[show abstract][hide abstract] ABSTRACT: 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).
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.
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.
Individuals with CP experience improved motor outcomes after CIMT, independent of corticomotor projection pattern and lesion characteristics.
Developmental Medicine & Child Neurology 12/2013; · 2.68 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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. 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 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, 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.
Journal of Neurophysiology 07/2013; · 3.30 Impact Factor
[show abstract][hide abstract] ABSTRACT: Several neurodevelopmental disorders with a strong genetic basis, including attention-deficit/hyperactivity disorder, autism spectrum disorders and developmental coordination disorder, involve deficits in fine motor skills. This phenotype may depend on heritable variation in components of the dopamine system, which is known to play a critical role in motor skill learning. In the present study, we took advantage of two inbred strains of mice (BALB/c and C57BL/6) that differ markedly in the number of midbrain dopamine neurons, in order to investigate the influence of such naturally occurring genetic variation on the acquisition and performance of fine motor skills. Gene expression analysis of midbrain, frontal cortex, and striatum revealed significant differences in the expression of pre- and postsynaptic dopaminergic markers (e.g., tyrosine hydroxylase, dopamine transporter, dopamine D4 receptor, dopamine D5 receptor, and DARPP-32) between these two strains. BALB/c mice had lower learning rate and performance scores in a complex skilled reaching task when compared to C57BL/6 mice. A negative correlation was found between the motor learning rate and level of DARPP-32 mRNA expression in the frontal cortex contralateral to the trained forelimb. The rate of motor learning was also negatively correlated with the levels of DARPP-32 and dopamine D1 receptor mRNAs in the striatum. Our results suggest that genetically driven variation in fronto-striatal dopaminergic neurotransmission is a major contributor to individual differences in motor skill learning. Moreover, these findings implicate the D1R/cAMP/DARPP-32 signaling pathway in those neurodevelopmental disorders that are associated with fine motor skills deficits.
Genes Brain and Behavior 07/2013; · 3.60 Impact Factor
[show abstract][hide abstract] ABSTRACT: Objective: To describe the reliability of an instrument (Neuro- Flexor) designed to be used in the clinic for quantification of the relative contribution of spasticity, elasticity and viscosity to resistance during passive wrist movements. Design: A test-retest and inter-rater reliability study. Subjects: A convenience sample of 34 adults with chronic stroke with spasticity in the hand, and a reference group of 10 healthy persons. Methods: Two raters assessed the participants with the NeuroFlexor. Elastic, viscous and neural components of passive movement resistance were quantified at the wrist. Test-retest and inter-rater intraclass correlation coefficient (ICC2.1) were calculated for each component for both raters and two sessions. Degree of measurement error was evaluated using the coefficient of variation and the repeatability coefficient. Results: Reliability was high for the neural component (test-retest: 0.90-0.96; inter-rater: 0.90-0.94), fair to good for the elastic component (test-retest: 0.79-0.88; inter-rater: 0.76-0.76), and fair to high for the viscous component (test-retest: 0.88-0.90; inter-rater: 0.75-0.80). Based on test-retest data, the coefficients of variation for the neural, elastic and viscous components were 25%, 26% and 16%, respectively, and the repeatability coefficients were 1.798, 1.897 and 1.404, respectively. Conclusion: The NeuroFlexor instrument is a reliable measure of spasticity and of muscle elasticity and viscosity in individuals with wrist and finger muscle resistance to passive stretch after stroke.
Journal of rehabilitation medicine: official journal of the UEMS European Board of Physical and Rehabilitation Medicine 05/2013; · 1.88 Impact Factor
[show abstract][hide abstract] ABSTRACT: OBJECTIVE: To investigate whether repeat courses of antenatal corticosteroids have long-term effects on cognitive and psychological functioning. STUDY DESIGN: In a prospective cohort study, 58 adolescents and young adults (36 males) who had been exposed to 2-9 weekly courses of betamethasone in utero were assessed with neuropsychological tests and behavior self-reports. Unexposed subjects (n = 44, 25 males) matched for age, sex, and gestational age at birth served as a comparison group. In addition, individuals exposed in utero to a single course (n = 25, 14 males) were included for dose-response analysis. Group differences were investigated using multilevel linear modeling. RESULTS: Mean scores obtained in 2 measures of attention and speed were significantly lower in subjects exposed to 2 or more antenatal corticosteroids courses (Symbol Search, P = .009; Digit Span Forward, P = .02), but these were not dose-dependent. Exposure to repeat courses of antenatal corticosteroids was not associated with general deficits in higher cognitive functions, self-reported attention, adaptability, or overall psychological function. CONCLUSIONS: Although this study indicates that repeat exposure to antenatal corticosteroids may have an impact on aspects of executive functioning, it does not provide support for the prevailing concern that such fetal exposure will have a major adverse impact on cognitive functions and psychological health later in life.
The Journal of pediatrics 02/2013; · 4.02 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
Neurorehabilitation and neural repair 06/2012; · 4.28 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
Experimental Brain Research 12/2011; 215(3-4):359-67. · 2.22 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aim of the study was to investigate coordination of fingertip forces during an asymmetrical bimanual task in children with unilateral cerebral palsy (CP).
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.
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.
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.
[show abstract][hide abstract] ABSTRACT: Diffusion MRI improves detection of abnormalities in white matter tracts in cerebral palsy (CP). Relationships between diffusion measurements and hand function are largely unexplored. We aimed first to assess microstructure of corticofugal fibers, and second to explore associations between tract injury as assessed by quantitative analysis of diffusion MRI and hand function in children with unilateral CP.
In this cross-sectional study, 15 children with unilateral CP (6 boys, median age 12.4 years, min 7.2, max 17) and 24 controls were included (9 boys, median age 12.7 years, min 8.8, max 17.3). Hand function was assessed with the Box and Blocks (B&B) test. Magnetic resonance diffusion data (b value = 1,000 s/mm(2), 45 directions) were collected on a 1.5-T scanner. Fractional anisotropy (FA), mean diffusivity (MD), and tensor eigenvalues were measured bilaterally in the cerebral peduncle (ROI1), the posterior limb of the internal capsule (PLIC, ROI2), and corticofugal fibers connecting these regions.
In children with CP, FA in both ROIs and the partial tract corresponding to the affected hand was significantly lower compared to controls. This was caused by an increase in diffusivity perpendicular to the tract. After controlling for age, mean FA contralateral to the affected hand correlated with B&B scores, which was independent of lesion type or number of voxels in the partial tract, cerebral peduncle, or PLIC.
FA in corticofugal fibers is a sensitive marker of damage to the motor system and correlates with hand function in CP. Using FA may improve early prediction of outcome.
[show abstract][hide abstract] ABSTRACT: There is no easy and reliable method to measure spasticity, although it is a common and important symptom after a brain injury.
The aim of this study was to develop and validate a new method to measure spasticity that can be easily used in clinical practice.
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.
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.
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.
Neurorehabilitation and neural repair 04/2011; 25(7):617-25. · 4.28 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
Proceedings of the National Academy of Sciences 02/2011; 108(7):3047-52. · 9.74 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
[show abstract][hide abstract] ABSTRACT: 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.
Movement Disorders 08/2010; 25(11):1538-49. · 4.56 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
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.
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.
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.
[show abstract][hide abstract] ABSTRACT: Age-dependent decrease in dopamine receptor density throughout adulthood is well described, meanwhile less is known about development of dopamine system in humans and in vivo it has not been investigated. We examined dopamine D1 receptor (D1DR) binding in the cerebral cortex and striatum of 12 adolescents (mean age 13.5+/-1.8 years) and 18 young adults (25+/-2.3 years) using positron emission tomography (PET) and radioligand [(11)C]SCH23390. Over the age span of 10-30 years [(11)C]SCH23390 binding (binding potential, BP) declined in all brain regions. The rate of BP decline was age-segment and brain region dependent. Most pronounced decline in BP was observed in the cortical regions during adolescence (mean BP in adults lower by 14-26% as compared to adolescents, P<0.0001). Significantly slower rate of decline in BP was observed in two cortical regions (orbitofrontal and posterior cingulate cortices) and striatal regions. The present PET-study provides new evidence on the development of D1DR in humans in vivo which is of critical importance for understanding of the biology of neurodevelopmental disorders.
[show abstract][hide abstract] ABSTRACT: 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.
Proceedings of the National Academy of Sciences 04/2010; 107(16):7574-9. · 9.74 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
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.
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.
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.
Behavioral and Brain Functions 03/2010; 6:18. · 2.79 Impact Factor
[show abstract][hide abstract] ABSTRACT: In this study the aim was to evaluate the effect of botulinum toxin A (BoNT-A) treatment on muscle tone, contracture development and gait pattern in young children with cerebral palsy (CP).
Fifteen children with spastic CP (mean age = 16 months) were included in a randomized control study. All received a daily stretching programme and children in the BoNT-A group additionally received two injections, 6 months apart in the gastrocnemius muscle. Outcomes were assessed at baseline, and after 1 and 3.5 years. A 3D gait-analysis was performed at 5 years of age.
Plantarflexor muscle tone in the BoNT-A group was significantly reduced after 3.5 years, while the muscle tone at the ankle and knee in the control group remained unchanged. The change-score in knee-flexion muscle tone between the groups was significantly different after 3.5 years. The knee joint ROM was significantly increased at 1 year in the BoNT-A group but reduced at the knee and ankle joints in the control group after 3.5 years. No group differences were found for gait analysis, GMFM-66 or PEDI.
Early treatment of BoNT-A in children with spastic CP may decrease muscle tone and decelerate contracture development after 3.5 years. The effect on gait development remains inconclusive.
[show abstract][hide abstract] ABSTRACT: 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.
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.
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.
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.
Behavioral and Brain Functions 01/2010; 6:51. · 2.79 Impact Factor