Biomechanical and electromyogram characterization of neuroleptic-induced rigidity in the rat.

Rodent models of Parkinson's disease (PD) are usually assessed using measures of akinesia, but other important parkinsonian symptoms such as rigidity are only rarely quantified. This is in part due to technical difficulties in obtaining such measures in small animals. In the present study we developed quantitative methods to provide time-course assessment of the alternations of muscle tone of parkinsonian rats. A portable and miniature biomechanical stretching device was established to manually stretch the hindlimb of awake rats with muscle rigidity induced by dopamine D2-receptor antagonist raclopride (5 mg/kg, i.p.). From the measured angular displacement angle and reactive torque of sinusoidal stretches at five varied frequencies, viscoelastic components of the muscle tone can be derived. In addition, non-invasive multielectrode was applied to record the tonic and phasic components of the gastrocnemius muscle electromyogram (EMG). Our biomechanical measurements showed not only increase in stiffness (P<0.05) but also increase in viscous components (P<0.05) that matched the time course of increased amplitude of EMG activity (P<0.05). There was a significant positive correlation between all of these measures and akinesia, as measured by the conventional bar-test for catalepsy (with a correlation coefficient of 0.87 at stiffness, 0.92 at viscosity and 0.96 at amplitude of EMG). Phasic contraction counts (PCC) of voluntary EMG exhibited a significantly negative correlation with the bar test scores (correlation coefficient=-0.78). These results confirm that akinesia induced by D2-receptor blockade also induces a rigidity that shares many features with human PD. These novel techniques for quantifying biomechanical and electromyographic parameters provide objective assessment methods for investigating the time-course changes of abnormal muscle tone in rat models of PD that will be useful for evaluating novel treatments.

Differing properties of putative fast-spiking interneurons in the striatum of two rat strains.

Local circuits within the striatum of the basal ganglia include a small number of γ-aminobutyric acid (GABA)-ergic fast-spiking interneurons (FSI). The number of these cells is reduced in disorders of behavioral control, but it is unknown whether this is accompanied by altered electrophysiological properties. The genetically hypertensive (GH) rat strain exhibits impulsiveness and hyperactivity. We investigated if resting-state FSI activity is affected in this strain using extracellular recordings. We also examined the effect of systemic amphetamine (AMPH), a stimulant drug used in the treatment of these particular behavioral deficits. Putative FSI (pFSI) were encountered less often in GH rats compared to the Wistar control strain. pFSI in GH rats also exhibited a higher mean firing rate, higher intraburst firing rate, lower interburst interval, and shorter bursts compared to controls. AMPH increased the mean overall firing rate of Wistar rat pFSI but did not significantly alter the firing properties of this subtype in GH rats. These differences in the resting-state electrophysiological activity of pFSI in GH rats point to them as a cell type of particular interest in understanding striatal functioning across different strains.

The migration of activated T lymphocytes in vitro. III. Paralysis and recovery of locomotor function during mitosis.

Previous reports have stated that activated lymphocytes are more motile than unsensitized lymphocytes and that certain subpopulations of lymphocytes are more motile than others. In order to determine at what stage of activation lymphocytes become motile, we have examined lymphocyte motility as well as other functions at various times after mitogenic or allogeneic stimulation in culture. Lymphocytes cultured with concanavalin A (Con A) or with alloantigen become most motile after peak thymidine incorporation has occurred. Allosensitized lymphocytes need not possess cytolytic capacity in order to become motile. Allosensitized lymphocytes retain the ability to locomote at near maximal rates for at least 2 weeks after stimulation. When these motile, allosensitized lymphocytes are recultured in the presence of fresh irradiated stimulator cells, they lose their ability to locomote during active thymidine incorporation and become motile again when thymidine incorporation has abated. Lymphocyte clones demonstrated motility cycles similar to cycles observed with bulk cultures (i.e., peak motility is observed only after peak thymidine incorporation has occurred in the subculture). All T lymphocyte clones tested are motile, regardless of Lyt phenotype or function, if tested for motility on the appropriate day of subculture. Studies of clone motility at intervals less than 24 hr after restimulation revealed that motility ceased before tritiated thymidine uptake occurred. The migratory potential of lymphocytes in vitro does not seem to depend on phenotype or the nature of the mitogenic stimulus. It seems instead to be part of the cyclic response of the cell to activation, with early inhibition of motility and subsequent recovery of locomotor function. Whether ability to locomote is intrinsic to the activated cell or depends on environmental factors requires further investigation.

Neuronal activity in rat red nucleus during forelimb reach-to-grasp movements.

The activity of 259 task-related red nucleus neurons was recorded using chronic electrophysiological methods in free moving rats. Modulations in activity were analysed in relation to onset (first detected wrist movement) and end (arrival of the paw over the food) of a reach-to-grasp movement. Excitatory peaks were found to begin before, during and after the reach, but there were clear peaks in the distribution of onset times after reach-onset and before reach-end, reflecting the fact that one third of all peaks began specifically during the reach, although this occupied only a small fraction of the analysis time. Both excitations and inhibitions showed a strong tendency to end in close temporal association with reach-end. Analysis of excitatory modulation amplitudes showed that the largest peaks were formed when data was aligned to reach-end, and that these largest peaks nearly all began during the reach and ended precisely at the time the paw would have been about to grasp the food. The spread of neural activation onset times throughout the course of the complex reach-to-grasp movement is consistent with a relationship of individual neurons in the rat red nucleus with movements of all parts of the forelimb, as would be expected if all limb muscle groups are represented in the nucleus. On the other hand the disproportionate number of modulations that occur during the reach and their strong alignment with time of reach-end suggests there is a bias in red nucleus function towards the control of distal motions associated with accurate grasp, consistent with the result of recent lesion studies. This provides indirect evidence that functionally the rat red nucleus may be organized in a similar way to that of monkeys, in which an important role in control of accurate distal movements is well established. The possibility is discussed that red nucleus offers a timing signal for co-ordination of movements across joints, in particular the precise distal-proximal binding normally seen in accurate reach-to-grasp movements.

Firing modes of midbrain dopamine cells in the freely moving rat.

There is a large body of data on the firing properties of dopamine cells in anaesthetised rats or rat brain slices. However, the extent to which these data relate to more natural conditions is uncertain, as there is little quantitative information available on the firing properties of these cells in freely moving rats. We examined this by recording from the midbrain dopamine cell fields using chronically implanted microwire electrodes. (1) In most cases, slowly firing cells with broad action potentials were profoundly inhibited by the dopamine agonist apomorphine, consistent with previously accepted criteria. However, a small group of cells was found that were difficult to classify because of ambiguous combinations of properties. (2) Presumed dopamine cells could be divided into low and high bursting (>40% of their spikes in bursts) groups, with the majority having low bursting rates. The distribution of burst incidence was similar to that previously reported with chloral hydrate anaesthesia, but the average intraburst frequency was higher in the conscious animal at rest and was higher again in bursts triggered by salient stimuli. (3) There was no evidence for spike frequency adaptation within bursts on average, consistent with the hypothesis that afterhyperpolarisation currents may be disabled during behaviourally induced bursting. (4) Presumed dopamine cells responded to reward-related stimuli with increased bursting rates and significantly higher intraburst frequencies compared to bursts emitted outside task context, indicating that modulation of afferent activity might not only trigger bursting, but may also regulate burst intensity. (5) In addition to the irregular single spike and bursting modes we found that extremely regular (clock-like) firing, previously only described for dopamine cells in reduced preparations, can also be expressed in the freely moving animal. (6) Cross-correlation analysis of activity recorded from simultaneously recorded neurones revealed coordinated activity in a quarter of dopamine cell pairs consistent with at least "functional" connectivity. On the other hand, most dopamine cell pairs showed no correlation, leaving open the possibility of functional sub-groupings within the dopamine cell fields. Taken together, the data suggest that the basic firing modes described for dopamine cells in reduced or anaesthetised preparations do reflect natural patterns of activity for these neurones, but also that the details of this activity are dependent upon modulation of afferent inputs by behavioural stimuli.

Effects of lesions in the mesial frontal cortex on bimanual co-ordination in monkeys.

The hypothesis was tested that the mesial frontal cortex, including the supplementary motor area, is engaged in bimanual co-ordination. Three monkeys, trained in a well-co-ordinated bimanual pull-and-grasp task, were subjected to unilateral or bilateral lesions of the mesial frontal cortex. With unilateral lesions, the deficit consisted in a delay in movement initiation of the contralateral arm. With a bilateral lesion, the deficit was more pronounced with marked bilateral delays in movement onset and slowing in reaching. However, in the three monkeys bimanual co-ordination at the moment of goal achievement remained intact with an excellent temporal co-variation of the two limbs. In the two unilateral cases, an adaptive strategy developed after a few sessions, either by catching up during reaching with the limb contralateral to the lesion (monkey M1) or by delaying movement initiation of the limb ipsilateral to the lesion (monkey M2). This outcome is discussed in terms of Lashley's principle of motor equivalence, i.e. invariant goal achievement with variable means. Bilateral lesions led to a transient and near-total impairment in movement self-initiation when all external cues were absent. It is concluded that in monkeys the mesial frontal cortex does not play a crucial role in bimanual co-ordination but rather in movement initiation, especially when sensory cues are absent.

Neural activity of supplementary and primary motor areas in monkeys and its relation to bimanual and unimanual movement sequences.

A chronic single-unit study of motor cortical activity was undertaken in two monkeys trained to perform a bimanually coordinated task. The hypothesis was tested that the supplementary motor area plays a specific role in coordinating the two hands for common goal-oriented actions. With this objective, a special search was made for neurons that might exhibit properties exclusively related to bimanual task performance. Monkeys learned to reach for and to pull open a spring-loaded drawer with one hand, while the other hand reached out to grasp food from the drawer recess. The two hands were precisely coordinated for achievement of this goal. Monkeys also performed, in separate blocks of trials, only the pulling or grasping movements, using the same hands as in the bimanual task. Task-related activity of 348 neurons from the supplementary motor area and 341 neurons from the primary motor area, each examined in the bimanual and in both unimanual tasks, was recorded in the two hemispheres. Most neurons from the supplementary motor area were recorded within its caudal microexcitable portion. Contrary to expectation, the proportion of neurons with activity patterns related exclusively to the bimanual task was small, but somewhat higher in the supplementary motor area (5%) than in the primary motor cortex (2%). Another group of neurons that were equally modulated during the bimanual as well as to both unimanual task components might also contribute in controlling bimanual actions. Such "task-dependent" rather than "effector-dependent" activity patterns were more common in neurons of the supplementary motor area (19%) than of the primary motor cortex (5%). Bilateral receptive fields were also more numerous among the supplementary motor area neurons. However, a large majority of neurons from primary and supplementary motor areas had activity profiles clearly related only to contralateral hand movements (65% in the primary motor and 51% in the supplementary motor area). A similar group of neurons showed an additional slight modulation with ipsilateral movements; they were equally common in the two areas (14% and 16%, respectively) and their significance for bimanual coordination is questionable. Summed activity profiles of all neurons recorded in the primary and supplementary motor areas of the same hemisphere were compared. The modulations of the three histograms, corresponding to the two unimanual and the bimanual tasks, were similar for the two motor areas, i.e. prominent with bimanual and contralateral movements and weak with ipsilateral movements. It is concluded that the supplementary motor area is likely to contribute to bimanual coordination, perhaps more than the primary motor cortex, but that it is not a defining function for the former cortical area. Instead, it is suggested that the supplementary motor area is part of a callosally interconnected and distributed network of frontal and parietal cortical areas that together orchestrate bimanual coordination.

What is the role of the supplementary motor area in movement initiation?

The hierarchical position of the supplementary motor area (SMA) relative to the primary motor cortex is discussed on the basis of neurological observations and of animal experiments. In the last 10 years evidence has accumulated, especially from studies on the human brain, that the supplementary motor area is a hierarchically superior structure involved in the processes of movement initiation. Single unit studies in subhuman primates also revealed neuronal populations related to aspects of movement preparation rather than to the movement per se. However, we report that a surprisingly large subpopulation of SMA neurones has features classically found in the primary motor cortex (MI). These MI-like neurones precede movement onset by a relatively short interval. The occurrence of such "short-lead neurones" was somewhat higher in MI, but the histograms of lead-times were completely overlapping in the two areas. Taken together with the fact that the SMA is microexcitable and is part of the origin of the pyramidal tract, these findings suggest that the SMA functions also in parallel with MI as concluded by Woolsey and coworkers (1952). Finally, the SMA and MI are reciprocally interconnected, a situation which is not unlike that of the cortical visual areas.

Further characterization of Kupffer cell/macrophage-mediated alterations in hepatocyte protein synthesis.

Alterations in hepatic function are seen in sepsis or multiple-system organ failure. We have hypothesized that Kupffer cells (KCs) within the liver alter the function of contiguous hepatocytes after exposure to septic stimuli. Using an in vitro coculture system, we have found that lipopolysaccharide (LPS) induced a 40% to 60% decrease in cocultured hepatocyte protein synthesis but had no effect on hepatocytes alone. Coculture in the absence of LPS resulted in enhanced hepatocyte protein synthesis proportional to the number of KCs or macrophages (M0s). Conditioned medium (CM) from LPS-triggered coculture or KC alone decreased protein synthesis of hepatocytes whereas CM from hepatocytes alone had no effect. Gel filtration of active M0-CM showing maximal hepatocyte inhibitory activity was present in fractions between 15,000 and 30,000 daltons. This inhibitory activity was inactivated by exposure to 65 degrees C for 30 minutes. Although CM from untriggered M0 did not inhibit hepatocyte protein synthesis, lysates from both LPS-triggered and control M0 were inhibitory. These results show that M0s/KCs exposed to septic stimuli decrease hepatocyte protein synthesis via heat labile, soluble mediator(s) that may already be synthesized within untriggered cells. We hypothesize that soluble M0/KC mediators normally modulate hepatocyte function and that this normal homeostatic control is profoundly altered during sepsis.

Hepatocyte function in sepsis: Kupffer cells mediate a biphasic protein synthesis response in hepatocytes after exposure to endotoxin or killed Escherichia coli.

Alterations in hepatic function are seen in sepsis and/or multiple system organ failure. We hypothesized that Kupffer cells (KC) within the liver may mediate functional alterations in adjacent hepatocytes (HC) in response to bacterial products. We have previously described decreases in rat HC protein synthesis during in vitro cocultivation with peritoneal macrophages in the presence of gentamicin-killed Escherichia coli (GKEC) or endotoxin (LPS). The present studies demonstrate that purified (greater than 95%), syngeneic, or allogeneic KC exposed to GKEC or LPS impart a biphasic response in cultured HC. When HC were cultured alone there was no alteration in 3H-leucine incorporation into HC protein after the addition of GKEC or LPS. When HC were cocultured with KC there was increased protein synthesis compared with HC alone (p less than 0.001). After the addition of GKEC or LPS there was an immediate increase in coculture HC protein synthesis. However, a marked decrease in coculture protein synthesis was seen 16 degrees later (p less than 0.001). To ensure that KC alone were responsible, splenic lymphocytes were added to HC alone or HC/KC coculture, but they did not alter the results. HC viability and appearance were unchanged throughout the experiments. These results show that exposure of KC to microbial products can profoundly alter HC function and support the concept of local KC modulation of HC function during sepsis.

Splenectomy alters Kupffer cell response to endotoxin.

The spleen is a potential source for lymphokines, substances known to prime or activate macrophages. Liver macrophages or Kupffer cells are directly exposed to these products via the portal circulation. To determine whether a loss of splenic factors would alter Kupffer cell responses, we studied the effect of splenectomy or sham operation on Kupffer cell responses to endotoxin lipopolysaccharide (LPS). We determined Kupffer cell activation using an in vitro rat hepatocyte-Kupffer cell coculture system in which Kupffer cells normally mediate a significant decrease in hepatocyte protein synthesis if triggered by LPS. We found that Kupffer cells from splenectomized rats were significantly less responsive to LPS three to 60 days after splenectomy. Kupffer cells from sham-operated animals responded normally to LPS. This was contrasted to an increased sensitivity to LPS in the first two days following splenectomy. These data suggest that both splenectomy and a loss of splenic factors alter Kupffer cell responses to septic stimuli. We propose that the decreased sensitivity to LPS after splenectomy may be due to a loss of the priming effects of splenic lymphokines. This decreased responsiveness might contribute to the increased incidence of overwhelming infection after splenectomy.

Neural activity related to reaching and grasping in rostral and caudal regions of rat motor cortex.

The objective of this study was to assess the relation of motor cortical neural activity in the rat to self-paced reach-to-grasp movements. Overall, around 40% of excitatory and 60% of inhibitory modulations in neuronal activity began prior to reach onset. These data are consistent with a role for rat motor cortex in the initiation and control of the reaching movement. In addition, although the reach only lasted a short time, 30% of excitations and inhibitions began while it was in progress. The existence of such modulations occurring during the reach is consistent with previous data showing activity of cortical neurons late in the reach, and suggests a heavy involvement of cortical neurons in controlling the recently described, complex movements associated with grasping that are seen in the rat. These features were broadly similar in neurones from both the caudal and rostral subdivisions of rat motor cortex.

Muscle activity during forelimb reaching movements in rats.

The absolute timing, and correlation in time of activity in a number of shoulder, elbow and wrist muscles in the rat was analysed in relation to onset and termination of the extension phase of a skilled forelimb reaching movement. Movement onsets were analysed separately in the component upward, forward and medial directions. On average, movements in the upward and medial directions occurred together, prior to forward movement. Latissimus dorsi activity was the earliest muscle event, occurring approximately 150 ms prior to movement, whilst onset of teres major activity, possibly related to paw elevation, had the highest temporal correlation with movement onset. Triceps activity was strongly time locked to the end of the reach, and may have provided final extensor thrust to complete the reaching movement. Although it is possible to speculate on possible roles of particular EMG bursts, multiple (often anatomically antagonistic) muscles were active at all stages of the reach, and no unique muscle relationships to initiation of individual movement components could be identified. It is concluded that reaching movements are produced by temporal variation in distributed activity among all available muscles.

Responses in the diagonal band of Broca, adjacent septal nuclei and the islands of Calleja of cats to stimulation of the subcallosal fornix, medial basal hypothalamus and medial forebrain bundle.

The projection of neurons in the septal nuclei and the insula magna of the islands of Callaja (IC) was explored together with their response to stimulation of the fornix. The septal nuclei all contained neurons projecting in the medial forebrain bundle (MFB). Only the diagonal band of Broca (DBB) and the lateral septal nucleus (LS) contained many neurons projecting toward the medial basal hypothalamus (MBH). The spatial distribution of neurons excited by stimulation of the fornix in the DBB was almost identical with the distribution of neurons projecting toward the MBH and there was considerable overlap (10/28 cells). In the medial septal nucleus the spatial distribution of neurons excited by stimulation of the fornix and neurons projecting in the MFB was similar and there was considerable overlap (6/21 cells). The connectivity of the IC resembled that of the MS but there was little overlap between the neurons excited by fornix stimulation and those projecting in the MFB (1/27 cells). In the LS there were almost equal numbers of neurons projecting in the MFB and toward the MBH but there was very little input from the fornix. Neurons were significantly more often excited by stimulation of the lateral fornix, carrying axons from the subiculum, than they were by medial stimulation exciting axons from Ammon's horn. Axons projecting toward the MBH or in the MFB had conduction velocities less than 1 m/s.

Stimulation of the LH release by naloxone in anaesthetized cats after ovariectomy.

The effect of intravenous injections or infusions of the opioid receptor antagonist naloxone on the secretion of luteinizing hormone (LH) was studied in 18 spayed cats anaesthetized with Althesin. Effective injections significantly increased the LH concentration of plasma samples (taken every 10-15 min and measured by radio-immunoassay) to a peak 20-30 min after injection. The concentration thereafter declined exponentially (ke = 0.42), and, in 4/8 trials rose again significantly and declined again without further injection. The threshold dose was between 0.4 and 0.5 mg/kg. There did not appear to be a dose dependence of the effect above threshold. Infusion of naloxone at levels up to 5 mg/kg/h was effective in producing a pulsatile release of LH and repeated injections of threshold doses (0.5 mg/kg) could produce a maintained plateau and pulsatile release at frequencies comparable to pulse frequencies in vivo.

Different tonic regulation of neuronal activity in the rat dorsal raphe and medial prefrontal cortex via 5-HT(1A) receptors.

It has been established that 5-HT(1A) receptors are expressed both presynaptically as autoreceptors by 5-HT containing neurones, and postsynaptically by a variety of other neurones. Activation of either somatodendritic 5-HT(1A) autoreceptors or postsynaptic 5-HT(1A) receptors induces hyperpolarisation and inhibition of action potential discharge of the neurones, but it is unclear whether 5-HT(1A) receptors are under a general tonic influence by 5-HT. In the present study, using single unit recordings from both anesthetized and non-anesthetized rats, we show that the activity of neurones in the medial prefrontal cortex is not altered by systemic administration of the selective 5-HT(1A) receptor antagonist, WAY 100635. In contrast, WAY 100635 increased the firing rate of 5-HT neurones in the dorsal raphe nucleus. Our findings indicate a tonic activation of presynaptic somatodendritic but not postsynaptic cortical 5-HT(1A) receptors.

Dynamical cell assemblies in the rat auditory cortex in a reaction-time task.

Simultaneous single unit spike trains were recorded in the auditory cortex of freely moving rats performing a complex cognitive task. The experimental paradigm is based on a two-choice task (Go/Nogo) with a two-component (pitch and location) auditory stimulus lasting 500 ms. We report evidence that firstly functional interactions, measured by cross-correlation analysis, between single units in the auditory cortex are dynamically modified in the period preceding the onset of the auditory stimulation, referred to as the 'waiting period'. We secondly observed that spatio-temporal firing patterns both within, and across cell spike trains also tended to appear in the waiting period, several seconds before the actual stimulus delivery. These patterns indicate a very precise repetition of spike discharges separated by long intervals (up to several hundreds of milliseconds). No consistent changes in mean rate were observed. These results suggest that network activity in the auditory cortex is selectively modified in rate independent ways before the actual sensory stimulation. These modifications may reflect participation of recurrent neuronal networks in processes anticipating the expected sensory input.

Stimulus congruence affects perceptual processes in a novel Go/Nogo conflict paradigm in rats.

The performance of freely moving rats (n=18) in a decision-making reaction time task was analyzed to provide data that can be compared with noise-compatibility paradigms previously obtained in humans. Rats were first trained in an auditory pitch discrimination task involving a Go/Nogo response choice. In a subsequent phase, the two tones used in the previous phase were simultaneously presented in different combinations from two locations. Only the presence of the correct tone from the correct location was predictive of the reward. The observed behavioral strategies suggest a competition between two processes: one involving stimulus evaluation, response preparation and execution, the other involving recognition of the stimulus features associated with inhibition of the Go-response. The reaction times in the most adopted strategies towards the end of the experiment suggest an effect of stimulus congruence. Perceptual processes are affected by the congruence of 'pitch' and 'location' stimulus dimensions and the duration of the response may, but need not, be affected by overlapping dimensions. The analysis of error and aborted trials also suggest that subject's reaction and subsequent motor action may depend on whether stimulus identification processes can pass information to the response activation system prior to completion of sensory processing. The data are discussed in the framework of processing stages theory and dimensional overlap model.

Cortical cell assemblies: a possible mechanism for motor programs.

The concept of a motor program has been used to interpret a diverse range of empirical findings related to preparation and initiation of voluntary movement. In the absence of an underlying mechanism, its exploratory power has been limited to that of an analogy with running a stored computer program. We argue that the theory of cortical cell assemblies suggests a possible neural mechanism for motor programming. According to this view, a motor program may be conceptualized as a cell assembly, which is stored in the form of strengthened synaptic connections between cortical pyramidal neurons. These connections determine which combinations of corticospinal neurons are activated when the cell assembly is ignited. The dynamics of cell assembly ignition are considered in relation to the problem of serial order. These considerations lead to a plausible neural mechanism for the programming of movements and movement sequences that is compatible with the effects of precue information and sequence length on reaction times. Anatomical and physiological guidelines for future quantitative models of cortical cell assemblies are suggested. By taking into account the parallel re-entrant loops between the cerebral cortex and basal ganglia, the theory of cortical cell assemblies suggests a mechanism for motor plans that involve longer sequences. The suggested model is compared with other existing neural network models for motor programming.

Spatial coordination in a bimanual task related to regular switching of movement vectors.

The spatial aspect of cooperation between the two upper extremities was investigated using a bimanual task involving drawing simultaneous zig-zag lines on a vertical surface. In 62 trials by 31 strongly right-handed subjects three performance types were identified; Type I involved alternation of dominance in sideways and vertical movement components, in Type II a constant vertical movement was superimposed upon sideways movement, and Type III showed no consistent pattern across the two hands. These performance types differed significantly on the measure of spatial coordination, with Type I having the best, and Type III the poorest. These results suggest that on this bimanual task better spatial symmetry in limb movement is achieved when both hands employ similar within-hand strategies, involving switching between vectors for all muscle groups.