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Aim: To evaluate the efficacy of the Akwenda Intervention Program on motor, self‐care, and social function of children and young people with cerebral palsy (CP). Method: This was a cluster‐randomized, controlled, single‐blinded, intervention study of 100 participants with CP (2–23 years; 52 males) in rural eastern Uganda. Half were allocated to the intervention program, the remainder served as waitlist controls. Gross Motor Function Measure‐66 (GMFM‐66) and the Ugandan version of Pediatric Evaluation of Disability Inventory (PEDI‐UG) were collected before group allocation and after intervention. General linear models and t‐tests were used to compare changes within and between groups. Cohen's d estimated the effect size of group differences. Change scores were evaluated by age and mobility subgroups. Results: Significant group by time interactions were found for GMFM‐66 (p =0.003) and PEDI‐UG outcomes (p <0.001), except mobility, with the intervention group demonstrating greater changes. Both groups increased their scores on the GMFM‐66 and child PEDI‐UG, while only the intervention group had significant increases in caregiver assistance scores and across all age and mobility subgroups. Cohen's d showed large effect sizes (d >0.8) of differences for PEDI‐UG outcomes except mobility. Interpretation: The Akwenda Intervention Program had a large positive impact on functioning and activity across age and mobility levels. [ABSTRACT FROM AUTHOR]

This letter to the editor is on the commentary by Olusanya on pages 10–11 of this issue. [ABSTRACT FROM AUTHOR]

Background: Validity of the Ugandan version of the Pediatric Evaluation of Disability Inventory (PEDI‐UG) was previously investigated on typically developing children. This study aimed to investigate the validity, test–retest reliability and minimal detectable change (MDC) of the PEDI‐UG in children and youth (C&Y) with cerebral palsy (CP). Method: A cross‐sectional study design with 118 C&Y with CP (44.7% girls) aged 10 months–22.5 years were included in the study; 37 of them completed the PEDI‐UG twice to investigate test–retest reliability, determined by calculating the intraclass correlation coefficient (ICC). Additionally, data from 249 typically developing children were used for differential item functioning (DIF) analysis. The validity of the PEDI‐UG was investigated by Rasch analysis. The Kruskal–Wallis test and Spearman's correlation coefficient were calculated to investigate associations between PEDI‐UG scores and external classification systems. Results: The principal component analysis of residuals indicated unidimensionality in all domains. The ICC values were excellent (0.98–0.99), and the MDCs were less than 6 and 13 (on a 0–100 scale) for the functional skills and caregiver assistance parts, respectively. The four‐category caregiver assistance rating scale fulfilled the criteria for the analysis of rating scale functioning. In total, 78 of 189 items in the functional skills domain and two items in the caregiver assistance domain demonstrated DIF between C&Y with CP and TD children. The Kruskal–Wallis test (p < 0.05) and Spearman's correlation (coefficients of −0.93 to −0.78) supported the validity of PEDI‐UG. Conclusion: The current diagnose‐specific version of PEDI‐UG demonstrates evidence for validity as a measure of ability in C&Y with CP in Uganda and other similar settings, being a promising tool for use in clinical practice and research. Conversion tables and MDC values are provided to facilitate clinical adoption of the measure. [ABSTRACT FROM AUTHOR]

In this exploratory study, we investigate whether goal-directed intervention for wheelchairs can increase the activities of daily living for children and young people with cerebral palsy (CP) when implemented in rural Uganda. Thirty-two children and young people with CP (aged 3–18 years) participated in a home-visit intervention program, which included donating wheelchairs and setting individual goals. Goal achievement, frequency of wheelchair use, condition of wheelchairs, and caregivers' perspectives were collected by interviews at 6–10 month after the start of intervention and the after three years. Our result show that most wheelchairs were in good condition and frequently used after 6–10 month with 83% goal achievement (132/158 goals; mean 4.3 (range 0–7). The caregivers reported several advantages (e.g., the child being happier) and few disadvantages (e.g., poor design and durability). At the three-year follow-up, only eleven wheelchairs were still used by 23 available participants (seven deceased and two moved). The children achieved 60% of their goals (32/53 goals mean 2.9; range 1–5). This demonstrates that the goal-directed intervention program for wheelchairs can be successfully implemented in a low-income setting with a high rate of goal achievement and frequent wheelchair use, facilitating participation. However, maintenance services are crucial to obtain sustainable results. [ABSTRACT FROM AUTHOR]

Aim: To compare the participation attendance and involvement of children and young people with and without cerebral palsy (CP) in a low‐resource area of Uganda. Method: Eighty‐two children and young people with CP aged 6 to 22 years (49 males, 33 females) and 81 age‐ and sex‐matched peers without CP (6 to 22 years; 48 males, 33 females) participated in this population‐based, cross‐sectional study. Data on attendance and involvement in 20 home and community activities were obtained using Picture My Participation, an instrument intended to measure participation in children with disabilities, particularly in low‐ and middle‐income countries. Non‐parametric statistical methods were used to assess between‐group differences. Effect size estimates were calculated. Results: Pooled attendance across all activities was lower in children and young people with CP than in children and young people without CP (p < 0.001) and for each activity item (p = 0.004 to p < 0.001). The effect sizes for each activity were 0.2 to 0.7. Between‐group differences were larger for community activities than for home activities. Pooled involvement across all activities was less in the group with CP (p < 0.001) and for each activity (p = 0.014 to p < 0.001). The effect sizes for each activity were 0.2 to 0.5. Children and young people in Gross Motor Function Classification System (GMFCS) levels I and II had higher attendance (p < 0.001) and involvement (p = 0.023) than those in GMFCS levels III to V. Interpretation: Participation of young people living with CP in Uganda was restricted, especially for community activities. There is a need to identify context‐specific participation barriers and develop strategies to overcome them. What this paper adds: Children and young people with cerebral palsy (CP) attended all activities less than their peers without CP.Differences in attendance were larger for community‐based activities than home activities.When attending activities, children and young people with CP were less involved than their peers.Children and young people with milder impairments attended less frequently than their peers without CP.Children and young people with milder impairments attended more frequently than their peers with severe impairments. [ABSTRACT FROM AUTHOR]

Aim: To follow the functional development of a population‐based cohort of children with cerebral palsy (CP) in rural Uganda and compare their development with the developmental trajectories of children from high‐income countries (HIC). Method: Eighty‐one children (33 females, 48 males) aged 2 to 17 years (mean 8y 6mo, SD 4y 6mo) with CP were initially assessed in 2015 and then 4 years later using the 66‐item Gross Motor Function Measure (GMFM‐66), Pediatric Evaluation of Disability Inventory, Ugandan version (PEDI‐UG), and functional classification systems. We calculated actual and reference scores (level of deviation from the developmental trajectories in HIC). A Wilcoxon signed‐rank test was used for statistical analyses. Results: Children and young people with CP in Uganda exhibited no differences in scores between the first and second assessments for the GMFM‐66 and PEDI‐UG mobility skills, whereas they exhibited increased PEDI‐UG social function (p<0.001) and self‐care skills scores (p<0.001). Reference scores were more negative at the second assessment than at the first for the GMFM‐66 (p=0.002) and PEDI‐UG mobility (p=0.036) but not for PEDI‐UG self‐care. The increased difference in reference scores over the 4 years was primarily driven by younger children (2–5y) and children with milder impairments. Interpretation: The increased difference in reference scores between assessments suggests that children with CP in Uganda develop motor skills at a slower rate than peers in HIC. Limited access to health care and rehabilitation likely contributed to the lower scores and slower rate of development. This original article is commented by Tann on page 11 of this issue. [ABSTRACT FROM AUTHOR]

Background: Although, there is no population-level data in Ethiopia, a previous retrospective hospital-based study identified CP as the most common developmental disability in children. The overall aim of this study is to describe the clinical spectrum of CP in Tikur Anbessa Specialized Hospital in Addis Ababa, including CP subtype, gross and fine motor function, presence and pattern of associated impairments, and possible risk factors in children aged 2 to 18 years.Methods: A hospital-based descriptive cross-sectional study conducted- July - September of 2018 among 207 children with suspected motor symptoms. The Surveillance of CP in Europe (SCPE) decision tree was used as a guideline for inclusion and evaluation was by standardized questionnaire and clinical examination. Descriptive, bivariate and multivariate statistical analyses, Chi-square test, crudes association and adjusted odds ratio with 95% confidence interval employed.Result: One hundred seventy four children who fulfilled the clinical criteria were included. Half (50.6%) were under the age of 5 years with a mean age of 5.6 (SD 3.6) years; 55.2 were male. The majority had bilateral spastic CP (60.4%) followed by unilateral spastic CP 21.8%, dyskinetic CP 10.4%, and ataxic CP 3.4%; 4% were unclassifiable. Of the children, 95.4% had speech difficulty, 87.4% learning disabilities, 60.9% epilepsy, 24.7% visual impairment and 8.6% hearing impairment. On gross motor function (GMFCS) and manual ability (MACS) classification systems, 75.3% of the children had level IV and V functional impairment. More than 80% of the mothers had complications during delivery Half of the neonates did not cry immediately after birth,44% were resuscitated with bag mask ventilation at birth and 64% immediately admitted to NICU. During the first month of life, 50% had infection, 62% had trouble feeding, 49.4% had difficulty breathing, 35% had seizure and 13.8% had jaundice.Conclusion: The severe forms of CP predominate; most children are dependent on their parents for routine activities of daily living and cannot communicate well. Multidisciplinary care approaches and focused functional habilitation services are needed. Causal relationships cannot be drawn from these data but findings make a strong argument for improving maternal and child health care. [ABSTRACT FROM AUTHOR]

Background: Studies from high-income countries reported reduced life expectancy in children with cerebral palsy (CP), while no population-based study has evaluated mortality of children with CP in sub-Saharan Africa. This study aimed to estimate the mortality rate (MR) of children with CP in a rural region of Uganda and identify risk factors and causes of death (CODs). Methods and findings: This population-based, longitudinal cohort study was based on data from Iganga-Mayuge Health and Demographic Surveillance System in eastern Uganda. We identified 97 children (aged 2–17 years) with CP in 2015, whom we followed to 2019. They were compared with an age-matched cohort from the general population (n = 41 319). MRs, MR ratios (MRRs), hazard ratios (HRs), and immediate CODs were determined. MR was 3952 per 100 000 person years (95% CI 2212–6519) in children with CP and 137 per 100 000 person years (95% CI 117–159) in the general population. Standardized MRR was 25·3 in the CP cohort, compared with the general population. In children with CP, risk of death was higher in those with severe gross motor impairments than in those with milder impairments (HR 6·8; p = 0·007) and in those with severe malnutrition than in those less malnourished (HR = 3·7; p = 0·052). MR was higher in females in the CP cohort, with a higher MRR in females (53·0; 95% CI 26·4–106·3) than in males (16·3; 95% CI 7·2–37·2). Age had no significant effect on MR in the CP cohort, but MRR was higher at 10–18 years (39·6; 95% CI 14·2–110·0) than at 2–6 years (21·0; 95% CI 10·2–43·2). Anaemia, malaria, and other infections were the most common CODs in the CP cohort. Conclusions: Risk of premature death was excessively high in children with CP in rural sub-Saharan Africa, especially in those with severe motor impairments or malnutrition. While global childhood mortality has significantly decreased during recent decades, this observed excessive mortality is a hidden humanitarian crisis that needs to be addressed. [ABSTRACT FROM AUTHOR]

Copyright of Developmental Medicine & Child Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Cerebral palsy (CP) is one of the most common childhood-onset motor disabilities, attributed to injuries of the immature brain in the foetal or early postnatal period. The underlying mechanisms are poorly understood, rendering prevention and treatment strategies challenging. The aim of the present study was to establish a mouse model of CP for preclinical assessment of new interventions. For this purpose, we explored the impact of a double neonatal insult (i.e. systemic inflammation combined with hypoxia) on behavioural and cellular outcomes relevant to CP during the prepubertal to adolescent period of mice. Pups were subjected to intraperitoneal lipopolysaccharide (LPS) injections from postnatal day (P) 3 to P6 followed by hypoxia at P7. Gene expression analysis at P6 revealed a strong inflammatory response in a brain region-dependent manner. A comprehensive battery of behavioural assessments performed between P24 and P47 showed impaired limb placement and coordination when walking on a horizontal ladder in both males and females. Exposed males also displayed impaired performance on a forelimb skilled reaching task, altered gait pattern and increased exploratory activity. Exposed females showed a reduction in grip strength and traits of anxiety-like behaviour. These behavioural alterations were not associated with gross morphological changes, white matter lesions or chronic inflammation in the brain. Our results indicate that the neonatal double-hit with LPS and hypoxia can induce subtle long-lasting deficits in motor learning and fine motor skills, which partly reflect the symptoms of children with CP who have mild gross and fine motor impairments. [ABSTRACT FROM AUTHOR]

Copyright of Developmental Medicine & Child Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Executive function deficits are often reported as a specific weakness in preterm children. Yet, executive function development is still not fully understood. In a prospective longitudinal study, 115 preterm born children, ≤31 weeks of gestation, were recruited at birth and subject to neuropsychological assessments at ages 5.5 and 18 years. By applying Miyake and colleagues' integrative framework of executive function to our data, two core components of executive function, working memory and cognitive flexibility, were identified through confirmatory factor analysis. Developmental stability was investigated in a serial multiple mediator structural equation model. Biological, medical, and social factors as well as mental development at 10 months were entered as predictors. Both components of executive function were highly stable from 5.5 to 18 years. Gestational age, intrauterine growth, lack of perinatal medical complications, and female sex were positively related to mental development at 10 months, which together with parental education influenced both core executive functions at 5.5 years. Working memory at 5.5 years mediated outcome in working memory at 18 years. In addition to the mediation of cognitive flexibility at 5.5 years, perinatal medical complications and restricted intrauterine growth had a continued direct negative impact on cognitive flexibility at 18 years. The application of a theoretical framework added to our understanding of executive function development in preterm born children. The study supports early identification of executive deficits among children born preterm, as deficits are unlikely to diminish with maturation. [ABSTRACT FROM AUTHOR]

Main objectives: Executive functions are frequently a weakness in children born preterm. We examined associations of executive functions and general cognitive abilities with brain structure in preterm born adolescents who were born with appropriate weight for gestational age and who have no radiological signs of preterm brain injury on neuroimaging. Methods: The Stockholm Neonatal Project (SNP) is a longitudinal, population-based study of children born preterm (<36 weeks of gestation) with very low birth weight (<1501g) between 1988–1993. At age 18 years (mean 18 years, SD 2 weeks) 134 preterm born and 94 full term participants underwent psychological assessment (general intelligence, executive function measures). Of these, 71 preterm and 63 full term participants underwent Magnetic Resonance Imaging (MRI) at mean 15.2 years (range 12–18 years), including 3D T1-weighted images for volumetric analyses and Diffusion Tensor Imaging (DTI) for assessment of white matter microstructure. Group comparisons of regional grey and white matter volumes and fractional anisotropy (FA, as a measure of white matter microstructure) and, within each group, correlation analyses of cognitive measures with MRI metrics were carried out. Results: Significant differences in grey and white matter regional volumes and widespread differences in FA were seen between the two groups. No significant correlations were found between cognitive measures and brain volumes in any group after correction for multiple comparisons. However, there were significant correlations between FA in projection fibres and long association fibres, linking frontal, temporal, parietal, and occipital lobes, and measures of executive function and general cognitive abilities in the preterm born adolescents, but not in the term born adolescents. Overall significance of the study: In persons born preterm, in the absence of perinatal brain injury on visual inspection of MRI, widespread alterations in regional brain tissue volumes and microstructure are present in adolescence/young adulthood. Importantly, these alterations in WM tracts are correlated with measures of executive function and general cognitive abilities. Our findings suggest that disturbance of neural pathways, rather than changes in regional brain volumes, are involved in the impaired cognitive functions. [ABSTRACT FROM AUTHOR]

Aim: There is limited literature on brain imaging studies of children with cerebral palsy (CP) in low and middle income countries. We investigated neuroimaging patterns of children with CP attending a tertiary referral centre in Uganda to determine how they differed from studies reported from high income countries and their relationship with prenatal and postnatal factors.Methods: Precontrast and postcontrast computed tomography (CT) scans of 78 CP children aged 2-12 years were conducted using a Philips MX 16-slice CT scanner. Two radiologists, blinded to the patient's clinical status, independently reviewed the scans.Results: Abnormal CT scans were detected in 69% of the children sampled, with very few having primary white matter injuries (4%). Primary grey matter injuries (PGMI) (44%) and normal scans (31%) were most frequent. Children with a history of hospital admission following birth were three times more likely to have PGMI (odds ratio [OR] 2.8; 95% CI 1.1-7.1), suggesting a perinatal period with medical complications.Conclusion: Brain imaging patterns in this group of CP children differed markedly from imaging studies reported from high income countries, suggesting a perinatal aetiology in full-term infants and reduced survival in preterm infants. [ABSTRACT FROM AUTHOR]

Aim: Poor growth and malnutrition are frequently reported in children with cerebral palsy in developed countries, but there is limited information from developing countries. We investigated the nutritional status of Ugandan children with cerebral palsy and described the factors associated with poor nutrition.Methods: We examined 135 children from two to 12 years with cerebral palsy, who attended Uganda's national referral hospital. A child was considered underweight, wasted, stunted or thin if the standard deviation scores for their weight for age, weight for height, height for age and body mass index for age were ≤-2.0 using World Health Organization growth standards. Multivariable logistic regression identified the factors associated with nutritional indicators.Results: Over half (52%) of the children were malnourished, with underweight (42%) being the most common category, followed by stunting (38%), thinness (21%) and wasting (18%). Factors that were independently associated with being malnourished were as follows: presence of cognitive impairment, with an adjusted odds ratio (aOR) of 4.5, being 5 years or older (aOR = 3.4) and feeding difficulties in the perinatal period (aOR = 3.2).Conclusion: Malnutrition was common in Ugandan children with cerebral palsy and more likely if they were 5 years or more or had experienced neonatal complications. [ABSTRACT FROM AUTHOR]

Abundant evidence points to a key role of dopamine in motor skill learning, although the underlying cellular and molecular mechanisms are still poorly understood. Here, we used a skilled-reaching paradigm to first examine changes in the expression of the plasticity-related gene Arc to map activity in cortico-striatal circuitry during different phases of motor skill learning in young animals. In the early phase, Arc mRNA was significantly induced in the medial prefrontal cortex (mPFC), cingulate cortex, primary motor cortex, and striatum. In the late phase, expression of Arc did not change in most regions, except in the mPFC and dorsal striatum. In the second series of experiments, we studied the learning-induced changes in the phosphorylation state of dopamine and cAMP-regulated phosphoprotein, 32k Da (DARPP-32). Western blot analysis of the phosphorylation state of DARPP-32 and its downstream target cAMP response element-binding protein (CREB) in the striatum revealed that the early, but not late, phase of motor skill learning was associated with increased levels of phospho-Thr34-DARPP-32 and phospho-Ser133-CREB. Finally, we used the DARPP-32 knock-in mice with a point mutation in the Thr34 regulatory site (i.e., protein kinase A site) to test the significance of this pathway in motor skill learning. In accordance with our hypothesis, inhibition of DARPP-32 activity at the Thr34 regulatory site strongly attenuated the motor learning rate and skilled reaching performance of mice. These findings suggest that the cAMP/PKA/DARPP-32 signaling pathway is critically involved in the acquisition of novel motor skills, and also demonstrate a dynamic shift in the contribution of cortico-striatal circuitry during different phases of motor skill learning. [ABSTRACT FROM AUTHOR]

Cognitive outcome after preterm birth is heterogeneous, and group level analyses may disguise individual variability in development. Using a person-oriented approach, this study investigated individual cognitive patterns and developmental trajectories from preschool age to late adolescence. As part of a prospective longitudinal study, 118 adolescents born preterm, with a birth weight < 1,500 g, participated in neuropsychological assessments at age 5½ years and at 18 years. At each age, four cognitive indices, two tapping general ability and two tapping executive functions, were formed to reflect each individual’s cognitive profile. Cluster analyses were performed at each age separately, and individual movements between clusters across time were investigated. At both 5½ and 18 years, six distinct, and similar, cognitive patterns were identified. Executive functions were a weakness for some but not all subgroups, and verbal ability was a strength primarily among those whose overall performance fell within the normal range. Overall, cognitive ability at 5½ years was highly predictive of ability at age 18. Those who performed at low levels at 5½ years did not catch up but rather deteriorated in relative performance. Over half of the individuals who performed above the norm at 5½ years improved their relative performance by age 18. Among those performing around the norm at 5½ years, half improved their relative performance over time, whereas the other half faced increased problems, indicating a need for further developmental monitoring. Perinatal factors were not conclusively related to outcome, stressing the need for cognitive follow-up assessment of the preterm-born child before school entry. [ABSTRACT FROM AUTHOR]

Background: Cerebral palsy (CP) is a common chronic childhood disorder worldwide. There is limited information about the CP panorama in sub-Saharan Africa. Our aim was to describe the clinical subtypes, gross and fine motor functions and presence of co-morbidities in a group of children with CP attending a tertiary hospital in Uganda. Methods: Children with CP in the age range of 2-12 years visiting the paediatric CP clinic at Mulago Hospital, Kampala, were enrolled. Screening and inclusion were based on a three-stage procedure: i) Two screening questions from the Ten Question Screen; ii) Clinical assessments adapted from the Surveillance for Cerebral Palsy in Europe (SCPE); iii) Clinical examinations and diagnoses of subtype, severity level and co-morbidities. Caregivers were interviewed using questionnaires to provide information on child's medical history and co-morbidities. Co-morbidity scores were calculated for each child. Results: One hundred and thirty five children with CP were enrolled (72 males, 63 females, median age 3 years 5 months, IQR-2 years 4 months-5 years 6 months). Bilateral spastic type was commonest (45%); moderate impairment in gross motor function was present in 43%, with comparable numbers (37%) in the mild and severely impaired fine motor function groups. The severe gross and fine motor function levels were seen in the bilateral spastic and dyskinetic CP subtypes. Signs of learning disability (75%) and epilepsy (45%) were the commonest co-morbidities. Higher co-morbidity scores were obtained in children with dyskinetic CP and severe levels of gross and fine motor function. There was a significant difference in distribution of the co-morbidity scores between the CP subtypes, gross motor and fine motor function levels (p <0.001). Signs of speech and language impairments were associated with bilateral spastic CP and severe gross and fine motor dysfunction (p < 0.05). Conclusions: Bilateral spastic CP was the main clinical subtype, with signs of learning disability and epilepsy as major causes of co-morbidity. The severity of gross and fine motor function levels was related to severity of clinical CP subtypes. Our findings imply a higher occurrence of birth asphyxia or post natally acquired infections. Improvement in emergency obstetric and postnatal care may reduce this burden. [ABSTRACT FROM AUTHOR]

Cerebral palsy (CP) is a heterogeneous group of neurodevelopmental disorders associated with lifelong motor impairment and disability. Current intervention programmes aim to capitalize on the neuroplasticity of the undamaged part of the brain to improve motor functions, by engaging individuals in active motor learning and training. In this review, we highlight recent animal studies (1) exploring cellular and molecular mechanisms contributing to neuroplasticity during motor training, (2) assessing the functional role of the mesocortical dopaminergic system in motor skill learning, and (3) exploring the impact of naturally occurring genetic variation in dopamine-related gene expression on the acquisition and performance of fine motor skills. Finally, the potential influence of the dopamine system on the outcome of motor learning interventions in cerebral palsy is discussed. [ABSTRACT FROM AUTHOR]

Preterm birth has been shown to induce an altered developmental trajectory of brain structure and function. With the aid support vector machine (SVM) classification methods we aimed to investigate whether MRI data, collected in adolescence, could be used to predict whether an individual had been born preterm or at term. To this end we collected T1–weighted anatomical MRI data from 143 individuals (69 controls, mean age 14.6y). The inclusion criteria for those born preterm were birth weight ≤ 1500g and gestational age < 37w. A linear SVM was trained on the grey matter segment of MR images in two different ways. First, all the individuals were used for training and classification was performed by the leave–one–out method, yielding 93% correct classification (sensitivity = 0.905, specificity = 0.942). Separately, a random half of the available data were used for training twice and each time the other, unseen, half of the data was classified, resulting 86% and 91% accurate classifications. Both gestational age (R = –0.24, p<0.04) and birth weight (R = –0.51, p < 0.001) correlated with the distance to decision boundary within the group of individuals born preterm. Statistically significant correlations were also found between IQ (R = –0.30, p < 0.001) and the distance to decision boundary. Those born small for gestational age did not form a separate subgroup in these analyses. The high rate of correct classification by the SVM motivates further investigation. The long–term goal is to automatically and non–invasively predict the outcome of preterm–born individuals on an individual basis using as early a scan as possible. [ABSTRACT FROM AUTHOR]

Aim The aim of this study was to investigate long-term cognitive outcome in a cohort of 18-year-olds born preterm and previously assessed at the age of 5.5. Methods We tested 134 adolescents born preterm with a very low birthweight of <1500 g and 94 term-born controls with a comprehensive cognitive battery at 18 years of age. The cohort was subdivided into 73 extremely preterm, 42 very preterm and 19 moderately preterm infants with gestational ages of 23-27, 28-31 and 32-36 weeks, respectively. The moderately preterm group was dominated by adolescents born small for gestational age. Results Very preterm adolescents performed on a par with term-born controls. In contrast, extremely preterm adolescents displayed inferior results on all cognitive tests, more so if they had suffered neonatal complications. Moderately preterm adolescents scored lower than very preterm and full-term born adolescents, particularly on complex cognitive tasks. Conclusion Adolescents born at 28 weeks of gestation or later, with appropriate birthweight and no perinatal complications, functioned like term-born peers at 18 years of age. Extremely preterm birth per se posed a risk for long-term cognitive deficits, particularly executive deficits. Adolescents born moderately preterm but small for gestational age were at risk of general cognitive deficits. [ABSTRACT FROM AUTHOR]

Background: Mounting evidence indicates that the indigenous gut microbiota exerts long-lasting programming effects on brain function and behaviour. Objective: In this study, we used the germ-free (GF) mouse model, devoid of any microbiota throughout development, to assess the influence of the indigenous microbiota on social preference and repetitive behaviours (e.g. self-grooming). Methods and results: Using the three-chambered social approach task, we demonstrate that when adult GF mice were given a choice to spend time with a novel mouse or object, they spent significantly more time sniffing and interacting with the stimulus mouse compared to conventionally raised mice (specific pathogen-free, SPF). Time spent in repetitive self-grooming behaviour, however, did not differ between GF and SPF mice. Real-time PCR-based gene expression analysis of the amygdala, a key region that is part of the social brain network, revealed a significant reduction in the mRNA levels of total brain-derived neurotrophic factor (BDNF), BDNF exon I-, IV-, VI-, IX-containing transcripts, and NGFI-A (a signalling molecule downstream of BDNF) in GF mice compared to SPF mice. Conclusion: These results suggest that differential regulation of BDNF exon transcripts in the amygdala by the indigenous microbes may contribute to the altered social development of GF mice. [ABSTRACT FROM AUTHOR]

Aim The aim of the study was to explore individual variations in outcome of hand function after constraint-induced movement therapy ( CIMT) in relation to the organization of corticomotor projection and brain lesion characteristics in participants with unilateral cerebral palsy ( CP). Method Sixteen participants (eight males, eight females; mean age 13y, [ SD 2y] range 10-16y) with unilateral CP (nine right-sided; Manual Ability Classification System [ MACS] level I, n=1; level II, n=15) who participated in a 2-week CIMT day camp (63h) were included in the study. Various aspects of hand function were measured by the Jebsen-Taylor Hand Function Test ( JTHFT), the Assisting Hand Assessment ( AHA), and the Melbourne Assessment, both before and after the day camp. Transcranial magnetic stimulation was used to explore the corticomotor organization, and brain lesion characteristics were described by visual assessment of conventional structural magnetic resonance images. Results At a group level, the training was associated with significant improvements in JTHFT ( p=0.003) and AHA ( p=0.046), but not in Melbourne Assessment scores. Improvements were found in all types of corticomotor projection patterns, i.e. contralateral, mixed, and ipsilateral. There was no relationship between functional improvement and brain lesion characteristics. Interpretation Individuals with CP experience improved motor outcomes after CIMT, independent of corticomotor projection pattern and lesion characteristics. [ABSTRACT FROM AUTHOR]

First, we explore the performance of nonword repetition (NWR) in children with specific language impairment (SLI) and typically developing children (TD) in order to investigate the accuracy of NWR as a clinical marker for SLI in Swedish-speaking school-age children. Second, we examine the relationship between NWR, family aggregation, and parental level of education in children with SLI. A sample of 61 children with SLI, and 86 children with TD, aged 8–12 years, were administered an NWR test. Family aggregation, measured as the prevalence of language and/or literacy problems (LLP) in parents of the children with SLI, was based on family history interviews. The sensitivity and specificity of nonword repetition was analyzed in a binary logistic regression, cut-off values were established with ROC curves, and positive and negative likelihood ratios reported. Results from the present study show that NWR distinguishes well between Swedish-speaking school-children with and without SLI. We found 90.2% sensitivity and 97.7% specificity at a cut-off level of −2 standard deviations for binary scoring of nonwords. Differences between the SLI and TD groups showed large effect sizes for the two scoring measures binary (d = 2.11) and percent correct consonants (PCC) (d = 1.79). The children with SLI were split into two subgroups: those with no parents affected with LLP (n = 12), and those with one or both parents affected (n = 49). The subgroup consisting of affected parents had a significantly lower score on NWR binary (p = .037), and there was a great difference between the subgroups (d = 0.7). When compared to the TD group, the difference from the subgroup with affected parents was almost one standard deviation larger (d = 2.47) than the difference from the TD to the subgroup consisting of non-affected parents (d = 1.57). Our study calls for further exploration of the complex interaction between family aggregation, language input, and phenotypes of SLI. [ABSTRACT FROM AUTHOR]

While it is clear that the development of dexterous manipulation in children exhibits dramatic improvements over an extended period, it is difficult to separate musculoskeletal from neural contributors to these important functional gains. This is in part due to the inability of current methods to disambiguate improvements in hand strength from gains in finger dexterity (i.e., the dynamic control of fingertip force vectors at low magnitudes). We adapted our novel instrumentation to evaluate finger dexterity in 130 typically developing children between the ages of 4 and 16 yr. We find that finger dexterity continues to develop well into late adolescence and musculoskeletal growth and strength are poorly correlated with the improvements in dexterity. Importantly, because these behavioral results seem to mirror the known timelines of neuroanatomical development up to adolescence, we speculate that they reflect the functional benefits of such continual neural maturation. This novel perspective now enables the systematic study of the functional roles of specific neuroanatomical structures and their connectivity, maturity, and plasticity. Moreover, the temporal dynamics of the fingertip force vectors shows improvements in stability that provide a novel way to look at the maturation of finger control. From a clinical perspective, our results provide a practical means to chart functional development of dexterous manipulation in typically developing children and could be adapted for clinical use and for use in children with developmental disorders. [ABSTRACT FROM AUTHOR]

Background. Much variation is found in the development of hand function in children with unilateral cerebral palsy (CP). Objective. To explore how anatomic brain abnormalities can be used to predict the development of hand function. Methods. A total of 32 children with unilateral CP (16 boys and 16 girls) were evaluated at least once a year by the Assisting Hand Assessment (AHA). The data collection covered an age range from 18 months to 8 years (mean time in study, 4 years and 6 months). Computerized tomography or magnetic resonance imaging of the brain were assessed for patterns of brain damage, including the location of gray and extent of white-matter damage. The children were divided into groups according to lesion characteristics, and a series of univariate models were analyzed with a nonlinear mixed-effects model. The rate and maximum limit of development were calculated. Results. The highest predictive power of better development of hand function was the absence of a concurrent lesion to the basal ganglia and thalamus, independent of the basic type of brain lesion. This model predicted both the rate of increasing ability and hand function at age 8 years. Hand function was also predicted by the basic pattern of damage and by the extent of white-matter damage. The presence of unilateral or bilateral damage had no predictive value. Conclusions. Neuroradiological findings can be used to make a crude prediction of the future development of the use of the affected hand in young children with unilateral CP. [ABSTRACT FROM AUTHOR]

Multifinger dexterous manipulation of unstable or deformable objects requires control of both direction and magnitude of fingertip force vectors. Our aim was to study the neuroanatomical correlates of these two distinct control functions. Brain activity was measured using functional magnetic resonance imaging while 16 male subjects (age: 26-42, M = 32, SD ± 4 years) compressed four springs representing a 2 × 2 factorial design with two levels of force and instability requirements. Significant activations associated with higher instability were located bilaterally in the precentral gyri, the postcentral gyrus, and the cerebellum. In the main effect for high force, activity was found in areas located in the primary motor regions contralateral to the active hand and bilaterally in the cerebellum. An overlap in activation between the two main effects was found bilaterally in the cerebellum (lobule VI). This study not only confirms a recently described bilateral fronto-parieto-cerebellar network for manipulation of increasingly unstable objects, but critically extends our understanding by describing its differentiated modulation with both force magnitude and instability requirements. Our results, therefore, expose a previously unrecognized and context-sensitive system of brain regions that enable dexterous manipulation for different force magnitude and instability requirements of the task. [ABSTRACT FROM AUTHOR]

Aim The aim of the study was to investigate coordination of fingertip forces during an asymmetrical bimanual task in children with unilateral cerebral palsy (CP). Method Twelve participants (six males, six females; mean age 14y 4mo, SD 3.3y; range 9-20y;) with unilateral CP (eight right-sided, four left-sided) and 15 age-matched typically developing participants (five males, 10 females; mean age 14y 3mo, SD 2.9y; range 9-18y,) were included. Participants were instructed to hold custom-made grip devices in each hand and place one device on top of the other. The grip force and load force were recorded simultaneously in both hands. Results Temporal coordination between the two hands was impaired in the participants with CP (compared with that in typically developing participants), that is they initiated the task by decreasing grip force in the releasing hand before increasing the force in the holding hand. The grip force increase in the holding hand was also smaller in participants with CP (involved hand/non-dominant hand releasing, p<0.001; non-involved hand/dominant hand releasing, p=0.007), indicating deficient scaling of force amplitude. The impairment was greater when participants with CP used their non-involved hand as the holding hand. Interpretation Temporal coordination and scaling of fingertip forces were impaired in both hands in participants with CP. The non-involved hand was strongly affected by activity in the involved hand, which may explain why children with unilateral CP prefer to use only one hand during tasks that are typically performed with both hands. [ABSTRACT FROM AUTHOR]

Background. There is no easy and reliable method to measure spasticity, although it is a common and important symptom after a brain injury. Objective. The aim of this study was to develop and validate a new method to measure spasticity that can be easily used in clinical practice. Methods. A biomechanical model was created to estimate the components of the force resisting passive hand extension, namely (a) inertia (IC), (b) elasticity (EC), (c) viscosity (VC), and (d) neural components (NC). The model was validated in chronic stroke patients with varying degree of hand spasticity. Electromyography (EMG) was recorded to measure the muscle activity induced by the passive stretch. Results. The model was validated in 3 ways: (a) NC was reduced after an ischemic nerve block, (b) NC correlated with the integrated EMG across subjects and in the same subject during the ischemic nerve block, and (c) NC was velocity dependent. In addition, the total resisting force and NC correlated with the modified Ashworth score. According to the model, the neural and nonneural components varied between patients. In most of the patients, but not in all, the NC dominated. Conclusions. The results suggest that the model allows valid measurement of spasticity in the upper extremity of chronic stroke patients and that it can be used to separate the neural component induced by the stretch reflex from resistance caused by altered muscle properties. [ABSTRACT FROM PUBLISHER]

This study was undertaken to evaluate the effects of repeated courses of antenatal corticosteroids (ACS) on foetal growth. We studied 94 infants exposed to 2-9 courses of ACS. Mean gestational age (GA) at first exposure was 29 and at birth 34 weeks. Exposure data were retrieved from case record files. Information on potential confounders was collected from the Swedish Medical Birth Registry. Standard deviation scores (SDS) for birthweight (BW), birthlength (BL) and head circumference (HC) were calculated and considered as outcomes. GA at start of ACS did not affect outcome. BW-SDS, BL-SDS and HC-SDS were −0.21, −0.19 and +0.25 in infants exposed to two courses, compared to −1.01, −1.04 and −0.23 in infants exposed to ≥4 courses of ACS (p = 0.04-0.07). In multiple regression analyses, ≥4 courses were associated with lower BW-SDS, BL-SDS and HC-SDS (p = 0.007-0.04) compared to SDS after 2-3 courses. The effects from ≥4 courses on BW and BL were comparable to reduction in birth size seen in twins and on HC to that observed after maternal smoking. Multiple courses of ACS are associated with a dose-dependent decline in foetal growth, which may affect later development and health. [ABSTRACT FROM AUTHOR]

Microbial colonization of mammals is an evolution-driven process that modulate host physiology, many of which are associated with immunity and nutrient intake. Here, we report that colonization by gut microbiota impacts mammalian brain development and subsequent adult behavior. Using measures of motor activity and anxiety-like behavior, we demonstrate that germ free (GF) mice display increased motor activity and reduced anxiety, compared with specific pathogen free (SPF) mice with a normal gut microbiota. This behavioral phenotype is associated with altered expression of genes known to be involved in second messenger pathways and synaptic long-term potentiation in brain regions implicated in motor control and anxiety-like behavior. GF mice exposed to gut microbiota early in life display similar characteristics as SPF mice, including reduced expression of PSD-95 and synaptophysin in the striatum. Hence, our results suggest that the microbial colonization process initiates signaling mechanisms that affect neuronal circuits involved in motor control and anxiety behavior. [ABSTRACT FROM AUTHOR]

Aim Many everyday activities involve manipulation of objects with the fingertips. Impaired performance in manipulative tasks is common in neurodevelopmental disorders. Thus accurate assessment of an individual’s ability to coordinate fingertip forces is important for planning treatment. We evaluated a recently developed assessment tool (the Strength–Dexterity Test), which is based on manipulation of unstable objects, in a paediatric population. Method A Rasch model was used to examine the validity and reliability of the Strength–Dexterity Test in a sample of 56 typically developing children and adolescents (30 males, 26 females; age range 4y 10mo–17y 3mo; mean age 9y 8mo, SD 3y 8mo). In addition, we examined how performance on this test relates to widely used tests for assessment of gross manual dexterity (assessed with the Box and Blocks Test) and finger strength measured with a pinch meter. Results The constructs measured with the 78-item Strength–Dexterity Test include dexterity and strength, and form a unique unidimensional latent trait, named fingertip force coordination, that improves with age. The test has internal scale validity when applied to a typical paediatric population. Positive correlations (significant at p<0.001) were found among all three tests. Interpretation We provide preliminary evidence of construct validity in the Strength–Dexterity Test. Our findings suggest that this test has the potential to be developed into a promising tool for assessing dexterity in children. [ABSTRACT FROM AUTHOR]

Hyperkinetic movements are unwanted or excess movements that are frequently seen in children with neurologic disorders. They are an important clinical finding with significant implications for diagnosis and treatment. However, the lack of agreement on standard terminology and definitions interferes with clinical treatment and research. We describe definitions of dystonia, chorea, athetosis, myoclonus, tremor, tics, and stereotypies that arose from a consensus meeting in June 2008 of specialists from different clinical and basic science fields. Dystonia is a movement disorder in which involuntary sustained or intermittent muscle contractions cause twisting and repetitive movements, abnormal postures, or both. Chorea is an ongoing random-appearing sequence of one or more discrete involuntary movements or movement fragments. Athetosis is a slow, continuous, involuntary writhing movement that prevents maintenance of a stable posture. Myoclonus is a sequence of repeated, often nonrhythmic, brief shock-like jerks due to sudden involuntary contraction or relaxation of one or more muscles. Tremor is a rhythmic back-and-forth or oscillating involuntary movement about a joint axis. Tics are repeated, individually recognizable, intermittent movements or movement fragments that are almost always briefly suppressible and are usually associated with awareness of an urge to perform the movement. Stereotypies are repetitive, simple movements that can be voluntarily suppressed. We provide recommended techniques for clinical examination and suggestions for differentiating between the different types of hyperkinetic movements, noting that there may be overlap between conditions. These definitions and the diagnostic recommendations are intended to be reliable and useful for clinical practice, communication between clinicians and researchers, and for the design of quantitative tests that will guide and assess the outcome of future clinical trials. © 2010 Movement Disorder Society [ABSTRACT FROM AUTHOR]

A large body of literature suggests that motor sequence learning involves dopamine-modulated plastic processes in the basal ganglia. Sequence learning can occur both implicitly, without conscious awareness and intention to learn, and explicitly, i.e., under conscious control. Here, we investigated whether individual differences in implicit and explicit sequence learning of movement sequences in a group of 15 healthy participants are related to dopamine D2 receptor densities in functional subregions of the striatum. Sequence learning was assessed using the serial reaction time task, and measures of implicit and explicit knowledge were estimated using a process dissociation procedure. Correlation analyses were performed between these measures and D2 receptor densities, which had been measured previously with positron emission tomography. Striatal D2 densities were negatively related to measures of sequence learning. In the limbic subregion. D2 densities were specifically related to implicit but not explicit learning. These findings suggest that individual differences in striatal DA function underlie differences in sequence learning ability and support that implicit and explicit sequence learning depend on partly distinct neural circuitry. The findings are also in line with the general view that implicit learning systems are evolutionarily primitive and tend to rely more on phylogenetically old neural circuitry than does explicit learning and cognition. [ABSTRACT FROM AUTHOR]

Aim To investigate relationships between hand function, brain lesions, and corticomotor projections in children with unilateral cerebral palsy (CP). Method The study included 17 children (nine males, eight females; mean age 11.4 [SD 2.4] range 7–16y), with unilateral CP at Gross Motor Function Classification System level I and Manual Ability Classification System level I or II. Hand function was assessed with the Box and Blocks test and Assisting Hand Assessment (AHA). Conventional structural magnetic resonance images were assessed visually for type, location, and extent of brain lesions. Single-pulse transcranial magnetic stimulation (TMS) provided information on organization of corticomotor projections. Results The most favourable hand function was seen in children who had white-matter damage of immaturity with mild white-matter loss and contralateral motor projections. Children with ipsilateral projections had the most impaired function. Nevertheless, in this subgroup a range of ability was seen (AHA 29–59%). Motor-projection patterns appeared to be influenced by lesion extent and location, but not by lesion type. Interpretation Combining information from structural magnetic resonance images and TMS can improve prediction of hand function. A wide variation in hand function was seen within all motor-projection patterns. Although the most impaired hand function was seen in the ipsilateral motor-projection group, some children in this group had fairly good ability. Such information is important for treatment planning. [ABSTRACT FROM AUTHOR]

Background: In an attempt to model some behavioral aspects of Attention Deficit/Hyperactivity Disorder (ADHD), we examined whether an existing genetic animal model of ADHD is valid for investigating not only locomotor hyperactivity, but also more complex motor coordination problems displayed by the majority of children with ADHD. Methods: We subjected young adolescent Spontaneously Hypertensive Rats (SHRs), the most commonly used genetic animal model of ADHD, to a battery of tests for motor activity, gross motor coordination, and skilled reaching. Wistar (WIS) rats were used as controls. Results: Similar to children with ADHD, young adolescent SHRs displayed locomotor hyperactivity in a familiar, but not in a novel environment. They also had lower performance scores in a complex skilled reaching task when compared to WIS rats, especially in the most sensitive measure of skilled performance (i.e., single attempt success). In contrast, their gross motor performance on a Rota-Rod test was similar to that of WIS rats. Conclusion: The results support the notion that the SHR strain is a useful animal model system to investigate potential molecular mechanisms underlying fine motor skill problems in children with ADHD. [ABSTRACT FROM AUTHOR]

Background: Synthetic glucocorticoids such as dexamethasone (DEX) are commonly used to promote fetal lung maturation in at-risk preterm births, but there is emerging evidence of subsequent neurobehavioral abnormalities in these children e.g. problems with inattention/hyperactivity. However, molecular pathways mediating effects of glucocorticoid overexposure on motor and cognitive development are poorly understood. Methods: In this study with common marmoset monkeys, we investigated for neonatal and adulthood effects of antenatal DEX treatment on the expression of the corticosteroid receptors and also calcyon, a risk gene for attention-deficit/hyperactivity disorder, in the prefrontal cortex (PFC). Pregnant marmosets were exposed to DEX (5 mg/kg body weight) or vehicle during early (days 42-48) or late (days 90-96) stages of the 144-day pregnancy. Results: In neonates, relative to controls, glucocorticoid receptor (GR) mRNA levels were significantly reduced after the late DEX treatment in the medial, orbital and dorsal PFC and after the early DEX treatment in the dorsal PFC. The early DEX exposure, specifically, resulted in significant reduction in calcyon mRNA expression in the medial, orbital, dorsal and lateral PFC relative to controls. Mineralocorticoid receptor (MR) mRNA levels were not significantly affected by DEX treatment. In adults, PFC GR, calcyon, and MR mRNA levels were not significantly affected by early or late prenatal DEX treatment. Conclusion: These findings indicate that antenatal DEX treatment could lead to short-term alterations in PFC expression of the GR and calcyon genes, with possible neurodevelopmental functional consequences. [ABSTRACT FROM AUTHOR]

Background. The role of spinal networks in spasticity is well investigated, but little is known about possible cortical contributions to hypertonicity across a joint. Objective. The authors hypothesized that there are cortical activation correlates to spasticity in stroke patients with increased muscle tone of the wrist flexors. Methods. Stroke patients and controls were scanned using event-related functional magnetic resonance imaging (fMRI) during slow and fast passive movements of the hand with simultaneous recording of passive movement resistance (PMR). Results. Control participants had velocity-dependent activity (greater for slow than fast movements) of 2 types, in areas that were also more active in passive movement than rest (eg, relative increase in activation in contralateral S1 and M1 was greater for slow than fast) and in areas that were also more active in rest than passive movement (eg, relative decrease in activation in occipital areas and ipsilateral precentral gyrus was greater for fast than slow). In the patient group, with large interindividual variation of spasticity, we found an association between PMR and the velocity-dependent activity in ipsilateral S1 (area 3b) extending into M1 (area 4a), contralateral cingulate cortex, supplementary motor area (SMA), Brodmann Area 45 (BA 45), and cerebellum. Post hoc testing also revealed a similar correlation in S1 and M1 bilaterally in controls and showed that patients activated ipsilateral S1 and M1 more than controls in the velocity-dependent condition. Conclusions. The findings suggest the possibility of ipsilateral sensory and motor cortical involvement in spasticity after stroke, which warrant further investigation. [ABSTRACT FROM AUTHOR]

The long-term effects of botulinum toxin A (BoNT-A) treatment in children with cerebral palsy (CP) are still elusive. We studied a prospective clinical cohort of 94 children with different subtypes (50% spastic diplegic CP, 22% hemiplegic CP, 25% tetraplegic CP, 3% dyskinetic CP), sex (55% male, 45% female), severity according to Gross Motor Function Classification System (29% Level I, 15% Level II, 16% Level III, 17% Level IV, 23% Level V), and age (median 5y 4mo, range 11mo–17y 8mo). The longest follow-up time was 3 years 7 months (median 1y 6mo) and included a maximum of eight injections per muscle (median two injections to a specific muscle). Outcome measurements were muscle tone (Modified Ashworth Scale) and joint range of motion (ROM). Assessments were made at a minimum before and 3 months after each injection. Ninety-five per cent confidence intervals for differences from baseline were used to identify significant changes. BoNT-A injections induced reduction of long-term spasticity in all muscle-groups examined: the gastrocnemius, hamstring, and adductor muscles. The reduction in tone was most distinct in the gastrocnemius muscle, and each repeated injection produced an immediate reduction in muscle tone. However, improvement in ROM was brief and measured only after the first injections, whereupon the ROM declined. Thus, the results suggest that BoNT-A can be effective in reducing muscle tone over a longer period, but not in preventing development of contractures in spastic muscles. The dissociation between the effects on muscle tone and ROM indicates that development of contractures is not coupled to increased muscle tone only, but might be caused by other mechanisms. [ABSTRACT FROM AUTHOR]

This study investigates the early development of postural adjustments during external perturbations in two different standing positions: standing with support and standing without support. The aim of the study was to assess a group of 13 infants four times during the period in life when independent standing is achieved; at 8, 10, 12 and 14 months. However, longitudinal data could be achieved only in four infants. Muscle activations of the neck, hip and ankle were recorded using surface electromyography. Based on earlier studies and controversies, three main issues were addressed: (1) Is direction specificity present before independent standing is established? (2) How do postural adjustments change with increasing age (8–14 months)? (3) Are postural adjustments task-specific in the young child? The results showed that our small sample of infants aged 8 and 10 months, who were not yet able to stand independently, exhibited direction-specific postural adjustments both during standing with and without support, though not consistently during all trials and at all body levels. Therefore, we argue that direction specificity might constitute a prerequisite for the development of independent standing. We also found that the development of postural adjustments in standing with support resembles that of sitting, i.e. great variation in the postural adjustments at early age, and fine-tuning to the situation with increasing age and experience. This, we find that this is in agreement with the proposal that postural control develops through a selection process of the most suitable postural adjustments for the situation from a repertoire of direction-specific postural adjustments. The development of postural adjustments during standing without support is discussed. Additionally, differences in response rates were noted between the two standing positions, indicating that even before independent standing is established, sophisticated sensorimotor integration enables task-specific postural adjustments. [ABSTRACT FROM AUTHOR]

A central concept in neuroscience isthatthe CNS signalsthe sensory discrepancy betweenthe predicted and actual sensory consequences of action. It has been proposed that the cerebellum and parietal cortex are involved in this process. A discrepancy will trigger preprogrammed corrective responses and update the engaged sensorimotor memories. Here we use functional magnetic resonance imaging with an event-related design to investigate the neuronal correlates of such discrepancies. Healthy adults repeatedly lifted an object betweentheir right indexfingers andthumbs, and on some liftingtrials,the weight ofthe object was unpredictably changed between light (230 g) and heavy (830 g). Regardless of whether the weight was heavier or lighter than predicted, activity was found in the right inferior parietal cortex (supramarginal gyrus). This suggests that this region is involved in the comparison of the predicted and actual sensory input and the updating of the sensorimotor memories. When the object was lighter or heavier than predicted, two different types of preprogrammed force corrections occurred. There was a slow force increase when the weight of the object was heavier than predicted. This corrective response was associated with activity in the left primary motor and somatosensory cortices. The fast termination of the excessive force when the object was lighter than predicted activated the right cerebellum. These findings show how the parietal cortex, cerebellum, and motor cortex are involved in the signaling of the discrepancy between predicated and actual sensory feedback and the associated corrective mechanisms. [ABSTRACT FROM AUTHOR]

Background: Limited data from positron emission tomography (PET) studies of subjects with attention-deficit/hyperactivity disorder (ADHD) indicate alterations in brain dopamine neurotransmission. However, these studies have used conventional univariate approaches that are less sensitive to detect complex interactions that may exist between different brain dopamine pathways and individual symptoms of ADHD. We aimed to investigate these potential interactions in adolescents with ADHD. Methods: We used a 3D PET scan to measure utilization of native L-[11C]-DOPA to map dopamine presynaptic function in various cortical, striatal and midbrain regions in a group of 8 male adolescents with ADHD and 6 age matched controls. To evaluate the interactions between the studied brain regions, multivariate statistical methods were used. Results: Abnormal dopaminergic function was found in multiple brain regions of patients with ADHD. A main finding was lower L-[11C]-DOPA utilization in adolescent with ADHD as compared to control subjects, especially in subcortical regions. This pattern of dopaminergic activity was correlated specifically with symptoms of inattention. Conclusion: Dopamine signalling in the brain plays an important modulatory role in a variety of motor and cognitive functions. We have identified region-specific functional abnormalities in dopaminergic function, which may help better account for the symptoms of ADHD. [ABSTRACT FROM AUTHOR]

We investigated effector-independent aspects of voluntary motor timing, using behavioural measurements and functional magnetic resonance imaging. Two types of temporal pattern were investigated; one isochronous, the other a metric, rhythmic sequence of six temporal intervals. Each pattern was performed using tapping movements with the left or right index fingers, or rhythmic speech on one syllable. Deviations from the ideal temporal pattern in the rhythmic sequence tasks were consistent between the three different effectors, within subjects. This suggests that the same representation of the rhythm was used to time the movements with all effectors. To reveal brain regions involved in such effector-independent timing, we localized the overlap in brain activity when the rhythmic sequence was performed with the different effectors. Activity was found in the mesial and lateral premotor cortices, posterior and anterior regions of the superior temporal gyrus and the inferior frontal cortex. Subcortical activations were in the left globus pallidus, the vermis and bilaterally in the cerebellar hemispheres (lobule VI) and the thalamus. The overlap in activity between the isochronous tasks included the same set of brain regions, except for the basal ganglia and the thalamus. Rhythmic sequences had significantly higher activity in mesial premotor cortex, the left superior temporal gyrus and the cerebellum, than had isochronous movements. These findings reveal a set of brain regions likely to be involved in effector-independent representations of temporal patterns in voluntary motor timing. A subset of these regions plays important roles for the organization of rhythmic sequences of several intervals. [ABSTRACT FROM AUTHOR]