Susan H. Brown

Evidence for a functional link between profilin and CAP in the yeast S. cerevisiae

CAP is a component of the S. cerevisiae adenylyl cyclase complex. The N-terminal domain is required for cellular RAS responsiveness. Loss of the C-terminal domain is associated with morphological and nutritional defects. Here we report that cap- cells bud randomly and are defective in actin distribution. The morphological and nutritional defects associated with loss of the CAP C-terminal domain are suppressed by over-expression of PFY, the gene encoding profilin, an actin- and polyphosphoinositide-binding protein. The phenotype of cells lacking PFY resembles that of cells lacking the CAP C-terminal domain. Study of mutated yeast profilins and profilins from Acanthamoeba suggests that the ability of profilin to suppress cap- cells is dependent upon a property other than, or in addition to, its ability to bind actin. This property may be its ability to bind polyphosphoinositides. We propose that CAP and profilin provide a link between growth signals and remodeling of the cellular cytoskeleton.

Initial agonist burst duration depends on movement amplitude

SummaryThe initial burst of EMG activity associated with arm movements made by normal human subjects was studied. Subjects made visually guided, steptracking movements of different amplitudes and speeds. The duration of the initial agonist burst was greater for large than for small amplitude movements. The burst duration was not continuously graded but was either short (70 ms) for small amplitude movements (less than 20 deg) or long (140 ms) for large amplitude ones (greater than 50 deg). Movements of intermediate amplitudes (30–40 deg) were made with both short and long duration bursts. The increase in the duration of the initial agonist burst for large movements was produced by the appearance of a second component in the burst. Both components were of the same duration and occurred before movement peak velocity was reached. Intramuscular recording showed that both components originate from the same muscle. Similar observations were made in both fast and slow movements and in both the biceps and triceps muscles when they were being used as agonists. The data show that the central nervous system has two mechanisms for generation of large amplitude movements: modulation of the magnitude of the initial agonist burst and generation of a second component or pulse of agonist activity at the start of movement.

Upper limb asymmetries in the utilization of proprioceptive feedback

Despite the importance of proprioception during upper limb movement, the extent to which arm/hemisphere asymmetries exist in the utilization of proprioceptive feedback remains unclear. In the present study, movement accuracy and arm dynamics were examined in 20 right-handed adults during a proprioceptive matching task that required subjects to actively match remembered target positions of the elbow with the contralateral arm. As hypothesized, the results indicated an accuracy advantage in favor of the non-preferred left arm reflected by smaller absolute matching errors when compared to the preferred right arm. This advantage was most pronounced for larger amplitude movements and was not associated with any limb-specific difference in movement strategy as indicated by the dynamics of the matching movement. These results extend current theories of handedness by demonstrating that, in right-handed individuals, the non-preferred arm/hemisphere system is more adept at utilizing position-related proprioceptive information than the preferred arm/hemisphere system.

Initial agonist burst duration changes with movement amplitude in a deafferented patient.

SummaryChanges in the duration of the initial agonist burst were studied in a deafferented human. The patient had been functionally deafferented for five years, having no touch, vibration, pressure or kinesthetic sensation nor any tendon reflexes in the four limbs. Pain and temperature sensation were intact and motor fibres were unaffected. The subject made visually guided step-tracking movements using flexion/extension movements about the elbow. Initial agonist burst duration increased with movement amplitude. Burst duration was approximately 65 ms in small movements (6–12 deg) increasing to 136 ms in intermediate (36 deg) and 200 ms in large (54 and 60 deg) movements. Similar changes in initial burst duration with movement amplitude were seen when the subject made non-visually guided movements. It is concluded that the duration of the initial agonist burst is centrally determined.

Task-dependent asymmetries in the utilization of proprioceptive feedback for goal-directed movement

Whereas the majority of studies regarding upper limb asymmetries in motor performance have focused on preferred arm dominance for producing motor output, studies exploring the role of sensory feedback have suggested that the preferred and non-preferred arms are specialized for different aspects of movement. A recent study by Goble et al. (2006) found evidence of a non-preferred left arm (and presumably right hemisphere) proprioceptive dominance for a target matching task that required subjects to both memorize and transfer across hemispheres proprioceptive target information. This paradigm contrasted previous studies of proprioceptive matching asymmetry that explored only memory-based matching and produced equivocal results. The purpose of the present study, therefore, was to examine task-dependent asymmetries in proprioceptive matching performance, including differences related to active versus passive presentation of the matching target. It was found that the non-preferred left arm of right handers matched target elbow angles more accurately than the preferred arm, but only in the matching condition that required both memory and interhemispheric transfer. Task-dependent asymmetries were not affected by the mode of target presentation and assessment of matching kinematics revealed differences in strategy for both the speed and smoothness of targeted movements. Taken together, these results suggest that the non-preferred arm/hemisphere system is specialized for the processing of movement-related proprioceptive feedback.

AGE-RELATED DIFFERENCES IN UPPER LIMB PROPRIOCEPTIVE ACUITY '.'

Although upper limb movements are known to be slower and more variable in elderly persons, the extent to which these changes are associated with deficits in movement-related sensory feedback is poorly understood, despite the importance of proprioception in the control of skilled movement. Age-related changes were examined with 22 participants (10 of M age 27 years and 12 of M age 75 years) in performance of an elbow position-matching task which varied in terms of interhemispheric transfer and/or the need to retrieve memory-based proprioceptive information. Matching errors were significantly greater, and movements more prolonged, and irregular in their time course in the elderly group than in the young group. Impaired performance in conditions requiring interhemispheric transfer and retrieval of memory-based proprioceptive information reflected the importance of cognitive processing during complex sensorimotor tasks. This novel matching paradigm provided a sensitive means of manipulating the demands of the task and may be an effective method for as sessing both cognitive and sensorimotor declines associated with aging.

Responses to force perturbations preceding voluntary human arm movements.

Brief force perturbations were applied 30-120 ms prior to onset of step-tracking forearm movements by normal humans. The perturbations altered the first agonist burst of the movement-related triphasic EMG pattern. Perturbations opposing the movement resulted in an increase in the magnitude of the late part of the first agonist burst, the early part being unchanged. Conversely, in movements which would be assisted by the perturbation, EMG magnitude decreased during the late part of the burst. No reflex EMG responses were elicited during the period following the perturbation and preceding onset of the first agonist burst.

Movement-related phasic muscle activation - III. The duration of phasic agonist activity initiating movement

To test the hypothesis that phasic muscle activation is related to the acceleration-deceleration characteristics of the resulting movement, we examined the relation between the duration of the acceleratory phase of a variety of movement types and the duration of the phasic muscle activity producing the acceleration (the initial agonist burst, AG1). Movements of five types were studied: (1) step-tracking movements of different amplitudes (10–90 deg) and durations (200–800 ms), (2) movements of the same amplitude (40 deg) and duration (600 ms) varying only in their symmetry ratio (SR, ratio of acceleration to deceleration durations), (3) movements in which acceleration duration was changed while acceleration magnitude was held constant, (4) oscillatory movements of different frequencies and peak amplitudes, (5) step-tracking movements against different inertial loads. Subjects made movements about the elbow joint in the horizontal plane. Surface electromyographic (EMG) activity was recorded from the biceps and the lateral head of the triceps muscles. Under all movement conditions tested and with acceleration duration ranging from 100 to 500 ms, acceleration duration varied linearly with the duration of AG1. Correlation coefficients for the linear regression lines ranged from 0.8 to 0.99. The slope of the best fit linear regression lines ranged from 0.5 to 1.6 and tended to be higher for extensions than flexions. The variations in slope may arise from differing mechanical properties of the biceps and triceps muscles, as well as from active forces produced in the antagonist. AG1 duration was unchanged by inertial loading when subjects kept acceleration duration constant. If subjects responded to an increase in inertial load with an increase in acceleration duration, there was a corresponding increase in AG1 duration. The data demonstrate a general relation between one characteristic of muscle activation (AG1 duration) and the resulting movement. The linear form of the relation is invariant across movement amplitude (range 10–90 deg), speed, duration (range 200–800 ms) and temporal profile (SR range 0.3-2.7), and is also independent of movement type (step, oscillatory). Such a general and simple relation between EMG and movement suggests that, at least to a first approximation, the nervous system can rather simply determine the muscle activation patterns needed to produce movements with desired characteristics.

Role of the cerebellum in visuomotor coordination I. Delayed eye and arm initiation in patients with mild cerebellar ataxia

The initiation of coupled eye and arm movements was studied in six patients with mild cerebellar dysfunction and in six age-matched control subjects. The experimental paradigm consisted of 40 deg step-tracking elbow movements made under different feedback conditions. During tracking with the eyes only, saccadic latencies in patients were within normal limits. When patients were required to make coordinated eye and arm movements, however, eye movement onset was significantly delayed. In addition, removal of visual information about arm versus target position had a pronounced differential effect on movement latencies. When the target was extinguished for 3 s immediately following a step change in target position, both eye and arm onset times were further prolonged compared to movements made to continuously visible targets. When visual information concerning arm position was removed, onset times were reduced. Eye and arm latencies in control subjects were unaffected by changes in visual feedback. The results of this study clearly demonstrate that, in contrast to earlier reports of normal saccadic latencies associated with cerebellar dysfunction, initiation of both eye and arm movements is prolonged during coordinated visuomotor tracking thus supporting a coordinative role for the cerebellum during oculo-manual tracking tasks.

Effects of gravitational forces on single joint arm movements in humans

We have examined the kinematics and muscle activation patterns of single joint elbow movements made in the vertical plane. Movements of different amplitudes were performed during a visual, step-tracking task. By adjusting shoulder position, both elbow flexion and extension movements were made under three conditions: (a) in the horizontal plane, (b) in the vertical plane against gravity, and (c) in the vertical plane with gravity. Regardless of the gravitational load, all movements were characterized by time symmetric velocity profiles. In addition, no differences were found in the relationships between movement duration, peak velocity, and movement amplitude in movements with or against gravity. The pattern of muscle activation was influenced however, by the gravitational load. Both flexion and extension movements made with gravity were characterized by a reciprocally organized pattern of muscle activity in which phasic agonist activity was followed by phasic antagonist activity. Flexion and extension movements made against gravity were characterized by early phasic antagonist activity occurring at about the same time as the initial agonist burst. These findings suggest that EMG patterns are modified in order to preserve a common temporal structure in the face of different gravitational loads.