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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.
Neurology 08/2011; 77(8):775-83. · 8.31 Impact Factor
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ABSTRACT: Aims: 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).Method: 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.Results: 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.Conclusion: 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.
Acta Paediatrica 07/2010; 99(8):1156 - 1162. · 2.07 Impact Factor
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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.
Neuroscience 04/2010; 167(1):104-10. · 3.38 Impact Factor
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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.
Acta Paediatrica 03/2010; 99(8):1156-62. · 2.07 Impact Factor
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ABSTRACT: Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral disorder of childhood onset that can include elements of inattention, hyperactivity and impulsive behavior. It is often treated with stimulant medications such as methylphenidate hydrochloride (MPH). The neurobiology of ADHD is not well understood, but there is converging evidence of the involvement of the catecholamine rich frontal-striatal circuitry. A prominent theory of ADHD is that there is a dysregulation of dopamine neurotransmission in this circuitry. Given support to this theory is the observation from human imaging studies that MPH blocks the dopamine transporter (DAT), the main mechanism for removing dopamine from the synapse; thereby increasing extracellular dopamine levels in the striatum. Genetic and molecular studies have also demonstrated an association between dopamine related genes (e.g., DAT, dopamine D4 and D5 receptors) and ADHD.
Studies using positron emission tomography (PET) and single photon emission tomography indicate alterations in dopamine markers in ADHD. The majority of the existing studies have reported increased DAT binding (ranging between 17 and 70%) in the striatum of both children and adults with ADHD, while a new PET study reported lower DAT binding in the midbrain (where the dopaminergic neurons of the substantia nigra and ventral tegmental area are located) of adolescents with ADHD. Studies using [18F]fluorodopa to assess dopamine synthesis and metabolism have demonstrated abnormalities in presynaptic activity in patients with ADHD; however the nature of these changes appears to be age-dependent. Some limited data also indicate potential alterations in dopamine D2 receptor availability in children with ADHD.
The results from the human brain imaging studies are still not definitive because of discrepancies in the findings. There is a great need to replicate and expand these findings in treatment-naïve patients with ADHD, taking into consideration potential variables such as drug and smoking history, ethnicity, and presence of comorbidity.
Revista de neurologia 03/2006; 42 Suppl 2:S19-23. · 0.65 Impact Factor
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ABSTRACT: The aim of this study was to explore whether children born preterm have deficient executive functions (EF) in comparison with children born at full term, and, if so, whether this is dependent on inferior intelligence scores and can be correlated to specific neonatal risk factors and gender.
In a population-based study, the executive functions of 182 preterm children (birthweight less than 1500 g, VLBW) and 125 controls from the Stockholm Neonatal Project were assessed at 5 1/2 y with a neuropsychological test battery (Nepsy 1990).
The controls surpassed the VLBW children on tests of executive functions (EF), even after controlling for intelligence (IQ); a necessary correction since there were significant correlations between measures of EF and IQ. EF was associated with retinopathy of prematurity (ROP), and with visual impairment as a whole. In both groups, girls surpassed boys on tests of executive functions.
We conclude that it is possible to analyse executive functions already at preschool age. Preterm children are at risk of having subnormal levels of executive functioning, even though their general IQ is normal.
Acta Paediatrica 11/2004; 93(10):1363-71. · 2.07 Impact Factor
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ABSTRACT: The present study addressed the question whether the deviant postural adjustments in children with spastic diplegia can be attributed to their crouched sitting position or primarily to their neural deficit. Postural adjustments during sitting in an erect and in a crouched position on a movable platform were assessed in 10 children, aged 3 to 7 years 6 months, with mild-to-severe forms of spastic diplegia and 10 age- and sex-matched control children. Multiple surface EMGs of neck, trunk, and leg muscles and kinematics of head, body sway, and pelvis were recorded during forward and backward translations. The children with normal motor development showed a distinct adaptation of postural adjustments to sitting position. The children with cerebral palsy (CP) had a deficient adaptational capacity which was more pronounced in the erect than in the crouched position. Thus, the crouched sitting position did not induce postural deficiency but seemed to offer a solution to the sensory-motor problem of the instability experienced. Children with severe diplegia exhibited a lack of direction specificity in the leg muscles during backward body sway, which points to a basic deficit in postural control. In addition, these children showed marked dysfunctions in the precise tuning of the postural adjustments to task-specific conditions. In the children with mild-to-moderate forms of CP the basic level of control was intact.
Developmental Medicine & Child Neurology 09/2001; 43(8):534-46. · 2.92 Impact Factor
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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 skillful 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.
European Journal of Neuroscience 08/2001; 14(2):382-90. · 3.63 Impact Factor
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ABSTRACT: Recent functional magnetic resonance imaging (fMRI) studies suggest that the control of fingertip forces between the index finger and the thumb (precision grips) is dependent on bilateral frontal and parietal regions in addition to the primary motor cortex contralateral to the grasping hand. Here we use fMRI to examine the hypothesis that some of the areas of the brain associated with precision grips are more strongly engaged when subjects generate small grip forces than when they employ large grip forces. Subjects grasped a stationary object using a precision grip and employed a small force (3.8 N) that was representative of the forces that are typically used when manipulating small objects with precision grips in everyday situations or a large force (16.6 N) that represents a somewhat excessive force compared with normal everyday usage. Both force conditions involved the generation of time-variant static and dynamic grip forces under isometric conditions guided by auditory and tactile cues. The main finding was that we observed stronger activity in the bilateral cortex lining the inferior part of the precentral sulcus (area 44/ventral premotor cortex), the rostral cingulate motor area, and the right intraparietal cortex when subjects applied a small force in comparison to when they generated a larger force. This observation suggests that secondary sensorimotor related areas in the frontal and parietal lobes play an important role in the control of fine precision grip forces in the range typically used for the manipulation of small objects.
Journal of Neurophysiology 07/2001; 85(6):2613-23. · 3.32 Impact Factor
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ABSTRACT: Functional magnetic resonance imaging experiments were performed in human motor cortex at 1.5 T by sampling two successive gradient recalled echo images in a single shot. Several aspects of brain mapping methods based on T2*-weighted imaging and R2* mapping were quantitatively compared. These include the detected activation volume, functional contrast (FC), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR). Studies based on the R2* mapping method have the following potential advantages: maximum functional contrast, less dependent on TE; and reduced inflow effects. R2* mapping produced the highest functional contrast, but not the largest activation volume due to the reduced signal-to-noise ratio and inflow effects. The sensitivity for activation detection is significantly correlated with the contrast-to-noise ratio, which is determined by both the SNR and FC.
NMR in Biomedicine 03/2001; 14(1):41-7. · 3.21 Impact Factor
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ABSTRACT: In order to keep subscribers up-to-date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of NMR in biomedicine. Each bibliography is divided into 9 sections: 1 Books, Reviews ' Symposia; 2 General; 3 Technology; 4 Brain and Nerves; 5 Neuropathology; 6 Cancer; 7 Cardiac, Vascular and Respiratory Systems; 8 Liver, Kidney and Other Organs; 9 Muscle and Orthopaedic. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted.
NMR in Biomedicine 02/2001; 14(1):48-53. · 3.21 Impact Factor
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ABSTRACT: Twenty boys with developmental coordination disorder (DCD), 11 of whom had associated attention deficit disorder (ADD), were compared with an age-matched control group of 12 boys to examine mechanisms that adapt the grip force at the digit-object interface in a precision grip task. An experimental grip object equipped with pressure transducers registered the grip forces (normal to the surface) and the load force (tangential to the surface) generated by the fingertips. The surface of the object was changed to vary the frictional properties. Both study groups exhibited disturbances of the basic coordination of forces in the initial phase of the movement, manifested by longer time latencies and higher force levels than the control group. All subjects were able to adapt the force output in response to the friction at the digit-object interface. Higher grip forces and safety margins were documented for the DCD group in comparison to the controls. Furthermore, there was greater variation in the parametric control of the grip force in the DCD group. The results suggest that the control of the grip force is similar in children with DCD, regardless of whether they have associated ADD or not, but it is impaired in comparison to that of controls.
Neuropsychologia 02/2001; 39(5):478-88. · 3.64 Impact Factor
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H Forssberg
Lakartidningen 02/2001; 98(5):468-9.
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ABSTRACT: Mirror movements in individuals with hemiplegic cerebral palsy (CP) may result from a reorganization of the central sensorimotor system. Motor performances of both hands were measured to characterize mirror activity (or mirroring) and hand functions in 22 participants (6 to 18 years) with hemiplegic CP and in 17 control participants. During a unimanual repetitive squeezing task, contractions of the active hand and fingertip forces of the opposite hand were recorded simultaneously. In the control group, slight mirror activity (or mirroring) was found that decreased with age. In participants with CP, mirror activity was 15 times stronger than in the control group, and was found at all age levels. Mirroring was more prominent in the unaffected hand of the CP group. The amount of mirror activity was not related to the degree of hemiplegia, which was assessed with measures of spasticity, strength, and dexterity. Mirror movements disturbed functional bimanual skills, although to some extent they could be suppressed by voluntary effort.
Developmental Medicine & Child Neurology 12/2000; 42(11):728-36. · 2.92 Impact Factor
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ABSTRACT: A linear model of the dynamics of the human precision grip is presented. The transfer function is identified as representing the peripheral motor subsystem, from the motoneuron pool to the final production of a grip force between the tip of the index finger and the thumb. The transfer function captures the limiting isometric muscle dynamics that, e.g., cortical motor areas have to act through. When identifying the transfer function we introduce a novel technique, common subsystem identification. This characterizes a specific subsystem in a complex biomechanical system. This technique requires data from two functionally different experiments that both involve the subsystem of interest. Two transfer functions, one for each experiment, are then estimated using a linear black box technique. The common mathematical factors, represented by poles and zeros, are used to form a new transfer function. It is concluded that this transfer function represents the common biological subsystem involved in both experiments. Here, we use one active and one reactive isometric grip force experiment to capture the subsystem of interest, i.e., the motoneuron pool, motor units, muscles, tendons and fingertip tissue. The characteristics of the dynamics are in agreement with previously published experiments on human neuro-muscular systems. The model, H(s) = 280/(s2 + 22s + 280), is well suited for the representation of a force producing end-effector in simulations including a control system with sensory feedback.
IEEE Transactions on Biomedical Engineering 11/2000; 47(10):1366-75. · 2.28 Impact Factor
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ABSTRACT: The purpose of this study was to examine the cerebral control of simultaneous movements of the upper and lower limbs. We examined two hypotheses on how the brain coordinates movement: (i) by the involvement of motor representations shared by both limbs; or (ii) by the engagement of specific neural populations. We used positron emission tomography to measure the relative cerebral blood flow in healthy subjects performing isolated cyclic flexion-extension movements of the wrist and ankle (i.e. movements of wrist or ankle alone), and simultaneous movements of the wrist and ankle (a rest condition was also included). The simultaneous movements were performed in the same directions (iso-directional) and in opposite directions (antidirectional). There was no difference in the brain activity between these two patterns of coordination. In several motor-related areas (e.g. the contralateral ventral premotor area, the dorsal premotor area, the supplementary motor area, the parietal operculum and the posterior parietal cortex), the representation of the isolated wrist movement overlapped with the representation of the isolated ankle movement. Importantly, the simultaneous movements activated the same set of motor-related regions that were active during the isolated movements. In the contralateral ventral premotor cortex, dorsal premotor cortex and parietal operculum, there was less activity during the simultaneous movements than for the sum of the activity for the two isolated movements (interaction analysis). Indeed, in the ventral premotor cortex and parietal operculum, the activity was practically identical regardless whether only the wrist, only the ankle, or both the wrist and the ankle were moved. Taken together, these findings suggest that interlimb coordination is mediated by motor representations shared by both limbs, rather than being mediated by specific additional neural populations.
European Journal of Neuroscience 10/2000; 12(9):3385-98. · 3.63 Impact Factor
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ABSTRACT: The aim was to investigate the performance of children with attention-deficit-hyperactivity disorder (ADHD) in tasks involving motor-memory representations. A special grip object recorded forces generated by the fingertips during a precision grip-lift task. Common objects were lifted from a linear scale. Twenty-five boys with ADHD were evaluated and grouped according to the presence (ADHD+) or absence (ADHD) of movement dysfunction using the Movement Assessment Battery for Children (Henderson and Sugden 1992). Mean group ages were 11.4 years (range 9.0 to 11.0 years) and 11.7 years (9.0 to 15.6 years), respectively. They were compared to a control group of 25 age-matched boys, mean group age 11.8 years (range 9.0 to 13.0 years). Variability of motor performance was predominant in the ADHD+ group. Several of these participants presented a higher grip-force output during the gripping movement. They also had difficulties in adapting the motor output to target different weights, suggesting deficient anticipatory parameter control based on memory representations. The results suggest that in some children motor problems are due to detrimental neural control functions rather than core symptoms of ADHD.
Developmental Medicine & Child Neurology 09/2000; 42(8):545-53. · 2.92 Impact Factor
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ABSTRACT: Between 1987 and 1998, 470 patients visited the national clinic for obstetrical brachial plexus palsies at the Karolinska Hospital, Stockholm, Sweden. This study reports on 247 children examined at 5 years of age using a special protocol for testing the sensory and motor function of the hand. The children were distributed in various groups depending on the number of injured nerves, whether they had some muscle activity in their biceps or deltoid muscles at 3 months of age, and whether any operations with nerve reconstruction had been performed. The shoulder range of movement in C5-6 palsies was significantly better in the group which had been operated on (operated group), but otherwise there were no differences between children who had been operated on (non-operated group) and those who had not. A decrease in grip strength and bimanual function in level C5-6 palsies was found, though these roots should not innervate the distal hand. Outcome was not influenced by the number of avulsions in upper-plexus palsies or whether the operation took place before or after the age of 6 months. The group with extensive lesions (C5-Th1) had the most root avulsions, showing a correlation between increased avulsions and decreased hand function. This study does not support operating on children with no activity of the biceps and deltoid muscles at 3 months of age, as other authors have concluded. Rather, it favours waiting for a late recovery.
Developmental Medicine & Child Neurology 04/2000; 42(3):148-57. · 2.92 Impact Factor
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ABSTRACT: In previous studies of fingertip forces during precision grip in subjects with Parkinson's disease (PD), we observed regular oscillations in isometric force. The present study characterizes the nature of these oscillations. Fingertip forces were recorded from the index finger and thumb during precision grip-lifts with a 300 g and 900 g object in 10 subjects with PD and 20 healthy control subjects. Fourier analysis confirmed that all subjects with PD exhibited force oscillations with a clearly definable frequency (approximately 7-11 Hz). Five of these subjects also exhibited a second lower frequency peak (approximately 5 Hz). Approximately half of the 20 control subjects displayed a single frequency peak (approximately 8-12 Hz), which was generally lower in amplitude than in the subjects with PD (representing enhanced physiological tremor), whereas the remaining control subjects had low-amplitude, broad-based spectra (representing physiological tremor). The amplitude of the force oscillations was higher for lifts with the heavier object in both the control subjects and subjects with PD. L-Dopa resulted in a decreased tremor amplitude but did not influence the frequency. The force oscillations of the two opposing digits normal to the grip surfaces were in phase, whereas the oscillations tangential to the grip surfaces were often out of phase. The results suggest that the multipeaked force rate trajectories reported previously are caused by action tremor. The similarity of force oscillations in subjects with PD and healthy control subjects suggests common tremor-generating mechanisms and supports the notion that the parkinsonian action tremor (AT) is an exaggerated form of physiological tremor. These findings provide insight into the impaired hand function observed in individuals with PD.
Movement Disorders 04/2000; 15(2):244-54. · 4.51 Impact Factor
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ABSTRACT: Most manual grips can be divided in precision and power grips on the basis of phylogenetic and functional considerations. We used functional magnetic resonance imaging to compare human brain activity during force production by the right hand when subjects used a precision grip and a power grip. During the precision-grip task, subjects applied fine grip forces between the tips of the index finger and the thumb. During the power-grip task, subjects squeezed a cylindrical object using all digits in a palmar opposition grasp. The activity recorded in the primary sensory and motor cortex contralateral to the operating hand was higher when the power grip was applied than when subjects applied force with a precision grip. In contrast, the activity in the ipsilateral ventral premotor area, the rostral cingulate motor area, and at several locations in the posterior parietal and prefrontal cortices was stronger while making the precision grip than during the power grip. The power grip was associated predominately with contralateral left-sided activity, whereas the precision-grip task involved extensive activations in both hemispheres. Thus our findings indicate that in addition to the primary motor cortex, premotor and parietal areas are important for control of fingertip forces during precision grip. Moreover, the ipsilateral hemisphere appears to be strongly engaged in the control of precision-grip tasks performed with the right hand.
Journal of Neurophysiology 02/2000; 83(1):528-36. · 3.32 Impact Factor
