Kinematic properties of rapid hand movements in a knob turning task

In order to understand how the central nervous system controls the kinematics of rapid finger and hand movements, we studied the motions of subjects turning a knob to light-emitting diode targets, similar to tuning a radio dial. On many trials, subjects turned the knob with a single, smooth, and regular motion as revealed by the angular position and velocity trajectories, but on others, subjects produced irregularities in the kinematics. Like many past studies, we interpreted these irregularities as discrete corrective submovements. Unlike other studies, we used a direct, objective algorithm to identify overlapping submovements, detecting appreciable inflections in the acceleration traces by examining zero crossings in their derivatives, jerk and snap. The movements without overlapping submovements on average had a near symmetric, bell-shaped velocity profile that was independent of speed, and which matched the theoretical minimum jerk velocity very closely. We proposed three plausible mechanisms for altering the shape of movement kinematics, and implemented a mass-spring model with nonlinear damping to explore the possibilities. Although there was relatively little variability in the shape and symmetry of movements across trials, there was a fair amount of variability in their amplitude. We show that subjects attempted to eliminate the need for corrective submovements by making more accurate primary movements with practice, but that the variability inherent in rapid movements dictated the need for corrective submovements. Subjects used corrective submovements to improve final endpoint accuracy while reducing endpoint variability, resulting in higher task success rates.     

Multiple task interference is greater in children with ADHD

There is considerable lay discussion that children with attention deficit hyperactivity disorder (ADHD) have increased difficulty with multitasking, but there are few experimental data. In the current study, we examine the simultaneous processing of two stimulus-response tasks using the Psychological Refractory Period (PRP) effect. We hypothesized that children with ADHD would show a greater PRP effect, suggesting a prolonged "bottleneck" in stimulus-response processing. A total of 19 school-aged children with ADHD showed a prolonged PRP effect compared with 25 control children, suggesting a higher cognitive cost in ADHD for multitasking.     

Cutaneomotor integration in humans is somatotopically organized at various levels of the nervous system and is task dependent

Integration of tactile afferent signals with motor commands is crucial for the performance of purposeful movements such as during manipulation of an object in the hand. To study the somatotopic organization of sensorimotor integration we applied electrical peripheral conditioning stimuli to a digit located near (homotopic stimulation) or distant from (heterotopic stimulation) relaxed or isometrically contracted intrinsic hand muscles at variable time intervals prior to transcranial magnetic stimulation (TMS). Cutaneous stimulation has previously been shown to modulate the amplitude of the motor evoked potential (MEP) and to shorten the duration of the silent period (SP) evoked by TMS. In relaxed target muscles the time-dependent modulation of TMS-evoked motor responses by homotopic conditioning stimulation differed from modulation by heterotopic stimulation. Similar differences in the modulation pattern evoked by homotopic and heterotopic conditioning stimulation were observed for two distinct target muscles of the hand (abductor digiti minimi, abductor pollicis brevis muscle). Differences in modulation were maximal when the conditioning stimulation was applied 25–30 ms and 150–200 ms prior to TMS. Comparison of the modulation of the amplitudes of MEPs evoked by transcranial electrical stimulation (TES) and the modulation of those evoked by TMS suggests that differences between homotopic and heterotopic stimulation originate subcortically at 25- to 30-ms and, at least partially, cortically at 150- to 200-ms interstimulus intervals. In isometrically contracted intrinsic hand muscles the degree to which the SP was shortened reflected the location and the timing of the conditioning stimulus. Shortening was maximal when the conditioning stimulus was applied nearest to the contracted target muscle and 20 ms prior to the test stimulus. In contrast to the SP duration, the MEP size in voluntarily contracted target muscles was unaffected by the location of the conditioning stimulus. The somatotopic gradient of SP shortening was abolished when the two target muscles were simultaneously activated isometrically. Together, our findings suggest that somatotopy of input-output relationships is implemented at both a spinal and a cortical level in the human central nervous system and may also depend on the motor task involved. Received: 25 August 1998 / Accepted: 11 June 1999     

Bimanual coordination during rhythmic movements in the absence of somatosensory feedback

We investigated the role of somatosensory feedback during bimanual coordination by testing a bilaterally deafferented patient, a unilaterally deafferented patient, and three control participants on a repetitive bimanual circle-drawing task. Circles were drawn symmetrically or asymmetrically at varying speeds with full, partial, or no vision of the hands. Strong temporal coupling was observed between the hands at all movement rates during symmetrical drawing and at the comfortable movement rate during asymmetrical drawing in all participants. When making asymmetric movements at the comfortable and faster rates, the patients and controls exhibited similar evidence of pattern instability, including a reduction in temporal coupling and trajectory deformation. The patients differed from controls on measures of spatial coupling and variability. The amplitudes and shapes of the two circles were less similar across limbs for the patients than the controls and the circles produced by the patients tended to drift in extrinsic space across successive cycles. These results indicate that somatosensory feedback is not critical for achieving temporal coupling between the hands nor does it contribute significantly to the disruption of asymmetrical coordination at faster movement rates. However, spatial consistency and position, both within and between limbs, were disrupted in the absence of somatosensory feedback.     

Looking at the task in hand: vergence eye movements and perceived size

A retinal afterimage of the hand changes size when the same unseen hand is moved backwards and forwards in darkness. We demonstrate that arm movements per se are not sufficient to cause a size change and that vergence eye movements are a necessary and sufficient condition for the presence of the illusory size change. We review previous literature to illustrate that changing limb position in the dark alters vergence angle and we explain the illusion via this mechanism. A discussion is provided on why altering limb position causes a change in vergence and we speculate on the underlying mechanisms. Received: 6 May 1997 / Accepted: 16 July 1997     

Connection between finger task movements and contralaterally associated movements in children

Two experiments were carried out to investigate the connection between finger task movements (TM) and contralaterally associated movements (CAM). In Experiment I, 40 children ranging in age from five to six were required to play "marbles" (TM) with the right thumb or forefinger, while two investigators checked CAM on their left fingers. The result showed the local relation between TM and CAM wasn't strictly symmetric. In Experiment II, 60 children ranging in age from five to seven were required to consciously control their contralateral finger movements while they played TM. Following three conditions were provided; 1) The free condition with no control, 2) the inhibitory condition with conscious inhibition of CAM, and 3) the imitative condition with a typical CAM pattern. Findings were that, though all children could inhibit CAM consciously, the five-year-olds couldn't. Furthermore, TM performance improved in the lower performance group, but it deteriorated in the higher group in association with the contralateral control. These results suggest that there is a cooperative and reciprocal relationship between TM and the contralateral finger movements.     

Learning-induced plasticity of N-methyl-D-aspartate receptors is task and region specific.

Changes in binding of [3H]dizocilpine maleate to N-methyl-D-aspartate-sensitive ion channel receptors were evaluated after learning in order to specify brain regions which might be involved in memory formation. Rats were trained in a five-trial session of 40 min, to discriminate among three odours to obtain food reinforcement. Another group was trained in an eight-arm maze to choose always the same three arms to obtain food reinforcement (nine trials over 150 min). In rats killed 30 min after odour discrimination learning, dizocilpine maleate binding was significantly reduced in hippocampal sub-regions CA3, CA1 and fascia dentata and in frontal cortex. After spatial learning, changes in binding were limited to the amygdala, where a decrease was also observed. These results indicate that functional changes occur in specific brain regions after learning and suggest anatomical loci for further study of synaptic changes at a morphological level, after spatial learning or odour discrimination.     

Negative selection by endogenous antigen and superantigen occurs at multiple thymic sites

The site of negative selection in the thymus has been inferredfrom a range of different experiments. Analysis of thymic deletionof Vß5⁺, V_ß11⁺ or Vß17a⁺ cellsH-2E transgenic mice led to the theory that negative selectionoccurs predominantly in the medulla (specifically, through presentationby medullary dendritic cells). Other experiments investigatedwhether transgenic TCR are deleted at the double-positive (DP)or single-positive stage following encounter with peptide ligand:by flow cytometric analysis deletion is generally found to occurat the DP thymocyte stage and as these cells are found predominantlyin the cortex, it has been inferred that this is the key siteof negative selection. The visualization of apoptotic thymocytesin situ has recently been reported for specific examples ofnegative selection. Using a panel of TCR transgenic lines inwhich negative selection occurs at different stages of thymocytedevelopment, we have used TUNEL staining to analyse the anatomicalsites of thymocyte apoptosis. For the first time we have beenable to compare directly the sites of deletion induced by theendogenous cognate peptides or by endogenous superantigen. Weshow that generalization from the medullary deletion of V_ß5⁺,V_ß11⁺ or V_ß17a⁺ cells by the endogenoussuperantigens Mtv 8 and 9 and from limited examples of corticaldeletion by exogenous peptide administered to TCR transgenicmice is over-simplified. Apoptotic thymocytes in mice lackingMtv superantigens are indeed localized in the cortex. However,when deletion is induced by cognate self peptide, apoptosiscan occur in the cortex, the medulla or at the junction betweenthe two.     

Attentional blink reflex modulation in a continuous performance task is modality specific

Four experiments investigated the attentional modulation of acoustic blinks during continuous spatial tracking tasks. Experiment 1 found blink magnitude inhibition in a visual tracking task. Experiment 2 replicated this finding and also found blink latency slowing. Experiment 3 varied the difficulty of the task and found larger blink inhibition in the easy condition. Blink latency slowing did not differ and was significant at both difficulty levels. Experiment 4 employed less difficult visual and acoustic tracking tasks at two levels of task load. Blink magnitude inhibition during the visual and facilitation during the acoustic task was significant during high load in both modality groups. Blink latency was slowed in all visual task conditions and shortened in the difficult acoustic task. These results indicate that attentional blink modulation in a continuous spatial tracking task is modality specific.     

Facilitation and interference components in the joint Simon task

Two experiments were conducted to assess whether the joint Simon effect is composed of facilitation and interference and whether facilitation is increased by a joint spatially compatible practice performed before performing the joint Simon task. In both experiments, participants were required to perform a Simon task along another person. Trials could be corresponding, non-corresponding, and neutral. In Experiment 1, participants performed only the Simon task. In Experiment 2, participants first practiced on a joint spatial compatibility task with a compatible mapping and, after a 5-min delay, transferred to a joint Simon task. Results indicated that the joint Simon effect consisted primarily of interference, which was significantly increased by a spatially compatible practice performed jointly. These results allow us to better define in what ways the presence of the other influences performance, in showing that when participants perform a task along with another individual, they display a disadvantage (i.e., slower RTs) when they have to respond to stimuli appearing on the other agent's side.     

Judgment and control of velocity in rapid voluntary movements

Summary Control of velocity in rapid flexion movements of the interphalangeal joint of the thumb was investigated by examining movement trajectories and patterns of activity in the extensor pollicis longus (EPL) and flexor pollicis longus (FPL) muscles. Although velocity was controlled with considerable accuracy, it was not sensed with the same precision. Consistent errors were made when subjects attempted to match the peak velocities under conditions in which the relationship between muscle activity and joint acceleration had been altered, i.e. changing the angle from which movement was initiated or varying the load. Rather than relying on afferent feedback from peripheral sensory receptors for information about velocity during rapid movements, it is suggested that subjects were more likely to base their judgment of velocity on sensations evoked by the voluntary motor command.     

A three-dimensional analysis of vergence movements at various levels of elevation

Earlier studies have shown that eye positions, recorded in subjects scanning a distant visual scene with the head in a stable position, have only two degrees of freedom (Listing's law). Due to cyclovergence, this law is modified in near-vision. Two previous quantitative studies have documented that the sign of the torsional vergence component depends systematically on elevation: when fixating a nearby target, the eyes show intorsion in up gaze, extorsion in down gaze and no cyclotorsion at some intermediate elevation level (to be denoted as the null elevation). Both studies found a linear cyclovergence/elevation relation, but disagreed on the amount of cyclotorsion. A further uncertainty is how this phenomenon develops dynamically when the binocular fixation point shifts from a far to a near position. Therefore, we have investigated the dynamic coupling between the horizontal and torsional components of vergence in human subjects who were instructed to refixate a light target after it stepped in depth. The target steps were presented at various vertical and horizontal directions relative to the straight-ahead axis of the cyclopean eye. We found that the quantitative relations among horizontal vergence, torsional vergence and elevation were intermediate between those found in the two earlier near-vision studies and that they correspond reasonably to the predictions of a model by Mok and co-workers. The cyclotorsion vergence component had about the same latency and dynamics as the horizontal component. When refixations were studied at different elevations, the torsional vergence component changed from incyclotorsion in up gaze to excyclotorsion in down gaze. In agreement with expectations derived from two quantiative models, the null elevation of cyclovergence was near the binocular primary position. Furthermore, we found no consistent additional dependence on the horizontal direction of the refixation trajectory relative to the midsaggital plane. Other experiments showed that the cyclotorsional changes accompanying convergence were not critically dependent upon the visual conditions. Quantitatively similar cyclotorsional components were found even in convergent refixations executed in full darkness towards the location of a remembered (flashed) near target. We conclude that visual feedback is unlikely to be very important in controlling cyclovergence in these various conditions.     

Proprioceptive feedback during point-to-point arm movements is tuned to the expected dynamics of the task

It has previously been found that in point-to-point movements against inertial loads, proprioceptive feedback is centrally suppressed in the beginning of movement and is facilitated at a time that is correlated with the expected time of peak velocity. This suggests that the modulation of proprioceptive feedback is governed by the desired movement kinematics. Here we show that in movements against inertial and viscous loads, the correlation of the time when the feedback is facilitated is strongest with the time when the joint torque is expected to be maximal. This suggests that the modulation of proprioceptive feedback is governed by the desired movement dynamics. We applied unexpected perturbations in point-to-point elbow flexion movements against known light and heavy inertial and viscous loads and determined the time and magnitude of responses in the electromyogram (EMG) of the biceps and triceps muscles. In movements against the inertial and viscous loads, the time of the EMG responses was better predicted by the time of the peak joint torque in the unperturbed movement than by the time of peak velocity or the time of peak acceleration or by measures related to the agonist EMG. Moreover, the EMG response changed from a reciprocal pattern in the inertial load conditions to a co-contraction pattern in the viscous load conditions. Our results suggest that during movements against known stable dynamic loads, proprioceptive feedback is tuned to the expected task dynamics and is facilitated so as to maintain muscle stiffness at a time when the muscles are expected to generate maximal force.     

Coordination of fast eye and arm movements in a tracking task

Summary Eye and arm movements to single and double-step target displacements were studied to investigate whether or not the motor systems of the eye and arm share common command signals from the internal representation, which specify a) when a movement is initiated and b) the end position of a movement. The correlation between the time of onset of eye and arm movements was significant for single-step and double-step target displacements into the same direction. However, it was small and not significant for double-step target displacements into opposite directions if the time interval between first and second target displacement was 75 or 100 ms. This indicates that the command signal which specifies when a movement is started is different for both systems. However, the reconstructed signal in the internal representation, which specifies the end position of movements, is rather similar for eye and arm movements which seems to point to a common command signal. This result was corroborated by experiments in which eye and arm were found to jump always to the same target in the condition that two different targets were presented simultaneously.     

Frameshift mutation in p53 regulator RPL26 is associated with multiple physical abnormalities and a specific pre-ribosomal RNA processing defect in diamond-blackfan anemia

Diamond-Blackfan anemia (DBA) is an inherited form of pure red cell aplasia that usually presents in infancy or early childhood and is associated with congenital malformations in ～30-50% of patients. DBA has been associated with mutations in nine ribosomal protein (RP) genes in about 53% of patients. We completed a large-scale screen of 79 RP genes by sequencing 16 RP genes (RPL3, RPL7, RPL8, RPL10, RPL14, RPL17, RPL19, RPL23A, RPL26, RPL27, RPL35, RPL36A, RPL39, RPS4X, RPS4Y1, and RPS21) in 96 DBA probands. We identified a de novo two-nucleotide deletion in RPL26 in one proband associated with multiple severe physical abnormalities. This mutation gives rise to a remarkable ribosome biogenesis defect that affects maturation of both the small and the large subunits. We also found a deletion in RPL19 and missense mutations in RPL3 and RPL23A, which may be variants of unknown significance. Together with RPL5, RPL11, and RPS7, RPL26 is the fourth RP regulating p53 activity that is linked to DBA.     

Regulation of WAVE1 expression in macrophages at multiple levels

M-CSF (or CSF-1) controls macrophage lineage development and function. A CSF-1-dependent culture system was established, which monitored the differentiation of CSF-1-responsive macrophage populations over time and upon adherence. Wiskott-Aldrich syndrome protein verprolin homologous (WAVE) proteins are involved in actin reorganization, a process critical to many cell functions. WAVE2 but not WAVE1 has been considered significant for macrophage function. Using the CSF-1-dependent differentiation system, we were able to demonstrate the contrasting regulation of the expression of WAVE1 and WAVE2; the levels of the latter rose over time and as the macrophage population became adherent, although those of the former increased over time but were down-regulated upon adherence. Evidence was obtained that WAVE1 was also cleaved to a novel, 60-kDa fragment by macrophage adherence and by another pathway involving calpain-mediated proteolysis. Mutagenesis studies indicated that cleavage of WAVE1 by calpain results in the removal of the verprolin-homology, cofilin-like, and acidic domain and thus, the loss of WAVE1 activity. We suggest that WAVE1 is also important for macrophage biology and that it could have separate functions to those of WAVE2.