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The Journal of Neurophysiology Vol. 80 No. 4 October 1998, pp. 2177-2199
Copyright ©1998 by the American Physiological Society
1 Departments of Radiology, 2 Neurology and Neurological Surgery, and 3 Anatomy and Neurobiology, Washington University School of Medicine; and 4 Department of Psychology, Washington University, St. Louis, Missouri 63110
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ABSTRACT |
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 Abstract
 Introduction
Methods
Results
Discussion
References
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van Mier, H., L. W. Tempel, J. S. Perlmutter, M. E. Raichle, and S. E. Petersen. Changes in brain activity during motor learning measured with PET: effects of hand of performance and practice. J. Neurophysiol. 80: 2177-2199, 1998. The aim of this study is to assess brain activity measured during continuous performance of design tracing tasks. Three issues were addressed: identification of brain areas involved in performing maze and square tracing tasks, investigation of differences and similarities in these areas related to dominant and nondominant hand performance, and most importantly, examination of the effects of practice in these areas. A total of 32 normal, right-handed subjects were instructed to move a pen with the dominant right hand (16 subjects) or nondominant left hand (16 subjects) continuously through cut-out maze and square patterns with their eyes closed during a 40-s positron emission tomography (PET) scan to measure regional blood flow. There were six conditions: 1) holding the pen on a writing tablet without moving it (rest condition); 2) tracing a maze without practice; 3) tracing the same maze after 10 min of practice; 4) tracing a novel maze; and tracing an easily learned square design at 5) high or 6) low speed. To identify brain areas generally related to continuous tracing, data analyses were performed on the combined data acquired during the five tracing scans minus rest conditions. Areas activated included: primary and secondary motor areas, somatosensory, parietal, and inferior frontal cortex, thalamus, and several cerebellar regions. Then comparisons were made between right- and left-hand performance. There were no significant differences in performance. As for brain activations, only primary motor cortex and anterior cerebellum showed activations that switched with hand of performance. All other areas, with the exception of the midbrain, showed activations that were common for both right- and left-hand performance. These areas were further analyzed for significant conditional effects. We found patterns of activation related to velocity in the contralateral primary motor cortex, related to unskilled performance in right premotor and parietal areas and left cerebellum, related to skilled performance in supplementary motor area (SMA), and related to the level of capacity at which subjects were performing in left premotor cortex, ipsilateral anterior cerebellum, right posterior cerebellum and right dentate nucleus. These findings demonstrate two important principles: 1) practice produces a shift in activity from one set of areas to a different area and 2) practice-related activations appeared in the same hemisphere regardless of the hand used, suggesting that some of the areas related to maze learning must code information at an abstract level that is distinct from the motor performance of the task itself.
Motor performance changes with practice from initially slow, inaccurate, and uncoordinated movements to fast, accurate, and coordinated actions (Schmidt 1988 Subjects
A total of 32 normal adult volunteers, divided in two groups of 16 subjects each, participated in the study. Each group consisted of nine females and seven males. For both males and females, age varied from 19 to 35 yr with an average age of 24 yr for both. All subjects were strongly right handed based on the Edinburgh handedness inventory (Raczkowski et al. 1974 Positron emission tomography (PET) imaging
We used the PET scanning activation methodology developed at Washington University (Fox and Mintun 1989
Material
One square design and three maze designs were used in the experiment (see Fig. 2). The square and mazes were cut-out designs, creating paths for the pen to traverse. The square consisted of 4 segments of 6 cm each, the maze designs consisted of 8 or 10 line segments. The complete path length of each maze, if traced correctly, was 24 cm. The width of the paths was 0.5 cm, the depth was 0.15 cm. To simplify decision making, the maze designs consisted of straight lines with 90° angles. Only two opposite-direction choices could be made at each intersection, one of which came to a dead end. The length of each dead end path was 0.5 cm. All designs formed closed loops, i.e., the endpoint of one loop was the starting-point of the next loop and the designs could be traced continuously. The mazes that were used in the LH performance group were mirror images of the mazes used in the RH performance group. For each subject, two versions were used for the eight-segment maze designs, versions A and B. The B versions were 90° rotations of the A versions. One version of the eight-segment maze was traced during naive and practiced performance, the other version during novel performance, with the version of maze presentation counterbalanced across subjects.
Task description and procedure
Subjects performed the tasks with eyes closed while lying in the PET-scanner with their arms lying in arm rests. The arm that was used to perform the tasks was fixed with straps at the upper arm to minimize movement of the upper arm, shoulder, and head. The cut-out designs were taped on a writing tablet positioned on a table to the right or left of the subject (see Fig. 3). The height of the table and the position of the writing tablet on the table were adjusted for each subject to achieve the most comfortable drawing position. Hand, wrist, and forearm were positioned freely above the writing tablet to minimize tactile stimulation in these areas. The pen was kept on the writing tablet during all of the scans.
Data analysis
PERFORMANCE.
Data records for all conditions were low-pass filtered at 10 Hz, and the drawing trajectories were displayed on the computer screen. The beginning and end of the 1-min tracing movement was determined by means of an interactive computer program. The mean tracing velocity was calculated for the total period of 1 min. For each condition, one maze or square loop, traced at the middle of the 1-min period, was segmented in line and angle segments based on velocity minima and x and y displacements. Duration, mean, and minimum velocity were determined for each angle segment. The tracing also was checked for stops and incorrect turns. A stop was assigned when the velocity at an angle was lower than 1 cm/s for a period >100 ms. When a dead-end path was traced, indicating that an incorrect turn was taken or when a segment was retraced, an error was assigned (see also van Mier et al. 1993). For all angle segments, the number of errors, the percentage of stops and the mean stop duration was calculated. For each of the four dependent variables, analyses of variance (ANOVAs) were performed to study effects of hand of performance, scan position, and condition (superANOVA, version 1.1, Abacus Concepts). When a significant effect of condition was observed, specific comparisons were examined post hoc to assess the pattern of significant differences between particular conditions. Probabilities were adjusted using the Greenhouse-Geisser epsilon.
PET.
General. The PET images were reconstructed with filtered backprojection using a Butterworth 0.5 filter with an order of 5, producing a transaxial resolution of 14-mm full width at half-maximum (FWHM). A linear normalization was applied to the images to negate the effects of global fluctuations in blood flow due to changes in arterial pCO2 and variations in the amount of tracer administered. Because we did not measure arterial blood radioactivity, our data represent changes in the distribution of radioactivity. In the text we refer to these changes as changes in blood flow because there is a tight linear relationship between blood flow and radioactivity in brain tissue under normal physiological conditions (Fox and Mintun 1989
EMG and EOG recordings
None of the subjects showed gross deltoid muscle EMG activity during the REST scans. If muscle activity was apparent during the other scans, it was in all cases much lower than the activity produced by the subjects during EMG testing. Furthermore, no differences in deltoid activity were noted among the five conditions mentioned above. The EOG recordings revealed that eye movements were minimal. No differences in EOG activity were noted among the five conditions.
Behavioral data
To be able to combine the PET data from the "top" and "bottom" subjects (subjects from which either the top 2/3 of the brain was imaged or the bottom 2/3), performance for both had to be similar. The means and standard deviations for each scan position and group are given in Table 2. For each group, an ANOVA was performed, with scan position (top vs. bottom) as the between factor, which showed that there were no significant differences between top and bottom positions with respect to velocity and duration of stops (P > 0.37 for the RH and P > 0.72 for the LH performance groups, respectively). Percentage of stops and number of errors were nearly identical in both scan positions (P > 0.90 for both variables in each group).
EFFECT OF HAND OF PERFORMANCE.
Next any differences between right and left hand performance were assessed. For each dependent variable, an ANOVA was performed with group (right vs. left hand) and scan position (top vs. bottom) as between factors. As can be seen in Table 3, the main effect of group was not significant for any of the variables. Although subjects were a bit faster and stopped less when the tasks were performed with the right hand compared with the left hand, these differences did not approach significance. Number of errors and percentage of stops were nearly the same in both groups. As expected, the main effect of scan position on the above mentioned variables was not significant nor was the interaction of group and scan position.
EFFECT OF CONDITION.
Data concerning velocity, errors, and stops for the five conditions (3 conditions for the errors because "dead-end" errors were not relevant in both SQ conditions) are presented in Fig. 4. Only when an increase in velocity is accompanied by a decrease in errors can an improvement in performance be surmised (Fitts 1964
PET data
None of the subtractions used to generate the difference images had to be excluded because of movement artifacts. As was stated before, for the composite difference images data from the following five conditions were combined in each group; NAIVE, PRAC, NOVEL, SQ. FAST, and SQ. SLOW. Data from the same five conditions also were used to study conditional effects. For the SQ. FAST condition, the data from the second square tracing (scan 7) were used in the analysis, representing clockwise tracing in the RH performance group and counterclockwise tracing in the LH performance group.
IDENTIFICATION OF BRAIN ACTIVATIONS AND EFFECT OF HAND OF PERFORMANCE.
Blood-flow increases. As can be seen in Fig. 5, in each group the combined image of the five maze and square tracing conditions shows activations in primary motor cortex (area A), secondary motor areas [dorsal premotor cortex (area B) and SMA (area C)], inferior and superior parietal (areas D and E), somatosensory (area F), and ventral premotor (area G, BA 44/6) areas, insular cortex, thalamus, as well as several cerebellar regions [anterior (area H), right (area I), left (area J) and right posterior (area K) cerebellum]. Figure 5 shows that most of these areas were activated similarly for both right- and left-hand performance. Areas that shifted lateralization of responses between right- and left-hand performance were primary motor cortex (area A) and anterior cerebellum (area H), with right-hand performance mainly activating left primary motor cortex and right anterior cerebellum, left-hand performance activating the same areas in the opposite hemispheres. Not surprisingly, differences in magnitudes between right- and left-hand performance in right and left primary motor cortex as well as in right and left anterior cerebellum were highly significant (P < 0.001 for all 4 comparisons).
IDENTIFICATION OF AREAS AFFECTED BY CONDITION.
Blood-flow increases. All regions with
The aim of this paper was to identify brain areas that are involved in tracing cutout designs with the eyes closed, to investigate differences and similarities related to dominant- and nondominant-hand performance and to examine effects related to practice. During the tracing tasks an increase in blood flow was observed in cortical, subcortical, and cerebellar areas, in many of these areas bilaterally.
Blood-flow increases
Performing the tracing task resulted in increased rCBF in SMA, in the contralateral primary motor cortex, and ipsilateral anterior cerebellum, while premotor, inferior, and superior parietal, inferior frontal, and somatosensory cortex were activated bilaterally as was the thalamus. A cerebellar activation, located in the dentate area, was observed on the right side. More posteriorly the cerebellum was activated bilaterally; however, anterior activation was only found in the left cerebellar cortex. Most of the above-mentioned areas also were activated in a learning study during which right-handed subjects performed a motor sequence with the right hand and eyes closed (Jenkins et al. 1994 PRIMARY AND SOMATOSENSORY MOTOR CORTEX.
The tracing task increased rCBF significantly in the contralateral primary motor cortex. The site of the activations in primary motor cortex is consistent with the somatotopic representation of the hand area in humans (Grafton et al. 1991 SECONDARY MOTOR AREAS.
Whereas the peak activation in the SMA was found in the hemisphere contralateral to the hand used, the replication data of the SMA in Table 5 show that in both groups the medial SMA activations most likely extended across both hemispheres. Because the FWHM in our experiment was 14 mm, it is hard to draw any conclusions from this. We did not replicate the findings of Grafton et al. (1992b) PARIETAL REGIONS.
Both right- and left-hand tracing activated the ipsi- and contralateral inferior and superior parietal cortex (BA 40 and 7). In Jenkins' (1994) motor learning study, right-hand performance also activated both inferior and superior parietal cortices bilaterally. No parietal activity was reported by Rao et al. (1993) CEREBELLAR ACTIVATIONS.
There is one other PET study that compared cerebellar activations during right- and left-hand performance (Grafton et al. 1992b OTHER REGIONS.
Thalamus was activated bilaterally in both groups. In each group, activations were slightly, but not significantly, larger on the contralateral side. Bilateral activation of the thalamus is not surprising because the thalamus can relay information between cerebellum and (pre)motor cortex (Shinoda et al. 1993 Blood-flow decreases
As was the case with blood-flow increases, most areas showing decreases were identified during both RH and LH performance. Areas that were less activated during tracing performance in general than during the rest condition were found in temporal, occipital, cingulate, and prefrontal cortex and caudate. Results from PET studies that reported decreases suggest that when subjects attend to a specific modality, activity in modalities not needed for the task is suppressed (Buckner et al. 1995 Order effects
The fact that all subjects performed the tasks in the same fixed order could be seen as a limitation of the study. A fixed-task order is inherent in the experimental design. We are, however, confident that the practice-related effects are indeed related to practice and not to consolidation or time effects. The finding that when subjects were presented after practice with a novel maze, the same areas that showed changes in activation during naive maze tracing became activated or deactivated again, almost to the same extent, supports this hypothesis. That the changes were not related to changes in movement kinematics per se is demonstrated by comparison of brain activity in areas measured during PRAC as well as during both SQ. conditions. Several areas showed no significant differences in brain activations among these three conditions, although the velocity was three to five times higher during PRAC and SQ. FAST than during SQ. SLOW. Furthermore although somatosensory and proprioceptive input might have been different among these three tasks, these differences did not translate to differences in activations in practice-related areas between the three conditions, again strongly suggesting that the changes were related to level of skill. A direct comparison between the first and last fast square tracing did not reveal any significant differences in brain activations, although subjects performed the second square tracing Conclusions
The results of this study demonstrate two important principles: that practice produces a shift in activity from one set of areas to a different area and that these practice-related activations appeared in the same areas and hemisphere regardless of the hand used, suggesting that these areas code information at a level abstract from motor implementation itself.
INTRODUCTION
Abstract
Introduction
Methods
Results
Discussion
References
). In studies of motor performance and cognitive psychological studies of skill acquisition, these changes often have been attributed to shifts in underlying processes, such as motor planning and programming (e.g., Fitts 1964; Posner and Keele 1968; van Mier and Hulstijn 1993; van Mier et al. 1993). Neural mechanisms related to these processing shifts might be identified with functional neuroimaging, by measuring modifications in brain-activation patterns.
using functional magnetic resonance imaging (fMRI), showed a shift in brain activations in a visuomotor learning task. Whereas frontal areas were activated mostly during early learning, involvement of the parietal cortex increased in the more advanced learning stage.
; Friston et al. 1992; Jueptner et al. 1997b; Roland and Seitz 1989) or when a movement had to be selected based on internal or external cues (Deiber et al. 1991). Activity decreased in these areas after practice (Grafton et al. 1992a; Haier et al. 1992; Jenkins et al. 1994; Jueptner et al. 1997b; Mazziotta et al. 1991). Cerebellar activity was found during the learning of a motor task (Grafton et al. 1992a; Roland et al. 1989), whereas activity in the basal ganglia was found only when the movement was highly overlearned and automatic (Mazziotta et al. 1985, 1991). When subjects had to select a motor response randomly, i.e., when they had to choose freely which movement to make, the anterior part of the cingulate was activated (Deiber et al. 1991; Frith et al. 1991; Jueptner et al. 1997a). Aizawa et al. (1991) and Roland et al. (1980a) found little or no activity in SMA when an extensively overlearned motor task was performed.
METHODS
Abstract
Introduction
Methods
Results
Discussion
References
). None of the subjects had a history of neurological disorders. The Human Studies Committee as well as the Radioactive Drug Research Committee of Washington University approved the study. Subjects gave informed consent conforming to the guidelines and procedures set forth by these committees. Subjects were paid for participation.
; Fox et al. 1985, 1988; Mintun et al. 1989), which will be briefly outlined here.
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FIG. 1.
Positioning of subjects in the scanner. Area between solid lines shows the part of the brain that was in the field of view of the camera, area between striped lines shows the part of the brain from which the data were used in the analysis. In half of the subjects, the top 2/3 of the brain was scanned, in the other half the bottom 2/3. Dark shaded area corresponds to the extent of the area in which both groups overlapped.
), that collects data for 31 axial planes with center-to-center slice separation of 3.38 mm. Data were collected in the three-dimensional mode (Kinahan and Rogers 1989), which provided an axial field of view of 10.5 cm. Because of this somewhat limited axial field of view, we scanned one group of 16 subjects (8 performing the tasks with the right hand and 8 with the left hand) while they were positioned low in the scanner, thereby ensuring coverage of the upper two-thirds of the brain. In the same way, a second group of 16 subjects was positioned high in the scanner, thereby ensuring coverage of the lower two-thirds of the brain. Combining the data acquired from these two groups optimized data collection for the supplementary and lateral dorsal premotor areas as well as most of the cerebellum (see Fig. 1).
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FIG. 2.
Square and maze designs used in the study; total (correct) path was 24 cm for all designs. Arrows indicate the starting position for the tracing of each design. RH, right-hand performance; LH, left-hand performance; CW, clockwise; CCW, counterclockwise. Note that tracing in the RH mazes had to be done in a clockwise direction, in the LH mazes in a counterclockwise direction.
; Raichle et al. 1983). As soon as the bolus entered the brain, as noted by a sudden rise in the system count rate, a 40-s scan was initiated. The short half-life of H215O (~2 min), the short scanning time of 40 s, and the relatively low dose of radiation made it possible to perform 10 scans within a subject in a single session.
), both connected to an IBM PS2/30 microcomputer, were used to record the x and y coordinates of the pen movements. During each experimental scan, movements were registered for a period of 1 min, starting 10 s before and finishing 10 s after each scan. Recording was done at a precision of 1 mm and a frequency of 100 Hz. In other words, the position of the pen was recorded every 10 ms.
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FIG. 3.
Experimental setup showing subject positioned supine in the scanner. Upper arm was strapped while the wrist and hand were positioned freely above the writing tablet.
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TABLE 1.
PET protocol with task description, maze versions, and hand used as well as drawing direction
; Herscovitch et al. 1983).
) into stereotaxic space defined in Talairach and Tournoux's atlas (Talairach and Tournoux 1988). At the time of testing, no MRI data were collected; however, we could collect high-resolution anatomic MRI data for six subjects at a later time. Comparison of Talairach coordinates for peak activations in these six subjects based on the skull X-ray method were within 5 mm distance from coordinates obtained by the MRI method and are most likely due to methodological variability (Hunton et al. 1996), indicating that the use of a skull X-ray for anatomic standardization was also valid for the high-resolution scanner that was used for the experiment. For each subject, images were grouped in experimental-control pairs and subtracted from each other. All subtracted image pairs were checked for movement artifacts and eliminated if excessive movement was found. To improve signal to noise, single subtraction images of identical conditions were averaged across subjects (Fox et al. 1988; Mintun et al. 1989). Averaged subtraction images then were searched by an automatic maximum-detection algorithm to identify and record all positive and negative maxima by location in stereotaxic coordinates and by magnitude in PET counts (Mintun et al. 1989).
; Hunton et al. 1996) or replicate in the same subject group but performing under identical or comparable conditions (Corbetta et al. 1993). Activations that reproduce across groups are the best indication that the activations are reliable and can be attributed to the particular task demands and not to noise or other irrelevant factors. In this study, a combination of above-mentioned replication methods was used.
for PETT VI data, to establish the magnitude cutoff for our 953B data. Based on a small sample set (6 < n < 12, depending on the peak location) of our data acquired in the RH performance group, noise peaks were acquired in a control data set in which the same tasks were performed during the active and reference scan. Magnitudes of noise peaks were all under 80 PET counts, and "noise" peaks did not significantly replicate at a magnitude of 
50 (P > 0.05). Signal peaks also were acquired in a small experimental data set (6 < n < 10) acquired in the RH performance group, in which different tasks were performed during the active and reference scan. Of the peaks with a PET count of 50, 61% replicated, areas with peaks of 100 PET counts replicated 100%. On the basis of these data and on the visual inspection of several image sets, a magnitude cutoff of 50 PET counts was used in the replication analysis.
50 PET counts; 2) to assess reliability of the activations and examine the effect of hand of performance, in each group brain areas showing magnitudes of 50 PET counts were tested for replication in the other group; and 3) to examine the effect of practice, differences in magnitudes between conditions were examined in areas showing reliability and/or replication.
50 PET counts were specified. To assess within-data set reliability of these areas, in each group t values were calculated. Areas then were tested for replication.
50 PET counts (increases and decreases) were identified in the summed image of each group by using an automatic maximum-detection algorithm which averaged magnitudes over a 7-voxel (14 mm) diam (Mintun et al. 1989).
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TABLE 2.
Means for each group and scan position
50 PET counts were used to find the average regional value in each subject, creating per region and per subject a magnitude for each subtracted condition. For each region, a repeated-measures ANOVA was performed on the magnitudes in the five conditions for those subjects in which 80% of the voxels in the region was sampled. When a significant effect of condition was observed in the overall ANOVA, specific comparisons were examined post hoc to assess the pattern of significant differences between particular conditions. Probabilities were adjusted using the Greenhouse-Geisser epsilon.
50 PET counts and a t value of 3.5 were also identified in the composite images. Another source of variance could be introduced by comparing the experimental scans to a REST condition. We tried to make the REST condition as comparable with the tracing conditions as possible except for the movement. Subjects never were told what they were expected to do during the next scan to prevent preprocessing of the next task. To make sure any additional processing during the REST scan would not influence our data, each experimental condition also was compared directly with each of the other experimental conditions and again areas with 50 PET counts and a t value of 3.5 were checked for occurrence in the combined image.
RESULTS
Abstract
Introduction
Methods
Results
Discussion
References
View this table:
TABLE 3.
F and P values of ANOVA for velocity, percent of stops, stop duration, and errors
). Furthermore, a decrease in the number and duration of stops at corners is an indication that the movements are performed smoothly (van Mier et al. 1993). As can be seen in Fig. 4, performance after maze practice (PRAC) and during SQ. FAST clearly shows the characteristics of more skilled behavior; the movements are performed quickly with few stops or errors. The performance study by van Mier et al. (1993) has shown that the square is learned easily and needs hardly any practice to become skilled. Because we used the data from the second SQ. FAST condition, it seems justified to describe square performance as skilled. On the other hand, a skilled task also can be performed differently as is shown in Fig. 4 for the SQ. SLOW condition. Subjects indeed traced the square at a low speed and stopped at each corner. Repeated measurement ANOVAs, using the Greenhouse-Geisser epsilon adjustment, showed that the mean effect of condition was highly significant (P < 0.001) for each dependent variable (see Table 4).
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FIG. 4.
Mean velocity, number of errors, and percentage and duration of stops for each group as a function of condition.
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TABLE 4.
Values of dependent variables for each condition and P values for specific post hoc comparisons between conditions for the RH and LH performance groups
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FIG. 5.
Horizontal sections showing areas of positive blood-flow changes during maze and square tracing from a rest control condition. Six top sections: changes during right-hand performance; 6 bottom sections: during left-hand performance. Subtraction images are shown in Talairach space (1988) with the z-coordinate labels. These sections show the blood-flow changes that were common in both performance groups. Left in the images corresponds to left and top to frontal. A, primary motor cortex; B, dorsal premotor cortex; C, supplementary motor area (SMA); D, inferior parietal cortex; E, superior parietal cortex; F, somatosensory cortex; G, inferior frontal cortex; H, anterior cerebellum; I, cerebellar dentate; J, lateral cerebellum; K, posterior cerebellum.
50 PET counts were assessed in the composite image. Within-data set reliability was tested in these activated regions in each group by calculating t values for each region and a threshold of t of 3.5 was set. Activations in regions that significantly replicated, showing across-data set reliability and had a t value of 3.5, showing high within-data set reliability, can be considered dependable. On the other hand, in this study areas that didn't replicate but had a high t value might be related to hand of performance. Areas that met these criteria are given in Table 5.
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TABLE 5.
Regions showing increases in activity of 50 PET counts and t value >3.5 during maze and square tracing in RH and LH performance groups and t value, magnitudes, and significance level of replication in the other group
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FIG. 6.
Horizontal sections showing areas of negative blood-flow changes during maze and square tracing from a rest control condition. Six top sections: changes during right-hand performance; 6 bottom sections: during left-hand performance. Subtraction images are shown in Talairach space (1988) with the z-coordinate labels. These sections show the blood flow changes that were common in both performance groups. Left in the images corresponds to left and top to frontal. Labeled areas refer to areas described in the text.
50 PET counts and had t values of 3.5 are listed in Table 6. As can be seen, all of these areas significantly replicated in the other group. Differences in magnitude between right- and left-hand performance in these areas were not significant.
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TABLE 6.
Regions showing decreases in activity of 50 PET counts and t value >3.5 during maze and square tracing in RH and LH performance groups and t value, magnitudes, and significance level of replication in the other group
50 PET counts in the composite image (all 5 conditions-REST) of the RH and LH performance group were tested for conditional effects. As described in METHODS, for each region and condition, the average regional value in each subject was calculated. Activated areas located adjacent to the primary motor cortex in the hemisphere contralateral to the hand used could not be identified as significantly distinct from the nearby large primary motor response. Distinction of two separate foci required separation by 14 mm (FWHM). Filtering at a higher resolution (10 mm) did not separate the dorsal premotor, somatosensory, and parietal responses from the response in the primary motor area. However, the replication data showed that dorsal premotor, parietal, and somatosensory cortex were highly activated in the contralateral hemispheres. To calculate the average regional value in these areas contralateral to the hand used, we applied the coordinates of the foci that were identified in the same areas and same hemisphere in the other group (ipsilateral to the hand used). These coordinates are italicized in Tables 7 and 8. Each region included all voxels within a 7-voxel-diam (14 mm) sphere centered at each location.
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TABLE 7.
Regions showing significant effects of condition in RH and LH performance groups with magnitudes given per condition and the significance level of condition
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TABLE 8.
Areas with significant condition effects in RH and LH performance groups and significance level of specific post hoc comparisons between conditions
80% of the voxels in the region was sampled. Regions that showed a significant effect of condition (P < 0.05, Greenhouse-Geisser adjusted; except for right inferior parietal cortex in the LH performance group for which a P < 0.07 was found) are presented in Table 7, showing for each group the P values for the main effect of condition as well as the magnitudes per condition. The only area in which a significant effect of group was found was the left dorsal premotor cortex (P < 0.05), which was more activated in the RH group. The interaction of group and condition was not significant in any of the other regions, suggesting that differences in magnitude between conditions showed the same pattern in each group. This also was confirmed by the similarity of the specific post hoc tests.
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FIG. 7.
Horizontal sections showing areas of positive blood-flow changes during maze and square tracing from a rest control condition. Cortical activations are shown in A, cerebellar in B. Top: changes during right-hand performance; bottom: changes during left-hand performance. Subtraction images are shown in Talairach space (1988) with the z-coordinate label. These sections show the blood-flow changes that were common in both performance groups. Left in the images corresponds to left and top to frontal. A, primary motor cortex; B, right dorsal premotor cortex; BB, left dorsal premotor cortex; C, SMA; D, inferior parietal cortex; E, right superior parietal cortex; EE, left superior parietal cortex; J, lateral cerebellum; K, posterior cerebellum.
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FIG. 8.
Mean regional blood-flow changes in contralateral primary motor cortex in each group are shown for the CONDITION-REST subtractions.
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FIG. 9.
Mean regional blood-flow changes in right dorsal premotor cortex, right inferior, and superior parietal cortex, and left lateral anterior cerebellum in each group are shown for the CONDITION-REST subtractions.
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FIG. 10.
Mean regional blood-flow changes in supplementary motor area in each group are shown for the CONDITION-REST subtractions.
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FIG. 11.
Mean regional blood-flow changes in left dorsal premotor cortex, ipsilateral anterior cerebellum, right medial cerebellum, and right cerebellar dentate in each group are shown for the CONDITION-REST subtractions.
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FIG. 12.
Mean regional blood-flow changes in left middle temporal gyrus in each group are shown for the CONDITION-REST subtractions.
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FIG. 13.
Activation patterns between cortical areas and contralateral cerebellar regions. Images are shown in Talairach space (1988) with the z-coordinate label. Left in the images: corresponds to left and top to frontal. B, right dorsal premotor cortex; BB, left dorsal premotor cortex; C, SMA; D, right inferior parietal cortex; E, right superior parietal cortex; I, right cerebellar dentate; J, left lateral cerebellum; K, right posterior cerebellum.
DISCUSSION
Abstract
Introduction
Methods
Results
Discussion
References
. Using fMRI they showed a shift in brain activations in a visuomotor learning task. Left dorsolateral prefrontal cortex and pre-SMA were mostly activated during early learning, precuneus and right dorsolateral prefrontal cortex were most highly activated in intermediate stages, whereas involvement of the parietal cortex increased in the more advanced learning stage.
) as well as in other motor performance studies (Seitz et al. 1997; Stephan et al. 1995; Winstein et al. 1997).
, 1992b, 1993). Left-hand performance activated the left primary motor cortex with a magnitude that was only 10% of that activated by right-hand performance, but this ipsilateral response was significant. In contrast, right-hand performance did not produce a significant activation in the right primary motor cortex. This hemispheric asymmetry in the primary motor cortex also was observed in another PET study (Kawashima et al. 1994) as well as in a fMRI study (Kim et al. 1993). In both studies, subjects were tested on a sequential opposition of thumb-to-finger task with the dominant and nondominant hand. We have no reason to believe that the activation in the ipsilateral motor cortex was related to inadvertent movement of the contralateral hand. Before each scan, subjects were instructed explicitly to move only the hand that performed the tracing tasks. The other hand and arm were checked visually. No movements were observed in the latter. Furthermore, inspection of the EMG recordings of the left arm in the LH performance group during tracing of the 10-segment maze, which was performed with the right hand, showed little or no EMG activity. Activation in ipsilateral primary motor cortex without contralateral hand movement also has been observed in single-unit recordings (Tanji et al. 1988) and cortical microstimulation studies (Aizawa et al. 1990) in monkeys and might be due to the fact that ~10-15% of the fibers in the lateral cortical spinal tracts are uncrossed in humans (Nyberg-Hansen and Rinvik 1963) and monkeys (Glees and Cole 1952; Yakovlev and Rakic 1966).
; Bonde et al. 1995; Roland et al. 1980a, 1989; Schlaug et al. 1996; Seitz et al. 1990, 1997). The above-mentioned increases are most likely not simply an effect of practice or skill as illustrated by the relatively low magnitude in primary motor cortex in the more skilled SQ. SLOW condition in our experiment. Furthermore, in studies where movement rate and amplitude was kept constant in novel and practiced conditions, no differences in primary motor cortex activation was found (Friston et al. 1992; Jenkins et al. 1994; Raichle et al. 1994).
; Hazeltine et al. 1997; Karni et al. 1995; Pascual-Leone et al. 1994). Although our subjects were more skilled after practice, they had not reached asymptotic performance, as was the case in the study by Karni et al. (1995).
and Kawashima et al. (1994) that the SMA was more activated when subjects performed the task with the left hand. The former studied changes in brain activity while subjects performed visuomotor tracking tasks with the right (12 subjects) or left hand (2 subjects).
, who studied subjects while they performed simple and complex finger tapping sequences with either the right or left hand. Although results from other PET studies (Kawashima et al. 1994; Roland et al. 1980b; Shibasaki et al. 1993) demonstrated that the dorsal premotor area contralateral to the hand used was more activated than the ipsilateral area, we found that the left dorsal premotor area was activated more than the right one in both RH and LH performance groups, suggesting lateralized differences with respect to tracing movements.
; Grafton et al. 1992a; Jenkins et al. 1994; Jueptner et al. 1997b). The dichotomy in SMA and dorsal premotor neuronal activity often is explained by the difference between internal and external cues. It is hypothesized that during initial learning, performance is guided mainly by external sensory cues that are likely to be controlled by the dorsal premotor cortex. However, when the task is overlearned, the movements mostly are self-initiated and guided by internal cues, most likely controlled by SMA (Chen et al. 1995; Deiber et al. 1991; Demiralp et al. 1990; Halsband and Freund 1990; Jenkins et al. 1994; Kawashima et al. 1994; Mushiake et al. 1991; Passingham 1985, 1988; Praamstra et al. 1996; Rizzolatti et al. 1983; Roland et al. 1980a,b; Thaler et al. 1995; Wise 1985).
; Hikosaka et al. 1996; Jueptner et al. 1997a). Evidence that the SMA is likely to be involved because of the sequential character of the task comes from a PET study by Shibasaki et al. (1993), in which sequential finger movements (right thumb had to touch each of the other fingers a different number of times) were compared with repetitively touching the thumb against the tips of all other fingers. SMA activation was significantly higher in the more complex sequential task, a finding that also was reported by Rao et al. (1993) in a fMRI study and in a single cell recording study by Tanji and Shima (1994). Recently, Gerloff et al. (1997) showed that high-frequency repetitive transcranial magnetic stimulation over the supplementary motor area interfered with the organization of subsequent elements in an complex overlearned finger-movement sequence on an electronic piano, indicating a critical role of the SMA in the organization of forthcoming movements in complex motor sequences that are rehearsed from memory and fit into a precise timing plan.
). The left dorsal premotor area has been postulated to be involved in the acquisition and execution of motor skills, in particular with respect to the temporal aspects of the task (Seitz et al. 1994). These temporal aspects play a role when learning the maze but also when tracing the maze and square at a high speed. The latter requires a precise timing plan as to when to decelerate and accelerate to turn smoothly at corners. When temporal aspects were less demanding, as during SQ. SLOW, when subjects were instructed to bump into the sides, left dorsal premotor area was significantly less activated. We would have expected more or less the same activation in left dorsal premotor cortex during all conditions if this area processes movement-related rules or is involved in motor mapping (Wise 1985). When professional pianists were asked to play a musical score with the right hand, left premotor area was activated, whereas SMA was activated when they played ascending and descending scales (Sergent et al. 1992), again suggesting an involvement of the left premotor area in performance tasks with greater temporal demands.
, who concluded that "... the relation between neuronal activity and the laterality of hand movements is much more complex in the secondary motor areas (premotor cortex and SMA) than in the primary motor area. In secondary areas, the activity of a majority of neurons is not simply related to contralateral movement execution." Shen and Alexander (1997) showed that when the direction of forelimb movement was dissociated from the spatial location of a target, by varying the spatial mappings between joystick and cursor, the activity of a majority (94%) of directionally tuned neurons in the dorsal premotor cortex was target dependent, whereas none was limb dependent. These findings suggest that the role of the dorsal premotor cortex could be more related to context-dependent processing than to pure motor processing.
also found bilateral activation in premotor areas 44/6 in subjects performing a spatial task; however, activation was much larger in the right compared with the left hemisphere. Although our tasks had a spatial aspect, subjects did not have to make decisions based only on spatial cues; this might explain the almost similar activations in the right and left premotor areas 44/6 in our study.
, while Kawashima et al. (1994) did not measure activity in parietal areas. In our study, the posterior areas were activated similarly regardless of which hand was used. Responses in the inferior parietal cortex, however, were larger when the task was performed with the contralateral hand, a finding consistent with results reported by Grafton et al. (1992b), suggesting a hand effect without hemispheric lateralization. The inferior parietal cortex is known to be involved in spatial attention tasks (Petersen et al. 1994) and was activated when subjects attended to tactile stimulation (Pardo et al. 1991) and when subjects covertly shifted attention to different locations in the visual field (Corbetta et al. 1993).
) or when subjects perform a perceptual maze task (Ghatan et al. 1995), parietal activations also are found without any visual input with imagined movements (Stephan et al. 1995), with auditory cues (Deiber et al. 1991), with performance of a prelearned saccade sequence in darkness (Petit et al. 1996), or with construction of mental three-dimensional images based on verbally presented instructions. This suggests that spatial processing demanded by the tasks requires the involvement of the posterior parietal cortex.
; Ghatan et al. 1995; Haxby et al. 1994; Mellet et al. 1995; Petit et al. 1996), including those not associated with movement (Mellet et al. 1996).
; Jueptner et al. 1997b). In the NAIVE and NOVEL conditions, subjects most likely have to attend to the spatial aspects of the task, aspects that need less or no attention once the task can be performed more skillfully. In a study by Roland et al. (1980b) in which subjects were guided through a maze by verbal commands, inferior and superior parietal cortex also were activated bilaterally, as was the case in a study by Ghatan et al. (1995), who used a perceptual maze test. In the latter study, no activation in these areas was found when subjects randomly pressed keys to guide a cursor from bottom to top in a control condition. The practice-related effects found in right parietal cortex were again hand independent.
report activation in left inferior and superior parietal cortex during both novel and practiced performance on finger movement sequences.
). They measured only the ipsilateral anterior cerebellum and reported significant changes during performance with either hand. However, the changes were bigger when the task was performed with the left hand, consistent with our results. The finding that movement planning and/or execution activate the ipsilateral anterior cerebellum is supported by several other PET studies (Colebatch et al. 1991; Decety et al. 1992; Deiber et al. 1996; Grafton et al. 1991, 1992a, 1993, 1994; Seitz et al. 1994; Stephan et al. 1995). Apart from the anterior cerebellum, we also found activation bilaterally in the inferior cerebellar cortex and right cerebellar dentate.
; Fiez 1996; Raichle et al. 1994; Schmahmann 1996; Thach 1997) and cognitive processing (Kim et al. 1994; Middleton and Strick 1994, 1997), findings that are in line with results from studies involving cerebellar patients (Doyon 1997; Doyon et al. 1997; Fiez et al. 1992; Molinari et al. 1997; Sanes et al. 1990). Our results support this hypothesis. It is, however, still unclear which aspects of learning are controlled by the cerebellum
temporal, spatial, attentional, and/or sequentialand which areas of the cerebellum control these aspects. Recently Middleton and Strick (1997) showed evidence that different output channels in the cerebellar dentate project to different cortical areas and therefore might be concerned with distinct aspects of behavior at a motoric as well as cognitive level.
). As in the primary motor cortex, this area shifted lateralization when the opposite hand was used. However, the activation did not show a velocity-related change but rather a capacity-related change. The latter is consistent with results reported by Seitz et al. (1990), who found no increase in anterior cerebellar activity from initial to skilled performance, although the frequency of finger movements almost doubled. The fact that the anterior cerebellum was significantly less activated during SQ. SLOW than during the other conditions, but that the activation was lateralized, suggests that this area might relate to movement timing at a muscle-specific level. The other cerebellar activations showed significant conditional effects that were independent of the hand used and suggest processing at a more abstract level.
and Jueptner et al. (1997b). Left cerebellar activations also are reported by Ghatan et al. (1995), who tested subjects on a perceptual maze with little pretraining. Furthermore Lalonde and Botez (1990) showed that animals with cerebellar damage were impaired on maze learning. Flament et al. (1996) reported a strong correlation between cerebellar activation and errors. The fact that the six (RH performance group) and eight (LH performance group) subjects in which this left cerebellar area was scanned still made some errors during the PRAC condition, in contrast to both SQ. conditions, might have accounted for the trend effect when activations in this area were compared between NAIVE and PRAC.
) as well as issues of timing more generally (Ivry 1997; Keele and Ivry 1990).
found that although patients with cerebellar lesions were severely impaired on a procedural motor learning task, patients with lesions in the left cerebellum had even more problems learning the motor task than patients with right cerebellar lesions. Furthermore, their patients were impaired during both right- and left-hand performance.
), areas which also were activated bilaterally in our tracing tasks.
report activation in this area in their right-handed subjects performing the task with the right hand and suggest that this activation, which seems to be located in the red nucleus, might represent a cerebellorubral pathway. The red nucleus is known to mediate voluntary movement especially distal limb movements probably through an indirect pathway (Kuypers 1973, 1981). It is possible that this pathway is used mainly when subjects perform the tasks with their nondominant hand or when subjects, as in the Jenkins' study, have to relearn a new sequence, tasks that both might require increased attention. This is in agreement with a study by Sadato et al. (1997), who only found increased activation in the midbrain when bimanual sequential parallel movements were performed but not during bimanual sequential mirror movements, the latter requiring less attention.
; Friston et al. 1991; Frith et al. 1991; Grafton et al. 1994; Haxby et al. 1994; Jenkins et al. 1994; O'Sullivan et al. 1994; Seitz and Roland 1992). Compared with the resting condition, attending to the somatosensory motor aspects of the tracing task depressed activity in medial occipital cortex and temporal cortex, areas involved in the processing of visual and auditory information, information that might not be relevant for this task. Most of the other areas in which the observed decreases were replicated might be areas in which activations commonly are depressed during active conditions compared with passive tasks, regardless of the task performed. In an across-study analysis, involving nine studies of human visual information processing, Shulman et al. (1997) found reduced activity during active scans in many of the same areas seen here. This suggests that these decreases generalize over tasks and might be caused by increased activation during passive conditions reflecting common ongoing processes.
45 min after the first.
) and might contain sequential, temporal, and/or spatial aspects.
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ACKNOWLEDGEMENTS |
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We thank D. Hunton, M. Makram, L. Lich, J. Hood, T. Videen, and the staff of the Cyclotron Unit for technical assistance.
This work was supported by National Institutes of Health Grants NS-32979, NS-06833, and HL-13851 and the McDonnell Center for the Study of Higher Brain Function.
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FOOTNOTES |
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Address for reprint requests: H. van Mier, Dept. of Neurology and Neurological Surgery, Washington University School of Medicine, 660 S. Euclid, P.O. Box 8111, St. Louis, MO 63110.
Received 27 June 1997; accepted in final form 12 July 1998.
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REFERENCES |
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Abstract
Introduction
Methods
Results
Discussion
References
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