposals that statistical-sequential learning is not a unified construct but depends on the interaction of multiple neurocognitive mechanisms acting together.

Cerebellar Contributions to Proactive and Reactive Control in the Stop Signal Task: A Systematic Review and Meta-Analysis of Functional Magnetic Resonance Imaging Studies.

The cerebellum facilitates and modulates cognitive functions using forward and inverse internal models to predict and control behavior, respectively. Despite neuroimaging evidence that regions of the cerebellum are active during executive function (EF) tasks in general, little is known about the cerebellum's role in specific EFs and their underlying neural networks. Inhibitory control specifically may be facilitated by cerebellar internal models predicting responses during proactive control (withholding), and controlling responses during reactive control (inhibiting). The stop signal task (SST) is an inhibitory control task often used in neuroimaging studies to measure neural responses to both proactive and reactive control. Thus, in this review, we examine evidence for the cerebellum's role in inhibitory control by reviewing studies of healthy adults that utilized the SST in event-related functional magnetic resonance imaging (fMRI) experiments. Twenty-one studies that demonstrated cerebellar results were eligible for review, including 749 participants, 28 contrasts, and 38 cerebellar clusters. We also performed activation likelihood estimation (ALE) meta-analysis of contrasts derived from reviewed studies. This review illustrates evidence for the cerebellum participating in inhibitory control independent of motor control. Most significant cerebellar clusters were located in the left posterior cerebellum, suggesting that it communicates with the established cortical right-lateralized inhibitory control network. Cerebellar activity was most consistently observed for contrasts that measured proactive control, and ALE analysis confirmed that left Crus I is most likely to be activated in studies of proactive control measuring monitoring and anticipation. Results suggest that the left posterior cerebellum may communicate with right frontal and parietal cortices, using forward models to predict appropriate responses. Reactive control contrasts indicated a possible role for cerebellar regions in enhancing inhibition efficiency through inverse models, but ALE meta-analysis did not confirm this hypothesis. Limitations in the current literature, clinical implications, and directions for future research are discussed.

Early Brain Injury and Adaptive Functioning in Middle Childhood: The Mediating Role of Pragmatic Language.

OBJECTIVE: Traumatic brain injuries (TBIs) often adversely affect adaptive functioning (AF). However, the cognitive mechanisms by which AF is disrupted are not well understood in young children who sustain TBI. This study examined pragmatic language (PL) and executive functioning (EF) as potential mechanisms for AF disruption in children with early, predominantly mild-complicated, TBI. METHOD: The sample consisted of 76 children between the ages of 6 and 10 years old who sustained a TBI (n = 36) or orthopedic injury (OI; n = 40) before 6 years of age and at least 1 year prior to testing (M = 4.86 years, SD = 1.59). Children's performance on a PL and an expressive vocabulary task (which served as a control task), and parent report of child's EF and AF were examined at two time points 1 year apart (i.e., at age 8 and at age 9 years). RESULTS: Injury type (TBI vs. OI) significantly predicted child's social and conceptual, but not practical, AF. Results indicated that PL, and not expressive vocabulary or EF at time 1, mediated the relationship between injury type and both social and conceptual AF at time 2. CONCLUSIONS: A TBI during early childhood appears to subtly, but uniquely, disrupt complex language skills (i.e., PL), which in turn may disrupt subsequent social and conceptual AF in middle childhood. Additional longitudinal research that examines different aspects of PL and adaptive outcomes into adolescence is warranted.

Double Dissociation of Auditory Attention Span and Visual Attention in Long-Term Survivors of Childhood Cerebellar Tumor: A Deterministic Tractography Study of the Cerebellar-Frontal and the Superior Longitudinal Fasciculus Pathways.

OBJECTIVE: Right cerebellar-left frontal (RC-LF) white matter integrity (WMI) has been associated with working memory. However, prior studies have employed measures of working memory that include processing speed and attention. We examined the relationships between the RC-LF WMI and processing speed, attention, and working memory to clarify the relationship of RC-LF WMI with a specific cognitive function. Right superior longitudinal fasciculus II (SLF II) WMI and visual attention were included as a negative control tract and task to demonstrate a double dissociation. METHODS: Adult survivors of childhood brain tumors [n = 29, age: M = 22 years (SD = 5), 45% female] and demographically matched controls were recruited (n = 29). Tests of auditory attention span, working memory, and visual attention served as cognitive measures. Participants completed a 3-T MRI diffusion-weighted imaging scan. Fractional anisotropy (FA) and radial diffusivity (RD) served as WMI measures. Partial correlations between WMI and cognitive scores included controlling for type of treatment. RESULTS: A correlational double dissociation was found. RC-LF WMI was associated with auditory attention (FA: r = .42, p = .03; RD: r = -.50, p = .01) and was not associated with visual attention (FA: r = -.11, p = .59; RD: r = -.11, p = .57). SLF II FA WMI was associated with visual attention (FA: r = .44, p = .02; RD: r = -.17, p = .40) and was not associated with auditory attention (FA: r = .24, p = .22; RD: r = -.10, p = .62). CONCLUSIONS: The results show that RC-LF WMI is associated with auditory attention span rather than working memory per se and provides evidence for a specificity based on the correlational double dissociation.

Oral processing speed as a key mechanism in the relationship between neurological risk and adaptive functioning in survivors of pediatric brain tumors.

PURPOSE: Brain tumor (BT) survivors are at risk for difficulties with adaptive functioning (AF). Recent work has associated neurological risk with poorer AF outcomes using the Neurological Predictor Scale (NPS), a quantification of neurological risk factors. Survivors also have poorer attention, processing speed, and working memory, which are all important for AF. The current study examined whether these cognitive constructs explain the relationship between the NPS and AF in survivors. METHODS: Ninety-five adult BT survivors and 135 healthy controls were recruited from the Atlanta area. The Oral Symbol Digits Modalities test was used to measure processing speed, Digit Span Backward assessed working memory, and Digit Span Forward measured attention. Informants completed the Scales of Independent Behavior (SIB-R) to measure AF. Group differences and correlations were assessed, and the PROCESS macro for SPSS tested indirect effects. RESULTS: Survivors were significantly lower on AF and cognitive measures compared with controls. Attention span and processing speed had significant indirect effects in relationship between NPS and AF individually, but processing speed was the only variable with a significant indirect effect when all cognitive variables were included in the model. The NPS and processing speed together account for approximately 39% of variance in AF outcomes. CONCLUSIONS: BT survivors in our sample have lower AF than controls, and processing speed appears to be particularly important in explaining the relationship between neurological risk and AF. In the future, the development of interventions aimed at increasing young adult independence should target both cognitive processing speed and AF skills.

A novel social attribution paradigm: The Dynamic Interacting Shape Clips (DISC).

The Dynamic Interacting Shape Clips (DISC) is a novel stimulus set designed to examine mentalizing, specifically social attribution, suitable for use with diverse methodologies including fMRI. The DISC offer some advantages compared to other social attribution stimuli including a large number of stimuli, subsets of stimuli depicting different kinds of social interactions (i.e., friendly approach, aggression, and avoidance), and two control tasks-one that contrasts interpretations of socially contingent movement versus random, inanimate movement, and the other that examines the impact of attentional shifts on mentalizing using the same visual stimuli with a different cue. This study describes both behavioral and fMRI findings from a sample of 22 typically developing adults (mage = 21.7 years, SD = 1.72). Behavioral data supports participants anthropomorphized the stimuli and the social intent of the clips were perceived as intended. Neuroimaging findings demonstrate that brain areas associated with processing animacy and mental state attribution were activated when participants were shown clips featuring social interactions compared to random movement, and when attention was cued to social versus physical aspects of the same stimuli. Results lend empirical support for the use of the DISC in future studies of social cognition.

Caregiver- and Clinician-Reported Adaptive Functioning in Rett Syndrome: a Systematic Review and Evaluation of Measurement Strategies.

Rett syndrome is the second most common cause of intellectual disability in females worldwide. The severity of many individuals' impairment limits the effectiveness of traditional assessment. However, clinician and parent reports of adaptive functioning may provide insight into these patients' abilities. This review aims to synthesize the current literature assessing adaptive functioning in Rett syndrome and evaluate existing measurement tools in this population. A search was conducted on PubMed using the search term "Rett syndrome." Studies that quantitatively assessed adaptive functioning outcomes in Rett syndrome with published and normed questionnaire measures were included. Twenty-three studies met inclusion criteria. Overall results indicate that the population of people with Rett syndrome is highly impaired, both in overall adaptive functioning as well as in specific subdomains (e.g., mobility, activities of daily living). Atypical Rett syndrome groups performed better on measures of adaptive functioning relative to patients with classic Rett syndrome. Our findings identified measurement weaknesses, as many of the studies found floor effects and therefore were unable to capture meaningful variability in outcomes. Individuals with Rett syndrome are highly reliant on caregivers due to disrupted adaptive functioning abilities. Optimizing measurement of adaptive skills in Rett syndrome will facilitate the quantification of meaningful change in skills and the identification of efficacious interventions aimed at improving outcomes and quality of life.

Neurological predictor scale is associated with academic achievement outcomes in long-term survivors of childhood brain tumors.

INTRODUCTION: Survivors of childhood brain tumors exhibit impairments in academic performance and have lower rates of educational attainment compared to healthy same-aged peers. Prior research has demonstrated the concurrent validity of the Neurological Predictor Scale (NPS), a measure that incorporates tumor-related treatments and complications into one cumulative score, in predicting IQ, adaptive functioning, and core neurocognitive skills. The purpose of this study is to determine whether the NPS predicts academic achievement outcomes over and above the effects of individual treatment factors alone. METHODS: Sixty-two adult survivors completed four untimed measures of academic achievement from the Woodcock-Johnson III. RESULTS: NPS scores significantly predicted performance on all four academic measures: Letter Word ID (R2 = - 0.454, p < .01), Calculation (R2 = - 0.494, p < .01), Spelling (R2 = - 0.428, p < .01) and Passage Comprehension (R2 = - 0.447, p < .01). 16% of survivors were impaired on the Letter Word ID, 23% on Calculation, 19% on Spelling, and 11% on Passage Comprehension subtests with impairment defined as z ≤ - 1.5. The NPS predicted academic outcomes over and above chemotherapy, surgery, seizure medication, endocrine dysfunction, hydrocephalus, and radiation on all measures. CONCLUSION: This study extends prior research by demonstrating that the NPS is significantly associated with academic achievement in survivors on average 15.9 years after diagnosis. The NPS may be especially helpful in clinical research when studies lack the statistical power to investigate how treatments and neurological conditions individually contribute to outcomes.

The Effects of Radiation and Sex Differences on Adaptive Functioning in Adult Survivors of Pediatric Posterior Fossa Brain Tumors.

OBJECTIVE: Radiation therapy (RT) improves rates of survival of patients with childhood brain tumors but increases deficits in cognition and independent living skills. Previous literature has studied difficulties in basic cognitive processes, but few explore impairment in higher-order skills such as adaptive functioning. Some studies identify females as at risk for cognitive deficits due to RT, but few investigate sex differences in adaptive functioning. It was hypothesized that females would exhibit poorer long-term independent living skills and core cognitive skills relative to males following RT. METHODS: Forty-five adult survivors of posterior fossa childhood brain tumors (24 females) completed the Wechsler Abbreviated Scale of Intelligence (WASI-II), Wechsler Memory Scale, Third Edition (WMS-III) Digit Span Forward (DSF) and Backward (DSB), and Oral Symbol Digit Modalities Test (OSDMT). Informants completed the Scales of Independent Behavior-Revised (SIB-R). RESULTS: DSF and OSDMT were positively correlated with all five SIB-R domains, full-scale IQ (FSIQ) was positively correlated with four SIB-R domains, and DSB was positively correlated with three SIB-R domains. There was an interaction between sex and RT for OSDMT and community living skills with trend level interactions for personal living skills and broad independent living skills, where females without RT had higher scores than females with RT. CONCLUSIONS: Female survivors were more affected by RT than males across the community living skills domain of adaptive functioning as well as processing speed. Processing speed deficits may have a cascading impact on daily living skills. Future studies should investigate how clinical and biological factors may contribute to personalized treatment plans between sexes. (JINS, 2019, 25, 729-739).

Early Elementary School Outcome in Children With a History of Traumatic Brain Injury Before Age 6 Years.

OBJECTIVE: To describe elementary school outcomes for children who experienced a traumatic brain injury (TBI) before age 6 years compared with a control group of children with orthopedic injuries. PARTICIPANTS: Children ages 6 to 9 years recruited from community and trauma registries in a large southeastern state. DESIGN: Descriptive findings from the first year of a 3-year longitudinal study. MAIN MEASURES: Child assessment and parent report measures were administered to capture cognitive, language, reading, and behavior outcomes. Medical record review confirmed injuries and injury severity. RESULTS: The TBI group (n = 39) had a mean age of 7.55 years (standard deviation = 1.29) and was 5.15 (standard deviation = 1.56) years postinjury. The TBI group had primarily classified as mild complicated TBI (63%). On average, children in both groups performed within normal limits on most cognitive, language, and reading measures. Group differences were identified in verbal IQ, receptive language, and reading comprehension, with robust performance differences in pragmatic language, story retell and word fluency, and parent report of executive functions. CONCLUSIONS: Findings indicate the importance of in-depth follow-up specialist assessments (eg, neuropsychologist and speech and language pathologists) to identify potential nuanced difficulties in children with mild complicated TBI that may be missed by general evaluations.

Roles of positive psychological outcomes in future health perception and mental health problems: A report from the Childhood Cancer Survivor Study.

OBJECTIVE: Positive psychological outcomes among adolescent and young adult survivors of childhood cancer may influence long-term health status. We examined posttraumatic growth (PTG) and Life satisfaction (LS) in adolescence, and their impact on future emotional and physical health status in young adulthood. METHODS: Survivors (n = 2802) from the Childhood Cancer Survivor Study were longitudinally analyzed across social, emotional, and physical factors during adolescence (12-17 years old), and PTG (PTG-Inventory) and LS (Cantril-Ladder-of-Life) during young adulthood (19-24 years old). The impact of PTG and LS on survivors' future long-term mental health, physical health, and social skills was also examined (23-28 years old) using Structural Equation Modeling. RESULTS: Survivors reported high levels of LS (M = 7.43, range 1 to 10) and a positive impact from their cancer experience (M = 48.78, range 0 to 105). Adolescent predictors of higher PTG included older age at diagnosis (p = 0.001), experiencing more severe chronic health conditions (p = 0.01), cancer recurrence/relapse (p = 0.01), and being diagnosed with a non-CNS cancer (p = 0.001). Higher perceived general health (p = 0.01), higher social skills (p = 0.001), and diagnosis with a non-CNS cancer (p = 0.02) were associated with higher LS. Higher PTG during young adulthood predicted poorer perceived health (p = 0.04) and worse emotional health (p = 0.001) in later adulthood. Higher LS predicted better emotional health (p = 0.001) and better perceived health (p = 0.001). CONCLUSIONS: While LS was found to help survivors have better perceived long-term emotional and physical health outcomes, survivors with higher PTG fond both positive and negative impacts from cancer. Future therapeutic trials to improve LS should be considered.