Neurodevelopmental outcomes of school-age children conceived after hysterosalpingography with oil-based or water-based iodinated contrast: long-term follow-up of a nationwide randomized controlled trial.

STUDY QUESTION: Does preconceptional exposure to oil-based iodinated contrast media during hysterosalpingography (HSG) impact children's neurodevelopment compared with exposure to water-based alternatives? SUMMARY ANSWER: Our study found no large-sized effects for neurodevelopment in children with preconceptional exposure to oil-based iodinated contrast media during HSG compared with water-based alternatives. WHAT IS KNOWN ALREADY: HSG is widely used as a diagnostic tool in the female fertility work-up. Tubal flushing with oil-based iodinated contrast has been shown to enhance fertility outcomes in couples with unexplained infertility, increasing the chances of pregnancy and live birth compared with water-based alternatives. However, oil-based contrast contains higher doses of iodine and has a longer half-life, and concerns exist that iodinated contrast media can affect women's iodine status and cause temporary (sub)clinical hypothyroidism in mothers and/or foetuses. Considering that thyroid hormones are vital to embryonal and foetal brain development, oil-based contrast media use could increase the risk of impaired neurodevelopment in children conceived shortly after HSG. Here we examine neurodevelopmental outcomes in school-aged children conceived after HSG. STUDY DESIGN, SIZE, DURATION: This is a long-term follow-up of the H2Oil trial in which oil-based or water-based contrast was used during HSG (Netherlands; 2012-2014; NTR3270). Of 369 children born <6 months after HSG in the study, we contacted the mothers of 140 children who gave consent to be contacted for follow-up. The follow-up study took place from January to July 2022 (NCT05168228). PARTICIPANTS/MATERIALS, SETTINGS, METHODS: The study included 69 children aged 6-9 years who were conceived after HSG with oil-based (n = 42) or water-based contrast (n = 27). The assessments targeted intelligence (Wechsler Intelligence Scale for Children), neurocognitive outcomes (computerized neurocognitive tests), behavioural functioning (parent and teacher questionnaires), and academic performance. Linear regression models, adjusted for age, sex, and parental educational attainment were employed to compare groups. MAIN RESULTS AND THE ROLE OF CHANCE: School-aged children born to mothers after oil-based contrast HSG did not significantly differ from children born to mothers after water-based contrast HSG, in regards to intelligence, neurocognitive functioning, behavioural functioning, or academic performance, with the exception of better performance for visuomotor integration functions in children exposed to oil-based contrast preconception. After exploratory correction for multiple comparisons, none of the group differences was statistically significant. LIMITATIONS, REASONS FOR CAUTION: The small sample size of this follow-up study limited statistical power. This study provides evidence for the absence of large-sized differences between preconceptional exposure to the two contrast media types but does not rule out more subtle effects on neurodevelopment compared to naturally conceived children without preconceptional exposure to HSG. WIDER IMPLICATIONS OF THE FINDINGS: This study contributes to our knowledge about the long-term effects of different types of iodinated contrast media used in fertility work-up, indicating that choosing oil-based over water-based iodinated contrast media is unlikely to have major effect on the long-term neurodevelopmental outcomes of children conceived shortly after HSG. However, further research should focus on the overall safety of iodine exposure during HSG, comparing children conceived after HSG to those conceived naturally as both types of contrast contain high amounts of iodine. STUDY FUNDING/COMPETING INTEREST(S): The original H2Oil randomized controlled trial was an investigator-initiated study that was funded by the two academic hospitals now merged into the Amsterdam University Medical Centre. The current follow-up study (Neuro-H2Oil) is funded through a research grant awarded to the authors by the Amsterdam Reproduction & Development (AR&D) research institute. S.K. is funded by a AMC MD/PhD Scholarship from the Amsterdam UMC. S.K. reports holding voluntary roles in the civil society organizations Universities Allied for Essential Medicines and People's Health Movement. V.M. reports receiving travel and speaker fees as well as research grants from Guerbet, Merck and Ferring. K.D. reports receiving travel and speaker fees as well as research grants from Guerbet. BWM is supported by a NHMRC Investigator grant (GNT1176437) and reports consultancy, travel support and research funding from Merck, consultancy for Organon and Norgine, and holding stock from ObsEva. The other authors report no conflict of interest. TRIAL REGISTRATION NUMBER: NCT05168228.

Team functioning in Neurorehabilitation: a mixed methods study.

The objective of this study was to enhance understanding of team functioning in a neurorehabilitation team by identifying the factors that impede and facilitate effective interprofessional team collaboration. We focused on team identification, psychological safety, and team learning, and conducted the research at a neurorehabilitation center treating young patients with severe acquired brain injury in the Netherlands. A mixed-methods approach was employed, integrating quantitative data from questionnaires (N = 40) with qualitative insights from a focus group (n = 6) and in-depth interviews (n = 5) to provide a comprehensive perspective on team dynamics. Findings revealed strong team identification among participants, denoting a shared sense of belonging and commitment. However, limited psychological safety was observed, which negatively affected constructive conflict and team learning. Qualitative analysis further identified deficiencies in shared mental models, especially in shared decision-making and integrated care. These results highlight the crucial role of psychological safety in team learning and the development of shared mental models in neurorehabilitation settings. Although specific to neurorehabilitation, the insights gained may be applicable to enhancing team collaboration in various healthcare environments. The study forms a basis for future research to investigate the impact of improvements in team functioning on patient outcomes in similar settings.

Bronchopulmonary dysplasia is not related to neurofilament light for neuroaxonal damage in preterm infants.

BACKGROUND: Neurofilament light (NfL) has been identified as a biomarker for neuroaxonal damage in preterm infants, but its relation with bronchopulmonary dysplasia (BPD) has not been established. We hypothesized that BPD is associated with increased NfL levels at an early stage, indicative of early neuroaxonal damage. METHODS: We included preterm infants born <30 weeks of gestation for assessment of NfL levels from cord blood and blood obtained at postnatal days 3, 7, 14, and 28. We used linear regression analysis to compare NfL levels between infants with moderate/severe BPD and infants with no/mild BPD, and linear mixed model analysis to compare the effect of time on NfL levels between groups. RESULTS: Sixty-seven infants with a gestational age (GA) of 27 ± 1.3 weeks were included for analysis, of whom 19 (28%) developed moderate/severe BPD. Although NfL levels were higher at every time point in infants with BPD, statistical significance was lost after adjustment for GA, small for gestational age (SGA) and intraventricular hemorrhage (IVH). Groups did not differ in NfL change over time. CONCLUSIONS: The positive association between BPD and NfL in the first weeks of life could be explained by GA, SGA and IVH rather than by development of BPD. IMPACT: Neurofilament light chain (NfL) is a known biomarker for neuroaxonal damage. Biomarkers for brain damage during the first weeks of life in preterm infants developing BPD are lacking. NfL levels obtained during the first weeks of life did not differ between infants with and without BPD in analyses adjusted for GA, SGA, and IVH.

Risk factors for neurocognitive impairment and the relation with structural brain abnormality in children and young adults with severe chronic kidney disease.

BACKGROUND: Severe chronic kidney disease (CKD) in children and young adults has shown to be associated with abnormal brain development, which may contribute to neurocognitive impairments. We aimed to investigate risk factors for neurocognitive impairment and investigate the relation with structural brain abnormalities in young severe CKD patients. METHODS: This cross-sectional study includes 28 patients with severe CKD (eGFR < 30), aged 8-30 years (median 18.5 years), on different treatment modalities (pre-dialysis [n = 8], dialysis [n = 8], transplanted [n = 12]). We assessed neurocognitive functioning using a comprehensive test battery and brain structure by magnetic resonance imaging metrics of brain volume and white matter integrity (fractional anisotropy [FA] and mean diffusivity [MD] measured with diffusion tensor imaging). Multivariate regression and mediation analyses were performed between clinical CKD parameters, brain structure, and neurocognitive outcome. RESULTS: A combination of risk factors (e.g., longer time since kidney transplantation, longer dialysis duration and late CKD onset) was significantly associated with lower intelligence and/or worse processing speed and working memory. Lower FA in a cluster of white matter tracts was associated with lower intelligence and mediated the relation between clinical risk factors and lower intelligence. CONCLUSIONS: Young severe CKD patients with a prolonged duration of kidney replacement therapy, either dialysis or transplantation are at particular risk for impairments in intelligence, processing speed, and working memory. Disrupted white matter integrity may importantly contribute to these neurocognitive impairments. Prospective, longitudinal studies are needed to elucidate the mechanisms involved in CKD and treatment that affect white matter integrity and neurocognitive outcome in young patients. A higher resolution version of the Graphical abstract is available as Supplementary information.

Structural brain abnormalities in children and young adults with severe chronic kidney disease.

BACKGROUND: The pathophysiology of neurological dysfunction in severe chronic kidney disease (CKD) in children and young adults is largely unknown. We aimed to investigate brain volumes and white matter integrity in this population and explore brain structure under different treatment modalities. METHODS: This cross-sectional study includes 24 patients with severe CKD (eGFR < 30) aged 8-30 years (median = 18.5, range = 9.1-30.5) on different therapy modalities (pre-dialysis, n = 7; dialysis, n = 7; transplanted, n = 10) and 21 healthy controls matched for age, sex, and parental educational level. Neuroimaging targeted brain volume using volumetric analysis on T1 scans and white matter integrity with tract-based spatial statistics and voxel-wise regression on diffusion tensor imaging (DTI) data. RESULTS: CKD patients had lower white matter integrity in a widespread cluster of primarily distal white matter tracts compared to healthy controls. Furthermore, CKD patients had smaller volume of the nucleus accumbens relative to healthy controls, while no evidence was found for abnormal volumes of gray and white matter or other subcortical structures. Longer time since successful transplantation was related to lower white matter integrity. Exploratory analyses comparing treatment subgroups suggest lower white matter integrity and smaller volume of the nucleus accumbens in dialysis and transplanted patients relative to healthy controls. CONCLUSIONS: Young CKD patients seem at risk for widespread disruption of white matter integrity and to some extent smaller subcortical volume (i.e., nucleus accumbens). Especially patients on dialysis therapy and patients who received a kidney transplant may be at risk for disruption of white matter integrity and smaller volume of the nucleus accumbens.

Resting state networks mediate the association between both cardiovascular fitness and gross motor skills with neurocognitive functioning.

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.

Measurement Feedback System for Intensive Neurorehabilitation after Severe Acquired Brain Injury.

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.

The relationship between white matter microstructure, cardiovascular fitness, gross motor skills, and neurocognitive functioning in children.

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 executive functioning in primary school-aged children.

Previous research in children has shown that higher cardiovascular fitness is related to better executive functioning. However, the available literature is hampered by methodological limitations. The present study investigates the relationship between cardiovascular fitness and executive functioning in a large sample of healthy children (N = 814). Cardiovascular fitness was assessed with estimated VO2Max from 20 m Shuttle Run Test performance. Executive functioning was assessed using a set of computerized neurocognitive tasks aimed at executive functions (working memory, motor inhibition, interference control) and lower-level neurocognitive functions (information processing and attention). Dependent measures derived from the neurocognitive tests were subjected to principal component analysis. Mixed model analyses tested the relation between cardiovascular fitness and neurocognitive functioning components. Results showed that children with higher cardiovascular fitness performed better on the neurocognitive function components Information Processing and Control, Visuospatial Working Memory and Attention Efficiency. The following measures contained in these components contributed to the observed relations: information processing measures, visuospatial working memory, and speed of alerting attention. No relationship was found between cardiovascular fitness and the other components: Verbal Working Memory, Attention Accuracy, and Interference Control. The present study suggests that there is a relationship between cardiovascular fitness and a specific set of executive functions and lower level neurocognitive functions. These findings highlight the importance of cardiovascular fitness for the overall health of school-aged children.

Executive function training in very preterm children: a randomized controlled trial.

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.

The Effects of Aerobic Versus Cognitively Demanding Exercise Interventions on Executive Functioning in School-Aged Children: A Cluster-Randomized Controlled Trial.

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.

Effects of Timing and Intensity of Neurorehabilitation on Functional Outcome After Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

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<.001; 95% confidence interval [CI], 0.56-1.47) and a medium-sized positive effect for intensive neurorehabilitation programs (d=.67; P<.001; 95% CI, .38-.97) compared with usual care. These effects were replicated based solely on studies with a low overall risk of bias. CONCLUSIONS: The available evidence indicates that early onset neurorehabilitation in the trauma center and more intensive neurorehabilitation in the rehabilitation facility promote functional recovery of patients with moderate to severe TBI compared with usual care. These findings support the integration of early onset and more intensive neurorehabilitation in the chain of care for patients with TBI.

The structural connectome of children with traumatic brain injury.

This study aimed to investigate the impact of mild to severe pediatric TBI on the structural connectome. 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 = 16) at 2.8 years post-injury. Probabilistic tractography on diffusion tensor imaging data was used in combination with graph theory to study structural connectivity. Functional outcome was measured using neurocognitive tests and parent and teacher questionnaires for behavioral functioning. The results revealed no evidence for an impact of mildRF+ TBI on the structural connectome. In contrast, the moderate/severe TBI group showed longer characteristic path length (P = 0.022, d = 0.82) than the TC group. Furthermore, longer characteristic path length was related to poorer intelligence and poorer working memory in children with TBI. In conclusion, children have abnormal organization of the structural connectome after moderate/severe TBI, which may be implicated in neurocognitive dysfunction associated with pediatric TBI. These findings should be interpreted in the context of our exploratory analyses, which indicate that the definition and weighting of connectivity (e.g., streamline density, fractional anisotropy) influence the properties of the reconstructed connectome and its sensitivity to the impact and outcome of pediatric TBI. Hum Brain Mapp 38:3603-3614, 2017. © 2017 Wiley Periodicals, Inc.

Executive functions of sedentary elderly may benefit from walking: a systematic review and meta-analysis.

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 <0.0001). In older persons with cognitive impairment, walking did not show improvements in executive functioning (d = 0.14; 95% confidence interval: -0.36-0.64; z = 0.35; p = 0.56). CONCLUSION: This finding is clinically relevant because participation in a walking program may prevent or postpone a (further) decline in executive function in those who are sedentary.

Physical exercise and executive functions in preadolescent children, adolescents and young adults: a meta-analysis.

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<0.001). There were no significant differences between the three age groups (Q (2)=0.13, p=0.94). Furthermore, no significant overall effect of chronic physical exercise (d=0.14, 95%CI -0.04 to 0.32, p=0.19) on executive functions (Q (1)=5.08, p<0.05) was found. Meta-analytic effect sizes were calculated for the effects of acute physical exercise on the domain's inhibition/interference control (d=0.46, 95% CI 0.33 to 0.60, p<0.001) and working memory (d=0.05, 95% CI -0.51 to 0.61, p=0.86) as well as for the effects of chronic physical exercise on planning (d=0.16, 95% CI 0.18 to 0.89, p=0.18). CONCLUSIONS: Results suggest that acute physical exercise enhances executive functioning. The number of studies on chronic physical exercise is limited and it should be investigated whether chronic physical exercise shows effects on executive functions comparable to acute physical exercise. This is highly relevant in preadolescent children and adolescents, given the importance of well-developed executive functions for daily life functioning and the current increase in sedentary behaviour in these age groups.

Effects of Bumetanide on Neurocognitive Functioning in Children with Autism Spectrum Disorder: Secondary Analysis of a Randomized Placebo-Controlled Trial.

We present the secondary-analysis of neurocognitive tests in the 'Bumetanide in Autism Medication and Biomarker' (BAMBI;EUDRA-CT-2014-001560-35) study, a randomized double-blind placebo-controlled (1:1) trial testing 3-months bumetanide treatment (≤ 1 mg twice-daily) in unmedicated children 7-15 years with ASD. Children with IQ ≥ 70 were analyzed for baseline deficits and treatment-effects on the intention-to-treat-population with generalized-linear-models, principal component analysis and network analysis. Ninety-two children were allocated to treatment and 83 eligible for analyses. Heterogeneous neurocognitive impairments were found that were unaffected by bumetanide treatment. Network analysis showed higher modularity after treatment (mean difference:-0.165, 95%CI:-0.317 to - 0.013,p = .034) and changes in the relative importance of response inhibition in the neurocognitive network (mean difference:-0.037, 95%CI:-0.073 to - 0.001,p = .042). This study offers perspectives to include neurocognitive tests in ASD trials.

Pharmacotherapy to Improve Cognitive Functioning After Acquired Brain Injury: A Meta-Analysis and Meta-Regression.

Cognitive impairments, common sequelae of acquired brain injury (ABI), significantly affect rehabilitation and quality of life. Currently, there is no solid evidence-base for pharmacotherapy to improve cognitive functioning after ABI, nevertheless off-label use is widely applied in clinical practice. This meta-analysis and meta-regression aims to quantitatively aggregate the available evidence for the effects of pharmacological agents used in the treatment of cognitive impairments following ABI. We conducted a comprehensive search of Embase, Medline Ovid, and Cochrane Controlled Trials Register databases for randomized controlled and crossover trials. Meta-analytic effects were calculated for each pharmaceutical agent and targeted neuromodulator system. Cognitive outcome measures were aggregated across cognitive domains. Of 8,216 articles, 41 studies (4,434 patients) were included. The noradrenergic agent methylphenidate showed a small, significant positive effect on cognitive functioning in patients with traumatic brain injury (TBI; k = 14, d = 0.34, 95% confidence interval: 0.12-0.56, P = 0.003). Specifically, methylphenidate was found to improve cognitive functions related to executive memory, baseline speed, inhibitory control, and variability in responding. The cholinergic drug donepezil demonstrated a large effect size, albeit based on a limited number of studies (k = 3, d = 1.68, P = 0.03). No significant effects were observed for other agents. Additionally, meta-regression analysis did not identify significant sources of heterogeneity in treatment response. Our meta-analysis supports the use of methylphenidate for enhancing cognitive functioning in patients with TBI. Although donepezil shows potential, it warrants further research. These results could guide clinical decision making, inform practice guidelines, and direct future pharmacotherapeutic research in ABI.

Long-Term Neurodevelopmental Outcome of Children With Mild Traumatic Brain Injury.

BACKGROUND: To investigate the long-term outcome of pediatric mild traumatic brain injury (mTBI) in terms of neurocognitive, behavioral, and school functioning and to identify clinical risk factors for adverse outcomes. METHODS: This study describes the follow-up of a prospective multicenter sample of 89 children with mTBI 3.6 years postinjury and 89 neurologically healthy children matched for sex, age, and socioeconomic status. Neurodevelopmental outcomes were assessed using an intelligence test, behavioral questionnaires, computerized neurocognitive tests, and longitudinal (pre- and postinjury) standardized school performance data. RESULTS: Children with mTBI exhibited intelligence in the average range but had more behavioral problems related to inattentiveness (P = 0.004, d = 0.47) and hyperactive impulsivity (P = 0.01, d = 0.40) and showed poorer neurocognitive performance in information processing stability (P = 0.003, d = -0.55) and Visual Working Memory (P = 0.04, d = -0.39) compared with matched peers. Longitudinal school performance data revealed poorer performance in Technical Reading up to two years postinjury (P = 0.005, d = -0.42) when compared with normative data. Clinical risk factors did not reveal predictive value for adverse outcomes in children with mTBI. CONCLUSIONS: This study indicates that children with mTBI are at risk of long-term deficits in neurocognitive and behavioral functioning, with longitudinal evidence suggesting shortfalls in school performance up to two years postinjury. Clinical risk factors do not provide a solid basis for long-term neurodevelopmental prognosis. Findings emphasize the importance of, and challenges for, early identification of children at risk for adverse neurodevelopmental outcome after mTBI.

ENIGMA's simple seven: Recommendations to enhance the reproducibility of resting-state fMRI in traumatic brain injury.

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.

The mediating role of neurocognitive functions in the relation between physical competencies and academic achievement of primary school children.

Previous studies into associations between physical, neurocognitive and academic skills have reported inconsistent results. This study aimed to get more insight into these relations by examining all three domains simultaneously, testing a complete mediational model including measures of physical competencies (cardiovascular fitness and motor skills), neurocognitive skills (attention, information processing, and core executive functions), and academic achievement (reading, mathematics, and spelling). Dutch primary school students (n = 891, 440 boys, mean age 9.17 years) were assessed on the Shuttle Run Test (cardiovascular fitness), items of the Körperkoordinationstest für Kinder and Bruininks-Oseretsky Test-II (fundamental motor skills), computerized neurocognitive tests, and standardized academic achievement tests. A multilevel structural equation model showed that physical competencies were only indirectly related to academic achievement, via specific neurocognitive functions depending on the academic domain involved. Results provide important implications, highlighting the importance of well-developed physical competencies in children.