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BACKGROUND: Pediatric brain tumor survivors (PBTS) experience neurocognitive late effects, including problems with working memory, processing speed, and other higher order skills. These skill domains are subserved by various white matter (WM) pathways, but not much is known about these brain-behavior links in PBTS. This study examined the anterior corona radiata (ACR), inferior fronto-occipital fasciculi (IFOF), and superior longitudinal fasciculi (SLF) by analyzing associations among diffusion metrics and neurocognition. PROCEDURE: Thirteen PBTS and 10 healthy controls (HC), aged 9-14 years, completed performance-based measures of processing speed and executive function, and parents rated their child's day-to-day executive skills. Children underwent magnetic resonance imaging (MRI) with diffusion weighted imaging that yielded fractional anisotropy (FA) and mean diffusivity (MD) values. Independent samples t-tests assessed group differences on neurocognitive and imaging measures, and pooled within-group correlations examined relationships among measures across groups. RESULTS: PBTS performed more poorly than HC on measures of processing speed, divided attention, and shifting (d = -1.08 to -1.44). WM microstructure differences were significant in MD values for the bilateral SLF and ACR, with PBTS showing higher diffusivity (d = 0.75 to 1.21). Better processing speed, divided attention, and shifting were associated with lower diffusivity in the IFOF, SLF, and ACR, but were not strongly correlated with FA. CONCLUSIONS: PBTS demonstrate poorer neurocognitive functioning that is linked to differences in WM microstructure, as evidenced by higher diffusivity in the ACR, SLF, and IFOF. These findings support the use of MD in understanding alterations in WM microstructure in PTBS and shed light on potential functions of these pathways.
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Neoplasias Encefálicas , Substância Branca , Criança , Humanos , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Imagem de Tensor de Difusão/métodos , Encéfalo/patologia , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Sobreviventes , AnisotropiaRESUMO
OBJECTIVE: To understand how methylphenidate (MPH) is used in youth with traumatic brain injury (TBI) during inpatient pediatric rehabilitation. SETTING: Inpatient pediatric rehabilitation. PARTICIPANTS: In total, 234 children with TBI; 62 of whom received MPH and 172 who did not. Patients were on average 11.6 years of age (range, 2 months to 21 years); 88 of 234 were female; the most common mechanism of injury was motor vehicle collision (49%); median (IQR) acute hospital length of stay (LOS) and inpatient rehabilitation LOS were 16 (10-29) and 23 (14-39), respectively; 51 of 234 were in a disorder of consciousness cognitive state at time of inpatient rehabilitation admission. DESIGN: Multicenter, retrospective medical record review. MAIN MEASURES: Patient demographic data, time to inpatient pediatric rehabilitation admission (TTA), cognitive state, MPH dosing (mg/kg/day). RESULTS: Patients who received MPH were older (P = .011); TTA was significantly longer in patients who received MPH than those who did not (P =.002). The lowest recorded dose range by weight was 0.05 to 0.89 mg/kg/d, representing an 18-fold difference; the weight-based range for the maximum dose was 0.11 to 0.97 mg/kg/d, a 9-fold difference. Patients in lower cognitive states at admission (P = .001) and at discharge (P = .030) were more likely to receive MPH. Five patients had side effects known to be associated with MPH; no serious adverse events were reported. CONCLUSION: This multicenter study indicates that there is variable use of MPH during acute inpatient rehabilitation for children with TBI. Children who receive MPH tend to be older with lower cognitive states. Dosing practices are likely consistent with underdosing. Clinical indications for MPH use during inpatient pediatric rehabilitation should be better defined. The use of MPH, as well as its combination with other medications and treatments, during inpatient rehabilitation needs to be further explored.
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Lesões Encefálicas Traumáticas , Estimulantes do Sistema Nervoso Central , Metilfenidato , Padrões de Prática Médica , Humanos , Metilfenidato/uso terapêutico , Metilfenidato/administração & dosagem , Criança , Feminino , Lesões Encefálicas Traumáticas/reabilitação , Masculino , Adolescente , Pré-Escolar , Estudos Retrospectivos , Estimulantes do Sistema Nervoso Central/uso terapêutico , Estimulantes do Sistema Nervoso Central/administração & dosagem , Lactente , Padrões de Prática Médica/estatística & dados numéricos , Adulto Jovem , Pacientes Internados , Tempo de Internação , Centros de ReabilitaçãoRESUMO
OBJECTIVE: To examine predictive utility of the Glasgow Coma Scale (GCS), time to follow commands (TFC), length of posttraumatic amnesia (PTA), duration of impaired consciousness (TFC+PTA), and the Cognitive and Linguistic Scale (CALS) scores in predicting outcomes on the Glasgow Outcome Scale-Extended, Pediatric Revision (GOS-E Peds) for children with traumatic brain injury (TBI) at 2 months and 1 year after discharge from rehabilitation. SETTING: A large, urban pediatric medical center and inpatient rehabilitation program. PARTICIPANTS: Sixty youth with moderate-to-severe TBI (mean age at injury = 13.7 years; range = 5-20). DESIGN: A retrospective chart review. MAIN MEASURES: Lowest postresuscitation GCS, TFC, PTA, TFC+PTA, inpatient rehabilitation admission and discharge CALS scores, GOS-E Peds at 2-month and 1-year follow-ups. RESULTS: CALS scores were significantly correlated with the GOS-E Peds at both time points (weak-to-moderate correlation for admission scores and moderate correlation for discharge scores). TFC and TFC+PTA were correlated with GOS-E Peds scores at a 2-month follow-up and TFC remained a predictor at a 1-year follow-up. The GCS and PTA were not correlated with the GOS-E Peds. In the stepwise linear regression model, only the CALS at discharge was a significant predictor of the GOS-E Peds at the 2-month and 1-year follow-ups. CONCLUSIONS: In our correlational analysis, better performance on the CALS was associated with less long-term disability, and longer TFC was associated with more long-term disability, as measured by the GOS-E Peds. In this sample, the CALS at discharge was the only retained significant predictor of GOS-E Peds scores at 2-month and 1-year follow-ups, accounting for roughly 25% of the variance in GOS-E scores. As previous research suggests, variables related to rate of recovery may be better predictors of outcome than variables related to severity of injury at a single time point (eg, GCS). Future multisite studies are needed to increase sample size and standardize data collection methods for clinical and research purposes.
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Lesões Encefálicas Traumáticas , Lesões Encefálicas , Humanos , Criança , Adolescente , Lesões Encefálicas/reabilitação , Estudos Retrospectivos , Estado de Consciência , Pacientes Internados , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/diagnóstico , Escala de Coma de GlasgowRESUMO
OBJECTIVES: To describe dosing practices for amantadine hydrochloride and related adverse effects among children and young adults with traumatic brain injury (TBI) admitted to pediatric inpatient rehabilitation units. SETTING: Eight pediatric acute inpatient rehabilitation units located throughout the United States comprising the Pediatric Brain Injury Consortium. PARTICIPANTS: Two-hundred thirty-four children and young adults aged 2 months to 21 years with TBI. DESIGN: Retrospective data revie. MAIN OUTCOME MEASURES: Demographic variables associated with the use of amantadine, amantadine dose, and reported adverse effects. RESULTS: Forty-nine patients (21%) aged 0.9 to 20 years received amantadine during inpatient rehabilitation. Forty-five percent of patients admitted to inpatient rehabilitation with a disorder of consciousness (DoC) were treated with amantadine, while 14% of children admitted with higher levels of functioning received amantadine. Children with DoC who were not treated with amantadine were younger than those with DoC who received amantadine (median 3.0 vs 11.6 years, P = .008). Recorded doses of amantadine ranged from 0.7 to 13.5 mg/kg/d; the highest total daily dose was 400 mg/d. Adverse effects were reported in 8 patients (16%); nausea/abdominal discomfort and agitation were most common, each reported in 3 patients. The highest reported dose without an adverse effect was 10.1 mg/kg/d. CONCLUSION: During pediatric inpatient rehabilitation, amantadine was prescribed to children across a range of ages and injury severity and was most commonly prescribed to older children with DoC. Dosing varied widely, with weight-based dosing for younger/smaller children at both lower and higher doses than what had been previously reported. Prospective studies are needed to characterize the safety and tolerability of higher amantadine doses and optimize amantadine dosing parameters for children with TBI.
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Lesões Encefálicas Traumáticas , Lesões Encefálicas , Adolescente , Amantadina/uso terapêutico , Lesões Encefálicas/reabilitação , Lesões Encefálicas Traumáticas/complicações , Criança , Humanos , Pacientes Internados , Estudos Retrospectivos , Estados Unidos , Adulto JovemRESUMO
OBJECTIVES: To characterize the demographics, clinical course, and predictors of cognitive recovery among children and young adults receiving inpatient rehabilitation following pediatric traumatic brain injury (TBI). DESIGN: Retrospective observational, multicenter study. SETTING: Eight acute pediatric inpatient rehabilitation facilities in the United States with specialized programs for treating patients with TBI. PARTICIPANTS: Children and young adults (0-21 years) with TBI (n = 234) receiving inpatient rehabilitation. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Admission and discharge status assessed by the WeeFIM Cognitive Developmental Functional Quotient (DFQ) and Cognitive and Linguistic Scale (CALS). RESULTS: Patients admitted to pediatric inpatient rehabilitation are diverse in cognitive functioning. While the majority of patients make improvements, cognitive recovery is constrained for those admitted with the most severe cognitive impairments. Age, time since injury to rehabilitation admission, and admission WeeFIM Cognitive DFQ are significant predictors of cognitive functioning at discharge from inpatient rehabilitation. CONCLUSIONS: This work establishes a multicenter Pediatric Brain Injury Consortium and characterized the demographics and clinical course of cognitive recovery during inpatient rehabilitation of pediatric patients with TBI to aid in prospective study design.
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Lesões Encefálicas Traumáticas , Lesões Encefálicas , Lesões Encefálicas Traumáticas/diagnóstico , Criança , Cognição , Humanos , Pacientes Internados , Tempo de Internação , Estudos Prospectivos , Recuperação de Função Fisiológica , Centros de Reabilitação , Estudos Retrospectivos , Estados Unidos , Adulto JovemRESUMO
PURPOSE: After treatment, pediatric brain tumor survivors (PBTS) face emotional and behavioral challenges, perhaps due to tumor or treatment-related changes in brain structures involved in emotion regulation, including those with fronto-limbic connections. We hypothesized that relative to healthy controls (HCs), PBTS would exhibit greater difficulties with behavior and emotional functioning, and display reduced mean fractional anisotropy (mFA) in white matter tracts with fronto-limbic connections including the cingulum bundle (CB), inferior fronto-occipital fasciculus (IFOF), and uncinate fasciculus (UF). We further predicted that mFA would account for variance in the relationship between group and emotional/behavioral outcome. METHODS: Eleven 8-16 year old PBTS and 14 HCs underwent MRI, including diffusion tensor imaging to assess white matter microstructure. Tractography quantified mFA of selected tracts. Parents rated children's emotional and behavioral functioning. RESULTS: Compared to HCs, caregivers of PBTS reported poorer behavioral regulation and greater internalizing and externalizing symptoms. Relative to HCs, PBTS had lower mFA within the bilateral CB, IFOF, and UF (ds = 0.59-1.15). Across groups, several medium-to-large correlations linked tract mFA and increased internalizing, externalizing, and poor behavioral regulation. Tract mFA also accounted for significant variance in the group-outcome association. CONCLUSIONS: Reduced mFA in fronto-limbic associated tracts may be associated with reduced behavioral regulation following pediatric brain tumor. PBTS with treatment known to impact white matter may be most susceptible. Research with larger, longitudinal samples should clarify this relationship, allow for multiple mediators across time, and consider factors like tumor and treatment type.
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Neoplasias Encefálicas/fisiopatologia , Sobreviventes de Câncer/estatística & dados numéricos , Emoções/fisiologia , Lobo Frontal/patologia , Sistema Límbico/patologia , Comportamento Problema , Substância Branca/patologia , Adolescente , Anisotropia , Mapeamento Encefálico/métodos , Neoplasias Encefálicas/psicologia , Estudos de Casos e Controles , Criança , Imagem de Tensor de Difusão/métodos , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Taxa de SobrevidaRESUMO
BACKGROUND: Children are at risk for behavioral and adaptive difficulties following pediatric brain tumor. This study explored whether familial/demographic, developmental, diagnostic, or treatment-related variables best predict posttreatment behavioral and adaptive functioning. METHODS: Participants included 40 children (mean age = 12.76 years, SD = 4.01) posttreatment (mean time since diagnosis = 1.99 years, SD = 0.21) for pediatric brain tumor. Parents rated children's behavioral adjustment and adaptive functioning and provided demographic and developmental histories. Diagnostic and treatment-related information was abstracted from medical records. RESULTS: Ratings of adaptive and behavioral functioning approximately 2 years postdiagnosis were within the average range, although the percentage of children exceeding clinical cutoffs for impairment in adaptive skills exceeded expectation, particularly practical skills. Premorbid behavior problems and tumor size predicted posttreatment adaptive functioning. After accounting for adaptive functioning near diagnosis, premorbid behavior problems predicted declines in adaptive functioning 2 years postdiagnosis. After accounting for adjustment near diagnosis, no variables predicted declines in behavioral adjustment. CONCLUSIONS: Children may be vulnerable to reduced adaptive functioning following pediatric brain tumor treatment, especially in practical skills. Assessing prediagnosis functioning and diagnostic and treatment-related variables may improve our ability to predict those at greatest risk, although those factors may be less helpful in identifying children likely to develop behavioral difficulties. Screening of these factors in tertiary care and long-term follow-up settings may improve identification of those at greatest need for support services.
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Adaptação Psicológica/efeitos da radiação , Neoplasias Encefálicas/psicologia , Neoplasias Encefálicas/radioterapia , Transtornos do Comportamento Infantil/etiologia , Comportamento Infantil/efeitos da radiação , Desempenho Psicomotor/efeitos da radiação , Adolescente , Neoplasias Encefálicas/diagnóstico , Criança , Transtornos do Comportamento Infantil/psicologia , Feminino , Humanos , Masculino , Pais , Ajustamento SocialRESUMO
OBJECTIVES: The current study examines whether psychosocial outcomes following pediatric traumatic brain injury (TBI) vary as a function of children's rejection sensitivity (RS), defined as their disposition to be hypersensitive to cues of rejection from peers. METHODS: Children ages 8-13 with a history of severe TBI (STBI, n=16), complicated mild/moderate TBI (n=35), or orthopedic injury (OI, n=49) completed measures assessing self-esteem and RS on average 3.28 years post-injury (SD=1.33, range=1.25-6.34). Parents reported on their child's emotional and behavioral functioning and social participation. RESULTS: Regression analyses found moderation of group differences by RS for three outcomes: social participation, self-perceptions of social acceptance, and externalizing behavior problems. Conditional effects at varying levels of RS indicated that externalizing problems and social participation were significantly worse for children with STBI at high levels of RS, compared to children with OI. Social participation for the STBI group remained significantly lower than the OI group at mean levels of RS, but not at low levels of RS. At high levels of RS, self-perceptions of social acceptance were lower for children with moderate TBI compared to OI, but group differences were not significant at mean or low levels of RS. No evidence of moderation was found for global self-worth, self-perceptions of physical appearance or athletic ability, or internalizing problems. CONCLUSIONS: The findings highlight the salient nature of social outcomes in the context of varying levels of RS. These findings may have implications for the design of interventions to improve social outcomes following TBI. (JINS, 2017, 23, 451-459).
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Osso e Ossos/lesões , Lesões Encefálicas Traumáticas/psicologia , Comportamento Infantil/psicologia , Comportamento Problema/psicologia , Distância Psicológica , Participação Social/psicologia , Adolescente , Concussão Encefálica/psicologia , Criança , Feminino , Humanos , MasculinoRESUMO
Resting state functional magnetic resonance imaging (rsfMRI) provides researchers and clinicians with a powerful tool to examine functional connectivity across large-scale brain networks, with ever-increasing applications to the study of neurological disorders, such as traumatic brain injury (TBI). While rsfMRI holds unparalleled promise in systems neurosciences, its acquisition and analytical methodology across research groups is variable, resulting in a literature that is challenging to integrate and interpret. The focus of this narrative review is to address the primary methodological issues including investigator decision points in the application of rsfMRI to study the consequences of TBI. As part of the ENIGMA Brain Injury working group, we have collaborated to identify a minimum set of recommendations that are designed to produce results that are reliable, harmonizable, and reproducible for the TBI imaging research community. Part one of this review provides the results of a literature search of current rsfMRI studies of TBI, highlighting key design considerations and data processing pipelines. Part two outlines seven data acquisition, processing, and analysis recommendations with the goal of maximizing study reliability and between-site comparability, while preserving investigator autonomy. Part three summarizes new directions and opportunities for future rsfMRI studies in TBI patients. The goal is to galvanize the TBI community to gain consensus for a set of rigorous and reproducible methods, and to increase analytical transparency and data sharing to address the reproducibility crisis in the field.
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Lesões Encefálicas Traumáticas , Imageamento por Ressonância Magnética , Humanos , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Lesões Encefálicas Traumáticas/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/normas , Reprodutibilidade dos Testes , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Descanso/fisiologia , Processamento de Imagem Assistida por Computador/métodos , Processamento de Imagem Assistida por Computador/normas , Mapeamento Encefálico/métodos , Mapeamento Encefálico/normasRESUMO
Deficits in memory performance have been linked to a wide range of neurological and neuropsychiatric conditions. While many studies have assessed the memory impacts of individual conditions, this study considers a broader perspective by evaluating how memory recall is differentially associated with nine common neuropsychiatric conditions using data drawn from 55 international studies, aggregating 15,883 unique participants aged 15-90. The effects of dementia, mild cognitive impairment, Parkinson's disease, traumatic brain injury, stroke, depression, attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and bipolar disorder on immediate, short-, and long-delay verbal learning and memory (VLM) scores were estimated relative to matched healthy individuals. Random forest models identified age, years of education, and site as important VLM covariates. A Bayesian harmonization approach was used to isolate and remove site effects. Regression estimated the adjusted association of each clinical group with VLM scores. Memory deficits were strongly associated with dementia and schizophrenia (p < 0.001), while neither depression nor ADHD showed consistent associations with VLM scores (p > 0.05). Differences associated with clinical conditions were larger for longer delayed recall duration items. By comparing VLM across clinical conditions, this study provides a foundation for enhanced diagnostic precision and offers new insights into disease management of comorbid disorders.
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Critical congenital heart disease (cCHD) has neurodevelopmental sequelae that can carry into adulthood, which may be due to aberrant brain development or brain injury in the prenatal and perinatal/neonatal periods and beyond. Health disparities based on the intersection of sex, geography, race, and ethnicity have been identified for poorer pre- and postnatal outcomes in the general population, as well as those with cCHD. These disparities are likely driven by structural racism, disparities in social determinants of health, and provider bias, which further compound negative brain development outcomes. This review discusses how aberrant brain development in cCHD early in life is affected by reduced access to quality care (ie, prenatal care and testing, postnatal care) due to divestment in non-White neighbourhoods (eg, redlining) and food insecurity, differences in insurance status, location of residence, and perceived interpersonal racism and bias that disproportionately affects pregnant people of colour who have fewer economic resources. Suggestions are discussed for moving forward with implementing strategies in medical education, clinical care, research, and gaining insight into the communities served to combat disparities and bias while promoting cultural humility.
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Cardiopatias Congênitas , Racismo , Recém-Nascido , Gravidez , Feminino , Humanos , Racismo Sistêmico , Determinantes Sociais da Saúde , Cardiopatias Congênitas/epidemiologia , Encéfalo , Disparidades em Assistência à SaúdeRESUMO
OBJECTIVE: Adolescents born extremely preterm (EPT, gestational age [GA] <28 weeks) are at higher risk for problems in peer socialization than those born full-term (FT, GA >36 weeks). This study was designed to examine the possibility that adolescents born EPT may also have difficulty in transitioning from parents to peers for socialization, a process referred to as "social reorienting." A secondary aim was to investigate associations of social reorienting with other neurodevelopmental characteristics. METHODS: The Network of Relationships Inventory, Relationship Quality Version was administered to 24 adolescents (ages 11-16 years) born EPT and 29 born FT to obtain self-ratings of closeness and discord with parents and peers. Measures of other neurodevelopmental characteristics included tests of cognitive and social skills, adolescent self-ratings of adjustment and victimization, and parent ratings of youth behavior and adaptive skills. Mixed model analyses controlling for sex, socioeconomic status, and race were conducted to examine group differences in measures of relationship quality and their associations with other neurodevelopmental characteristics. RESULTS: The EPT group had higher ratings of closeness with parents than the FT group. For adolescents from lower socioeconomic backgrounds, those born EPT had lower closeness with peers. Higher closeness with parents was associated with lower test scores. Lower closeness and more discord with peers were associated with more behavior problems. CONCLUSION: Findings suggest that adolescents born EPT have difficulties in social reorientation toward peers and identify factors related to these difficulties. Results imply a need for interventions to improve peer socialization in youth born EPT.
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Lactente Extremamente Prematuro , Relações Interpessoais , Recém-Nascido , Humanos , Adolescente , Criança , Lactente , Pais , Grupo Associado , Idade GestacionalRESUMO
Introduction: Extremely preterm (EPT) birth, defined as birth at a gestational age (GA) <28 weeks, can have a lasting impact on cognition throughout the life span. Previous investigations reveal differences in brain structure and connectivity between infants born preterm and full-term (FT), but how does preterm birth impact the adolescent connectome? Methods: In this study, we investigate how EPT birth can alter broadscale network organization later in life by comparing resting-state functional magnetic resonance imaging connectome-based parcellations of the entire cortex in adolescents born EPT (N = 22) to age-matched adolescents born FT (GA ≥37 weeks, N = 28). We compare these parcellations to adult parcellations from previous studies and explore the relationship between an individual's network organization and behavior. Results: Primary (occipital and sensorimotor) and frontoparietal networks were observed in both groups. However, there existed notable differences in the limbic and insular networks. Surprisingly, the connectivity profile of the limbic network of EPT adolescents was more adultlike than the same network in FT adolescents. Finally, we found a relationship between adolescents' overall cognition score and their limbic network maturity. Discussion: Overall, preterm birth may contribute to the atypical development of broadscale network organization in adolescence and may partially explain the observed cognitive deficits.
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Conectoma , Nascimento Prematuro , Lactente , Feminino , Adulto , Humanos , Recém-Nascido , Adolescente , Encéfalo/diagnóstico por imagem , Lactente Extremamente Prematuro , Imageamento por Ressonância Magnética/métodos , Conectoma/métodosRESUMO
Importance: Traumatic brain injury (TBI) is known to cause widespread neural disruption in the cerebrum. However, less is known about the association of TBI with cerebellar structure and how such changes may alter executive functioning. Objective: To investigate alterations in subregional cerebellum volume and cerebral white matter microstructure after pediatric TBI and examine subsequent changes in executive function. Design, Setting, and Participants: This retrospective cohort study combined 12 data sets (collected between 2006 and 2020) from 9 sites in the Enhancing Neuroimaging Genetics Through Meta-Analysis Consortium Pediatric TBI working group in a mega-analysis of cerebellar structure. Participants with TBI or healthy controls (some with orthopedic injury) were recruited from trauma centers, clinics, and institutional trauma registries, some of which were followed longitudinally over a period of 0.7 to 1.9 years. Healthy controls were recruited from the surrounding community. Data analysis occurred from October to December 2022. Exposure: Accidental mild complicated-severe TBI (msTBI) for those in the TBI group. Some controls received a diagnosis of orthopedic injury. Main Outcomes and Measures: Volume of 18 cerebellar lobules and vermal regions were estimated from 3-dimensional T1-weighted magnetic resonance imaging (MRI) scans. White matter organization in 28 regions of interest was assessed with diffusion tensor MRI. Executive function was measured by parent-reported scores from the Behavior Rating Inventory of Executive Functioning. Results: A total of 598 children and adolescents (mean [SD] age, 14.05 [3.06] years; range, 5.45-19.70 years; 386 male participants [64.5%]; 212 female participants [35.5%]) were included in the study, with 314 participants in the msTBI group, and 284 participants in the non-TBI group (133 healthy individuals and 151 orthopedically injured individuals). Significantly smaller total cerebellum volume (d = -0.37; 95% CI, -0.52 to -0.22; P < .001) and subregional cerebellum volumes (eg, corpus medullare; d = -0.43; 95% CI, -0.58 to -0.28; P < .001) were observed in the msTBI group. These alterations were primarily seen in participants in the chronic phase (ie, >6 months postinjury) of injury (total cerebellar volume, d = -0.55; 95% CI, -0.75 to -0.35; P < .001). Smaller cerebellum volumes were associated with higher scores on the Behavior Rating Inventory of Executive Functioning Global Executive Composite score (ß = -208.9 mm3; 95% CI, -319.0 to -98.0 mm3; P = .008) and Metacognition Index score (ß = -202.5 mm3; 95% CI, -319.0 to -85.0 mm3; P = .02). In a subset of 185 participants with longitudinal data, younger msTBI participants exhibited cerebellum volume reductions (ß = 0.0052 mm3; 95% CI, 0.0013 to 0.0090 mm3; P = .01), and older participants slower growth rates. Poorer white matter organization in the first months postinjury was associated with decreases in cerebellum volume over time (ß=0.52 mm3; 95% CI, 0.19 to 0.84 mm3; P = .005). Conclusions and Relevance: In this cohort study of pediatric msTBI, our results demonstrated robust cerebellar volume alterations associated with pediatric TBI, localized to the posterior lobe. Furthermore, longitudinal cerebellum changes were associated with baseline diffusion tensor MRI metrics, suggesting secondary cerebellar atrophy. These results provide further understanding of secondary injury mechanisms and may point to new opportunities for intervention.
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Concussão Encefálica , Lesões Encefálicas Traumáticas , Adolescente , Humanos , Criança , Feminino , Masculino , Estudos de Coortes , Estudos Retrospectivos , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Cerebelo/diagnóstico por imagem , AtrofiaRESUMO
Investigators in neuroscience have turned to Big Data to address replication and reliability issues by increasing sample sizes, statistical power, and representativeness of data. These efforts unveil new questions about integrating data arising from distinct sources and instruments. We focus on the most frequently assessed cognitive domain - memory testing - and demonstrate a process for reliable data harmonization across three common measures. We aggregated global raw data from 53 studies totaling N = 10,505 individuals. A mega-analysis was conducted using empirical bayes harmonization to remove site effects, followed by linear models adjusting for common covariates. A continuous item response theory (IRT) model estimated each individual's latent verbal learning ability while accounting for item difficulties. Harmonization significantly reduced inter-site variance while preserving covariate effects, and our conversion tool is freely available online. This demonstrates that large-scale data sharing and harmonization initiatives can address reproducibility and integration challenges across the behavioral sciences.
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This pilot study examined the associations among functional connectivity in the salience, central executive, and default mode networks, and neurocognition in pediatric brain tumor survivors and healthy children. Thirteen pediatric brain tumor survivors (9 boys, M = 12.76 years) and 10 healthy children (6 boys, M = 12.70 years) completed magnetic resonance imaging (MRI) and assessment of processing speed and executive function. Pediatric brain tumor survivors performed more poorly than healthy children on measures of processing speed, divided attention, and working memory; parent ratings of day-to-day executive function did not differ significantly by group, though both pediatric brain tumor survivors who underwent only surgical resection and healthy children were rated by parents as having difficulties approaching a standard deviation above the normative mean. Connectivity was lower in the salience network and greater in the default mode network in pediatric brain tumor survivors. Cross-method correlations showed that increased salience network and default mode network connectivity were associated with better task performance and parent-rated executive skills and higher central executive network connectivity with poorer parent-rated executive skills. This perhaps reflects an adaptive pattern of hyperconnectivity in pediatric brain tumor survivors.
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Neoplasias Encefálicas , Função Executiva , Masculino , Criança , Humanos , Projetos Piloto , Imageamento por Ressonância Magnética , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Sobreviventes , Mapeamento Encefálico , Encéfalo , Vias Neurais , Rede NervosaRESUMO
OBJECTIVE: Extremely preterm birth has been associated with atypical visual and neural processing of faces, as well as differences in gray matter structure in visual processing areas relative to full-term peers. In particular, the right fusiform gyrus, a core visual area involved in face processing, has been shown to have structural and functional differences between preterm and full-term individuals from childhood through early adulthood. The current study used multiple neuroimaging modalities to build a machine learning model based on the right fusiform gyrus to classify extremely preterm birth status. METHOD: Extremely preterm adolescents (n = 20) and full-term peers (n = 24) underwent structural and functional magnetic resonance imaging. Group differences in gray matter density, measured via voxel-based morphometry (VBM), and blood-oxygen level-dependent (BOLD) response to face stimuli were explored within the right fusiform. Using group difference clusters as seed regions, analyses investigating outgoing white matter streamlines, regional homogeneity, and functional connectivity during a face processing task and at rest were conducted. A data driven approach was utilized to determine the most discriminative combination of these features within a linear support vector machine classifier. RESULTS: Group differences in two partially overlapping clusters emerged: one from the VBM analysis showing less density in the extremely preterm cohort and one from BOLD response to faces showing greater activation in the extremely preterm relative to full-term youth. A classifier fit to the data from the cluster identified in the BOLD analysis achieved an accuracy score of 88.64% when BOLD, gray matter density, regional homogeneity, and functional connectivity during the task and at rest were included. A classifier fit to the data from the cluster identified in the VBM analysis achieved an accuracy score of 95.45% when only BOLD, gray matter density, and regional homogeneity were included. CONCLUSION: Consistent with previous findings, we observed neural differences in extremely preterm youth in an area that plays an important role in face processing. Multimodal analyses revealed differences in structure, function, and connectivity that, when taken together, accurately distinguish extremely preterm from full-term born youth. Our findings suggest a compensatory role of the fusiform where less dense gray matter is countered by increased local BOLD signal. Importantly, sub-threshold differences in many modalities within the same region were informative when distinguishing between extremely preterm and full-term youth.
Assuntos
Encéfalo , Nascimento Prematuro , Adolescente , Adulto , Criança , Feminino , Humanos , Lactente Extremamente Prematuro , Recém-Nascido , Aprendizado de Máquina , Imageamento por Ressonância Magnética/métodos , Nascimento Prematuro/patologia , Lobo TemporalRESUMO
Adolescents born preterm (<37 weeks of gestation) are at elevated risk for deficits in social cognition and peer relationships. Theory of Mind (ToM) is a complex form of social cognition important for regulating social interactions. ToM and the underlying mentalizing network continue to develop across adolescence. The present study recruited 48 adolescents (12-17 years old) who were either born extremely preterm (EPT; <28 weeks of gestation) or full-term (FT) at birth. Cortical thickness, gray matter volume and surface area were measured in four regions of the mentalizing network: the temporoparietal junction, anterior temporal cortex, posterior superior temporal sulcus and frontal pole (mBA10). We also assessed the adolescents' performance on a ToM task. Findings revealed both group differences and group-by-age interaction effects in the gray matter indices within the temporal lobe regions of the mentalizing network. The EPT group also performed significantly worse than the FT group on the ToM task. The cortical structural measures that discriminated the EPT and FT groups were not related to ToM performance. These results highlight altered developmental changes in brain regions underlying mentalizing functions in EPT adolescents relative to FT controls.
Assuntos
Mentalização , Teoria da Mente , Recém-Nascido , Adolescente , Humanos , Criança , Teoria da Mente/fisiologia , Imageamento por Ressonância Magnética , Lactente Extremamente Prematuro , Encéfalo/diagnóstico por imagem , Mapeamento EncefálicoRESUMO
The purpose of this study was to determine associations among neurocognitive outcomes and white matter integrity in the inferior fronto-occipital fasciculus (IFOF), uncinate fasciculus (UF), and genu of the corpus callosum (gCC) in survivors of pediatric brain tumor and healthy controls (HCs). Eleven survivors (ages 8-16; >2 years post-treatment) and 14 HCs underwent MRI; diffusion tensor imaging tractography (DSI Studio) was used to assess white matter integrity. Participants completed neuropsychological assessment of overall cognitive ability, executive function, processing speed, divided attention, and memory. As previously reported, survivors performed significantly worse than HCs on measures of overall IQ, working memory, processing speed, and executive function (ps < .01), but not on measures of long-delay memory. Mean fractional anisotropy was significantly lower in survivors than HC in the right IFOF, left UF, and gCC (ps < .05). Correlations with the total sample revealed a number of significant positive associations among white matter tracts and scores on neurocognitive measures. Survivors show deficits on measures of cognitive function and decreased white matter integrity compared to HCs. Results revealed a more general pattern of associations among white matter pathways and neurocognitive outcomes than initially hypothesized. It is possible that survivors with diffuse pathology from treatment effects (i.e., hydrocephalus or posterior fossa syndrome) show more general decreases in cognitive functioning and white matter integrity. Additional research with a larger and more diverse group of survivors is needed to better understand white matter integrity and neurocognitive outcome associations in this population.
Assuntos
Neoplasias Encefálicas , Substância Branca , Adolescente , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/diagnóstico por imagem , Criança , Imagem de Tensor de Difusão , Humanos , Projetos Piloto , Sobreviventes , Substância Branca/diagnóstico por imagemRESUMO
The aim of this study was to examine the feasibility of cognitive assessment from pre-surgery through 2-year follow-up in a sample of pediatric brain tumor (BT) patients. We sought to investigate cognitive function over the course of diagnosis and treatment, and as a function of presenting problems, tumor location, treatment type, and tumor severity. Using a prospective, longitudinal design, standardized IQ measures were administered to pediatric BT patients (ages 6-16) prior to surgery (n = 25), 6 months post-diagnosis (n = 24), and 24 months post-diagnosis (n = 23). Group differences emerged based on tumor severity and treatment type at multiple time points, including prior to surgical intervention; children with high grade tumors performed more poorly than children with low grade tumors, and children receiving surgery plus adjuvant therapy performed more poorly than children who received surgery only. When considered together, an analysis of covariance demonstrated that tumor grade significantly accounted for variability in cognitive functioning, while treatment type did not. Although there is overlap clinically between tumor severity and treatment received, results suggest that tumor severity is an important factor contributing to variability in cognitive functioning and should also be considered when monitoring risk for cognitive deficits in children diagnosed with BT.