Kinematics of a coordinated goal-directed bimanual task.

The experiments address the problem of bimanual coordination in a familiar task of everyday life. A goal-directed drawer-pulling task, with asymmetrical assignments among hands, was analyzed with the objective to detect discrete kinematic events ('anchors') that potentially could serve in proper goal synchronization. The left hand reached out for the drawer and opened it while the right hand performed a prehension movement to pick up a peg from the drawer. The task was smoothly performed, independently of vision. Typically, trajectories and velocity profiles of the leading pull-hand were more stereotypical than the more variable ones of the pick-hand. The pull-hand had a large velocity peak during reaching, followed by a small peak during pulling. Velocity profiles of the pick-hand were not bell-shaped and exhibited one or two broad waves, often with an irregular and probing evolution. Velocity profiles of both hands were aligned with the first or the second velocity peak of the leading pull-hand. In the majority of cases, temporal associations of events in the kinematics of the two limbs could thus be identified, which could serve to synchronize the hands at the goal. The nearly straight biphasic reach-and-pull trajectory of the leading hand contrasted with the more curved trajectory of the right pick-hand whereas, in the same unimanual action, the latter trajectories were quasi-rectilinear. Changing constraints (no vision, cutaneous anesthesia of pulling fingers) could change the coordination pattern. We argue that bimanual coordination relies on two interacting mechanisms: (1) feedforward control on the basis of sensorimotor memory; (2) temporal adjustments during the evolving bimanual synergy. Multiple strategies, imposed by the leading pull-hand, appeared to be responsible for feedback-induced corrections in the pick-hand and were found to contribute to the goal-invariance and to the principle of motor equivalence.

Neurological problems affecting hand dexterity.

The first objective of this review is to summarize how grip force and load force (holding and transporting forces) are coordinated. Usually, the two forces vary in parallel, thereby resulting in a constant force ratio. Departures from this rule have been observed, however, depending on dynamic task constraints. The second objective is to summarize some of the pathophysiology of grasping in movement disorders. By means of a drawer-pulling task, regulation of grip force was analyzed when pulling was perturbed either by self-induced or externally applied load disturbances. Normal subjects automatically increased grip force in anticipation to the expected load. In the same situation, hemiparetic patients failed to generate proactive grip force and frequent slips were observed. Cerebellar patients were shown to adopt a 'default' strategy in producing high grip force output when the drawer had to be pulled up to its mechanical stop. This differed from the more flexible normal mode of raising grip force in accord with the pulling speed. In patients with Huntington's Chorea, grip/load force coordination differed from that of normal subjects, as expressed in an overscaled grip force. This might be a secondary, less flexible 'default' strategy to overcome the failure in adapting grip force to upcoming disturbances. Writer's cramp patients overscaled grip force in both the dominant and non-dominant hand, and grip force further increased when hand muscles were vibrated, suggesting an abnormal sensorimotor integration. The results illustrate the degrading consequences of cortical and subcortical pathology on manual dexterity, which is sometimes partly compensated for by new, less flexible default strategies.

Regulation of grasping forces during bimanual in-phase and anti-phase coordination.

When a hand-held object is moved, grip force is adapted in an anticipatory manner to load force due to a dynamic coupling between both forces. The present study addressed the issue of grip-load force regulation when moving rhythmically two hand-held objects in the vertical dimension, and more specifically the divergence of force control when performing according to the in-phase versus anti-phase mode. Results revealed that grip-load force ratio profiles were similar in both bimanual conditions. That is, force ratio was not constant throughout the movement cycles but followed a fairly regular pattern with maxima and minima, attained at upward and downward hand positions, respectively. However, anti-phase patterns showed an increased maximum grip-load force ratio as compared to in-phase patterns, whereas the latter did not differ from unimanual movements. The magnification of maximum force ratio during anti-phase movements suggests that rescaling occurred. This is likely due to the complexity of the anti-phase mode that necessitates increased monitoring and attention relative to the other performance conditions, creating a coordinative situation that imposes an additional degree of uncertainty. Therefore, the safety margin is amplified during anti-phase movements, probably as a strategy to prevent a potential destabilization of the grip during an asymmetrical load condition. Accordingly, these findings also demonstrate that grip-load force regulation is more proficiently controlled during bimanual in-phase than anti-phase movements. Herewith, the data add content to earlier work illustrating kinematic dissimilarities between both coordination modes.

Toward a physiological understanding of human dexterity.

Dexterity, defined as the skillful manipulation of the hands, is now amenable to physiological investigation. Two topics are discussed here: grasping (i.e., hand-object coupling) and bimanual coordination. Dexterity depends on powerful, distributed neural networks and is particularly vulnerable to brain lesions. A knowledge of physiological mechanisms is needed to deal with these neurological problems.

Damage to the parietal lobe impairs bimanual coordination.

Moving the upper limbs at a common tempo according to a mirror or parallel mode represents elementary coordination dynamics. Previously, the role of the medial wall areas have been emphasized for successful production of these bimanual patterns. The involvement of the parietal lobe is less clear despite its importance for the representation of motor skill and sensorimotor integration. The objective of this study was to investigate temporal control in patients with parietal pathology when performing isofrequency configurations. As compared to control subjects, these patients showed desynchronization of movement trajectories that was most apparent during parallel patterns. These observations suggest the significant role of the parietal lobe for bimanual coordination which becomes increasingly relevant as a function of task complexity.

Bimanual organization of manipulative forces: evidence from erroneous feedforward programming of precision grip.

The objective of the present study was to investigate grip-load force regulation during a bimanual lifting task with two hand-held objects. Various conditions were included during which the weight of one or both objects was changed in an unpredictable order every fourth trial. Results showed that force control of heavy weight movements preceded by light weight movements was not strongly influenced across trials. Conversely, force responses of light weight movements preceded by heavy weight movements were overestimated due to an augmented degree of grip force. However, successful updating of force output occurred after one trial. Furthermore, bimanual interactions between the grasping forces were observed, suggestive of a coordinative command that assimilated the individual response specifications. The latter also became apparent from a similar grip-load force ratio for both hands when the objects' physical properties had become predictable, independent of the forces that were produced according to the individual weight requirements. These data indicate that the grip-load force ratio is the controlled variable for bimanual manipulative behaviour.

Grip force scaling and sequencing of events during a manipulative task in Huntington's disease.

The aim of the study was to investigate force regulation and sequencing of events in Huntington's disease (HD) patients when performing a drawer opening task using the precision grip. Results revealed that HD patients used excessive grip force levels that were unrelated to the actual task demands. Also, they demonstrated a higher grip force value at load force onset in addition to an increased delay between initiation of grip force and load (pulling) force. These data indicate a deficit in the coordinated activation of both forces due to HD. Furthermore, the patients showed bradykinesia along with a prolonged interval between the movement phases underlying the task, denoting an impairment in encoding serially ordered events. Together, these results illustrate the deteriorating effect of striatal pathology on manual function. Accordingly, an amended control of grasping forces and serial encoding of movement-related events due to HD are likely to affect the proficiency of common manipulative skills.

Different ipsilateral representations for distal and proximal movements in the sensorimotor cortex: activation and deactivation patterns.

Each hemisphere is known to be also involved in controlling the ipsilateral arm, but with an asymmetry favoring the dominant hemisphere. However, the relative role of primary and secondary motor areas in ipsilateral control is not well defined. We used whole brain functional magnetic resonance imaging in healthy human subjects to differentiate between contributions from primary and secondary areas during discrete unilateral distal finger and proximal shoulder movements. It was found that ipsilateral distal movements activated secondary areas only, while sparing or even significantly deactivating the primary sensorimotor cortex. Ipsilateral proximal movements substantially activated both SM1 and secondary areas. A newly defined small territory within the precentral gyrus, extending from the premotor cortex and intruding toward SM1, showed an activation pattern corresponding to secondary motor areas. Finally, the effects of hemispheric dominance were confirmed, but attributed exclusively to secondary areas. These new imaging findings agree well with functional requirements as well as established anatomical and neurophysiological data.

Dissociation of grip/load-force coupling during a bimanual manipulative assignment.

The aim of the present study was to examine interlimb interactions of grasping forces during a bimanual manipulative assignment that required the execution of a drawer-opening task with the left hand and an object-holding task with the right hand. Compared with the unimanual performance, the grip/load-force ratio of the object-holding task was shifted towards that of the simultaneously executed drawer-opening task. This shows that force parameterization of the dynamic activity interacted with that of the static activity. That the increased force ratio only involved modification of grip force, while load force was held constant, indicates a disruption of the commonly observed co-variation of both forces during a manipulative action. These data are consistent with the notion that the coordinative constraint between grip and load force is a flexible parameter.

A higher-order mechanism overrules the automatic grip-load force constraint during bimanual asymmetrical movements.

The aim of the present study was to examine grip-load force regulation during unimanual and bimanual movements. Two protocols were included which manipulated the object's weight and covered distance. Results showed that grip-load ratio was adapted to the task requirements. During unimanual and bimanual symmetrical movements, an increased grip-load force ratio for long versus short amplitude movements as well as for light versus heavy weight movements was noted. These findings could be related to the observed movement speed variations associated with the tasks. During bimanual asymmetrical movements, the grip-load force ratio became comparable for both sides. When transporting different object's weights to constant distances, the grip-load force ratio of light weight movements decreased towards that of heavy weight movements. As movement speed was reduced, it indicates that grasping forces were adapted accordingly. When transporting constant object's weights to different distances, the grip-load force ratio of short amplitude movements increased towards that of long amplitude movements. Since movement speed was decreased, it suggests that a bimanual coordinative command overruled the automatic grip-load coupling. In conclusion, these data show that interlimb coupling induced a rescaling towards a common control structure, leading to similar grasping forces during bimanual movements with dissimilar actions.

Role of the corpus callosum in bimanual coordination: a comparison of patients with congenital and acquired callosal damage.

The objective of the study was to investigate temporal control in patients with congenital as compared to acquired pathology of the corpus callosum during two different bimanual paradigms: (i) a drawer-opening task during which one hand opened a drawer while the other hand reached and grasped a small object, and (ii) rhythmical circling movements that were executed according to the in-phase or antiphase mode. Synchronization values revealed that patients with acquired callosal dysfunction generally showed optimal behaviour during the goal-directed and familiar drawer-opening task but demonstrated strong tendencies towards desynchronization during circling movements, which became most apparent for antiphase coordination. Whereas one patient with callosal agenesis showed a similar performance, the other acallosal patients performed both activities successfully. These observations indicate that patients with congenital absence of the corpus callosum can make use of compensatory mechanisms for allowing temporal synchronization during bimanual movements whereas patients with acquired callosal dysfunction are severely hampered when the task places significant demands on the control processes. The data also underline that the ability of callosal patients to precisely time events in coordinated actions depend on the task constraints.

Disturbed sensorimotor processing during control of precision grip in patients with writer's cramp.

The aim of the study was to investigate force regulation in patients with writer's cramp when performing a drawer-opening task using the precision grip. Experimental conditions included intervening load pulses and vibratory manipulations for examining grip force responses to sensory disturbances. The data revealed that grip force was increased in patients with writer's cramp compared with normal subjects, with a stronger modulation in the symptomatic compared with the asymptomatic hand. This denotes a change in force scaling capabilities and most notably for the preferred hand used in manipulative activities. Vibratory stimulation of the extrinsic hand/finger muscles resulted in an increased grip force of both hands in the patients with writer's cramp. The latter was not observed in normal subjects and supports a bilateral dysfunction in sensorimotor integration resulting from focal dystonia. In conclusion, the disturbed regulation of the precision grip during a drawer-opening task is illustrative for the inability of patients with writer's cramp to efficiently control the force output during manipulative activities.

Impaired proactive and reactive grip force control in chronic hemiparetic patients.

OBJECTIVES: The aim of the study was to test manipulative capacities of hemiparetic patients with partial recovery in a drawer task. The main objective was to assess adjustments of grip force in the face of load perturbations. METHODS: The task was to pull and to hold the drawer manipulandum during predictable or unpredictable perturbations with short (90 ms) load pulses (factor set). RESULTS: The following novel observations were made. (1) Load pulses elicited, at a latency of about 70 ms, a transient grip force response and a corresponding phasic EMG response. These reactive adjustments were larger during holding than during pulling (factor task). In patients, the reactive grip force adjustments and the EMG response in the grip muscles were reduced. (2) The above deficit was set-dependent. (3) With regular perturbations, grip force was scaled already before perturbation onset. This proactive adjustment was greatly reduced in the patient group. (4) Coordination between grip force and pull force before onset of the perturbation was also disturbed in the patients who generated less grip force per unit pull force than control subjects. CONCLUSIONS: It is concluded that the patients had difficulties in adapting proactively and reactively to external load disturbances, in addition to their hand weakness.

Temporal control of a bimanual task in patients with cerebellar dysfunction.

The objective of the study was to investigate whether temporal control during a goal-directed bimanual action is disturbed in cerebellar patients. The task was to open a drawer with one hand and to reach and grasp a small object with the other hand. Interlimb coupling was determined at start and end positions. Cerebellar patients as compared to normal subjects showed an increased offset for initiating the hand movements which denotes the involvement of the cerebellum for organizing the components underlying the bimanual task. The reduced simultaneity was caused by a delayed movement onset of the grasping (non-leading) hand as compared to the pulling hand. Lack of vision increased the degree of desynchronization for the patients at the start position, indicating that they depended on external cues for organizing the temporal coordinates of the combined motion pattern. At the goal, the magnitude of temporal offset was similar/smaller than at movement onset which can be related to feedforward mechanisms that are used to anticipate the limbs' end positions. These results confirm the role of the cerebellum for planning the temporal ordering of movement sequences into a synergic action.

Somatic hypermutation in MutS homologue (MSH)3-, MSH6-, and MSH3/MSH6-deficient mice reveals a role for the MSH2-MSH6 heterodimer in modulating the base substitution pattern.

Although the primary function of the DNA mismatch repair (MMR) system is to identify and correct base mismatches that have been erroneously introduced during DNA replication, recent studies have further implicated several MMR components in somatic hypermutation of immunoglobulin (Ig) genes. We studied the immune response in mice deficient in MutS homologue (MSH)3 and MSH6, two mutually exclusive partners of MSH2 that have not been examined previously for their role in Ig hypermutation. In Msh6(-)/- and Msh3(-)/-/Msh6(-)/- mice, base substitutions are preferentially targeted to G and C nucleotides and to an RGYW hot spot, as has been shown previously in Msh2(-)/- mice. In contrast, Msh3(-)/- mice show no differences from their littermate controls. These findings indicate that the MSH2-MSH6 heterodimer, but not the MSH2-MSH3 complex, is responsible for modulating Ig hypermutation.

Role of the cerebellum in tuning anticipatory and reactive grip force responses.

The aim of our study was to determine if load perturbations that could destabilize grasp control are adequately controlled by cerebellar patients. We examined patients with unilateral cerebellar lesions who had largely recovered from their initial symptoms and compared grip force regulation for the affected and unaffected hand during a drawer-opening task. Two experimental paradigms were included: (1) a brief load perturbation during a self-stopped drawer pull and (2) a loading impact when the drawer was pulled out to the mechanical stop. The results showed that when a self-stopped movement was perturbed during its trajectory, anticipatory grip force increase was smaller for the affected than for the unaffected hand, illustrating a disturbed gain control due to cerebellar dysfunction. When the mechanical stop arrested the movement, the amount of grip force did not differ significantly between the affected and unaffected side; however, both hands used different control strategies. Whereas the unaffected hand anticipated the load perturbation by a ramp-like increase of grip force toward the impending impact, the affected hand increased grip force at movement onset to a default level and maintained this value until the task was ended. In addition, the latency between impact and reactive peak in grip force was prolonged for the affected hand, suggesting a delayed cerebellar transmission of reactive responses. In conclusion, these findings demonstrate that the cerebellum is involved in anticipatory and reactive mechanisms dealing with load perturbations during goal-directed behavior.

Grip-load force coordination in cerebellar patients.

The study examined the anticipatory grip force modulations to load force changes during a drawer-opening task. An impact force was induced by a mechanical stop which abruptly arrested movement of the pulling hand. In performing this task, normal subjects generated a typical grip force profile characterized by an initial force impulse related to drawer movement onset, followed by a ramp-like grip force increase prior to the impending load perturbation. Finally, a reactive response was triggered by the impact. In patients with bilateral cerebellar dysfunction, the drawer-opening task was performed with an alternative control strategy. During pulling, grip force was increased to a high (overestimated) default level. The latter suggests that cerebellar patients were unable to adjust and to scale precisely the grip force according to the load force. In addition, the latency between impact and reactive activity was prolonged in the patients, suggesting an impaired cerebellar transmission of the long-latency responses. In conclusion, these data demonstrate the involvement of cerebellar circuits in both proactive and reactive mechanisms in view of predictable load perturbations during manipulative behavior.

Eye-hand coordination in uni- and bimanual goal-oriented tasks.

Two different drawer tasks were investigated with the aim of assessing the role of eye movements in well-coordinated hand movements. In an unimanual step-tracking task, which had a predictive and an unpredictive movement, a two-way repeated-measures ANOVA showed a significant effect of prediction on the onset of grip-force (GF) rate (300+/-39 ms for the predictive condition versus 394+/-53 ms for the non-predictive condition, P<0.0001). Correlation coefficients, computed from the eye and the hand movements were low for the right and the left hand. The saccade was more coupled with the visual step change than with the action of the hand per se. In a second bimanual pull-and-pick task, the instruction was to pull a drawer with the left hand from a closed position to a LED-cued open position and then to grasp and reinsert a small peg in the drawer with the right hand. Correlation coefficients, computed from the latencies of saccades and of the leading left hand or of the right hand, were significant in four of five subjects. Intermanual correlations were significant in all five subjects. In conclusion, we found that the initial saccade in the unimanual task was best related with the visual step change, but was poorly correlated with the pulling/pushing hand. In the bimanual task, a moderate, but significant temporal coupling between the eyes and hand events was observed. This coupling was, however, less tight than that between both hands.

Time structure of a goal-directed bimanual skill and its dependence on task constraints.

The aim of the study was to elucidate the underlying principles of bimanual coordination and to establish quantitative coordination criteria. Healthy human subjects were instructed to open a loaded drawer with the left hand and to grasp, lift and reinsert with the right hand a small peg in the drawer recess. This bimanual goal-oriented task was executed promptly and consistently after a few trials. The temporal structure of the individual limb actions was assessed for computing interlimb synchronization and temporal correlation. In all subjects, both hands were well synchronized at the goal with high intermanual correlation in reaching the goal (event times of drawer opening and grasping the peg). This temporal goal-invariance was independent of movement speed and of the highly variable timing of the individual hands and persisted when subjects were blindfolded. Unilateral loading of the pulling hand and cutaneous anesthesia of the left index finger and thumb used for grasping the drawer handle significantly increased the pull-phase. This slowing of the left hand was matched by an adaptive delay of the right non-disturbed hand, thus preserving goal invariance. As a working hypothesis, we propose that multimodal sensory signals generated in the leading arm be transmitted centrally to re-parameterize the non-disturbed arm.