Elucidating the molecular mechanisms that underlie the target control of motoneuron death

Approximately half of the motoneurons generated during normal embryonic development undergo programmed cell death. Most of this death occurs during the time when synaptic connections are being formed between motoneurons and their target, skeletal muscle. Subsequent muscle activity stemming from this connection helps determine the final number of surviving motoneurons. These observations have given rise to the idea that motoneuron survival is dependent upon access to muscle derived trophic factors, presumably through intact neuromuscular synapses. However, it is not yet understood how the muscle regulates the supply of such trophic factors, or if there are additional mechanisms operating to control the fate of the innervating motoneuron. Recent observations have highlighted target independent mechanisms that also operate to support the survival of motoneurons, such as early trophic-independent periods of motoneuron death, trophic factors derived from Schwann cells and selection of motoneurons during pathfinding. Here we review recent investigations into motoneuron cell death when the molecular signalling between motoneurons and muscle has been genetically disrupted. From these studies, we suggest that in addition to trophic factors from muscle and/or Schwann cells, specific adhesive interactions between motoneurons and muscle are needed to regulate motoneuron survival. Such interactions, along with intact synaptic basal lamina, may help to regulate the supply and presentation of trophic factors to motoneurons.

Development of motor system dysfunction following whiplash injury

Dysfunction in the motor system is a feature of persistent whiplash associated disorders. Little is known about motor dysfunction in the early stages following injury and of its progress in those persons who recover and those who develop persistent symptoms. This study measured prospectively, motor system function (cervical range of movement (ROM), joint position error (JPE) and activity of the superficial neck flexors (EMG) during a test of cranio-cervical flexion) as well as a measure of fear of re-injury (TAMPA) in 66 whiplash subjects within 1 month of injury and then 2 and 3 months post injury. Subjects were classified at 3 months post injury using scores on the neck disability index: recovered (30). Motor system function was also measured in 20 control subjects. All whiplash groups demonstrated decreased ROM and increased EMG (compared to controls) at 1 month post injury. This deficit persisted in the group with moderate/severe symptoms but returned to within normal limits in those who had recovered or reported persistent mild pain at 3 months. Increased EMG persisted for 3 months in all whiplash groups. Only the moderate/severe group showed greater JPE, within 1 month of injury, which remained unchanged at 3 months. TAMPA scores of the moderate/severe group were higher than those of the other two groups. The differences in TAMPA did not impact on ROM, EMG or JPE. This study identifies, for the first time, deficits in the motor system, as early as 1 month post whiplash injury, that persisted not only in those reporting moderate/severe symptoms at 3 months but also in subjects who recovered and those with persistent mild symptoms. (C) 2002 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.

Rites of passage: Understanding participation of children with developmental coordination disorder

Children with developmental coordination disorder (DCD) experience difficulty participating in the typical activities of childhood and are known to have a more sedentary pattern of activities than their peers. Little research has been done to investigate the impact of these deficits on the lives of children with DCD and the importance of their participation in the typical activities of childhood. This qualitative study explored the impact of the disorder and the importance of participation for children with DCD from the perspective of the parent. Twelve in-depth interviews were conducted with parents of children with DCD who attended a university clinic specializing in using the Cognitive Orientation to daily Occupational Performance (COOP) approach, a cognitive-based intervention. Findings revealed that incompetence in everyday activities had serious negative effects for the children. Conversely, intervention that was focused on enablement at the activity and participation level had a significant positive impact on the children's quality of life. Emerging themes highlighted the notion that performance competency played an important role in being accepted by peers and being able to be part of the group. As well, parents reported that successful participation built confidence in their children and allowed them to try other new activities. The World Health Organization's International Classification of Functioning, Disability, and Health provides a unique framework for analyzing and understanding the impact of the physical disability on the lives of families with children with DCD. Results illustrate how intervention that focuses on enabling children to choose their own functional goals in the area of physical activity has important implications for enabling participation and building the social networks of children with DCD. (C) 2003 Elsevier B.V. All rights reserved.

Perceptual evaluation of motor speech following treatment for childhood cerebellar tumour

The speech characteristics, oromotor function and speech intelligibility of a group of children treated for cerebellar tumour (CT) was investigated perceptually. Assessment of these areas was performed on 11 children treated for CT with dysarthric speech as well as 21 non-neurologically impaired controls matched for age and sex to obtain a comprehensive perceptual profile of their speech and oromotor mechanism. Contributing to the perception of dysarthria were a number of deviant speech dimensions including imprecision of consonants, hoarseness and decreased pitch variation, as well as a reduction in overall speech intelligibility for both sentences and connected speech. Oromotor assessment revealed deficits in lip, tongue and laryngeal function, particularly relating to deficits in timing and coordination of movements. The most salient features of the dysarthria seen in children treated for CT were the mild nature of the speech disorder and clustering of speech deficits in the prosodic, phonatory and articulatory aspects of speech production.

Neuromuscular synapses mediate motor axon branching and motoneuron survival during the embryonic period of programmed cell death

The embryonic period of motoneuron programmed cell death (PCD) is marked by transient motor axon branching, but the role of neuromuscular synapses in regulating motoneuron number and axonal branching is not known. Here, we test whether neuromuscular synapses are required for the quantitative association between reduced skeletal muscle contraction, increased motor neurite branching, and increased motoneuron survival. We achieved this by comparing agrin and rapsyn mutant mice that lack acetylcholine receptor (AChR) clusters. There were significant reductions in nerve-evoked skeletal muscle contraction, increases in intramuscular axonal branching, and increases in spinal motoneuron survival in agrin and rapsyn mutant mice compared with their wild-type littermates at embryonic day 18.5 (E18.5). The maximum nerve-evoked skeletal muscle contraction was reduced a further 17% in agrin mutants than in rapsyn mutants. This correlated to an increase in motor axon branch extension and number that was 38% more in agrin mutants than in rapsyn mutants. This suggests that specializations of the neuromuscular synapse that ensure efficient synaptic transmission and muscle contraction are also vital mediators of motor axon branching. However, these increases in motor axon branching did not correlate with increases in motoneuron survival when comparing agrin and rapsyn mutants. Thus, agrin-induced synaptic specializations are required for skeletal muscle to effectively control motoneuron numbers during embryonic development. (C) 2003 Elsevier Science (USA). All rights reserved.

Origins and early development of human body knowledge

As a knowable object, the human body is highly complex. Evidence from several converging lines of research, including psychological studies, neuroimaging and clinical neuropsychology, indicates that human body knowledge is widely distributed in the adult brain, and is instantiated in at least three partially independent levels of representation. Sensori-motor body knowledge is responsible for on-line control and movement of one's own body and may also contribute to the perception of others' moving bodies; visuo-spatial body knowledge specifies detailed structural descriptions of the spatial attributes of the human body; and lexical-semantic body knowledge contains language-based knowledge about the human body. In the first chapter of this Monograph, we outline the evidence for these three hypothesized levels of human body knowledge, then review relevant literature on infants' and young children's human body knowledge in terms of the three-level framework. In Chapters II and III, we report two complimentary series of studies that specifically investigate the emergence of visuospatial body knowledge in infancy. Our technique is to compare infants' responses to typical and scrambled human bodies, in order to evaluate when and how infants acquire knowledge about the canonical spatial layout of the human body. Data from a series of visual habituation studies indicate that infants first discriminate scrambled from typical human body pictures at 15 to 18 months of age. Data from object examination studies similarly indicate that infants are sensitive to violations of three-dimensional human body stimuli starting at 15-18 months of age. The overall pattern of data supports several conclusions about the early development of human body knowledge: (a) detailed visuo-spatial knowledge about the human body is first evident in the second year of life, (b) visuo-spatial knowledge of human faces and human bodies are at least partially independent in infancy and (c) infants' initial visuo-spatial human body representations appear to be highly schematic, becoming more detailed and specific with development. In the final chapter, we explore these conclusions and discuss how levels of body knowledge may interact in early development.

Effects of visual occlusion and fatigue on motor performance in water

The purpose of this study was to test the effects of visual occlusion and fatigue on the motor performance of vertical skills in synchronized swimming. Experienced synchronized swimmers (n = 12) were randomly assigned to either an exercise or nonexercise (control) activity group. Subjective ratings of fatigue were obtained from the swimmers who then each performed four vertical skills under alternating conditions of vision and visual occlusion before and after either a swimming (designed to induce fatigue) or nonphysical activity. A main effect of activity (p < .03) was found for two measures of performance accuracy (lateral and anterior total distance traveled) but not for lateral and anterior maximum deviation from vertical, indicating that fatigue played a role in executing the skills. The data also indicate that the maintenance of a stationary position is a skill of greater difficulty than maintaining a true vertical. In contrast with previous research findings on synchronized swimmers, a significant effect of vision in all conditions was found, with performance decrements in the conditions of visual occlusion showing that vision provided important sensory input for the swimmers.

Motor unit synchronization of the vasti muscles in closed and open chain tasks

Objectives: To investigate motor unit synchronization between medial and lateral vasti and whether such synchronization differs in closed and open chain tasks. Design: Electromyographic recordings of single motor unit action potentials were made from the vastus medialis obliquus (VMO) and multiunit recordings from vastus lateralis during isometric contractions at 30 degrees of knee flexion in closed and open chain conditions. Setting: Laboratory. Participants: Five volunteers with no history of knee pain (age, 30 +/- 3.32y). Interventions: Not applicable. Main Outcome Measure: The degree of synchronization between motor unit firing was evaluated by identifying peaks in the electromyographic averages of the vastus lateralis, triggered from motor unit action potentials in the VMO, and the proportion of power in the power spectral density of the triggered average at the firing frequency of the reference motor unit. The proportion of cases in which there was significant power and peaks in the triggered averages was calculated. Results: The proportion of trials with peaks in the triggered averages of the vastus lateralis electromyographic activity was greater than 61.5% in all tasks, and there was a significantly greater proportion of cases where power in the spectrum was greater than 7.5% (P = .01) for the closed chain condition. Conclusions: There was a high proportion of synchronized motor units between the 2 muscles during isometric contractions, with evidence for greater common drive between the VMO and vastus lateralis in closed chain tasks. This has implications for rehabilitation because it suggests that closed chain tasks may generate better coordination between the vasti muscles.

Neural pathways mediating bilateral interactions between the upper limbs

The ease with which we perform tasks such as opening the lid of a jar, in which the two hands execute quite different actions, belies the fact that there is a strong tendency for the movements of the upper limbs to be drawn systematically towards one another. Mirror movements, involuntary contractions during intended unilateral engagement of the opposite limb, are considered pathological, as they occur in association with specific disorders of the CNS. Yet they are also observed frequently in normally developing children, and motor irradiation, an increase in the excitability of the (opposite) homologous motor pathways when unimanual movements are performed, is a robust feature of the mature motor system. The systematic nature of the interactions that occur between the upper limbs has also given rise to the expectation that functional improvements in the control of a paretic limb may occur when movements are performed in a bimanual context. In spite of the ubiquitous nature of these phenomena, there is remarkably little consensus concerning the neural basis of their mediation. In the present review, consideration is given to the putative roles of uncrossed corticofugal fibers, branched bilateral corticomotoroneuronal projections, and segmental networks. The potential for bilateral interactions to occur in various brain regions including the primary motor cortex, the supplementary motor area, non-primary motor areas, the basal ganglia, and the cerebellum is also explored. This information may provide principled bases upon which to evaluate and develop task and deficit-specific programs of movement rehabilitation and therapy. (c) 2005 Elsevier B.V. All rights reserved.

Are the changes in postural control associated with low back pain caused by pain interference?

Background: Voluntary limb movements are associated with involuntary and automatic postural adjustments of the trunk muscles. These postural adjustments occur prior to movement and prevent unwanted perturbation of the trunk. In low back pain, postural adjustments of the trunk muscles are altered such that the deep trunk muscles are consistently delayed and the superficial trunk muscles are sometimes augmented. This alteration of postural adjustments may reflect disruption of normal postural control imparted by reduced central nervous system resources available during pain, so-called pain interference, or reflect adoption of an alternate postural adjustment strategy. Methods: We aimed to clarify this by recording electromyographic activity of the upper (obliquus extemus) and lower (transversus abdominis/obliquus internus) abdominal muscles during voluntary arm movements that were coupled with painful cutaneous stimulation at the low back. If the effect of pain on postural adjustments is caused by pain interference, it should be greatest at the onset of the stimulus, should habituate with repeated exposure, and be absent immediately when the threat of pain is removed. Sixteen patients performed 30 forward movements of the right arm in response to a visual cue (control). Seventy trials were then conducted in which arm movement was coupled with pain (pain trials) and then a further 70 trials were conducted without the pain stimulus (no pain trials). Results: There was a gradual and increasing delay of transversus abdominis/obliquus internus electromyograph and augmentation of obliquus externus during the pain trials, both of which gradually returned to control values during the no pain trials. Conclusion: The results suggest that altered postural adjustments of the trunk muscles during pain are not caused by pain interference but are likely to reflect development and adoption of an alternate postural adjustment strategy, which may serve to limit the amplitude and velocity of trunk excursion caused by arm movement.

General self-concept and life satisfaction for boys with differing levels of physical coordination: The role of goal orientations and leisure participation

Participation in leisure-time activities, self-concept perceptions and individual dispositional goal orientations were examined as mediators of relationships between physical coordination and self-evaluations of life satisfaction and general self-concept for 173 boys aged 10-13 years. Participants completed seven-day activity diaries and 12-month retrospective recall questionnaires recording participation in leisure-time activities. Self-report measures of self-concept, global life satisfaction and dispositional goal orientations were also completed. Results showed that boys with moderate to severe physical coordination difficulties had significantly lower self-concept perceptions of physical ability and appearance, peer and parent relations and general self-concept, as well as lower life satisfaction than boys with medium to high levels of physical coordination. The relationships between boys' physical coordination and their self-perceptions of life satisfaction and general self-concept were significantly influenced by individual self-concept appraisals of physical ability and appearance, peer and parent relations. Adopting task-oriented goals was found to positively change the relationship between physical coordination and both general self-concept and life satisfaction. Team sport participation positively mediated the relationship between physical coordination and life satisfaction. The potential for team sport participation and adoption of task-oriented goals to influence life satisfaction for boys with differing levels of physical coordination was discussed. (c) 2006 Elsevier B.V.. All rights reserved.

Molecular control of cell type diversity in the developing spinal cord

1, During embryonic development, a diverse array of neurons and glia are generated at specific positions along the dorsoventral and rostro-caudal axes of the spinal cord from a common pool of precursor cells. 2. This cell type diversity can be distinguished by the spatially and temporally coordinated expression of several transcription factors that are also linked to cell type specification at a very early stage of spinal cord development. 3, Recent studies have started to uncover that the generation of cell type diversity in the developing spinal cord. Moreover, distinct cell types in the spinal cord appear to be determined by the spatially and temporally coordinated expression of transcription factors. 4. The expression of these factors also appears to be controlled by gradients of factors expressed by ventral and dorsal midline cells, namely Sonic hedgehog and members of the transforming growth factor-beta family. 5, Changes in the competence of precursor cells and local cell interactions may also play important roles in cell type specification within the developing spinal cord.

Multi-robot control in highly dynamic, competitive environments

The control and coordination of multiple mobile robots is a challenging task; particularly in environments with multiple, rapidly moving obstacles and agents. This paper describes a robust approach to multi-robot control, where robustness is gained from competency at every layer of robot control. The layers are: (i) a central coordination system (MAPS), (ii) an action system (AES), (iii) a navigation module, and (iv) a low level dynamic motion control system. The multi-robot coordination system assigns each robot a role and a sub-goal. Each robot’s action execution system then assumes the assigned role and attempts to achieve the specified sub-goal. The robot’s navigation system directs the robot to specific goal locations while ensuring that the robot avoids any obstacles. The motion system maps the heading and speed information from the navigation system to force-constrained motion. This multi-robot system has been extensively tested and applied in the robot soccer domain using both centralized and distributed coordination.

The functional impact of developmental co-ordination disorder during adolescence and early adult life

PURPOSE: The purpose of this study was to increase the understanding of the functional impact that coordination problems have during adolescence and early adult life. In particular, this study aimed to investigate the impact coordination deficits have on day-to-day functioning, activity levels, self-concept with respect to coordination, leisure pursuits, occupational types, accidents and injuries, as well as experiences learning to drive. RELEVANCE: This study may enable clinicians to identify at risk situations, such that appropriate prevention and targeting of treatment can occur. SUBJECTS: The participants involved in this study comprised two groups; 40 subjects previously diagnosed with DCD, and their matched controls. METHODS: Participants were initially contacted by mail for their consent to the study. Consenting participants were then contacted via telephone, and interviewed. ANALYSES: Data analysis was performed using SPSS. Chi squared analysis and Mann Whitney U test was also used to compare groups. RESULTS: During both age periods, the number of DCD subjects participating in sport was significantly less than the number of controls. Although in the 12-14 years age category, the two groups displayed similar results for the type of sport chosen, the 18 – 20 years age group, showed significant differences, with the number of DCD subjects participating in High level coordination activities, being significantly less than controls. Self-perception with respect to coordination was also significantly different amongst groups with more DCD subjects, having perceived themselves as being clumsy. Similarly, a significantly greater number of DCD subjects admitted to tripping over themselves regularly. Some differences have also been noted in the experiences of subjects learning to drive. First, the number of DCD subjects, who had difficulties learning to drive was significantly greater than controls. Second, a much greater number of Control subjects, compared to DCD subjects were successful in obtaining drivers license. Finally, also of interest is the 58% of DCD subjects who have experienced an accident whilst driving, compared to the 35% of controls. The last result of this study was that whilst there was no significant difference between groups, in the number of broken bones, dislocated joints, sprain, burns, stitches, or other significant injuries, the number of control subjects suffering muscle strains was significantly greater than the number of DCD subjects. CONCLUSION: The results of this study indicate that DCD has many implications on day-to-day functioning, both in adolescence and early adulthood. Findings have shown despite the significant sensory-motor deficits displayed by DCD subjects, the impact that this has on day-to-day functioning may be reduced by lifestyle modification.