Bimanual coordination: constraints imposed by the relative timing of homologous muscle activation

It has often been supposed that patterns of rhythmic bimanual coordination in which homologous muscles are engaged simultaneously, are performed in a more stable manner than those in which the same muscles are activated in an alternating fashion. In order to assess the efficacy of this constraint, the present study investigated the effect of forearm posture (prone or supine) on bimanual abduction-adduction movements of the wrist in isodirectional and non-isodirectional modes of coordination. Irrespective of forearm posture, non-isodirectional coordination was observed to be more stable than isodirectional coordination. In the latter condition, there was a more severe deterioration of coordination accuracy/stability as a function of cycling frequency than in the former condition. With elevations in cycling frequency, the performers recruited extra mechanical degrees of freedom, principally via flexion-extension of the wrist, which gave rise to increasing motion in the vertical plane. The increases in movement amplitude in the vertical plane were accompanied by decreasing amplitude in the horizontal plane. In agreement with previous studies, the present findings confirm that the relative timing of homologous muscle activation acts as a principal constraint upon the stability of interlimb coordination. Furthermore, it is argued that the use of manipulations of limb posture to investigate the role of other classes of constraint (e.g. perceptual) should be approached with caution because such manipulations affect the mapping between muscle activation patterns, movement dynamics and kinematics.

Bimanual aiming and overt attention: one law for two hands

Reaching to interact with an object requires a compromise between the speed of the limb movement and the required end-point accuracy. The time it takes one hand to move to a target in a simple aiming task can be predicted reliably from Fitts' law, which states that movement time is a function of a combined measure of amplitude and accuracy constraints (the index of difficulty, ID). It has been assumed previously that Fitts' law is violated in bimanual aiming movements to targets of unequal ID. We present data from two experiments to show that this assumption is incorrect: if the attention demands of a bimanual aiming task are constant then the movements are well described by a Fitts' law relationship. Movement time therefore depends not only on ID but on other task conditions, which is a basic feature of Fitts' law. In a third experiment we show that eye movements are an important determinant of the attention demands in a bimanual aiming task. The results from the third experiment extend the findings of the first two experiments and show that bimanual aiming often relies on the strategic co-ordination of separate actions into a seamless behaviour. A number of the task specific strategies employed by the adult human nervous system were elucidated in the third experiment. The general strategic pattern observed in the hand trajectories was reflected by the pattern of eye movements recorded during the experiment. The results from all three experiments demonstrate that eye movements must be considered as an important constraint in bimanual aiming tasks.

Interaction of directional, neuromuscular and egocentric constraints on the stability of preferred bimanual coordination patterns

We investigated how the relative direction of limb movements in external space (iso- and non-isodirectionality), muscular constraints (the relative timing of homologous muscle activation) and the egocentric frame of reference (moving simultaneously toward/away the longitudinal axis of the body) contribute to the stability of coordinated movements. In the first experiment, we attempted to determine the respective stability of isodirectional and non-isodirectional movements in between-persons coordination. In a second experiment, we determined the effect of the relative direction in external space, and of muscular constraints, on pattern stability during a within-person bimanual coordination task. In the third experiment we dissociated the effects on pattern stability of the muscular constraints, relative direction and egocentric frame of reference. The results showed that (1) simultaneous activation of homologous muscles resulted in more stable performance than simultaneous activation of non-homologous muscles during within-subject coordination, and that (2) isodirectional movements were more stable than non-isodirectional movements during between-persons coordination, confirming the role of the relative direction of the moving limbs in the stability of bimanual coordination. Moreover, the egocentric constraint was to some extent found distinguishable from the effect of the relative direction of the moving limbs in external space, and from the effect of the relative timing of muscle activation. In summary, the present study showed that relative direction of the moving limbs in external space and muscular constraints may interact either to stabilize or destabilize coordination patterns. (C) 2003 Published by Elsevier B.V.

Let your feet do the walking: constraints on the stability of bipedal coordination

In this paper we consider whether the behaviour of the neural circuitry that controls lower limb movements in humans is shaped primarily by the spatiotemporal characteristics of bipedal gait patterns, or by selective pressures that are sensitive to considerations of balance and energetics. During the course of normal locomotion, the full dynamics of the neural circuitry are masked by the inertial properties of the limbs. In the present study, participants executed bipedal movements in conditions in which their feet were either unloaded or subject to additional inertial loads. Two patterns of rhythmic coordination were examined. In the in-phase mode, participants were required to flex their ankles and extend their ankles in synchrony. In the out-of-phase mode, the participants flexed one ankle while extending the other and vice versa. The frequency of movement was increased systematically throughout each experimental trial. All participants were able to maintain both the in-phase and the out-of-phase mode of coordination, to the point at which they could no longer increase their frequency of movement. Transitions between the two modes were not observed, and the stability of the out-of-phase and in-phase modes of coordination was equivalent at all movement frequencies. These findings indicate that, in humans, the behaviour of the neural circuitry underlying coordinated movements of the lower limbs is not constrained strongly by the spatiotemporal symmetries of bipedal gait patterns.

The rotational broadening of V395 Carinae. Implications on the compact object's mass

Context: The masses previously obtained for the X-ray binary 2S 0921-630 inferred a compact object that was either a high-mass neutron star or low-mass black-hole, but used a previously published value for the rotational broadening (v sin i) with large uncertainties. Aims: We aim to determine an accurate mass for the compact object through an improved measurement of the secondary star's projected equatorial rotational velocity. Methods: We have used UVES echelle spectroscopy to determine the v sin i of the secondary star (V395 Car) in the low-mass X-ray binary 2S 0921-630 by comparison to an artificially broadened spectral-type template star. In addition, we have also measured v sin i from a single high signal-to-noise ratio absorption line profile calculated using the method of Least-Squares Deconvolution (LSD). Results: We determine v sin i to lie between 31.3±0.5 km s-1 to 34.7±0.5 km s-1 (assuming zero and continuum limb darkening, respectively) in disagreement with previous results based on intermediate resolution spectroscopy obtained with the 3.6 m NTT. Using our revised v sin i value in combination with the secondary star's radial velocity gives a binary mass ratio of 0.281±0.034. Furthermore, assuming a binary inclination angle of 75° gives a compact object mass of 1.37±0.13 M_?. Conclusions: We find that using relatively low-resolution spectroscopy can result in systemic uncertainties in the measured v sin i values obtained using standard methods. We suggest the use of LSD as a secondary, reliable check of the results as LSD allows one to directly discern the shape of the absorption line profile. In the light of the new v sin i measurement, we have revised down the compact object's mass, such that it is now compatible with a canonical neutron star mass.

HOX genes: seductive science, mysterious mechanisms

HOX genes are evolutionarily highly conserved. The HOX proteins which they encode are master regulators of embryonic development and continue to be expressed throughout postnatal life. The 39 human HOX genes are located in four clusters (A-D) on different chromosomes at 7p15, 17q21 [corrected] 12q13, and 2q31 respectively and are assumed to have arisen by duplication and divergence from a primordial homeobox gene. Disorders of limb formation, such as hand-foot-genital syndrome, have been traced to mutations in HOXA13 and HOXD13. Evolutionary conservation provides unlimited scope for experimental investigation of the functional control of the Hox gene network which is providing important insights into human disease. Chromosomal translocations involving the MLL gene, the human homologue of the Drosophila gene trithorax, create fusion genes which exhibit gain of function and are associated with aggressive leukaemias in both adults and children. To date 39 partner genes for MLL have been cloned from patients with leukaemia. Models based on specific translocations of MLL and individual HOX genes are now the subject of intense research aimed at understanding the molecular programs involved, and ultimately the design of chemotherapeutic agents for leukaemia. Investigation of the role of HOX genes in cancer has led to the concept that oncology may recapitulate ontology, a challenging postulate for experimentalists in view of the functional redundancy implicit in the HOX gene network.

The pathophysiology of HOX genes and their role in cancer

The HOM-C clustered prototype homeobox genes of Drosophila, and their counterparts, the HOX genes in humans, are highly conserved at the genomic level. These master regulators of development continue to be expressed throughout adulthood in various tissues and organs. The physiological and patho-physiological functions of this network of genes are being avidly pursued within the scientific community, but defined roles for them remain elusive. The order of expression of HOX genes within a cluster is co-ordinated during development, so that the 3' genes are expressed more anteriorly and earlier than the 5' genes. Mutations in HOXA13 and HOXD13 are associated with disorders of limb formation such as hand-foot-genital syndrome (HFGS), synpolydactyly (SPD), and brachydactyly. Haematopoietic progenitors express HOX genes in a pattern characteristic of the lineage and stage of differentiation of the cells. In leukaemia, dysregulated HOX gene expression can occur due to chromosomal translocations involving upstream regulators such as the MLL gene, or the fusion of a HOX gene to another gene such as the nucleoporin, NUP98. Recent investigations of HOX gene expression in leukaemia are providing important insights into disease classification and prediction of clinical outcome. Whereas the oncogenic potential of certain HOX genes in leukaemia has already been defined, their role in other neoplasms is currently being studied. Progress has been hampered by the experimental approach used in many studies in which the expression of small subsets of HOX genes was analysed, and complicated by the functional redundancy implicit in the HOX gene system. Attempts to elucidate the function of HOX genes in malignant transformation will be enhanced by a better understanding of their upstream regulators and downstream target genes.

Under-water scene investigation using ground penetrating radar (GPR) in the search for a sunken jet ski, Northern Ireland

A search for a submerged jet ski and the lost limb of its driver involved in a collision with a speedboat was made in a shallow lake in Northern Ireland. The location of both was crucial to establishing events at the time of the accident. Local intelligence suggested both objects were likely to be partially-buried by lacustrine silt. To avoid sediment churning, this required non-invasive, completely non-destructive assessment and mapping of the scene. A MALA RAMAC ground-penetrating radar system (GPR) mounted on floats for surveying from walkways and jetties or placed in a small rubber dinghy for offshore profiling was used. A grid was established and each line surveyed with 100, 200 and 400MHz antennae. In waters over 6m deep GPR data showed the form of the lake floor but excessive ringing occurred in the data. In waters less than 6m deep ringing diminished on both 100 and 200MHz data, the latter displaying the best trade-off between depth penetration and horizontal object resolution. 400MHz data failed to be of use in waters over 2m deep and at these depths showed only limited improvement of image quality compared to 200MHz data. Surface objects such as a wooden walkway caused interference on 200 and 400MHz data when antennae were oriented both normal and parallel to survey direction; this may be a function of the low attenuation of radar waves in freshwater, allowing excellent lateral and vertical radar wave penetration. On 200MHz data the damaged jet-ski was clearly imaged in a location that contradicted the speedboat driver's account of the accident.

Training-induced changes in the pattern of triceps to biceps activation during reaching tasks after chronic and severe stroke

This exploratory study was undertaken to investigate the mechanisms that contributed to improvements in upper limb function following a novel training program. Surface electromyography (EMG) was used to examine training-induced changes in the pattern of triceps and biceps activation during reaching tasks in stroke survivors with severe paresis in the chronic stage of recovery. The EMG data were obtained in the context of a single blind randomised clinical trial conducted with 42 stroke survivors with minimal upper limb muscle activity and who were more than 6 months post-stroke. Of the 33 participants who completed the study, 10 received training of reaching using a non-robotic upper limb training device, the SMART Arm, with EMG triggered functional electrical stimulation (EMG-stim), 13 received training of reaching using the SMART Arm alone, and 10 received no intervention. Each intervention group engaged in 12 1-h training sessions over a 4-week period. Clinical and laboratory measures of upper limb function were administered prior to training (0 weeks), at completion (4 weeks) and 2 months (12 weeks) after training. The primary outcome measure was 'upper arm function' which is Item 6 of the Motor Assessment Scale (MAS). Laboratory measures consisted of two multijoint reaching tasks to assess 'maximum isometric force' and 'maximum distance reached'. Surface EMG was used to monitor triceps brachii and biceps brachii during the two reaching tasks. To provide a comparison with normal values, seven healthy adults were tested on one of the reaching tasks according to the same procedure. Study findings demonstrated a statistically significant improvement in upper limb function for stroke participants in the two training groups compared to those who received no training however no difference was found between the two training groups. For the reaching tasks, all stroke participants, when compared to normal healthy adults, exhibited lower triceps and biceps activation and a lower ratio of triceps to biceps activation. Following training, stroke participants demonstrated increased triceps activation and an increased ratio of triceps to biceps activation for the task that was trained. Better performance was associated with greater triceps activation and a higher ratio of triceps to biceps activation. The findings suggest that increased activation of triceps as an agonist and an improved coordination between triceps and biceps could have mediated the observed changes in arm function. The changes in EMG activity were small relative to the changes in arm function indicating that factors, such as the contribution of other muscles of reaching, may also be implicated.

Artificial gravity reveals that economy of action determines the stability of sensorimotor coordination.

Background
When we move along in time with a piece of music, we synchronise the downward phase of our gesture with the beat. While it is easy to demonstrate this tendency, there is considerable debate as to its neural origins. It may have a structural basis, whereby the gravitational field acts as an orientation reference that biases the formulation of motor commands. Alternatively, it may be functional, and related to the economy with which motion assisted by gravity can be generated by the motor system.
Methodology/Principal Findings
We used a robotic system to generate a mathematical model of the gravitational forces acting upon the hand, and then to reverse the effect of gravity, and invert the weight of the limb. In these circumstances, patterns of coordination in which the upward phase of rhythmic hand movements coincided with the beat of a metronome were more stable than those in which downward movements were made on the beat. When a normal gravitational force was present, movements made down-on-the-beat were more stable than those made up-on-the-beat.
Conclusions/Significance
The ubiquitous tendency to make a downward movement on a musical beat arises not from the perception of gravity, but as a result of the economy of action that derives from its exploitation.

Kinematic Design of a 6-DOF Parallel Manipulator with Decoupled Translation and Rotation

A new three-limb, six-degree-of-freedom (DOF) parallel manipulator (PM), termed a selectively actuated PM (SA-PM), is proposed. The end-effector of the manipulator can produce 3-DOF spherical motion, 3-DOF translation, 3-DOF hybrid motion, or complete 6-DOF spatial motion, depending on the types of the actuation (rotary or linear) chosen for the actuators. The manipulator architecture completely decouples translation and rotation of the end-effector for individual control. The structure synthesis of SA-PM is achieved using the line geometry. Singularity analysis shows that the SA-PM is an isotropic translation PM when all the actuators are in linear mode. Because of the decoupled motion structure, a decomposition method is applied for both the displacement analysis and dimension optimization. With the index of maximal workspace satisfying given global conditioning requirements, the geometrical parameters are optimized. As a result, the translational workspace is a cube, and the orientation workspace is nearly unlimited.

Does the level of graphical detail of a virtual handball thrower influence a goal-keeper's motor response?

The authors investigated how different levels of detail (LODs) of a virtual throwing action can influence a handball goalkeeper's motor response. Goalkeepers attempted to stop a virtual ball emanating from five different graphical LODs of the same virtual throwing action. The five levels of detail were: a textured reference level (L0), a non-textured level (L1), a wire-frame level (L2), a point-light-display (PLD) representation (L3) and a PLD level with reduced ball size (L4). For each motor response made by the goalkeeper we measured and analyzed the time to respond (TTR), the percentage of successful motor responses, the distance between the ball and the closest limb (when the stopping motion was incorrect) and the kinematics of the motion. Results showed that TTR, percentage of successful motor responses and distance with the closest limb were not significantly different for any of the five different graphical LODs. However the kinematics of the motion revealed that the trajectory of the stopping limb was significantly different when comparing the L1 and L3 levels, and when comparing the L1 and L4 levels. These differences in the control of the goalkeeper's actions suggests that the different level of information available in the PLD representations ( L3 and L4) are causing the goalkeeper to adopt different motor strategies to control the approach of their limb to stop the ball.

Real-time error detection but not error correction drives automatic visuomotor adaptation

We investigated the role of visual feedback of task performance in visuomotor adaptation. Participants produced novel two degrees of freedom movements (elbow flexion-extension, forearm pronation-supination) to move a cursor towards visual targets. Following trials with no rotation, participants were exposed to a 60A degrees visuomotor rotation, before returning to the non-rotated condition. A colour cue on each trial permitted identification of the rotated/non-rotated contexts. Participants could not see their arm but received continuous and concurrent visual feedback (CF) of a cursor representing limb position or post-trial visual feedback (PF) representing the movement trajectory. Separate groups of participants who received CF were instructed that online modifications of their movements either were, or were not, permissible as a means of improving performance. Feedforward-mediated performance improvements occurred for both CF and PF groups in the rotated environment. Furthermore, for CF participants this adaptation occurred regardless of whether feedback modifications of motor commands were permissible. Upon re-exposure to the non-rotated environment participants in the CF, but not PF, groups exhibited post-training aftereffects, manifested as greater angular deviations from a straight initial trajectory, with respect to the pre-rotation trials. Accordingly, the nature of the performance improvements that occurred was dependent upon the timing of the visual feedback of task performance. Continuous visual feedback of task performance during task execution appears critical in realising automatic visuomotor adaptation through a recalibration of the visuomotor mapping that transforms visual inputs into appropriate motor commands.

Hyperglycaemia-induced pro-inflammatory responses by retinal Müller glia are regulated by the receptor for advanced glycation end-products (RAGE)

Aims/hypothesis: Up-regulation of the receptor for AGEs (RAGE) and its ligands in diabetes has been observed in various tissues. Here, we sought to determine levels of RAGE and one of its most important ligands, S100B, in diabetic retina, and to investigate the regulatory role of S100B and RAGE in Müller glia.

Methods: Streptozotocin-diabetes was induced in Sprague-Dawley rats. RAGE, S100B and glial fibrillary acidic protein (GFAP) were detected in retinal cryosections. In parallel, the human retinal Müller cell line, MIO-M1, was maintained in normal glucose (5.5 mmol/l) or high glucose (25 mmol/l). RAGE knockdown was achieved using small interfering RNA (siRNA), while soluble RAGE was used as a competitive inhibitor of RAGE ligand binding. RAGE, S100B and cytokines were detected using quantitative RT-PCR, western blotting, cytokine protein arrays or ELISA. Activation of mitogen-activated protein kinase (MAPK) by RAGE was determined by western blotting.

Results: Compared with non-diabetic controls, RAGE and S100B were significantly elevated in the diabetic retina with apparent localisation in the Müller glia, occurring concomitantly with upregulation of GFAP. Exposure of MIO-M1 cells to high glucose induced increased production of RAGE and S100B. RAGE signalling via MAPK pathway was linked to cytokine production. Blockade of RAGE prevented cytokine responses induced by high glucose and S100B in Müller glia.

Conclusions/interpretation: Hyperglycaemia in vivo and in vitro exposure to high glucose induce upregulation of RAGE and its ligands, leading to RAGE signalling, which links to pro-inflammatory responses by retinal Müller glia. These data shed light on the potential clinical application of RAGE blockade to inhibit the progression of diabetic retinopathy.

Allelic depletion of grem1 attenuates diabetic kidney disease.

OBJECTIVE: Gremlin (grem1) is an antagonist of the bone morphogenetic protein family that plays a key role in limb bud development and kidney formation. There is a growing appreciation that altered grem1 expression may regulate the homeostatic constraints on damage responses in diseases such as diabetic nephropathy. RESEARCH DESIGN AND METHODS: Here we explored whether knockout mice heterozygous for grem1 gene deletion (grem1(+/-)) exhibit protection from the progression of diabetic kidney disease in a streptozotocin-induced model of type 1 diabetes. RESULTS: A marked elevation in grem1 expression was detected in the kidneys and particularly in kidney tubules of diabetic wild-type mice compared with those of littermate controls. In contrast, diabetic grem1(+/-) mice displayed a significant attenuation in grem1 expression at 6 months of diabetes compared with that in age- and sex-matched wild-type controls. Whereas the onset and induction of diabetes were similar between grem1(+/-) and wild-type mice, several indicators of diabetes-associated kidney damage such as increased glomerular basement membrane thickening and microalbuminuria were attenuated in grem1(+/-) mice compared with those in wild-type controls. Markers of renal damage such as fibronectin and connective tissue growth factor were elevated in diabetic wild-type but not in grem1(+/-) kidneys. Levels of pSmad1/5/8 decreased in wild-type but not in grem1(+/-) diabetic kidneys, suggesting that bone morphogenetic protein signaling may be maintained in the absence of grem1. CONCLUSIONS: These data identify grem1 as a potential modifier of renal injury in the context of diabetic kidney disease.