Control of aperture closure during reach-to-grasp movements in Parkinson's disease.

This study examined whether the pattern of coordination between arm-reaching toward an object (hand transport) and the initiation of aperture closure for grasping is different between PD patients and healthy individuals, and whether that pattern is affected by the necessity to quickly adjust the reach-to-grasp movement in response to an unexpected shift of target location. Subjects reached for and grasped a vertical dowel, the location of which was indicated by illuminating one of the three dowels placed on a horizontal plane. In control conditions, target location was fixed during the trial. In perturbation conditions, target location was shifted instantaneously by switching the illumination to a different dowel during the reach. The hand distance from the target at which the subject initiated aperture closure (aperture closure distance) was similar for both the control and perturbation conditions within each group of subjects. However, that distance was significantly closer to the target in the PD group than in the control group. The timing of aperture closure initiation varied considerably across the trials in both groups of subjects. In contrast, aperture closure distance was relatively invariant, suggesting that aperture closure initiation was determined by spatial parameters of arm kinematics rather than temporal parameters. The linear regression analysis of aperture closure distance showed that the distance was highly predictable based on the following three parameters: the amplitude of maximum grip aperture, hand velocity, and hand acceleration. This result implies that a control law, the arguments of which include the above parameters, governs the initiation of aperture closure. Further analysis revealed that the control law was very similar between the subject groups under each condition as well as between the control and perturbation conditions for each group. Consequently, the shorter aperture closure distance observed in PD patients apparently is a result of the hypometria of their grip aperture and bradykinesia of hand transport movement, rather than a consequence of a deficit in transport-grasp coordination. It is also concluded that the perturbation of target location does not disrupt the transport-grasp coordination in either healthy individuals or PD patients.

Movement precues in planning and execution of aiming movements in Parkinson's disease.

Two experiments tested how changing a planned movement affects movement initiation and execution in idiopathic Parkinson's disease (PD) patients. In Experiment 1, PD patients, elderly controls, and young adults performed discrete aiming movements to one of two targets on a digitizer. A precue (80% valid cue and 20% invalid cue of all trials) reflecting the subsequent movement direction was presented prior to the imperative stimulus. All groups produced slower reaction times (RTs) to the invalid precue condition. Only the subgroup of patients with slowest movement time showed a significant prolongation of movement for the invalid condition. This suggests that, in the most impaired patients, modifying a planned action also affects movement execution. In Experiment 2, two-segment aiming movements were used to increase the demand on movement planning. PD patients and elderly controls underwent the two precue conditions (80% valid, 20% invalid). Patients exhibited longer RTs than the controls. RT was similarly increased for the invalid condition in both groups. The patients, however, exhibited longer movement times, lower peak velocities, and higher normalized jerk scores of the first segment in the invalid condition compared to the valid condition. Conversely, the controls showed no difference between the valid and invalid cue conditions. Thus, PD patients demonstrated substantially pronounced movement slowness and variability when required to change a planned action. The results from both experiments suggest that modifying a planned action may continue beyond the initiation phase into the execution phase in PD patients.

Adaptation of reach-to-grasp movement in response to force perturbations.

This study examined how reach-to-grasp movements are modified during adaptation to external force perturbations applied on the arm during reach. Specifically, we examined whether the organization of these movements was dependent upon the condition under which the perturbation was applied. In response to an auditory signal, all subjects were asked to reach for a vertical dowel, grasp it between the index finger and thumb, and lift it a short distance off the table. The subjects were instructed to do the task as fast as possible. The perturbation was an elastic load acting on the wrist at an angle of 105 deg lateral to the reaching direction. The condition was modified by changing the predictability with which the perturbation was applied in a given trial. After recording unperturbed control trials, perturbations were applied first on successive trials (predictable perturbations) and then were applied randomly (unpredictable perturbations). In the early predictable perturbation trials, reach path length became longer and reaching duration increased. As more predictable perturbations were applied, the reach path length gradually decreased and became similar to that of control trials. Reaching duration also decreased gradually as the subjects adapted by exerting force against the perturbation. In addition, the amplitude of peak grip aperture during arm transport initially increased in response to repeated perturbations. During the course of learning, it reached its maximum and thereafter slightly decreased. However, it did not return to the normal level. The subjects also adapted to the unpredictable perturbations through changes in both arm transport and grasping components, indicating that they can compensate even when the occurrence of the perturbation cannot be predicted during the inter-trial interval. Throughout random perturbation trials, large grip aperture values were observed, suggesting that a conservative aperture level is set regardless of whether the reaching arm is perturbed or not. In addition, the results of the predictable perturbations showed that the time from movement onset to the onset of grip aperture closure changed as adaptation occurred. However, the spatial location where the onset of finger closure occurred showed minimum changes with perturbation. These data suggest that the onset of finger closure is dependent upon distance to target rather than the temporal relationship of the grasp relative to the transport phase of the movement.

Long-term retention of motor skill in macaque monkeys and humans.

Remarkable human performance, such as playing the violin, is often based on motor skills that, once acquired, are retained for a long time. To examine how motor skills are retained, we trained monkeys and humans extensively to perform many visuomotor sequences and examined their performance after a long retention period of up to 18 months. For both monkeys and humans, we found strong evidence for long-term retention of motor skills. Each of the monkey subjects initially learned 6-18 sequences of button presses extensively by trial-and-error for up to 18 months. After a long retention period, they were asked to perform the previously learned (OLD) sequences together with completely new (NEW) sequences. The performance for OLD sequences was much better than for NEW sequences in terms of accuracy (assessed by the number of errors to criterion) and speed (assessed by the performance time). However, the retention was interfered with in two conditions, but in selective manners: (1) Learning of other sequences during the retention period interfered with accuracy, but not speed, of performance; (2) Inter-manual transfer was absent for speed, but not accuracy, of performance. The human subjects performed basically the same task as the monkeys. Each subject initially learned one sequence of 20 button presses by trial-and-error during an 8-10 day learning session. After 16 months, they were asked to perform the previously learned sequence (OLD sequence) and additional sequences including RECENT sequences (learned one day before) and NEW sequences. Their performance was considerably better on OLD and RECENT sequences than NEW sequences. Whereas the number of errors (reflecting 'accuracy') was lower for RECENT than for OLD sequences, the performance time (reflecting 'speed') was shorter for OLD than for RECENT sequences. Interestingly, the subjects were unaware that they had experienced OLD sequences. The results suggest that a motor skill is acquired and retained in two different forms, accuracy and speed. This occurs separately but concurrently. This conclusion is consistent with the hypothesis that at least two neural mechanisms operate independently to represent a motor skill.

Effects of accuracy constraints on reach-to-grasp movements in cerebellar patients.

Reach-to-grasp movements of patients with pathology restricted to the cerebellum were compared with those of normal controls. Two types of paradigms with different accuracy constraints were used to examine whether cerebellar impairment disrupts the stereotypic relationship between arm transport and grip aperture and whether the variability of this relationship is altered when greater accuracy is required. The movements were made to either a vertical dowel or to a cross bar of a small cross. All subjects were asked to reach for either target at a fast but comfortable speed, grasp the object between the index finger and thumb, and lift it a short distance off the table. In terms of the relationship between arm transport and grip aperture, the control subjects showed a high consistency in grip aperture and wrist velocity profiles from trial to trial for movements to both the dowel and the cross. The relationship between the maximum velocity of the wrist and the time at which grip aperture was maximal during the reach was highly consistent throughout the experiment. In contrast, the time of maximum grip aperture and maximum wrist velocity of the cerebellar patients was quite variable from trial to trial, and the relationship of these measurements also varied considerably. These abnormalities were present regardless of the accuracy requirement. In addition, the cerebellar patients required a significantly longer time to grasp and lift the objects than the control subjects. Furthermore, the patients exhibited a greater grip aperture during reach than the controls. These data indicate that the cerebellum contributes substantially to the coordination of movements required to perform reach-to-grasp movements. Specifically, the cerebellum is critical for executing this behavior with a consistent, well-timed relationship between the transport and grasp components. This contribution is apparent even when accuracy demands are minimal.

Segment interdependency and difficulty in two-stroke sequences.

We previously demonstrated that velocity and movement time for the initial segment for a two-stroke movement are scaled in relation to the difficulty of the second segment. The interdependent kinematic changes were interpreted as evidence that movement planning/organization processes consider the movement parameters of both segments when determining the movement characteristics of the entire sequence. In this experiment we examined two-stroke movements where the difficulty of the first segment had either a low or high level of difficulty to determine if the interdependent kinematic changes are diminished when parameter specification is high for the initial segment. Two-stroke arm movements toward defined targets were made in the horizontal plane on an x-y digitizer. The direction of the first segment was an elbow extension movement away from the trunk. The direction of the second segment varied between forearm extension and flexion movements. Two different indexes of difficulty (IDs) of the first segment and two of the second segment were created by varying target size. In the low ID condition for the first segment, movement duration of the initial segment lengthened and peak velocity decreased when the ID of the second segment was increased, and this pattern was found for both the extension-extension and extension-flexion sequences. In contrast, when the level of difficulty was high for the first segment, the interdependencies disappeared for the extension-extension sequence: movement duration and peak velocity were unaffected by the difficulty of the second segment. For the extension-flexion sequence, however, the interdependencies were found in the movement time of the initial segment but were eliminated in the peak velocity, i.e., movement time increased, but the peak velocity did not change. Furthermore, for both the extension-extension and extension-flexion sequences, the intersegment interval was lengthened as the level of difficulty increased. These findings suggest that difficulty of the initial segment affects how the motor planning/organization processes treat adjacent segments of the sequence. In particular, the data support the hypothesis that when the initial movement segment has a high index of difficulty, motor planning/organization processes appear to treat the adjacent segments separately as two discrete actions.

EMG analysis of lower limb muscles in humans during quick change in running directions.

Open and cross maneuvers for changing running direction were studied to characterize selective EMG activity between the maneuvers. Eleven subjects turned towards the right or the left during running. The gluteus medius modified foot trajectory of the leading leg during the open maneuver, whereas the sartorius worked modestly during the cross maneuver. Compared with the cross maneuver the open maneuver exhibited greater vastus medialis and gastrocnemius activity during the ground support phase, faster running speed and wider turning angle. These results suggest that the open maneuver is more effective than the cross maneuver for quickly changing running direction.

Characteristics of sequential movements during early learning period in monkeys.

We previously demonstrated that the organization of a learned sequential movement, after long-term practice, is based on the entire sequence and that the information pertaining to the sequence is largely specific to the hand used for practice. However, it remained unknown whether these characteristics are present from the beginning of learning. To answer the question, we examined the performance of four monkeys for the same sequential procedure in the early stage of learning. The monkeys' task was to press five consecutive pairs of buttons (which were illuminated), in a correct order for every pair, which they had to find by trial-and-error during a block of trials. We first examined whether the memory of a sequential procedure that was learned once was specific to the hand used for practice. The second time that the monkeys attempted to learn a novel sequence, they were required to use either the same hand they used the first time or the opposite hand. The number of errors decreased to a similar degree in the same-hand condition and in the opposite-hand condition. The performance time decreased in the same-hand condition, but not in the opposite-hand condition. The results suggest that, in the early stage of learning, memory of the correct performance of a sequential procedure is not specific to the hand originally used to perform the sequence (unlike the well-learned stage, where the transfer was incomplete), whereas memory of the fast performance of a sequential procedure is relatively specific to the hand used for practice (like the well-learned stage). We then examined whether memory of a sequential procedure depends on the entire sequence, not individual stimulus sets. For the second learning block, we had the monkey learn the sequence in the same or reversed order. In the reversed order, the order within each set was identical, but the order of sets was reversed. The number of errors decreased in both the same-order and reversed-order conditions to a similar degree for two out of four monkeys; the decrease was larger in the same-order condition for the other two monkeys. For all monkeys, the performance time decreased in the same-order condition, but not in the reversed-order condition. The results suggest that the memory structure for correct performance varies among monkeys in the early stage of learning (unlike the well-learned stage, where the memory of individual sets was consistently absent). On the other hand, memory of the fast performance of a sequential procedure is relatively specific to the learned order used for practice (like the well-learned stage).

Movement accuracy constraints in Parkinson's disease patients.

This study examined the hypothesis that the kinematics of movements performed by PD (Parkinson's disease) patients are differentially affected depending on whether or not the aiming movement has an accuracy constraint. The aiming movements required elbow extension in the horizontal plane on a digitizer. There were two movement conditions: (1) one having a spatial accuracy requirement in which the subjects moved to the defined target and stopped on it; and (2) one requiring the subjects to move toward the defined target without stopping precisely on it. Subjects were instructed to make their movements as fast and as accurate as possible in response to the auditory imperative signal. PD patients modified the movement speed and kinematics depending on the two accuracy conditions. However, when the accuracy constraint was imposed, movement slowness observed in the patients was much more pronounced. The most revealing result was localized to the deceleration phase, particularly as the target was approached. The patients also were found to make a higher number of acceleration zero crossings from negative to positive to reach the target, indicating that the movements were more irregular. For the patients, the first acceleration zero crossing from negative to positive occurred much earlier in the movement than that for the controls. In addition, when movement accuracy was constrained, the number of zero crossings was accentuated. These data show that when PD patients make aiming movements to a target, their deceleration phase becomes longer and more variable.

Parallel neural networks for learning sequential procedures.

Recent studies have shown that multiple brain areas contribute to different stages and aspects of procedural learning. On the basis of a series of studies using a sequence-learning task with trial-and-error, we propose a hypothetical scheme in which a sequential procedure is acquired independently by two cortical systems, one using spatial coordinates and the other using motor coordinates. They are active preferentially in the early and late stages of learning, respectively. Both of the two systems are supported by loop circuits formed with the basal ganglia and the cerebellum, the former for reward-based evaluation and the latter for processing of timing. The proposed neural architecture would operate in a flexible manner to acquire and execute multiple sequential procedures.

Effects of increased stroke number on sequential arm movements in Parkinson's disease subjects.

To examine whether multiple-component movements performed by Parkinson's disease (PD) patients are impaired differentially depending on the number of strokes, 10 PD patients and 10 age-matched control subjects performed sequential arm movements with one, two or three strokes on a digitizer. The patients were slower than the controls in executing the movement sequences and showed prolonged delays between strokes. These slowing characteristics were accentuated as stroke number increased from two to three. These results suggest that PD patients have a reduced capacity to process information rapidly, thereby limiting their ability to perform complex movements.

Adaptive changes in responses to repeated locomotor perturbations in cerebellar patients.

This study examined the responses of cerebellar patients and a group of age- and sex-matched control subjects to repeated changes in treadmill speed in order to test whether cerebellar patients can adapt their gait to this type of perturbation and, if so, whether their responses are comparable to those of controls. While the subject walked on the treadmill, a perturbation consisting of a sudden slowing of the treadmill followed by a sudden increase back to the original speed was applied repeatedly at a specific time during the step cycle. Both the control subjects and cerebellar patients were able to compensate for the perturbations by minimizing their postural sway and changing step length. However, the nature of the compensatory changes in step length differed between these subject groups. Control subjects compensated for the perturbation by consistently using the same leg to initiate the response to the perturbation and by adapting a pattern of stepping such that the EMG characterizing the response occurred in a manner that was entrained to the timing of the normal locomotor cycle. In contrast, the patients, although undergoing modifications in step length, employed a much less consistent motor pattern from trial to trial than that of the normal subjects. An inconsistent pattern among their responses was apparent in both the analysis of stepping and in the EMG activity of the gastrocnemius and anterior tibial muscles. These results suggest that, although the cerebellar patients can adapt their behavior in response to locomotor perturbations, they do not establish a motor pattern comparable to that employed by normal subjects.

Characteristics of a long-term procedural skill in the monkey.

The purpose of this study was to characterize the nature and structure of procedural memory. We have previously studied the process of learning sequential behavioral procedures using monkeys. The monkey's task was to press five consecutive pairs of buttons (indicated by illumination) in the correct order for every pair, which he had to find by trial-and-error in a block of trials. The whole sequence was called a "hyperset"; each pair was called a "set". We first examined whether monkeys learned to perform a hyperset as a single sequence or learned the order of button-presses individually for each set. To answer this question, we generated hypersets that were the same as the hypersets that had been extensively learned except that the order of the sets was reversed. The performance of these "reversed hypersets" was much worse than the performance of the original learned hypersets and was similar to the performance of new hypersets, as regards both the number of errors and the performance time. The result suggests that monkeys learned a hyperset as a sequence. To examine whether the learned performance was specific to the hand used for practice, we had monkeys use the same hand throughout the long-term practice of each hyperset, and then tested the opposite hand. The performance using the opposite hand was worse than the performance using the trained hand, but was better than the performance for new hypersets. This indicates that the memory for the sequential procedure is only partially accessible to the hand that was not used for the practice.

Differential roles of monkey striatum in learning of sequential hand movement.

To study the role of the basal ganglia in learning of sequential movements, we trained two monkeys to perform a sequential button-press task (2x5 task). This task enabled us to examine the process of learning new sequences as well as the execution of well-learned sequences repeatedly. We injected muscimol (a GABA agonist) into different parts of the striatum to inactivate the local neural activity reversibly. The learning of new sequences became deficient after injections in the anterior caudate and putamen, but not the middle-posterior putamen. The execution of well-learned sequences was disrupted after injections in the middle-posterior putamen and, less severely, after injections in the anterior caudate/putamen. These results suggest that the anterior and posterior portions of the striatum participate in different aspects of learning of sequential movements.

The influence of movement segment difficulty on movements with two-stroke sequence.

Arm movements in the horizontal plane consisting of two segments were examined to determine whether the difficulty of the second segment influenced the kinematic characteristics of the first segment. The direction of the first segment was an elbow extension movement away from the trunk and remained constant throughout the experiment. The direction of the second segment varied between forearm extension and flexion movements. Based on Fitts' law, two different indexes of difficulty (ID) of the second segment were utilized by changing target size and movement amplitude. The effects of changing ID were examined for two different movement amplitudes. All movements were single-joint movements employing elbow flexion/extension and were recorded by an x-y digitizer. Variations in the ID of the second segment produced context-dependent kinematic changes in the performance of the initial segment. Movement duration increased when the ID was increased by reducing target size for both extension-extension sequence and extension-flexion sequences. Peak velocity also decreased for higher ID targets in the extension-flexion sequence. However, there was an interaction between the ID and movement amplitude in the extension-flexion sequence. In this sequence the duration of movement for the high ID/large movement amplitude condition increased substantially compared with the low ID/small movement amplitude condition. In addition, changing ID of the second segment influenced the time between the two segments (intersegment interval) in the extension-flexion sequence. Collectively, these data suggest that the planning of complex movements is based in part on the accuracy demands of multiple segments of the sequence.

Anticipatory saccades in sequential procedural learning in monkeys.

1. In a preceding paper we examined the short-term and long-term processes of learning of sequential procedures in monkeys. We now report that the pattern of eye movements changed along with the long-term learning. 2. The monkey's task was to press five consecutive pairs of target buttons (indicated by illumination) in the correct order for every pair, which the monkey had to find by trial and error (2 x 5 task). The whole sequence was called the "hyperset"; each pair was called the "set." 3. Initially, the saccade toward the correct target occurred after illumination of the targets (visually guided saccade). After sufficient learning, the saccade tended to occur before the target illumination (anticipatory saccade). This was true only for the hyperset that had been learned. 4. The likelihood of anticipatory saccade increased gradually over 20-30 days of practice of the particular hyperset. The time course was similar to how the hand learned (button press latency). 5. The monkeys were required to use the same hand for each hyperset throughout learning, except when we asked them to use the opposite hand. The nearly perfect performance due to the extensive practice was then deteriorated by the use of the opposite hand. We found, in addition, that anticipatory saccades became much less frequent. This finding suggests that critical for the skilled performance was the combination of the eyes and the side of the hand that was used for the practice of a given sequence.

Learning of sequential movements in the monkey: process of learning and retention of memory.

1. To characterize procedural learning and memory, we devised a behavioral paradigm that allows us to examine the process of learning of new procedures, repeatedly and without serious difficulties for primate subjects. We trained two monkeys to perform a sequential button press task. Upon pressing of a home key, 2 of 16 (4 x 4 matrix) light-emitting diode (LED) buttons (called "set") were illuminated simultaneously, and the monkey had to press them in a predetermined order that he had to find out by trial-and-error. A total of five sets (called "hyperset") was presented in a fixed order for completion of a trial; an error at any set aborted the trial. A given hyperset was repeated as a block of experiment until 20 successful trials were performed. Monkeys PI and BO experienced 313 and 92 hypersets, respectively. Most of these hypersets were experienced only once (1 block of experiment); the others (28 hypersets for monkey PI and 14 hypersets for monkey BO) were chosen for extensive practice. 2. The learning, indicated as the decrease in the number of trials to criterion and the decrease in the performance time, proceeded at three levels: 1) short-term and sequence-selective learning that occurred by repeating a particular hyperset during a block of experiment; our monkeys learned, to some degree, to perform a new hyperset within a short period (< 5 min); 2) long-term and sequence-selective learning that took place for each hyperset across days; by daily practice, they further improved their skills for performing the particular hyperset; and 3) long-term and sequence-unselective learning that was indicated by the improvement of performance for new hypersets; the monkeys were required to learn many hypersets, each just once (a block of trials), in which they performed gradually better with more experiences in the 2 x 5 task. 3. To examine whether the memory was retained for a long period, we had the monkey learn 12 hypersets sufficiently, then we stopped the training and retested them after 1 or 6 mo. After the 1-mo interruption the performance was significantly better than that for new hypersets. After the 6-mo interruption the performance was not different from new hypersets in terms of the number of trials but was significantly better than new hypersets in terms of the performance time. The results suggest that motor memory (measured by performance time) can be retained longer than procedural memory (measured by the number of trials).