Faculty Bibliography

We examine the role of visual feedback in the programming and execution of reaching movement in patients with Parkinson's disease without cognitive impairment and patients with Alzheimer's disease without extrapyramidal signs. Controls were normally aging subjects. All subjects moved a cursor to targets on a digitizing tablet without seeing their limb. Starting and target positions were always visible on a screen while, during movement, cursor position was either visible or blanked. They were instructed to make uncorrected movements, as fast and as accurate as possible without minimizing reaction time. In absence of visual feedback, movement accuracy in patients with AD was severely impaired. Hand paths of parkinsonian patients were as accurate as normal subjects' with similar temporal velocity profiles and movement speed. With cursor feedback, accuracy was the same in the three groups, although movement speed and transport phase in patients with Alzheimer's disease were significantly reduced compared to the other groups. Also, movements of parkinsonian patients showed shorter transport phase and lower mean velocity than controls'. The different characteristics of the motor performance suggests that in the two diseases visual information is used differently for both motor programming and execution: patients with Alzheimer's disease, while scarcely using feed forward commands, relied on continuous on-line external cues. The correlation of motor performance with cognitive impairment argues against the hypothesis of basal ganglia involvement in AD. The motor abnormalities we found may represent early subclinical manifestation of apraxic disturbance. Parkinsonian patients showed higher reliance on feedback commands only with cursor feedback: this could be explained by their difficulty in engaging effectively automatic routines when distractors are present

Psychophysical studies of reaching movements suggest that hand kinematics are learned from errors in extent and direction in an extrinsic coordinate system, whereas dynamics are learned from proprioceptive errors in an intrinsic coordinate system. We examined consolidation and interference to determine if these two forms of learning were independent. Learning and consolidation of two novel transformations, a rotated spatial reference frame and altered intersegmental dynamics, did not interfere with each other and consolidated in parallel. Thus separate kinematic and dynamic models were constructed simultaneously based on errors computed in different coordinate frames, and possibly, in different sensory modalities, using separate working-memory systems. These results suggest that computational approaches to motor learning should include two separate performance errors rather than one

Movement accuracy in normal subjects depends on feedforward commands based on representation in memory of spatial and biomechanical features. Here we ask whether memory deficits in Alzheimer's disease (AD) interfere with movement planning and execution. Nine AD patients and nine age-matched controls moved a cursor to targets without seeing their limb. Starting and target positions were always visible on a screen, while, during movement, cursor position was either visible or blanked. Patients' paths showed discontinuous segments and prolonged movement time; movement inaccuracy, which increased without visual feedback, correlated significantly with scores of disease severity, working memory and attention

We have previously demonstrated that, in preparing themselves to aim voluntary impulses of isometric elbow force to unpredictable targets, subjects selected default values for amplitude and direction according the range of targets that they expected. Once a specific target appeared, subjects specified amplitude and direction through parallel processes. Amplitude was specified continuously from an average or central default; direction was specified stochastically from one of the target directions. Using the same timed response paradigm, we now report three experiments to examine how the time available for processing target information influences trajectory characteristics in two-degree-of-freedom forces and multijoint movements. We first sought to determine whether the specification of force direction could also take the form of a discrete stochastic process in pulses of wrist muscle force, where direction can vary continuously. With four equiprobable targets (two force amplitudes in each of two directions separated by 22 degrees or 90 degrees), amplitude was specified from a central default value for both narrow and wide target separations as a continuous variable. Direction, however, remained specified as a discrete variable for wide target separations. For narrow target separations, the directional distribution of default responses suggested the presence of both discrete and central values. We next examined point-to-point movements in a multijoint planar hand movement task with targets at two distances and two directions but at five directional separations (from 30 degrees to 150 degrees separation). We found that extent was again specified continuously from a central default. Direction was specified discretely from alternative default directions when target separation was wide and continuously from a central default when separation was narrow. The specification of both extent and direction evolved over a 200-ms time period beginning about 100 ms after target presentation. As in elbow force pulses, extent was specified progressively in both correct and wrong direction responses through a progressive improvement in the scaling of acceleration and velocity peaks to the target. On the other hand, movement time and hand path straightness did not change significantly in the course of specification. Thus, the specification of movement time and linearity, global features of the trajectories, are given priority over the specific values of extent and direction. In a third experiment, we varied the distances between unidirectional target pairs and found that movement extent is specified discretely, like direction, when the disparity in distances is large. The implications of these findings for contextual effects on trajectory planning are discussed. The independence of extent and direction specification and the prior setting of response duration and straightness provide critical support for the hypothesis that point-to-point movements are planned vectorially

1. The dependence of directional biases in reaching movements on the initial position of the hand was studied in normal human subjects moving their unseen hand on a horizontal digitizing tablet to visual targets displayed on a vertical computer screen. 2. When initial hand positions were to the right of midline, movements were systematically biased clockwise. Biases were counterclockwise for starting points to the left. Biases were unaffected by the screen location of the starting and target positions. 3. Vision of the hand in relation to the target before movement, as well as practice with vision of the cursor during the movement, temporarily eliminated these biases. The spatial organization of the biases suggests that, without vision of the limb, the nervous system underestimates the distance of the hand from an axis or plane that includes its most common operating location. 4. To test the hypothesis that such an underestimate might represent an adaptation to a local area of work space or range effect, subjects were trained to reach accurately from right or left positions. After training, movements initiated from other locations, including ones that were previously error free, showed new biases that again represented underestimates of the distance of the initial hand position from the new trained location. 5. We conclude that hand path planning is dependent on learned representations of the location of the hand in the work space

1. We recently showed that patients lacking proprioceptive input from their limbs have particular difficulty performing multijoint movements. In a pantomimed slicing gesture requiring sharp reversals in hand path direction, patients showed large hand path distortions at movement reversals because of failure to coordinate the timing of the separate reversals at the shoulder and elbow joints. We hypothesized that these reversal errors resulted from uncompensated effects of inertial interactions produced by changes in shoulder joint acceleration that were transferred to the elbow. We now test this hypothesis and examine the role of proprioceptive input by comparing the motor performance of five normal subjects with that of two patients with large-fiber sensory neuropathy. 2. Subjects were to trace each of six template lines presented randomly on a computer screen by straight overlapping out-and-back movements of the hand on a digitizing tablet. The lines originated from a common starting position but were in different directions and had different lengths. Directions and lengths were adjusted so that tracing movements would all require the same elbow excursion, whereas shoulder excursion would vary. The effects of varying interaction torques on elbow kinematics were then studied. The subject's dominant arm was supported in the horizontal plane by a low-inertia brace equipped with ball bearing joints and potentiometers under the elbow and shoulder. Hand position was monitored by a magnetic pen attached to the brace 1 cm above a digitizing tablet and could be displayed as a screen cursor. Vision of the subject's arm was blocked and the screen cursor was blanked at movement onset to prevent visual feedback during movement. Elbow joint torques were calculated from joint angle recordings and compared with electromyographic recordings of elbow joint musculature. 3. In control subjects, outward and inward paths were straight and overlapped the template lines regardless of their direction. As prescribed by the task, elbow kinematics remained the same across movement directions, whereas interaction torques varied substantially. The timing of the onsets of biceps activity and the offsets of triceps activity during elbow flexion varied systematically with direction-dependent changes in interaction torques. Controls exploited or dampened these interaction torques as needed to meet the kinematic demands of the task. 4. In contrast, the patients made characteristic errors at movement reversals that increased systematically across movement directions. These reversal errors resulted from improper timing of elbow and shoulder joint reversals.(ABSTRACT TRUNCATED AT 400 WORDS)

1. The aim of this study was to determine how vision of a cursor indicating hand position on a computer screen or vision of the limb itself improves the accuracy of reaching movements in patients deprived of limb proprioception due to large-fiber sensory neuropathy. In particular, we wished to ascertain the contribution of such information to improved planning rather than to feedback corrections. We analyzed spatial errors and hand trajectories of reaching movements made by subjects moving a hand-held cursor on a digitizing tablet while viewing targets displayed on a computer screen. The errors made when movements were performed without vision of their arm or of a screen cursor were compared with errors made when this information was available concurrently or prior to movement. 2. Both monitoring the screen cursor and seeing their limb in peripheral vision during movement improved the accuracy of the patients' movements. Improvements produced by seeing the cursor during movement are attributable simply to feedback corrections. However, because the target was not present in the actual workspace, improvements associated with vision of the limb must involve more complex corrective mechanisms. 3. Significant improvements in performance also occurred in trials without vision that were performed after viewing the limb at rest or during movements. In particular, prior vision of the limb in motion improved the ability of patients to vary the duration of movements in different directions so as to compensate for the inertial anisotropy of the limb. In addition, there were significant reductions in directional errors, path curvature, and late secondary movements. Comparable improvements in extent, direction, and curvature were produced when subjects could see the screen cursor during alternate movements to targets in different directions. 4. The effects of viewing the limb were transient and decayed during a period of minutes once vision of the limb was no longer available. 5. It is proposed that the improvements in performance produced after vision of the limb were mediated by the visual updating of internal models of the limb. Vision of the limb at rest may provide configuration information while vision of the limb in motion provides additional dynamic information. Vision of the cursor and the resulting ability to correct ongoing movements, however, is considered primarily to provide information about the dynamic properties of the limb and its response to neural commands

1. This paper introduces a series of studies in which we analyze the impairments in a planar reaching task in human patients with severe proprioceptive deficits resulting from large-fiber sensory neuropathy. We studied three patients, all of whom showed absence of discriminative tactile sensation, position sense, and stretch reflexes in the upper extremities. Muscle strength was normal. We compared the reaching movements of the patients with those of normal control subjects. The purpose of this first paper was no characterize the spatial errors in these patients that result primarily from impairments in the planning and execution of movement rather than in feedback control. This was done by using a task in which visual feedback of errors during movement was prevented. 2. Subjects were instructed to move their hand from given starting positions of different targets on a horizontal digitizing tablet. Hand position and targets were displayed on a computer screen. Subjects could not see their hand, and the screen display of hand position was blanked at the signal to move. Thus visual feedback during movement could not be used to achieve accuracy. Movement paths were displayed as knowledge of results after each trial. 3. Compared with controls, the patients made large spatial errors in both movement direction and extent. Directional errors were evident from movement onset, suggesting that they resulted from improper planning. In addition, patients' hand paths showed large curves and secondary movements after initial stops. 4. The overall control strategy used by patients appeared the same as that used by controls. Hand trajectories were approximately bell shaped, and movement extent was controlled by scaling a trajectory waveform in amplitude and time. However, both control subjects and patients showed systematic errors in movement extent that depended on the direction of hand movement. In control subjects, these systematic dependencies of extent on direction were small, but in patients they produced large and prominent errors. Analysis of the hand trajectories revealed that errors were associated with differences in velocity and acceleration for movements in different directions. In an earlier study, we showed that in subjects with normal sensation that the dependence of acceleration and velocity on direction results from a failure to take the inertial properties of the limb into account in programming the initial trajectory. In control subjects, these differences in initial acceleration are partially compensated by direction-dependent variations in movement time.(ABSTRACT TRUNCATED AT 400 WORDS)

Somatosensory Evoked Potentials (SEPs) to median nerve stimuli were recorded in seven Cynomolgus monkeys before and after the induction of the MPTP-parkinsonian syndrome. SEPs recorded after the onset of parkinsonism showed a significant amplitude reduction of an anterior negative component peaking at about 15 ms (N15), independent of the severity of symptoms. The amplitude decrease was not reversed by the administration of I-dopa, despite clinical improvement, or cholinergic, noradrenergic and gabaergic agents. Amplitudes of N15 and of parietal P15 components were increased by the administration of the N-MDA antagonists ketamine and MK 801, and markedly increased when monkeys were given the anaesthetic agent etomidate. The present study shows that the reduced N15 SEP component of parkinsonian monkeys is similar to the reduced frontal N30 SEP component evidenced by other authors in patients affected by Parkinson's disease. The attenuation of N15 is not related to deficitary dopaminergic, noradrenergic, cholinergic and gabaergic systems. The implications of this finding and the role of glutamate toxicity are discussed

This study examined the variability in movement end points in a task in which human subjects reached to targets in different locations on a horizontal surface. The primary purpose was to determine whether patterns in the variable errors would reveal the nature and origin of the coordinate system in which the movements were planned. Six subjects moved a hand-held cursor on a digitizing tablet. Target and cursor positions were displayed on a computer screen, and vision of the hand and arm was blocked. The screen cursor was blanked during movement to prevent visual corrections. The paths of the movements were straight and thus directions were largely specified at the onset of movement. The velocity profiles were bell-shaped, and peak velocities and accelerations were scaled to target distance, implying that movement extent was also programmed in advance of the movement. The spatial distributions of movement end points were elliptical in shape. The major axes of these ellipses were systematically oriented in the direction of hand movement with respect to its initial position. This was true for both fast and slow movements, as well as for pointing movements involving rotations of the wrist joint. Using principal components analysis to compute the axes of these ellipses, we found that the eccentricity of the elliptical dispersions was uniformly greater for small than for large movements: variability along the axis of movement, representing extent variability, increased markedly but nonlinearly with distance. Variability perpendicular to the direction of movement, which results from directional errors, was generally smaller than extent variability, but it increased in proportion to the extent of the movement. Therefore, directional variability, in angular terms, was constant and independent of distance. Because the patterns of variability were similar for both slow and fast movements, as well as for movements involving different joints, we conclude that they result largely from errors in the planning process. We also argue that they cannot be simply explained as consequences of the inertial properties of the limb. Rather they provide evidence for an organizing mechanism that moves the limb along a straight path. We further conclude that reaching movements are planned in a hand-centered coordinate system, with direction and extent of hand movement as the planned parameters. Since the factors which influence directional variability are independent of those that influence extent errors, we propose that these two variables can be separately specified by the brain