Enrichment of rare copy number variation in children with developmental language disorder.

Developmental language disorder (DLD) is a common neurodevelopmental disorder with largely unknown etiology. Rare copy number variants (CNVs) have been implicated in the genetic architecture of other neurodevelopmental disorders (NDDs), which have led to clinical genetic testing recommendations for these disorders; however, the evidence is still lacking for DLD. We analyzed rare and de novo CNVs in 58 probands with severe DLD, their 159 family members and 76 Swedish typically developing children using high-resolution microarray. DLD probands had larger rare CNVs as measured by total length (P = .05), and average length (P = .04). In addition, the rate of rare CNVs overlapping coding genes was increased (P = .03 and P = .01) and in average more genes were affected (P = .006 and P = .03) in the probands and their siblings, respectively. De novo CNVs were found in 4.8% DLD probands (2/42) and 2.4% (1/42) siblings. Clinically significant CNVs or chromosomal anomalies were found in 6.9% (4/58) of the probands of which 2 carried 16p11.2 deletions. We provide further evidence that rare CNVs contribute to the etiology of DLD in loci that overlap with other NDDs. Based on our results and earlier literature, families with DLD should be offered molecular genetic testing as a routine in their clinical follow-up.

The Ugandan version of the Pediatric Evaluation of Disability Inventory (PEDI-UG). Part II: Psychometric properties.

BACKGROUND: The Pediatric Evaluation of Disability Inventory (PEDI) has been recommended as a gold standard in paediatric rehabilitation. A Ugandan version of PEDI (PEDI-UG) has been developed by culturally adapting and translating the original PEDI. The aim of this study was to investigate the psychometric properties of the PEDI-UG in Ugandan children by testing the instrument's rating scale functioning, internal structure, and test-retest reliability. METHODS: Two hundred forty-nine Ugandan children (125 girls) aged 6 months to 7.5 years (Mean = 3.4, SD = 1.9) with typical development were tested using the PEDI-UG. Forty-nine children were tested twice to assess test-retest reliability. Validity was investigated by Rasch analysis and reliability by intraclass correlation coefficient. RESULTS: The PEDI-UG domains showed good unidimensionality based on principal component analysis of residuals. Most activities (95%) showed acceptable fit to the Rasch model. Six misfit items were deleted from the Functional Skills scales and one from the Caregiver Assistance scales. The category steps on the Caregiver Assistance scales' rating scale were reversed but functioned well when changed from a 6-point to 4-point rating scale. The reliability was excellent; intraclass correlation coefficient was 0.87-0.92 for the domains of the Functional Skills scales and 0.86-0.88 for the domains of the Caregiver Assistance scales. CONCLUSION: The PEDI-UG has good to excellent psychometric properties and provides a valid measure of the functional performance of typically developing children from the age of 6 months to 7.5 years in Uganda. Further analysis of all items, including misfit and deleted items, in children with functional disability is recommended.

The Uganda version of the Pediatric Evaluation of Disability Inventory (PEDI). Part I: Cross-cultural adaptation.

BACKGROUND: The Pediatric Evaluation of Disability Inventory (PEDI) was developed and standardized to measure functional performance in American children. So far, no published study has examined the use of the PEDI in sub-Saharan Africa. This study describes the adaptation, translation, and validation process undertaken to develop a culturally relevant PEDI for Uganda (PEDI-UG). METHOD: The cross-cultural adaptation and translation of the PEDI was performed in a series of steps. A project manager and a technical advisory group were involved in all steps of adaptation, translation, cognitive debriefing, and revision. Translation and back-translation between English and Luganda were performed by professional translators. Cognitive debriefing of two subsequent adapted revisions was performed by a field-testing team on a total of 75 caregivers of children aged 6 months to 7.5 years. RESULTS: The PEDI-UG was established in both English (the official language) and Luganda (a local language) and comprises 185 items. Revisions entailed deleting irrelevant items, modifying wording, inserting new items, and incorporating local examples while retaining the meaning of the original PEDI. Item statements were rephrased as questions. Seven new items were inserted and 19 items deleted. To accommodate major differences in living conditions between rural and urban areas, 10 alternative items were provided. CONCLUSIONS: The PEDI-UG is to be used to measure functional limitations in both clinical practice and research, in order to assess and evaluate rehabilitative procedures in children with developmental delay and disability in Uganda. In this study, we take the first step by translating and adapting the original PEDI version to the culture and life conditions in both rural and urban Uganda. In subsequent studies, the tool's psychometric properties will be examined, and the tool will be tested in children with developmental delay and disability.

Toll-like receptor-4 regulates anxiety-like behavior and DARPP-32 phosphorylation.

Toll-like receptors (TLRs) play a crucial role in early innate immune responses to inflammatory agents and pathogens. In the brain, some members of the TLR family are expressed in glial cells and neurons. In particular, TLR4 has been involved in learning and memory processes, stress-induced adaptations, and pathogenesis of neurodegenerative disorders. However, the role of TLR4 in emotional behaviors and their underlying mechanisms are poorly understood. In this study, we investigated the role of TLR4 in emotional and social behavior by using different behavioral approaches, and assessed potential molecular alterations in important brain areas involved in emotional responses. TLR4 knockout (KO) mice displayed increased anxiety-like behavior and reduced social interaction compared to wild type control mice. This behavioral phenotype was associated with an altered expression of genes known to be involved in emotional behavior [e.g., brain-derived neurotrophic factor (BDNF) and metabotropic glutamate receptors (mGluRs)]. Interestingly, the mRNA expression of dopamine- and cAMP-regulated phosphoprotein-32 (DARPP-32) was strongly upregulated in emotion-related regions of the brain in TLR4 KO mice. In addition, the phosphorylation levels at Thr75 and Ser97 in DARPP-32 were increased in the frontal cortex of TLR4 KO male mice. These findings indicate that TLR4 signaling is involved in emotional regulation through modulation of DARPP-32, which is a signaling hub that plays a critical role in the integration of numerous neurotransmitter systems, including dopamine and glutamate.

Neural and non-neural related properties in the spastic wrist flexors: An optimization study.

Quantifying neural and non-neural contributions to increased joint resistance in spasticity is essential for a better understanding of its pathophysiological mechanisms and evaluating different intervention strategies. However, direct measurement of spasticity-related manifestations, e.g., motoneuron and biophysical properties in humans, is extremely challenging. In this vein, we developed a forward neuromusculoskeletal model that accounts for dynamics of muscle spindles, motoneuron pools, muscle activation and musculotendon of wrist flexors and relies on the joint angle and resistant torque as the only input measurement variables. By modeling the stretch reflex pathway, neural and non-neural related properties of the spastic wrist flexors were estimated during the wrist extension test. Joint angle and resistant torque were collected from 17 persons with chronic stroke and healthy controls using NeuroFlexor, a motorized force measurement device during the passive wrist extension test. The model was optimized by tuning the passive and stretch reflex-related parameters to fit the measured torque in each participant. We found that persons with moderate and severe spasticity had significantly higher stiffness than controls. Among subgroups of stroke survivors, the increased neural component was mainly due to a lower muscle spindle rate at 50% of the motoneuron recruitment. The motoneuron pool threshold was highly correlated to the motoneuron pool gain in all subgroups. The model can describe the overall resistant behavior of the wrist joint during the test. Compared to controls, increased resistance was predominantly due to higher elasticity and neural components. We concluded that in combination with the NeuroFlexor measurement, the proposed neuromusculoskeletal model and optimization scheme served as suitable tools for investigating potential parameter changes along the stretch-reflex pathway in persons with spasticity.

The bacterial peptidoglycan-sensing molecule Pglyrp2 modulates brain development and behavior.

Recent studies have revealed that the gut microbiota modulates brain development and behavior, but the underlying mechanisms are still poorly understood. Here, we show that bacterial peptidoglycan (PGN) derived from the commensal gut microbiota can be translocated into the brain and sensed by specific pattern-recognition receptors (PRRs) of the innate immune system. Using expression-profiling techniques, we demonstrate that two families of PRRs that specifically detect PGN (that is, PGN-recognition proteins and NOD-like receptors), and the PGN transporter PepT1 are highly expressed in the developing brain during specific windows of postnatal development in both males and females. Moreover, we show that the expression of several PGN-sensing molecules and PepT1 in the developing striatum is sensitive to manipulations of the gut microbiota (that is, germ-free conditions and antibiotic treatment). Finally, we used the PGN-recognition protein 2 (Pglyrp2) knockout mice to examine the potential influence of PGN-sensing molecules on brain development and behavior. We demonstrate that the absence of Pglyrp2 leads to alterations in the expression of the autism risk gene c-Met, and sex-dependent changes in social behavior, similar to mice with manipulated microbiota. These findings suggest that the central activation of PRRs by microbial products could be one of the signaling pathways mediating the communication between the gut microbiota and the developing brain.

Advanced fiber tracking in early acquired brain injury causing cerebral palsy.

BACKGROUND AND PURPOSE: Diffusion-weighted MR imaging and fiber tractography can be used to investigate alterations in white matter tracts in patients with early acquired brain lesions and cerebral palsy. Most existing studies have used diffusion tensor tractography, which is limited in areas of complex fiber structures or pathologic processes. We explored a combined normalization and probabilistic fiber-tracking method for more realistic fiber tractography in this patient group. MATERIALS AND METHODS: This cross-sectional study included 17 children with unilateral cerebral palsy and 24 typically developing controls. DWI data were collected at 1.5T (45 directions, b=1000 s/mm(2)). Regions of interest were defined on a study-specific fractional anisotropy template and mapped onto subjects for fiber tracking. Probabilistic fiber tracking of the corticospinal tract and thalamic projections to the somatosensory cortex was performed by using constrained spherical deconvolution. Tracts were qualitatively assessed, and DTI parameters were extracted close to and distant from lesions and compared between groups. RESULTS: The corticospinal tract and thalamic projections to the somatosensory cortex were realistically reconstructed in both groups. Structural changes to tracts were seen in the cerebral palsy group and included splits, dislocations, compaction of the tracts, or failure to delineate the tract and were associated with underlying pathology seen on conventional MR imaging. Comparisons of DTI parameters indicated primary and secondary neurodegeneration along the corticospinal tract. Corticospinal tract and thalamic projections to the somatosensory cortex showed dissimilarities in both structural changes and DTI parameters. CONCLUSIONS: Our proposed method offers a sensitive means to explore alterations in WM tracts to further understand pathophysiologic changes following early acquired brain injury.

Genetic variation in dopamine-related gene expression influences motor skill learning in mice.

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 (DA) system, which is known to play a critical role in motor skill learning. In this study, we took advantage of two inbred strains of mice (BALB/c and C57BL/6) that differ markedly in the number of midbrain DA 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 showed significant differences in the expression of presynaptic and postsynaptic dopaminergic (DAergic) markers (e.g. tyrosine hydroxylase, DA transporter, DA D4 receptor, DA 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 with 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 DA D1 receptor mRNAs in the striatum. Our results suggest that genetically driven variation in frontostriatal DAergic 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 skill deficits.

Family history interview of a broad phenotype in specific language impairment and matched controls.

The aim was to study a broader phenotype of language-related diagnoses and problems in three generations of relatives of children with specific language impairment (SLI). Our study is based on a family history interview of the parents of 59 children with SLI and of 100 matched control children, exploring the prevalence of problems related to language, reading, attention, school achievement and social communication as well as diagnoses such as attention-deficit hyperactivity disorder (ADHD), autism, Asperger syndrome, dyslexia, mental retardation, cleft palate and stuttering. The results show a spectrum of language-related problems in families of SLI children. In all three generations of SLI relatives, we found significantly higher prevalence rates of language, literacy and social communication problems. The risk of one or both parents having language-related diagnoses or problems was approximately six times higher for the children with SLI (85%) than for the control children (13%) (odds ratio = 37.2). We did not find a significantly higher prevalence of the diagnoses ADHD, autism or Asperger syndrome in the relatives of the children with SLI. However, significantly more parents of the children with SLI had problems with attention/hyperactivity when compared with the parents of controls. Our findings suggest common underlying mechanisms for problems with language, literacy and social communication, and possibly also for attention/hyperactivity symptoms.

Diffusion MRI in corticofugal fibers correlates with hand function in unilateral cerebral palsy.

UNLABELLED: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Botulinum toxin A treatment in toddlers with cerebral palsy.

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.

Age-related reduction in dopamine D1 receptors in the human brain: from late childhood to adulthood, a positron emission tomography study.

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.

[Alterations in the pattern of dopaminergic markers in attention-deficit/hyperactivity disorder]. / Alteraciones de los patrones de los marcadores de la dopaminaen el trastorno por déficit de atención e hiperactividad.

INTRODUCTION: 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. DEVELOPMENT: 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. CONCLUSIONS: 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.

Alteraciones de los patrones de los marcadores de la dopamina en el trastorno por déficit de atención e hiperactividad / Alterations in the pattern of dopaminergic markers in attention-deficit/hyperactivity disorder

Introducción. El trastorno por déficit de atención e hiperactividad(TDAH) es un trastorno neuroconductual frecuente que seinicia en la infancia y puede incluir elementos como la inatención,hiperactividad y conducta impulsiva. El tratamiento habitual consisteen la administración de fármacos estimulantes como el metilfenidatoclorhidrato (MPH). El mecanismo neurobiológico del TDAH nose comprende muy bien, pero hay pruebas que coinciden en la implicaciónde los circuitos frontoestriatales ricos en catecolaminas. Unade las teorías más destacadas es que existe un trastorno de la regularizaciónde la transmisión de la dopamina en estos circuitos. Esta teoría se apoya en los resultados de los estudios de imagen realizadosen humanos, en los que se ha observado que el MPH bloquea eltransportador de dopamina (DAT), el principal mecanismo por elcual se elimina la dopamina de las sinapsis; por ello, aumentan losniveles de dopamina extracelulares en el estriado. Estudios genéticosy moleculares han mostrado una asociación importante entre losgenes relacionados con la dopamina (como el DAT, los receptores dedopamina D4 y D5) y el TDAH. Desarrollo. Los estudios con PET ySPECT señalan alteraciones en los marcadores dopaminérgicos enel TDAH. La mayoría de estudios actuales han descrito un incrementoen la fijación de DAT (entre el 17 y el 70%) en el estriado de niñosy adultos con TDAH, mientras que en un estudio reciente realizadocon PET se encontró una fijación de DAT disminuida en el mesencéfalo(donde se ubican las neuronas dopaminérgicas de la sustancianegra y la zona tegmental ventral) de adolescentes con TDAH. Losestudios con [18F]fluorodopa para evaluar la síntesis y el metabolismode la dopamina han mostrado anomalías en la actividad presinápticade pacientes con TDAH; estos cambios parecen depender dela edad. Algunos datos limitados apuntan a alteraciones potencialesen las cantidades de receptor de dopamina D2 disponibles en niñoscon TDAH. Conclusiones. Los resultados de los estudios de imagencon cerebros humanos no son definitivos todavía debido a ciertasdiscrepancias en los hallazgos. Es necesario replicar y ampliar estosresultados en pacientes con TDAH que no han recibido tratamientoprevio, teniendo en cuenta posibles variables como los antecedentesrelacionados con el consumo de drogas y el tabaquismo, la etnicidady la comorbilidad

Introduction. Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral disorder of childhoodonset that can include elements of inattention, hyperactivity and impulsive behavior. It is often treated with stimulantmedications such as methylphenidate hydrochloride (MPH). The neurobiology of ADHD is not well understood, but there isconverging evidence of the involvement of the catecholamine rich frontal-striatal circuitry. A prominent theory of ADHD is thatthere is a dysregulation of dopamine neurotransmission in this circuitry. Given support to this theory is the observation fromhuman imaging studies that MPH blocks the dopamine transporter (DAT), the main mechanism for removing dopamine fromthe synapse; thereby increasing extracellular dopamine levels in the striatum. Genetic and molecular studies have alsodemonstrated an association between dopamine related genes (e.g., DAT, dopamine D4 and D5 receptors) and ADHD.Development. Studies using positron emission tomography (PET) and single photon emission tomography indicate alterationsin dopamine markers in ADHD. The majority of the existing studies have reported increased DAT binding (ranging between 17and 70%) in the striatum of both children and adults with ADHD, while a new PET study reported lower DAT binding in themidbrain (where the dopaminergic neurons of the substantia nigra and ventral tegmental area are located) of adolescents withADHD. Studies using [18F]fluorodopa to assess dopamine synthesis and metabolism have demonstrated abnormalities inpresynaptic activity in patients with ADHD; however the nature of these changes appears to be age-dependent. Some limiteddata also indicate potential alterations in dopamine D2 receptor availability in children with ADHD. Conclusions. The resultsfrom the human brain imaging studies are still not definitive because of discrepancies in the findings. There is a great need toreplicate and expand these findings in treatment-naïve patients with ADHD, taking into consideration potential variables suchas drug and smoking history, ethnicity, and presence of comorbidity

Impulse control, working memory and other executive functions in preterm children when starting school.

AIM: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Human brain activity in the control of fine static precision grip forces: an fMRI study.

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.

Influence of two different sitting positions on postural adjustments in children with spastic diplegia.

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.

Differential fronto-parietal activation depending on force used in a precision grip task: an fMRI study.

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.