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During the last decade, research on germ-free mice has discovered that the gut microbiome (i.e. the normal bacteria colonizing the gastrointestinal tract) can programme brain function and behaviour during early development. At the same time a growing number of clinical studies have shown altered gut microflora in children with autism spectrum disorder (ASD), in combination with altered bacterial metabolites and inflammatory cytokines being part of the gut-brain axis. This review covers the concept of the microbiome; how it is established during childhood; how it is affected by malnutrition; how it can programme the development of the brain through epigenetic mechanisms; which pathways are used from the gut to the brain; and assesses findings that suggest the gut microbiome may be involved in ASD and other neurodevelopmental disorders. This is a new research field with a number of exciting, but so far fragmented, findings indicating the important role of the normal microbiome in shaping the brain. Research also suggests that disruptions of the microbiome may be involved in the aetiology of neurodevelopmental disorders. WHAT THIS PAPER ADDS: The gut microbiome shapes the brain via the gut-brain axis. The microbiome may play a role in neurodevelopmental disorders. [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]

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]

Abstract: Phonological working memory (PWM) tasks consist of a sequence of stimulus-encoding, maintenance and response. Few previous functional magnetic resonance imaging (fMRI) studies of PWM have employed event-related designs that make it possible to analyze the activations associated with each phase of such a task. The exploration of the cortical activation that takes place during the maintenance of PWM has been of particular interest to us. It has been suggested that temporary storage is served by the inferior parietal cortex. However, to the best of our knowledge earlier studies have used visual stimuli that might generate different cortical activations than auditory stimuli, which, presumably, would be more dependent on the auditory association cortex in the temporal lobe. This study involved an auditory stimulus presentation and a forced two-choice task. We used a parametric event-related design with fMRI. The stimuli consisted of pseudo-words of five, seven and nine syllables in length. In the control task, acoustically analogous stimuli without phonetic or linguistic content were used for passive listening. The left inferior frontal gyrus was activated during the stimulus-encoding, maintenance and response, in agreement with previous studies. However, in contrast to previous studies using visual presentation of verbal material, the inferior parietal cortex was not activated during the maintenance in the present study, but only active in the comparison and decision phase. Significant activation of the auditory cortex in the middle temporal gyrus was observed during the maintenance phase, which, together with the inferior frontal gyrus activation might underly the maintenance of phonological information. [Copyright &y& Elsevier]

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]

The aim of the study was to examine whether infants, at an age when they have no or little experience in sitting, can produce direction specific postural adjustments, i.show $132#e. synergies of muscle activity on the ventral side of the body during backward sway and on the dorsal side during forward sway. In addition, we addressed the question whether postural adjustments at this young age are restricted to single muscle responses or consist of a variable repertoire of muscle activation patterns including one during which all direction specific muscles participate (‘complete’ pattern). Postural adjustments due to external perturbations in a sitting position were studied in eight healthy infants aged 1 month. Multiple surface EMGs of neck, trunk and leg muscles and kinematics were recorded while the infants were exposed to horizontal forward (Fw) and backward (Bw) displacements of the surface of support. Direction specific postural adjustments, defined as adjustments during which agonist activation or antagonist inhibition preceded antagonist activation, were present in 85% of Bw and 72% of Fw translations. The direction specific adjustments showed a large variability with the repertoire of adjustments including the activation of one, two or all of the recorded direction specific muscles. The finding of direction specific adjustments at 1 month of age support the opinion that the basic level of organisation of postural adjustments has an innate origin. The finding of a variable repertoire of muscle response patterns, including the ‘complete’ pattern, refutes the idea that the development of postural adjustments results from gradual addition of appropriate muscles to the synergies. [ABSTRACT FROM AUTHOR]

Working memory (WM) capacity is the ability to retain and manipulate informationduring a short period of time. This ability underlies complex reasoning andhas generally been regarded as a fixed trait of the individual. Children withattention deficit hyperactivity disorder (ADHD) represent one group of subjectswith a WM deficit, attributed to an impairment of the frontal lobe. In thepresent study, we used a new training paradigm with intensive and adaptivetraining of WM tasks and evaluated the effect of training with a double blind,placebo controlled design. Training significantly enhanced performance onthe trained WM tasks. More importantly, the training significantly improvedperformance on a nontrained visuo-spatial WM task and on Raven’s ProgressiveMatrices, which is a nonverbal complex reasoning task. In addition, motoractivity – as measured by the number of head movements during a computerizedtest – was significantly reduced in the treatment group. A second experimentshowed that similar training-induced improvements on cognitive tasks are alsopossible in young adults without ADHD. These results demonstrate that performanceon WM tasks can be significantly improved by training, and that the trainingeffect also generalizes to nontrained tasks requiring WM. Training improvedperformance on tasks related to prefrontal functioning and had also a significanteffect on motor activity in children with ADHD. The results thus suggest thatWM training potentially could be of clinical use for ameliorating the symptomsin ADHD. [ABSTRACT FROM AUTHOR]

The aim of this study was to identify changes in brain activity associated with the increase in working memory (WM) capacity that occurs during childhood and early adulthood. Functional MRI (fMRI) was used to measure brain activity in subjects between 9 and 18 years of age while they performed a visuospatial WM task and a baseline task. During performance of the WM task, the older children showed higher activation of cortex in the superior frontal and intraparietal cortex than the younger children did. A second analysis found that WM capacity was significantly correlated with brain activity in the same regions. These frontal and parietal areas are known to be involved in the control of attention and spatial WM. The development of the functionality in these areas may play an important role in cognitive development during childhood. [ABSTRACT FROM AUTHOR]

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]

In 2014, the three major academies of childhood disability, in Europe, North America, and Australia, signed a memorandum of understanding to establish an international, multidisciplinary network - the International Alliance of Academies of Childhood Disability (IAACD) - with the mission to 'improve the health and well-being of children with disabilities around the globe'. One is the Nurturing Care Framework (NCF), launched in 2018 by the World Health Organization (WHO), the United Nations Children's Fund (UNICEF), and the World Bank. [Extracted from the article]

An editorial is presented in which the author discusses global challenge of childhood disability. Topics discussed include improving the quality of life for surviving children with disabilities, medical treatment from the alleviation of impairments of body structures, and improving the health and well-being of children.

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]

The author assesses the progress made in the management of childhood disability in Europe. He says the European Academy of Childhood Disability (EACD) played an important role in the promotion of the care and management in children with disability in the continent. The author claims that the medical model for the management of childhood disability has become broader to address the multifaceted consequences of disease. He believes that the introduction of evidence-based medicine improved the interventions used in childhood disability.

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]

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]

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]

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]

Abstract: Dysregulation of dopamine (DA) neurotransmission in frontal–striatal circuitry has been hypothesized to underlie several neurodevelopmental disorders, including attention-deficit/hyperactivity disorder (ADHD). The actions of DA are mediated by five distinct receptor subtypes that belong to the G-protein-coupled receptor super-family and are divided into two major classes, D1-like (D1 and D5) and D2-like (D2, D3, and D4). Accumulating evidence implicates the D1 receptor subtype (D1R) in the regulation of motor and cognitive processes. It is generally assumed that D1R is linked to motor activity in a stimulatory fashion. However, recent findings in rodents suggest a potential role of D1R on motor inhibition, which emerges during late postnatal development. Several lines of evidence indicate that the locus of the inhibitory effects involve subregions of the prefrontal cortex (PFC). These results may be relevant for understanding the neurobiology of ADHD. [Copyright &y& Elsevier]

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]

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]

Working memory (WM) has been hypothesised to be impaired in attention-deficit/hyperactivity disorder (ADHD). However, there are few studies reported on tests measuring visuo-spatial WM (VSWM) in ADHD. Some of these studies used paradigms including episodic memory, others only used low memory loads. In the present study we used a VSWM test that has not been used previously in ADHD research. The sensitivity of the VSWM test and a choice reaction time (CRT) test was evaluated in a pilot study by comparing them to two commonly used tests in ADHD-research; the Continuous Performance Test (CPT) and a Go/no-go test, in children with and without ADHD. The groups differed significantly in performance on the VSWM test ( P <.01) and CRT ( P <.05) but not on the CPT ( P >.1) or on the Go/no-go test ( P >.1). The results from the VSWM and CRT tests were replicated in a larger sample of participants (80 boys; 27 boys with ADHD and 53 controls, mean age 11.4 years). The difference between the groups was significant for both the VSWM test ( P <.01) and the CRT test ( P <.01). The effect size (ES) of the VSWM test was 1.34. There was a significant age-by-group interaction on the VSWM test, with larger group differences for the older children ( P <.01). Our results show that the VSWM test is a sensitive measure of cognitive deficits in ADHD and it supports the hypothesis that deficits in VSWM is a major component of ADHD. [ABSTRACT FROM AUTHOR]

We used functional magnetic resonance imaging to investigate if different brain regions are controlling the temporal and ordinal structure of movement sequences during performance. Human subjects performed overlearned spatiotemporal sequences of key- presses using the right index finger Under different conditions, the temporal and the ordinal structure of the sequences were varied systematically in relation to each other, using a factorial design: COMBINED had a rhythm of eight temporal intervals and a serial order of eight keys; TEMPORAL had an eight-interval rhythm produced on one key; ORDINAL had an isochronous rhythm and an eight-key serial order; two control conditions had an isochronous pulse performed on one or two keys, respectively. Brain regions involved in rhythmic and ordinal control of the sequences were revealed by analysing main effect contrasts for the corresponding factors. TEMPORAL and ORDINAL were also compared directly to test for significant differences. A dissociation was found between largely the presupplementary motor area, the right inferior frontal gyrus and precentral sulcus, and the bilateral superior temporal gyri, involved in temporal control, and lateral fronto-parietal areas, the basal ganglia and the cerebellum, which were implicated in ordinal control. The vermis and the superior colliculus were the only regions with an activity increase specifically related to combining long temporal and ordinal sequences. We conclude that humans use different brain networks for temporal and ordinal sequence control, and that the performance of combined sequences activates both networks, the medial cerebellum, and the superior colliculus. [ABSTRACT FROM AUTHOR]

To explore how repetitive passive-active movement training effects upper limb motor function and cortical activation in patients with stroke. Design: Single-group treatment trial with baseline comparisons. Ten chronic patients with stroke with paresis of the upper limb. The group improved in range of motion and Motor Assessment Scale scores. Subjects reported improvements in a variety of daily tasks requiring the use of the affected upper limb. Increases in cortical activation in prefrontal and sensorimotor areas were observed in parallel with improvements of upper limb motor function in the 2 patients scanned. The 4-week training programme improved hand motor function and ability. Cortical activation on functional magnetic resonance imaging changed in parallel suggesting reorganization of areas related to movements of the paretic limb. [ABSTRACT FROM AUTHOR]

Dopamine D1 receptors have been implicated in various neurodevelopmental disorders, including attention-deficit/hyperactivity disorder. However, little is known about potential late maturational changes of the motor inhibitory and stimulatory role of these receptors. Here, we investigated the effects of a full and selective D1 receptor agonist, SKF-81297, on motor activity and expression of the plasticity-associated gene, c-fos , in the prefrontal cortex and striatum of juvenile and adolescent male rats. In general, SKF-81297 produced a biphasic effect on motor activity (locomotor and rearing activity), which consisted of an initial short inhibition followed by a long-lasting stimulation. These effects were dose- and age- dependent. The inhibitory phase was more pronounced in adolescent than in juvenile rats whereas the opposite was true for the stimulatory phase. During the initial inhibitory phase of the drug, c-fos mRNA expression was increased in the prefrontal cortex of juvenile rats but reduced in adolescent rats. There was also an increase in c-fos mRNA expression in the medial-dorsal striatum and olfactory tubercle, which was more evident in juvenile rats. In contrast, during the stimulatory phase, c-fos mRNA expression was increased in both the dorsal and ventral striatum, especially in the nucleus accumbens, as well as in the prefrontal cortex, in both age groups. The increase of c-fos mRNA in the dorsal striatum, however, was more pronounced in juvenile rats. These results indicate the presence of two distinct D1 receptor populations within the frontal-striatal circuitry, which have opposite effects on motor activity, and which have different maturational profiles. [ABSTRACT FROM AUTHOR]

Stimulant drugs such as amphetamine have, for many decades, been the drugs of choice in the treatment of children with attention-deficit/hyperactivity disorder. However, little is known about their therapeutic mechanisms or about the consequences of their long-term exposure. In the present study we investigated whether repeated exposure of a low dose of amphetamine (0.5 mg/kg) to juvenile rats could induce long-term morphological alterations in the prefrontal cortex. In addition, to assess possible behavioural consequences of prolonged exposure to this drug, we examined whether changes in the motor response to various dopamine agonists occurred after this treatment. We found that this dose of amphetamine promotes plasma concentrations of amphetamine sulphate in juvenile rats to levels corresponding to the clinical range used for children with attention-deficit/hyperactivity disorder. Amphetamine (0.5 mg/kg; s.c.) was administered twice daily during postnatal days 22–34, and then the brains of the animals were evaluated 2 weeks later. This treatment produced an increase in dendritic length and branches of pyramidal neurons of the medial prefrontal cortex, but not in the nucleus accumbens. These changes were associated with an increase in the expression of calcium/calmodulin-dependent protein kinase II, a highly abundant signalling protein in the postsynaptic densities of excitatory synapses. Interestingly, amphetamine pre-treatment did not alter the motor response to various dopamine agonists, including amphetamine. These data suggest that clinical doses of stimulant drugs may be acting as a trophic support at the glutamatergic synapses, thereby enhancing dopamine–glutamate interactions in the prefrontal cortex. [ABSTRACT FROM AUTHOR]

Precision grip and concomitant anticipatory postural adjustments were investigated in 11 children (three females, eight males; mean age 9 years 1 month, SD 11 months) with attention-deficit-hyperactivity disorder (ADHD); 12 children (three females, nine males; mean age 9 years, SD 7 months) with developmental coordination disorder (DCD), and 13 children (two females, 11 males; mean age 9 years 9 months, SD 11 months) with a combination of ADHD and DCD (ADHD+). There were two comparison groups: an age-matched group (four females, 11 males; mean age 9 years 1 month, SD 14 months) and a younger age group (five females, six males; mean age 6 years 5 months, SD 8 months). Adaptation to different weights was evaluated by lifting a specialized grip instrument monitoring grip force, load force, and centre of foot pressure displacements. Children with ADHD+ showed: (1) excessive grip forces, (2) decreased amplitude and prolonged onset of postural adjustments, and (3) reduced ability to adapt the motor output. Children with ADHD and DCD did not scale manual and postural forces in amplitude and time domains. Children with DCD also differed in delayed timing of postural adjustments. Results indicate that children with ADHD and DCD show a spectrum of neural dysfunctions underlying poor motor coordination, which are not specific to the clinical disorder. [ABSTRACT FROM AUTHOR]

We investigated temporal resolution of auditory perception (TRAP), verbal working memory, and speech perception in 15 children with language impairment (LI) in comparison with a control group of 99 typical children. A computerized two-choice test was used to assess these three abilities. No deficits in TRAP were found in the LI group, and the thresholds were similar for both study groups. It was interesting that the variability was high for both groups and that the control group's performance was poorer than reported in some previously published studies. There were significant differences in the two groups' performance on speech perception and verbal working memory. Working memory was the most sensitive of these two measures. [ABSTRACT FROM AUTHOR]

Examines selective up-regulation of dopamine D1 receptors in dendritic spines ny N-methyl-D-aspartate (NMDA) receptor activation. Recruitment of D1 receptors from the interior of the cell to the plasma membrane following NMDA activation; Ability of NMDA to balance between the D1 and D2 receptor signaling pathways.

Abstract Dexterous manipulation of delicate objects requires exquisite control of fingertip forces. We have used functional magnetic resonance imaging to identify brain regions involved in the skilful scaling of these forces when normal human subjects (n = 8) held with precision grip a small object (weight 200 g) in the dominant right hand. In one condition, they used their normal, automatically scaled grip force. The object was held gently in a second condition; the isometric grip force was maintained just above the critical level at which the object would have slipped. In a third condition, the force was increased to hold the object with a more firm grip. The supplementary and cingulate motor areas were significantly more active during the gentle force condition than during either of the other conditions in all subjects, despite weaker contractions of the hand muscles. In addition, the left primary sensorimotor cortex, the ventral premotor cortex and the left posterior parietal cortex were more strongly activated during gentle than during normal grasping. These novel results suggest that these regions are specifically involved in dexterous scaling of fingertip forces during object manipulation. [ABSTRACT FROM AUTHOR]

This study examined temporal resolution of auditory perception (TRAP) in relation to speech perception and phonological working memory in one experiment and in relation to measures of rapid naming, understanding of grammatical contrasts, and phonological awareness in a second experiment. In the TRAP test, 6- to 9-year-old children discriminated four pairs of two sine tones, 878 Hz and 1350 Hz, presented in blocks with stepwise decreasing interstimulus intervals from 256 ms to 8 ms. In Experiment 1, weak but significant correlations between TRAP and speech perception and phonological working memory were found, as well as a significantly lower TRAP performance by girls. Experiment 2 indicated a significant relation between TRAP and the phonological awareness task. The results give qualified support to the notion of a weak relationship between TRAP and speech perception and language skills among typical children. However, the gender differences in TRAP performance, the limited variance explained by the regression models, and the finding that only one of the language parameters correlated with TRAP do not support the notion of a causal relationship between language skills and TRAP. The possibility that TRAP is connected to general neurological maturation rather than specifically to language abilities is discussed. [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]

A letter to the editor in response to the article "A systematic review of interventions for children with cerebral palsy: state of the evidence" by I. Novak and colleagues in the 2013 issue is presented.

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]

Aim: To describe the functional limitations and associated impairments of children with cerebral palsy (CP) in rural Uganda, and care-seeking behaviour and access to assistive devices and education.Method: Ninety-seven children with CP (42 females, 55 males; age range 2-17y) were identified in a three-stage population-based screening with subsequent medical examinations and functional assessments. Information on school and access to care was collected using questionnaires. The data were compared with Swedish and Australian cohorts of children with CP. We used the χ2 test and linear regression models to analyse differences between groups.Results: Younger children were more severely impaired than older children. Two-fifths of the children had severe impairments in communication, about half had intellectual disability, and one third had seizures. Of 37 non-walking children, three had wheelchairs and none had walkers. No children had assistive devices for hearing, seeing, or communication. Care-seeking was low relating to lack of knowledge, insufficient finances, and 'lost hope'. One-third of the children attended school. Ugandan children exhibited lower developmental trajectories of mobility and self-care than a Swedish cohort.Interpretation: The needs for children with CP in rural Uganda are not met, illustrated by low care-seeking, low access to assistive devices, and low school attendance. A lack of rehabilitation and stimulation probably contribute to the poor development of mobility and self-care skills. There is a need to develop and enhance locally available and affordable interventions for children with CP in Uganda.What This Paper Adds: Development of mobility and self-care skills is lower in Ugandan than Swedish children with cerebral palsy (CP). Older children in Uganda with CP are less impaired than younger children. Untreated seizures and impairments of communication and intellect are common. Access to health services, assistive devices, and education is low. Caregivers lack knowledge and finances to seek care and often lose hope of their child improving. [ABSTRACT FROM AUTHOR]

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]

Objective: To study whether a temporary block of the tactile afferents from the fingers causes altered activity in the neural network for dexterous manipulation. Methods: Whole-brain functional Magnetic Resonance Imaging (fMRI) was conducted in 18 healthy subjects, while they compressed an unstable spring between the thumb and index finger of the right hand. Two sensory conditions – with and without tactile input from the fingers – were employed. In the latter condition the digital nerves were blocked by local anesthesia. Results: Compression of the unstable spring was associated with activity in an earlier described network for object manipulation. We found that this entire network remained active after a nerve block, and the activity was increased in the dorsal premotor cortex. Conclusions: The neural network for dexterous manipulation is robust with only minor alterations after acute loss of tactile information from the fingers. There was no loss of activity, but, unexpectedly, an increased activity in some parts of the network. Significance : This study gives new insights to possible neural compensatory mechanisms that make fine motor control possible after acute disruption of tactile information in natural situations like cold weather or wearing surgical gloves. [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]

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]

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]

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]