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Children with traumatic brain injury are at risk of neurocognitive and behavioural impairment. Although there is evidence for abnormal brain activity in resting-state networks after TBI, the role of resting-state network organisation in paediatric TBI outcome remains poorly understood. This study is the first to investigate the impact of paediatric TBI on resting-state network organisation using graph theory, and its relevance for functional outcome. Participants were 8–14 years and included children with (i) mild TBI and risk factors for complicated TBI (mildRF+, n = 20), (ii) moderate/severe TBI (n = 15), and (iii) trauma control injuries (n = 27). Children underwent resting-state functional magnetic resonance imaging (fMRI), neurocognitive testing, and behavioural assessment at 2.8 years post-injury. Graph theory was applied to fMRI timeseries to evaluate the impact of TBI on global and local organisation of the resting-state network, and relevance for neurocognitive and behavioural functioning. Children with TBI showed atypical global network organisation as compared to the trauma control group, reflected by lower modularity (mildRF + TBI and moderate/severe TBI), higher smallworldness (mildRF + TBI) and lower assortativity (moderate/severe TBI ps < .04, Cohen's ds: > .6). Regarding local network organisation, the relative importance of hub regions in the network did not differ between groups. Regression analyses showed relationships between global as well as local network parameters with neurocognitive functioning (i.e., working memory, memory encoding; R2 = 23.3 - 38.5%) and behavioural functioning (i.e., externalising problems, R2 = 36.1%). Findings indicate the impact of TBI on global functional network organisation, and the relevance of both global and local network organisation for long-term neurocognitive and behavioural outcome after paediatric TBI. The results suggest potential prognostic value of resting-state network organisation for outcome after paediatric TBI.

Recent evidence suggests that cardiovascular fitness and gross motor skill performance are related to neurocognitive functioning by influencing brain structure and functioning. This study investigates the role of resting-state networks (RSNs) in the relation of cardiovascular fitness and gross motor skills with neurocognitive functioning in healthy 8- to 11-year-old children (n = 90, 45 girls, 10% migration background). Cardiovascular fitness and gross motor skills were related to brain activity in RSNs. Furthermore, brain activity in RSNs mediated the relation of both cardiovascular fitness (Frontoparietal network and Somatomotor network) and gross motor skills (Somatomotor network) with neurocognitive functioning. The results indicate that brain functioning may contribute to the relation between both cardiovascular fitness and gross motor skills with neurocognitive functioning.

The beneficial effects of physical activity on neurocognitive functioning in children are considered to be facilitated by physical activity-induced changes in brain structure and functioning. In this study, we examined the effects of two 14-week school-based exercise interventions in healthy children on white matter microstructure and brain activity in resting-state networks (RSNs) and whether changes in white matter microstructure and RSN activity mediate the effects of the exercise interventions on neurocognitive functioning. A total of 93 children were included in this study (51% girls, mean age 9.13 years). The exercise interventions consisted of four physical education lessons per week, focusing on either aerobic or cognitively demanding exercise and were compared with a control group that followed their regular physical education program of two lessons per week. White matter microstructure was assessed using diffusion tensor imaging in combination with tract-based spatial statistics. Independent component analysis was performed on resting-state data to identify RSNs. Furthermore, neurocognitive functioning (information processing and attention, working memory, motor response inhibition, interference control) was assessed by a set of computerized tasks. Results indicated no Group × Time effects on white matter microstructure or RSN activity, indicating no effects of the exercise interventions on these aspects of brain structure and function. Likewise, no Group × Time effects were found for neurocognitive performance. This study indicated that 14-week school-based interventions regarding neither aerobic exercise nor cognitive-demanding exercise interventions influence brain structure and brain function in healthy children. This study was registered in the Netherlands Trial Register (NTR5341).

BACKGROUND AND OBJECTIVES Outcome prediction of preterm birth is important for neonatal care, yet prediction performance using conventional statistical models remains insufficient. Machine learning has a high potential for complex outcome prediction. In this scoping review, we provide an overview of the current applications of machine learning models in the prediction of neurodevelopmental outcomes in preterm infants, assess the quality of the developed models, and provide guidance for future application of machine learning models to predict neurodevelopmental outcomes of preterm infants. METHODS A systematic search was performed using PubMed. Studies were included if they reported on neurodevelopmental outcome prediction in preterm infants using predictors from the neonatal period and applying machine learning techniques. Data extraction and quality assessment were independently performed by 2 reviewers. RESULTS Fourteen studies were included, focusing mainly on very or extreme preterm infants, predicting neurodevelopmental outcome before age 3 years, and mostly assessing outcomes using the Bayley Scales of Infant Development. Predictors were most often based on MRI. The most prevalent machine learning techniques included linear regression and neural networks. None of the studies met all newly developed quality assessment criteria. Studies least prone to inflated performance showed promising results, with areas under the curve up to 0.86 for classification and R2 values up to 91% in continuous prediction. A limitation was that only 1 data source was used for the literature search. CONCLUSIONS Studies least prone to inflated prediction results are the most promising. The provided evaluation framework may contribute to improved quality of future machine learning models.

AimChildren with congenital gastrointestinal malformations may be at risk of neurodevelopmental impairment due to challenges to the developing brain, including perioperative haemodynamic changes, exposure to anaesthetics and postoperative inflammatory influences. This study aggregates existing evidence on neurodevelopmental outcome in these patients using meta-analysis.MethodPubMed, Embase and Web of Science were searched for peer-reviewed articles published until October 2019. Out of the 5316 unique articles that were identified, 47 studies met the inclusion criteria and were included. Standardised mean differences (Cohen’s d) between cognitive, motor and language outcome of patients with congenital gastrointestinal malformations and normative data (39 studies) or the studies’ control group (8 studies) were aggregated across studies using random-effects meta-analysis. The value of (clinical) moderators was studied using meta-regression and diagnostic subgroups were compared.ResultsThe 47 included studies encompassed 62 cohorts, representing 2312 patients. Children with congenital gastrointestinal malformations had small-sized cognitive impairment (d=−0.435, pInterpretationThis study shows that children with congenital gastrointestinal malformations exhibit impairments in neurodevelopmental outcome, highlighting the need for routine screening of neurodevelopment during follow-up.

Recent evidence indicates that both cardiovascular fitness and gross motor skill performance are related to enhanced neurocognitive functioning in children by influencing brain structure and functioning. This study investigates the role of white matter microstructure in the relationship of both cardiovascular fitness and gross motor skills with neurocognitive functioning in healthy children. In total 92 children (mean age 9.1 years, range 8.0–10.7) were included in this study. Cardiovascular fitness and gross motor skill performance were assessed using performance‐based tests. Neurocognitive functioning was assessed using computerized tests (working memory, inhibition, interference control, information processing, and attention). Diffusion tensor imaging was used in combination with tract‐based spatial statistics to assess white matter microstructure as defined by fractional anisotropy (FA), axial and radial diffusivity (AD, RD). The results revealed positive associations of both cardiovascular fitness and gross motor skills with neurocognitive functioning. Information processing and motor response inhibition were associated with FA in a cluster located in the corpus callosum. Within this cluster, higher cardiovascular fitness and better gross motor skills were both associated with greater FA, greater AD, and lower RD. No mediating role was found for FA in the relationship of both cardiovascular fitness and gross motor skills with neurocognitive functioning. The results indicate that cardiovascular fitness and gross motor skills are related to neurocognitive functioning as well as white matter microstructure in children. However, this study provides no evidence for a mediating role of white matter microstructure in these relationships., Cardiovascular fitness and gross motor skills were both related to neurocognitive functioning and white matter microstructure. No evidence was found for a mediating role of white matter microstructure in the relationship between both cardiovascular fitness and gross motor skills with neurocognitive functioning.

Item does not contain fulltext Conventional neurocognitive assessment does not account for the complex interplay between neurocognitive functions that gives rise to (goal-directed) behavior. This study aims to explore the value of the application of network analysis to individual neurocognitive data, in order to investigate neurocognitive network organization (i.e., the neurocognome). Participants were healthy young adults (N = 51, average age: 26 years [range: 18-34], 49% female) that underwent a single comprehensive neurocognitive assessment. To allow implementation of network analysis, we developed a new measure of connectivity between neurocognitive functions that can be calculated on a single neurocognitive assessment. Connectivity values between all possible pairs of neurocognitive functions were used to reconstruct individual neurocognitive networks. Graph theory was applied to extract measures of global and local network organization from neurocognitive networks at the individual level. The results confirmed the expectation that neurocognitive connectivity values should be higher for connections between neurocognitive functions that are more closely related (i.e., within neurocognitive domains) than for connections between neurocognitive functions that are less closely related (i.e., across neurocognitive domains). The results further showed that reconstruction of the neurocognitive network at the individual level has considerable agreement with a group-based approach, providing preliminary evidence for the validity of our approach. The reconstructed neurocognitive network also showed considerable consistency among (randomly selected) independent subgroups, supporting the stability of our approach. Lastly, neurocognitive network parameters were related to intelligence and behavior problems, reflecting relevance of neurocognitive network organization for other important domains of functioning. Moreover, local network parameters (i.e., the relative importance of neurocognitive functions in the network) may have stronger relevance for behavioral functioning than conventional measures of neurocognitive functioning (i.e., z-scores reflecting performance on individual neurocognitive tests). Taken together, this study indicates that analysis of individual neurocognitive network organization has potential value for neurocognitive assessment in research and clinical practice. 17 p.

Outcome of acquired brain injury (ABI) and the potential for neurorehabilitation are subject to distinct heterogeneity between patients. Limited knowledge of the complex constellation of determinants at play interferes with the possibility to deploy precision medicine in neurorehabilitation. Measurement Feedback Systems (MFS) structure clinical data collection and deliver the measurement results as feedback to clinicians, thereby facilitating progress monitoring, promoting balanced patient-centered discussion and shared decision making. Accumulation of clinical data in the MFS also enables data-driven precision rehabilitation medicine. This article describes the development and implementation of a MFS for neurorehabilitation after ABI. The MFS consists of specialized measurement tracks which are developed together with representatives of each discipline in the multidisciplinary team. The MFS is built into a digital platform that automatically distributes measurements among clinicians, at predetermined time points during the inpatient treatment, outpatient treatment and follow-up. The results of all measurements are visualized in individual patient dashboards that are accessible for all clinicians involved in treatment. Since step-wise implementation, 124 patients have been registered on the MFS platform so far, providing an average of more than 200 new measurements per week. Currently, more than 15,000 clinical measurements are captured in the MFS. The current overall completion rate of measurements is 86,4%. This study shows that structured clinical assessment and feedback is feasible in the context of neurorehabilitation after severe ABI. The future directions are discussed for MFS data in our Health Intelligence Program, which aims at periodic care evaluation and the transition of neurorehabilitation care towards precision medicine.

Objective Current clinical guidelines provide a unitary approach to manage sport-related concussion (SRC), while heterogeneity in the presentation of symptoms suggests that subtypes of SRC may exist. We systematically reviewed the available evidence on SRC subtypes and associated clinical outcomes. Data Sources Ovid Medline, Embase, PsycINFO, and SPORTDiscus Eligibility Criteria for Selecting Studies Electronic databases were searched for studies: (i) identifying SRC symptom clusters using classification methodology; or (ii) associating symptom clusters to clinical outcome variables. A total of 6,146 unique studies were identified, of which 75 full texts were independently assessed by two authors for eligibility. A total of 22 articles were included for systematic review. Data Extraction Two independent authors performed data extraction and risk of bias analysis using the Cochrane Collaboration tool. Data Synthesis Six studies found evidence for existence of SRC symptom clusters. Combining the available literature through Multiple Correspondence Analysis (MCA) provided evidence for the existence of a migraine cluster, a cognitive–emotional cluster, a sleep–emotional cluster, a neurological cluster, and an undefined feelings cluster. Nineteen studies found meaningful associations between SRC symptom clusters and clinical outcomes. Clusters mapping to the migraine cluster were most frequently reported in the literature and were most strongly related to aspects of clinical outcome. Conclusions The available literature provides evidence for the existence of at least five subtypes in SRC symptomatology, with clear relevance to clinical outcome. Systematically embedding the differentiation of SRC subtypes into prognosis, clinical management, and intervention strategies may optimize the recovery from SRC.

Traumatic brain injury (TBI) is a major cause of death and disability in children in both developed and developing nations. Children and adolescents suffer from TBI at a higher rate than the general population, and specific developmental issues require a unique context since findings from adult research do not necessarily directly translate to children. Findings in pediatric cohorts tend to lag behind those in adult samples. This may be due, in part, both to the smaller number of investigators engaged in research with this population and may also be related to changes in safety laws and clinical practice that have altered length of hospital stays, treatment, and access to this population. The ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Pediatric Moderate/Severe TBI (msTBI) group aims to advance research in this area through global collaborative meta-analysis of neuroimaging data. In this paper, we discuss important challenges in pediatric TBI research and opportunities that we believe the ENIGMA Pediatric msTBI group can provide to address them. With the paucity of research studies examining neuroimaging biomarkers in pediatric patients with TBI and the challenges of recruiting large numbers of participants, collaborating to improve statistical power and to address technical challenges like lesions will significantly advance the field. We conclude with recommendations for future research in this field of study.

Different types of physical activity are thought to differentially affect children's brain activation, via physiological mechanisms, or by activating similar brain areas during physical and cognitive tasks. Despite many behavioral studies relying on these mechanisms, they have been rarely studied. This study looks at both mechanisms simultaneously, by examining effects of two physical activity interventions (aerobic vs. cognitively-engaging) on children's brain activation. Functional Magnetic Resonance Imaging (fMRI) data of 62 children (48.4% boys, mean age 9.2 years) was analyzed. Children's visuospatial working memory related brain activity patterns were tested using a Spatial Span Task before and after the 14-week interventions consisting of four physical education lessons per week. The control group followed their regular program of two lessons per week. Analyses of activation patterns in SPM 12.0 revealed no activation changes between pretest and posttest (p > .05), and no differences between the three conditions in pretest-posttest changes in brain activation (p > .05). Large inter-individual differences were found, suggesting that not every child benefited from the interventions in the same way. To get more insight into the assumed mechanisms, further research is needed to understand whether, when, for whom, and how physical activity results in changed brain activation patterns.

Objective of the current study was to assess whether game-formatted executive function (EF) training, is effective in improving attention, EF and academic performance in very preterm and/or extremely low birthweight children aged 8–12 years. A multi-center, double-blind, placebo- and waitlist controlled randomized trial (NTR5365) in two academic hospitals in The Netherlands was performed. Eighty-five very preterm children with parent-rated attention problems on the Child Behavior Checklist were randomized to one of three treatment conditions: EF training, placebo training or waitlist condition. EF or placebo training was completed at home (6 weeks, 25 sessions of 30–45 min each). At baseline, 2 weeks after training or being on the waitlist, and five months after first follow-up visit, children underwent assessments of primary outcomes (parent and teacher ratings of attention) and secondary outcomes (parent and teacher ratings of daily-life EF, computerized EF tasks and academic performance). Linear mixed model analyses were performed for all outcome measures. There were no significant differences in improvement over time on parent- and teacher ratings of attention, parent- and teacher ratings of daily-life EF, computerized EF tasks, and academic performance (arithmetic and reading) between the EF training, placebo training and waitlist condition. In conclusion, game-formatted EF training does not improve attention, EF or academic performance in very preterm children with parent-rated attention problems. Electronic supplementary material The online version of this article (10.1007/s00787-020-01561-0) contains supplementary material, which is available to authorized users.

Infants born very preterm (

IntroductionTraumatic brain injury (TBI) in children can be associated with poor outcome in crucial functional domains, including motor, neurocognitive and behavioural functioning. However, outcome varies between patients and is mediated by complex interplay between demographic factors, premorbid functioning and (sub)acute clinical characteristics. At present, methods to understand let alone predict outcome on the basis of these variables are lacking, which contributes to unnecessary follow-up as well as undetected impairments in children. Therefore, this study aims to develop prognostic models for the individual outcome of children with TBI in a range of important developmental domains. In addition, the potential added value of advanced neuroimaging data and the use of machine learning algorithms in the development of prognostic models will be assessed.Methods and analysis210 children aged 4–18 years diagnosed with mild-to-severe TBI will be prospectively recruited from a research network of Dutch hospitals. They will be matched 2:1 to a control group of neurologically healthy children (n=105). Predictors in the model will include demographic, premorbid and clinical measures prospectively registered from the TBI hospital admission onwards as well as MRI metrics assessed at 1 month post-injury. Outcome measures of the prognostic models are (1) motor functioning, (2) intelligence, (3) behavioural functioning and (4) school performance, all assessed at 6 months post-injury.Ethics and disseminationEthics has been obtained from the Medical Ethical Board of the Amsterdam UMC (location AMC). Findings of our multicentre prospective study will enable clinicians to identify TBI children at risk and aim towards a personalised prognosis. Lastly, findings will be submitted for publication in open access, international and peer-reviewed journals.Trial registration numberNL71283.018.19 and NL9051.

This study is the first to systematically review and quantify the effects of physical activity on brain structure and neurophysiological functioning in children. Electronic data bases were searched for relevant studies. Studies that met the following criteria were included: (1) used an RCT or cross-over design, (2) examined the effects of physical activity on brain structure and/or neurophysiological functioning, (3) included children (5–12 years old) (4) included a control group (RCTs) or control condition (cross-over trials). A total of 26 and 20 studies were included in the systematic review and meta-analysis, respectively, representing and accompanying 973 and 782 unique children. Main analyses were separated for short-term and long-term physical activity and for effects on brain structure and neurophysiological functioning with a distinction between children from healthy and clinical populations. We found evidence for significant beneficial effects of long-term physical activity on neurophysiological functioning (d = 0.39, p < 0.001). In addition, short-term physical activity may induce changes in neurophysiological functioning (d = 0.32, p = 0.044), although this evidence showed limited robustness. No meta-analytic evidence was found for positive effects on brain structure. The results underline the importance of physical activity for brain development in children.

Relationships between gross motor skills and cardiovascular fitness with visuospatial working memory (VSWM) in children are hypothesized to be mediated by underlying functional brain mechanisms. Because there is little experimental evidence to support this mechanism, the present study was designed to investigate the relationships of gross motor skills and cardiovascular fitness with VSWM-related brain activation in 8- to 10-year-old children. Functional magnetic resonance imaging data obtained during a VSWM-task were analyzed for 80 children from grades 3 (47.5%) and 4 of 21 primary schools in the Netherlands (51.3% girls). Gross motor skills (Korper Koordinationstest für Kinder and Bruininks-Oseretsky Test of Motor Proficiency - 2nd Edition) and cardiovascular fitness (20-meter Shuttle Run Test) were assessed. VSWM-related brain activation was found in a network involving the angular gyrus, the superior parietal cortex, and the thalamus; deactivation was found in the inferior and middle temporal gyri. Although behavioral results showed significant relations of gross motor skills and cardiovascular fitness with VSWM performance, gross motor skills and cardiovascular fitness were not related to VSWM-related brain activation. Therefore, we could not confirm the hypothesis that brain activation underlies the relationship of gross motor skills and cardiovascular fitness with VSWM performance. Our results suggest that either the effects of physical activity on cognition do not necessarily go via changes in gross motor skills and/or cardiovascular fitness, or that brain activation patterns as measured with the blood-oxygen-level dependent (BOLD) signal may not be the mechanism underlying the relationships of gross motor skills and cardiovascular fitness with VSWM.

The authors performed a clustered randomized controlled trial to investigate the effects of an aerobic and a cognitively demanding exercise intervention on executive functions in primary-school-age children compared with the regular physical education program (N = 856). They hypothesized that both exercise interventions would facilitate executive functioning, with stronger effects for the cognitively demanding exercise group. The interventions were provided four times per week for 14 weeks. Linear mixed models were conducted on posttest neurocognitive function measures with baseline level as covariate. No differences were found between the exercise interventions and the control group for any of the measures. Independently of group, dose of moderate to vigorous physical activity was positively related to verbal working memory and attention abilities. This study showed that physical exercise interventions did not enhance executive functioning in children. Exposure to moderate to vigorous physical activity is a crucial aspect of the relationship between physical activity and executive functioning.

Objective We aimed to gain more insight into the pathomechanisms of metachromatic leukodystrophy (MLD), by comparing magnitude and direction of diffusion between patients and controls at diagnosis and during follow-up. Methods Four late-infantile, 16 juvenile and 8 adult onset MLD patients [of which 13 considered eligible for hematopoietic cell transplantation (HCT)] and 47 controls were examined using diffusion tensor imaging. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) were quantified and compared between groups using tract-based spatial statistics (TBSS). Diffusion measures were determined for normal-appearing white matter (NAWM), corpus callosum, thalamus (all based on subject-wise segmentation), and pyramidal tracts, determined with probabilistic tractography. Measures were compared between HCT-eligible patients, non-eligible patients and controls using general linear model and nonparametric permutation analyses (randomise) for TBSS data, considering family-wise error corrected p

This study aimed to systematically investigate the relation between gross motor skills and aspects of executive functioning (i.e. verbal working memory, visuospatial working memory, response inhibition and interference control) in 8-10 year old children. Additionally, the role of information processing (speed and variability) and lapses of attention in the relation between gross motor skills and executive functions was investigated. Data of 732 Dutch children from grade 3 and 4 were analyzed (50.0% boys, 50.4% grade 3, age = 9.16 +/- 0.64 years). Gross motor skills were assessed using three items of the Korper Koordinationstest fur Kinder and one item of the Bruininks-Oseretsky test of Motor Proficiency, Second Edition. Executive functions were assessed using the Wechsler Digit Span task (verbal working memory), the Visuospatial Memory task (visuospatial working memory), the Stop Signal task (response inhibition) and a modified version of the Flanker task (interference control). Information processing and lapses of attention were obtained by applying an ex-Gaussian analysis on go trials of the Stop Signal task. Multilevel regression analysis showed that gross motor skills were significantly related to verbal working memory, visuospatial working memory and response inhibition, but not to interference control. Lapses of attention was a significant predictor for all executive functions, whereas processing speed was not. Variability in processing speed was only predictive for visuospatial working memory. After controlling for information processing and lapses of attention, gross motor skills were only significantly related to visuospatial working memory and response inhibition. The results suggest that after controlling for information processing and lapses of attention, gross motor skills are related to aspects of executive functions that are most directly involved in, and share common underlying processes with, gross motor skills.

Background Very preterm birth has a detrimental impact on the developing brain, including widespread white matter brain abnormalities that threaten efficient sensory processing. Yet, sensory processing difficulties in very preterm children are scarcely studied, especially at school age. Aims To investigate somatosensory registration, multisensory integration and sensory modulation. Participants 57 very preterm school-age children (mean age = 9.2 years) were compared to 56 gender and age matched full-term children. Methods Group differences on somatosensory registration tasks (Registration of Light Touch, Sensory Discrimination of Touch, Position Sense, Graphestesia), a computerized multisensory integration task, and the parent-reported Sensory Profile were investigated using t-tests and Mann-Whitney U tests. Results In comparison to full-term children, very preterm children are less accurate on somatosensory registration tasks, including Registration of Light Touch (d = 0.34), Position Sense (d = 0.31) and Graphestesia (d = 0.42) and show more sensory modulation difficulties (d = 0.41), including both behavioral hyporesponsivity (d = 0.52) and hyperresponsivity (d = 0.56) to sensory stimuli. Tactile discrimination and multisensory integration efficiency were not affected in very preterm children. Aspects of sensory processing were only modestly related. Conclusion Very preterm children show sensory processing difficulties regarding somatosensory registration and sensory modulation, and preserved multisensory (audio-visual) integration. Follow-up care for very preterm children should involve screening of sensory processing difficulties at least up to school age.

This study aims to (1) investigate the neuropathology of mild to severe pediatric TBI and (2) elucidate the predictive value of conventional and innovative neuroimaging for functional outcome. Children aged 8–14 years with trauma control (TC) injury (n = 27) were compared to children with mild TBI and risk factors for complicated TBI (mildRF+,n = 20) or moderate/severe TBI (n = 17) at 2.8 years post-injury. Neuroimaging measures included: acute computed tomography (CT), volumetric analysis on post-acute conventional T1-weighted magnetic resonance imaging (MRI) and post-acute diffusion tensor imaging (DTI, analyzed using tract-based spatial statistics and voxel-wise regression). Functional outcome was measured using Common Data Elements for neurocognitive and behavioral functioning. The results show that intracranial pathology on acute CT-scans was more prevalent after moderate/severe TBI (65%) than after mildRF+TBI (35%;p = .035), while both groups had decreased white matter volume on conventional MRI (ps ≤ .029,ds ≥ −0.74). The moderate/severe TBI group further showed decreased fractional anisotropy (FA) in a widespread cluster affecting all white matter tracts, in which regional associations with neurocognitive functioning were observed (FSIQ, Digit Span and RAVLT Encoding) that consistently involved the corpus callosum. FA had superior predictive value for functional outcome (i.e. intelligence, attention and working memory, encoding in verbal memory and internalizing problems) relative to acute CT-scanning (i.e. internalizing problems) and conventional MRI (no predictive value). We conclude that children with mildRF+TBI and moderate/severe TBI are at risk of persistent white matter abnormality. Furthermore, DTI has superior predictive value for neurocognitive out-come relative to conventional neuroimaging.

Objective: To systematically review evidence on the effects of timing and intensity of neurorehabilitation on the functional recovery of patients with moderate to severe traumatic brain injury (TBI) and aggregate the available evidence using meta-analytic methods. Data Sources: PubMed, Embase, PsycINFO, and Cochrane Database. Study Selection: Electronic databases were searched for prospective controlled clinical trials assessing the effect of timing or intensity of multidisciplinary neurorehabilitation programs on functional outcome of patients with moderate or severe TBI. A total of 5961 unique records were screened for relevance, of which 58 full-text articles were assessed for eligibility by 2 independent authors. Eleven articles were included for systematic review and meta-analysis. Data Extraction: Two independent authors performed data extraction and risk of bias analysis using the Cochrane Collaboration tool. Discrepancies between authors were resolved by consensus. Data Synthesis: Systematic review of a total of 6 randomized controlled trials, 1 quasi-randomized trial, and 4 controlled trials revealed consistent evidence for a beneficial effect of early onset neurorehabilitation in the trauma center and intensive neurorehabilitation in the rehabilitation facility on functional outcome compared with usual care. Meta-analytic quantification revealed a large-sized positive effect for early onset rehabilitation programs (d=1.02; P

Objective The evaluation of discomfort in paediatric research is scarcely evidence-based. In this study, we make a start in describing children's self-reported discomfort during common medical research procedures and compare this with discomfort during dental check-ups which can be considered as a reference level of a ‘minimal discomfort’ medical procedure. We exploratory study whether there are associations between age, anxiety-proneness, gender, medical condition, previous experiences and discomfort. We also describe children's suggestions for reducing discomfort.Design Cross-sectional descriptive study.Setting Paediatric research at three academic hospitals.Patients 357 children with and without illnesses (8–18 years, mean=10.6 years) were enrolled: 307 from paediatric research studies and 50 from dental care.Main outcome measures We measured various generic forms of discomfort (nervousness, annoyance, pain, fright, boredom, tiredness) due to six common research procedures: buccal swabs, MRI scans, pulmonary function tests, skin prick tests, ultrasound imaging and venepunctures.Results Most children reported limited discomfort during the research procedures (means: 1–2.6 on a scale from 1 to 5). Compared with dental check-ups, buccal swab tests, skin prick tests and ultrasound imaging were less discomforting, while MRI scans, venepunctures and pulmonary function tests caused a similar degree of discomfort. 60.3% of the children suggested providing distraction by showing movies to reduce discomfort. The exploratory analyses suggested a positive association between anxiety-proneness and discomfort.Conclusions The findings of this study support the acceptability of participation of children in the studied research procedures, which stimulates evidence-based research practice. Furthermore, the present study can be considered as a first step in providing benchmarks for discomfort of procedures in paediatric research.

Purpose: The goal of this meta-analysis was to aggregate available empirical studies on the effects of physical exercise on executive functions in preadolescent children (6-12 years of age), adolescents (13-17 years of age) and young adults (18-35 years of age). Method: The electronic databases PubMed, EMBASE and SPORTDiscus were searched for relevant studies reporting on the effects of physical exercise on executive functions. Nineteen studies were selected. Results: There was a significant overall effect of acute physical exercise on executive functions (d=0.52, 95% CI 0.29 to 0.76, p

BackgroundFeedback learning is essential for behavioral development. We investigated feedback learning in relation to behavior problems after pediatric traumatic brain injury (TBI).MethodChildren aged 6–13 years diagnosed with TBI (n= 112; 1.7 years post-injury) were compared with children with traumatic control (TC) injury (n= 52). TBI severity was defined as mild TBI without risk factors for complicated TBI (mildRF−TBI,n= 24), mild TBI with ⩾1 risk factor for complicated TBI (mildRF+TBI,n= 51) and moderate/severe TBI (n= 37). The Probabilistic Learning Test was used to measure feedback learning, assessing the effects of inconsistent feedback on learning and generalization of learning from the learning context to novel contexts. The relation between feedback learning and behavioral functioning rated by parents and teachers was explored.ResultsNo evidence was found for an effect of TBI on learning from inconsistent feedback, while the moderate/severe TBI group showed impaired generalization of learning from the learning context to novel contexts (p= 0.03,d= −0.51). Furthermore, the mildRF+TBI and moderate/severe TBI groups had higher parent and teacher ratings of internalizing problems (p's⩽ 0.04,d's ⩾ 0.47) than the TC group, while the moderate/severe TBI group also had higher parent ratings of externalizing problems (p= 0.006,d= 0.58). Importantly, poorer generalization of learning predicted higher parent ratings of externalizing problems in children with TBI (p= 0.03,β= −0.21) and had diagnostic utility for the identification of children with TBI and clinically significant externalizing behavior problems (area under the curve = 0.77,p= 0.001).ConclusionsModerate/severe pediatric TBI has a negative impact on generalization of learning, which may contribute to post-injury externalizing problems.

Context: Worldwide, millions of patients with traumatic brain injury (TBI) suffer from persistent and disabling intelligence impairment. Post-traumatic amnesia (PTA) duration is a promising predictor of intelligence following TBI. Objectives: To determine (1) the impact of TBI on intelligence throughout the lifespan and (2) the predictive value of PTA duration for intelligence impairment, using meta-analytic methods. Methods: Electronic databases were searched for peer reviewed articles, published until February 2012. Studies reporting intelligence following TBI and injury severity by PTA duration were included. Meta-analytic methods generated effect sizes for full scale IQ (FSIQ), performance IQ (PIQ) and verbal IQ (VIQ), following mild TBI (PTA duration 1-24 h) and severe TBI (PTA duration >7 days), during the subacute phase of recovery (≤6 months post-injury) and the chronic phase (>6 months post-injury). Meta-regression elucidated the predictive value of PTA duration for intelligence impairment. Results: Patients with severe TBI exhibited large depressions in FSIQ in the subacute phase of recovery (d=-1.07, 95% CI to 1.52 to -0.62; p

BACKGROUND: We investigated the impact of pediatric traumatic brain injury (TBI) on attention, a prerequisite for behavioral and neurocognitive functioning. METHODS: Children aged 6 to 13 years who were diagnosed with TBI (n = 113; mean 1.7 years postinjury) were compared with children with a trauma control injury (not involving the head) (n = 53). TBI severity was defined as mild TBI with or without risk factors for complicated TBI (mildRF+ TBI, n = 52; mildRF− TBI, n = 24) or moderate/severe TBI (n = 37). Behavioral functioning was assessed by using parent and teacher questionnaires, and the Attention Network Test assessed alerting, orienting, and executive attention. Ex-Gaussian modeling determined the contribution of extremely slow responses (lapses of attention) to mean reaction time (MRT). RESULTS: The TBI group showed higher parent and teacher ratings of attention and internalizing problems, higher parent ratings of externalizing problems, and lower intelligence than the control group (P < .05, d ≥ 0.34). No effect of TBI on alerting, orienting, and executive attention was observed (P ≥ .55). MRT was slower in the TBI group (P = .008, d = 0.45), traced back to increased lapses of attention (P = .002, d = 0.52). The mildRF− TBI group was unaffected, whereas the mildRF+ TBI and moderate/severe TBI groups showed elevated parent ratings of behavior problems, lower intelligence, and increased lapses of attention (P ≤ .03, d ≥ 0.48). Lapses of attention fully explained the negative relation between intelligence and parent-rated attention problems in the TBI group (P = .02). CONCLUSIONS: Lapses of attention represent a core attention deficit in children with mildRF+ TBI (even in the absence of intracranial pathology) or moderate/severe TBI, and relate to daily life problems after pediatric TBI.

Background Axonal injury after traumatic brain injury (TBI) may cause impaired sensory integration. We aim to determine the effects of childhood TBI on visual integration in relation to general neurocognitive functioning. Methods We compared children aged 6-13 diagnosed with TBI (n = 103; M = 1.7 years post-injury) to children with traumatic control (TC) injury (n = 44). Three TBI severity groups were distinguished: mild TBI without risk factors for complicated TBI (mild(RF-)TBI, n = 22), mild TBI with >= 1 risk factor (mild(RF+) TBI, n = 46) or moderate/severe TBI (n = 35). An experimental paradigm measured speed and accuracy of goal-directed behavior depending on: (1) visual identification; (2) visual localization; or (3) both, measuring visual integration. Group-differences on reaction time (RT) or accuracy were tracked down to task strategy, visual processing efficiency and extra-decisional processes (e.g. response execution) using diffusion model analysis. General neurocognitive functioning was measured by a Wechsler Intelligence Scale short form. Results The TBI group had poorer accuracy of visual identification and visual integration than the TC group (Ps

Worldwide, 54-60 million individuals sustain traumatic brain injury (TBI) each year. This meta-analysis aimed to quantify intelligence impairments after TBI and to determine the value of age and injury severity in the prognosis of TBI. An electronic database search identified 81 relevant peer-reviewed articles encompassing 3890 patients. Full-scale IQ (FSIQ), performance IQ (PIQ) and verbal IQ (VIQ) impairments were quantified (Cohen's d) for patients with mild, moderate and severe TBI in the subacute phase of recovery and the chronic phase. Meta-regressions explored prognostic values of age and injury severity measures for intelligence impairments. The results showed that, in the subacute phase, FSIQ impairments were absent for patients with mild TBI, medium-sized for patients with moderate TBI (d = -0.61, P < 0.001) and large for patients with severe TBI (d = -1.09, P < 0.001). In the chronic phase, FSIQ impairments were small for patients with mild or moderate TBI (d = -0.37 and -0.19, P ≤ 0.008) and large for patients with severe TBI (d = -0.80, P < 0.001). Adults with mild TBI had larger PIQ and VIQ impairments in the chronic phase than children (both Q ≥ 5.21, P ≤ 0.02), whilst children with severe TBI had larger FSIQ and VIQ impairments than adults (both Q ≥ 4.40, P ≤ 0.04). Glasgow Coma Scale score, duration of loss of consciousness and post-traumatic amnesia duration moderately to strongly predicted FSIQ, PIQ and VIQ impairments (0.41 ≤ r ≤ 0.82, P ≤ 0.02), but no differences in predictive value were observed. In conclusion, TBI causes persisting intelligence impairments, where children may have better recovery from mild TBI and poorer recovery from severe TBI than adults. Injury severity measures predict intelligence impairments and do not outperform one another.

Objective: The goal of the present meta-analysis was to address studies that examined the relationship between walking as one of the most prevalent types of leisure-time activity and executive function being a higher-order cognitive function essential for independent functioning. Methods: The following data sources were used: English-language publications in PubMed, EMBASE, PsycINFO, Cinahl, and Cochrane; the last search took place in January 2012. From these data sources, only randomized controlled trials including older people with (N = 3) and without (N = 5) cognitive impairment were selected. Results: Walking has been shown to improve set-shifting and inhibition in sedentary older persons without cognitive impairment (d = 0.36; 95% confidence interval: 0.16-0.55; z = 3.56; p

Background and aims: The Bayley Scales of Infant Development (BSID) is the most widely used measure to assess neurodevelopment of very preterm (gestational age ≤. 32. weeks) and very low birth weight (VLBW, ≤. 1500. g) infants in the first three years of life. This meta-analysis determines the predictive value of the Mental Developmental Index (MDI) and the Psychomotor Developmental Index (PDI)/Motor Composite, collectively referred to as Bayley motor scale, of the BSID-I, -II and Bayley-III for later cognitive and motor functioning in very preterm/VLBW children. Methods: Cochrane Library, PubMed, PsychINFO and CINAHL were searched for English-language peer-reviewed studies published before March 2013. Studies were included if they reported odds ratios or correlations between the MDI or Bayley motor scale scores obtained in the first three years of life, and standardized cognitive or motor assessment obtained later in life in very preterm/VLBW children. Meta-analytic methods were applied to aggregate available data. Results: A total of 16 studies met inclusion criteria. Across 14 studies (n. =. 1330 children), MDI scores were strongly predictive for later cognitive functioning, r=. 0.61 (95%CI: 0.57-0.64), explained variance 37%, p.