Does Handedness for Prehension Predict Handedness for Role-Differentiated Bimanual Manipulation During Infancy?

The clearly observable behaviors that identify infant hand-use preferences make the development of this sensorimotor form of lateralization a valuable model for evaluating the development of other forms of lateral asymmetries of function. The current study examined the relation of individual patterns of development of handedness for reaching for objects (prehension) to the emergence of handedness in role-differentiated bimanual manipulation (RDBM). RDBM requires each hand to perform different, but complementary, actions on one or more objects. Hand-use reference for reaching for and grasping objects was assessed in a sample of 85 infants from the period of 6- to 11-months of age using a validated handedness assessment that consists of a series of presentations of 34 common infant toys. At 11 and 14 months, hand-use preferences for RDBM were assessed while the infants were involved in semiplay activity in which they were presented with a series of 13 toys (20-40 s for each presentation). Results revealed no significant relationship between prehension handedness and handedness for RDBM. However, multi-level modeling of the prehension data revealed interesting developmental changes in prehension handedness that can only be identified by using monthly sampling intervals with longitudinal methods

Using diffusion tensor imaging to identify corticospinal tract projection patterns in children with unilateral spastic cerebral palsy.

AIM: To determine whether diffusion tensor imaging (DTI) can be an independent assessment for identifying the corticospinal tract (CST) projecting from the more-affected motor cortex in children with unilateral spastic cerebral palsy (CP). METHOD: Twenty children with unilateral spastic CP participated in this study (16 males, four females; mean age 9y 2mo [standard deviation (SD) 3y 2mo], Manual Ability Classification System [MACS] level I-III). We used DTI tractography to reconstruct the CST projecting from the more-affected motor cortex. We mapped the motor representation of the more-affected hand by stimulating the more- and the less-affected motor cortex measured with single-pulse transcranial magnetic stimulation (TMS). We then verified the presence or absence of the contralateral CST by comparing the TMS map and DTI tractography. Fisher's exact test was used to determine the association between findings of TMS and DTI. RESULTS: DTI tractography successfully identified the CST controlling the more-affected hand (sensitivity=82%, specificity=78%). INTERPRETATION: Contralateral CST projecting from the lesioned motor cortex assessed by DTI is consistent with findings of TMS mapping. Since CST connectivity may be predictive of response to certain upper extremity treatments, DTI-identified CST connectivity may potentially be valuable for determining such connectivity where TMS is unavailable or inadvisable for children with seizures.K08 NS073796 - NINDS NIH HHS; TL1 RR024158 - NCRR NIH HHS; K01 NS062116 - NINDS NIH HHS; UL1 RR024156 - NCRR NIH HHS; KL2 RR024157 - NCRR NIH HHS; R01 HD076436 - NICHD NIH HHSPublished versio

Development of Infant Prehension Handedness: A Longitudinal Analysis During the 6- to 14-month Age Period.

Handedness is a developmental phenomenon that becomes distinctively identifiable during infancy. Although infant hand-use preferences sometimes have been reported as unstable, other evidence demonstrates that infant hand-use preference for apprehending objects can be reliably assessed during the second half of the infant's first year of life. The current study provides further insight into the stability of prehension preferences. We modeled individual and group level patterns of prehension handedness during the period from 6 to 14 months of age. We examined the developmental trajectories for prehension handedness in relation to the sampling rate at which preferences are assessed. The results revealed interesting developmental changes in prehension handedness that can only be identified when using monthly sampling intervals. We conclude that using non-linear multilevel models of infant handedness with monthly sampling intervals permit us to accurately capture the developmental changes in manual skills that occur during this period of infancy

Improved methodical approach for quantitative BRET analysis of G protein coupled receptor dimerization

G Protein Coupled Receptors (GPCR) can form dimers or higher ordered oligomers, the process of which can remarkably influence the physiological and pharmacological function of these receptors. Quantitative Bioluminescence Resonance Energy Transfer (qBRET) measurements are the gold standards to prove the direct physical interaction between the protomers of presumed GPCR dimers. For the correct interpretation of these experiments, the expression of the energy donor Renilla luciferase labeled receptor has to be maintained constant, which is hard to achieve in expression systems. To analyze the effects of non-constant donor expression on qBRET curves, we performed Monte Carlo simulations. Our results show that the decrease of donor expression can lead to saturation qBRET curves even if the interaction between donor and acceptor labeled receptors is non-specific leading to false interpretation of the dimerization state. We suggest here a new approach to the analysis of qBRET data, when the BRET ratio is plotted as a function of the acceptor labeled receptor expression at various donor receptor expression levels. With this method, we were able to distinguish between dimerization and non-specific interaction when the results of classical qBRET experiments were ambiguous. The simulation results were confirmed experimentally using rapamycin inducible heterodimerization system. We used this new method to investigate the dimerization of various GPCRs, and our data have confirmed the homodimerization of V2 vasopressin and CaSR calcium sensing receptors, whereas our data argue against the heterodimerization of these receptors with other studied GPCRs, including type I and II angiotensin, β2 adrenergic and CB1 cannabinoid receptors

A Perspective on the Development of Hemispheric Specialization, Infant Handedness, and Cerebral Palsy

Cerebral Palsy (CP), a common form of neurological pediatric disability, results from pre- or perinatal brain injury. Although there is growing evidence of the efficacy of motor learning-based therapies, several factors interact to produce variability in impairment and limit the effectiveness of these therapies. The variability of hand function present in children with CP indicates that a range of developmental pathways must contribute to the manifestation of individually unique characteristics of impairment. Despite two decades of progress using therapies derived from understanding the mechanisms controlling hand function, very little is known about the sensorimotor experiences occurring during development that likely shape later functional problems for children with CP. In this “perspective” paper, we propose that the study of the development of motor skills in typically developing infants may reveal experiential factors potentially important for creating remedial therapies for children with CP. Specifically, we use the development of infant handedness, a model of hemispheric specialization of function, as an example of how self-generated experiences and sensorimotor feedback can shape the development of limb control and hemispheric specialization. We illustrate how early sensorimotor asymmetries concatenate into pronounced differences in skill between the two hands. We suggest that this model of infant handedness provides a framework for studying the individual differences manifested in children with CP. These differences likely arise from aberrant sensorimotor experiences created by sensorimotor circuits disrupted by the early brain injury. We conclude that knowledge of the developmental events, including subtle motor behaviors, that shape sensorimotor pathways, can improve treatment options for children with CP

Intensive Bimanual Intervention for Children Who Have Undergone Hemispherectomy: A Pilot Study.

To conduct a pilot study to assess the feasibility and effectiveness of an intensive bimanual intervention on upper limb function in children who have undergone hemispherectomy. Thirteen children received 90 hours of intensive bimanual training (Hand-Arm Bimanual Intensive Therapy, HABIT). The Jebsen-Taylor Test of Hand Function (JTTHF), Box and Block Test (BBT), Assisting Hand Assessment (AHA), ABILHAND-Kids, and Canadian Occupational Performance Measure (COPM) were assessed by a masked clinician twice before, immediately, and 6 months after treatment. Significant improvements over time were found in the JTTHF, AHA, ABILHAND-Kids, and COPM. Completion of HABIT was feasible for children with hemispherectomy. Improvement of bimanual function and functional goals can be related to the nature of the activities prioritized in HABIT training

Does Corticospinal Tract Connectivity Influence the Response to Intensive Bimanual Therapy in Children With Unilateral Cerebral Palsy?

Background Reorganization of the corticospinal tract (CST) can occur in unilateral spastic cerebral palsy (USCP). The affected hand can be controlled via (1) typical contralateral projections from the lesioned hemisphere, (2) ipsilateral projections from the nonlesioned hemisphere, and (3) a combination of contralateral and ipsilateral projections (ie, bilateral). Intensive bimanual therapy and constraint-induced movement therapy (CIMT) improve hand function of children with USCP. Earlier it was suggested that the CST connectivity pattern may influence the efficacy of CIMT. Objective To examine whether CST projection pattern influences the efficacy of intensive bimanual therapy in children with USCP. Participants Thirty-three children with USCP (age 8.9 ± 2.6 years, 16 females). Methods Bimanual therapy was provided in a day-camp setting (90 hours). Participants were involved in different bimanual play and functional activities actively engaging both hands. Hand function was tested before and after the intervention with the Jebsen-Taylor Test of Hand Function, Assisting Hand Assessment, ABILHAND-Kids, and the Canadian Occupational Performance Measure. Single-pulse transcranial magnetic stimulation (TMS) was used to determine each child's CST projection pattern (ie, ipsilateral, contralateral, or bilateral). Results Children whose affected hand was controlled only by ipsilateral CST projections had worse Jebsen-Taylor Test of Hand Function and Assisting Hand Assessment scores than children in the contralateral group at baseline. Bimanual hand use and functional hand use was independent of CST projection pattern. After bimanual therapy, improvements on all outcome measures were observed, and these improvements were independent of the CST connectivity pattern. Conclusion The efficacy of bimanual therapy on hand function in children with USCP appears to be independent of CST connectivity pattern

The Relationship Between Hand Function and Overlapping Motor Representations of the Hands in the Contralesional Hemisphere in Unilateral Spastic Cerebral Palsy

BACKGROUND: In many children with unilateral spastic cerebral palsy (USCP), the corticospinal tract to the affected hand atypically originates in the hemisphere ipsilateral to the affected hand. Such ipsilateral connectivity is on average a predictor of poor hand function. However, there is high variability in hand function in these children, which might be explained by the complexity of motor representations of both hands in the contralesional hemisphere. OBJECTIVE: To measure the link between hand function and the size and excitability of motor representations of both hands, and their overlap, in the contralesional hemisphere of children with USCP. METHODS: We used single-pulse transcranial magnetic stimulation to measure the size and excitability of motor representations of both hands, and their overlap, in the contralesional hemisphere of 50 children with USCP. We correlated these measures with manual dexterity of the affected hand, bimanual performance, and mirror movement strength. RESULTS: The main and novel findings were (1) the large overlap in contralesional motor representations of the 2 hands and (2) the moderate positive associations of the size and excitability of such shared-site representations with hand function. Such functional associations were not present for overall size and excitability of representations of the affected hand. CONCLUSIONS: Greater relative overlap of the affected hand representation with the less-affected hand representation within the contralesional hemisphere was associated with better hand function. This association suggests that overlapping representations might be adaptively "yoked," such that cortical control of the child's less-affected hand supports that of the affected hand