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Neuronal Activity in the Supplementary Motor Area of Monkeys Adapting to a New Dynamic Environment

McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139

Submitted 1 October 2002; accepted in final form 4 September 2003

	ABSTRACT

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION DISCLOSURES REFERENCES

 
To execute visually guided reaching movements, the central nervous system (CNS) must transform a desired hand trajectory (kinematics) into appropriate muscle-related commands (dynamics). It has been suggested that the CNS might face this challenging computation by using internal forward models for the dynamics. Previous work in humans found that new internal models can be acquired through experience. In a series of studies in monkeys, we investigated how neurons in the motor areas of the frontal lobe reflect the movement dynamics and how their activity changes when monkeys learn a new internal model. Here we describe the results for the supplementary motor area (SMA-proper, or SMA). In the experiments, monkeys executed visually guided reaching movements and adapted to an external perturbing force field. The experimental design allowed dissociating the neuronal activity related to movement dynamics from that related to movement kinematics. It also allowed dissociating the changes related to motor learning from the activity related to motor performance (kinematics and dynamics). We show that neurons in SMA reflect the movement dynamics individually and as a population, and that their activity undergoes a variety of plastic changes when monkeys adapt to a new dynamic environment.

	INTRODUCTION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION DISCLOSURES REFERENCES

 
The mechanics of movements is described at two different levels: the dynamics and the kinematics. For a reaching movement, the dynamics describes the forces— exerted by contracting muscles—that cause the movement [f(t)]. The kinematics describes the position of the hand and the joint angles in time [x(t)], together with the time derivatives [(t) and (t)]. The mechanics of movements is described by Newton's equation, which relates the dynamics and the kinematics. For planning and executing visually guided reaching movements, it is widely assumed that the CNS undertakes a sequence of operations, which can be grouped in 1) processing of the visual stimuli (including all stages "upstream" of the kinematics, such as making the decision to reach), 2) designing the desired kinematics, and 3) computing the corresponding desired dynamics (Alexander and Crutcher 1990a; Bernstein 1967; Kalaska and Crammond 1992; Mussa-Ivaldi and Bizzi 2000; Saltzman 1979). Two fundamental issues remain open. First, what kinematic and dynamic variables are exactly coded? For instance, the endpoint, the total movement time, and the curvature of the trajectories are all valid kinematic variables. Likewise, the total force at the endpoint of the limb or the joint torques are valid dynamic variables. Second, how are these variables processed in the CNS? The present work investigated aspects of this second issue. Specifically, we investigated how the activity of neurons in the motor areas of the frontal lobe reflects the dynamics of movements.

Several investigators have proposed that the CNS processes the movement dynamics by the use of internal models, which describe the dynamics of the limb and the environment (Merfeld et al. 1999; Shadmehr and Mussa-Ivaldi 1994; Wolpert et al. 1995; for review see Desmurget and Grafton 2000; Kawato 1999; Wolpert and Ghahramani 2000). Work in humans and monkeys showed that new internal models can be acquired when subjects adapt to perturbing forces (Shadmehr and Mussa-Ivaldi 1994). In addition, new internal models for the dynamics allow some generalization (Gandolfo et al. 2000; Thoroughman and Shadmehr 2000) and undergo consolidation in the few hours after training (Brashers-Krug et al. 1996). Finally, internal models for the dynamics are learned independently of other internal models [e.g., internal models for the kinematics (Flanagan et al. 1999; Krakauer et al. 1999)]. In the present report, we describe how the activity of neurons in the supplementary motor area (SMA) reflects the internal model of the dynamics and how it is modified when a new internal model is acquired.

Investigation of the physiological underpinnings of movement dynamics has traditionally focused most extensively on the primary motor cortex (M1). Starting with Evarts (1968), many researchers found that neurons in M1 are modulated by external loads. This interest in M1 partly reflected a serial view of the motor systems. According to this view, several "premotor" areas process high sensorimotor processes and feed M1, which then projects to the spinal cord. More recently, however, it was found that direct corticospinal projections originate from multiple motor areas, including the SMA, the dorsal and ventral premotor areas, and the cingulate motor areas, in addition to M1 (He et al. 1993, 1995). These same areas are also intensely interconnected with each other (Luppino et al. 1990, 1993). Based on these findings and on the observation of often extensive functional overlap between different motor areas (Alexander and Crutcher 1990a,b; Crutcher and Alexander 1990; Scott and Kalaska 1997; Scott et al. 1997), it was proposed that different motor areas provide parallel contributions to the control of movements (Dum and Strick 1991; Prut and Fetz 1999). More specifically, corticospinal projections originating from multiple areas led us to hypothesize that multiple areas might contribute to the processing of the movement dynamics. The present experiments were conducted to test this hypothesis with respect to the SMA.

Our experiments focused on SMA (or SMA-proper, or F3), which constitutes the caudal portion of the traditionally defined "SMA" (Penfield and Welch 1951; Woolsey et al. 1952), and which we distinguished from the more rostral preSMA (or F6). Converging evidence from anatomy and microstimulation work in monkeys and from imaging studies in humans strongly indicates a more direct involvement of SMA in movement planning and execution, whereas preSMA seems involved in more complex tasks (Bates and Goldman-Rakic 1993; He et al. 1995; Luppino et al. 1990, 1991, 1993, 1994; Matelli et al. 1991; Rouiller et al. 1996; see review by Geyer et al. 2000; imaging work reviewed by Picard and Strick 1996). Indeed, Picard and Strick (2001) note that "the connectivity and physiology of the preSMA suggest that it is more like a prefrontal area than a premotor area." We focused our experiments on SMA because we expected it more likely to find neuronal correlates of the movement dynamics—a late motor processing stage—in a properly "motor" area, closer to the motor output.

Unfortunately, most of the previous single-cell recordings in monkeys did not distinguish between preSMA and SMA. Neurons in "SMA" were investigated for their relation to complex motor functions (Chen and Wise 1995; Kurata and Tanji 1985; Mushiake et al. 1991; Okano and Tanji 1987; Tanji and Kurata 1985; Tanji et al. 1980; Thaler et al. 1995). More recently, however, Matsuzaka et al. (1992; Matsuzaka and Tanji 1996) revisited previous experiments on the instruction dependency of neuronal activity in "SMA." They found that the phenomenon was relatively common in preSMA, but negligible in SMA. Their work also showed that neurons in SMA often responded to somatosensory stimulation. Phasic, movement-related activity was more frequent in SMA, and its onset was often time locked with the movement onset. In contrast, responses to visual cues were more abundant in preSMA. Along a similar vein, Hikosaka and coworkers concluded after a series of studies in humans and monkeys that SMA is more relevant for movement per se, and—with respect to motor learning—"works to acquire explicit skill" (Hikosaka et al. 2000; Nakamura et al. 1998). These results confirmed prior observations of Alexander and Crutcher (1990a,b). Although their study did not explicitly distinguish between preSMA and SMA, they analyzed the neuronal activity recorded in the medial wall relative to the rostrocaudal location of recording. They found that neurons with only preparatory activity—and not movement-related activity—were located mostly anterior to the gAS (alignment with the genu of the arcuate sulcus) (i.e., in preSMA). In contrast, neurons with only movement-related activity—and not preparatory activity—were generally located posterior to the gAS (i.e., in SMA). Neurons with both preparatory and movement-related activity were found in both areas (Alexander and Crutcher 1990a). Likewise, neurons with target-dependent activity were found almost exclusively rostral to the gAS (i.e., in preSMA), whereas the activity of neurons caudal to the gAS (i.e., in SMA) was limb-dependent (Alexander and Crutcher 1990b). In conclusion, single-cell recordings that distinguished between the two areas support the view that SMA is much more closely related to the motor output.

With respect to the difference between SMA and M1, two complementary aspects seem to emerge. On the one hand, SMA appears more involved in motor planning than M1 is. For instance, Alexander and Crutcher (1990a) found preparatory activity (during an instructed delay) in 55% of SMA neurons versus 37% of M1 neurons. Correspondingly, the "lead time" (i.e., time of neuronal discharge onset relative to movement onset) was significantly longer for SMA (47 ± 8 ms) than for M1 (23 ± 6 ms) (Crutcher and Alexander 1990). On the other hand, SMA also seems closely related to the implementation of movements. For instance, Matsuzaka et al. (1992) found that a majority of SMA neurons were "movement-locked." Likewise, Crutcher and Alexander (1990) found comparable activity in SMA and M1 during motor execution. A direct role of SMA in motor execution also emerges from the studies reviewed by Hikosaka et al. (2000).

With respect to the comparison between SMA and the other "premotor" areas, few studies have thoroughly investigated this issue. However, Halsband and coworkers analyzed the changes in activity during 5 time windows [instruction, delay, premovement, movement, and reward (Halsband et al. 1994)]. They found substantially similar percentages in SMA and in the (combined) PMd and PMv. Cadoret and Smith (1997) found similar activation in SMA and in the ventral cingulate motor area in a prehension task.

Dynamics-related activity of neurons in SMA was previously investigated by Alexander and Crutcher. With respect to the activity during motor execution, they found dynamics-related signals in comparable proportions in SMA and in M1 (41% of "muscle-like" cells in SMA versus 36% in M1) (Crutcher and Alexander 1990). With respect to the activity during motor planning, they found that 18% of SMA cells were "muscle-like" (Alexander and Crutcher 1990b). Thus, dynamics-related activity was present in SMA also during planning, although in smaller proportion. (Although the authors concluded that the dynamics-related signal was "nearly absent," with a criterion threshold of P < 0.001, the measure of 18% is quite significant.) In the present study, we confirm and strengthen these results by showing that the movement dynamics is significantly present at the level of the population in SMA both during motor planning and during motor execution. In addition, we show that neurons in SMA undergo a variety of plastic changes when a new internal model for the dynamics is acquired. These plastic changes are comparable to that found in M1 (Gandolfo et al. 2000; Li et al. 2001). Parts of this work were presented elsewhere (Padoa-Schioppa et al. 2000, 2002).

	METHODS

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The experimental setup, behavioral paradigm, and data analysis were the same used for a previous study of M1 (Li et al. 2001) except when otherwise specified. The National Institutes of Health guidelines on the care and use of animals were strictly followed throughout the experiment.

Behavioral task

Two young male rhesus monkeys (Macaca mulatta), C and F, took part in the experiment. Both monkeys weighed between 6.5 and 7.5 kg, and both performed with the right arm. In the experiment, the monkeys sat on a chair in an electrically isolated enclosure. They held the handle of a 2 degrees of freedom (df) robotic arm (the manipulandum), which allowed free movements confined to a horizontal plane. A computer monitor placed vertically 75 cm in front of the monkeys displayed the position of the handle (cursor: 3 x 3-mm square, 0.2° of visual angle) and the targets of the reaching movements (16 x 16-mm squares, 1° of visual angle). All the movements were from a central location (center square) to one of 8 peripheral targets (peripheral squares), equally spaced along a circle (45° apart). Actual reaching movements were 8 cm in length.

The monkeys performed an instructed delayed reaching task. At the beginning of each trial, the center square appeared on the monitor, and the monkey moved the cursor into the center square to initiate the trial. After 1 s, a target square appeared at one of the 8 peripheral locations (cue). The monkey held the cursor within the center square for a randomly variable delay (0.5-1.5 s) before the center square was extinguished (go signal). The monkey had then to move and acquire the peripheral square within 3 s, and to remain within the peripheral square for 1 s to receive a juice reward (rew). During the task, the trajectories had to be confined within 60° on both sides of the line passing through the center square and peripheral square. The trial was immediately aborted if the monkey made any error, and another trial started after an intertrial interval (iti) of 0.8-1.2 s. The peripheral targets were pseudo-randomly chosen.

Two motors attached at the base of the robotic arm allowed turning on and off perturbing forces (force fields). We used one of the 2 force fields described by F = BV, where B is the rotation matrix (B = [0, -b; b, 0], with b = ±0.06 N s cm^-1) and V is the instantaneous velocity vector. Thus the force field F was viscous (proportional in strength to the velocity V) and curl (orthogonal in direction to the velocity V). Depending on the sign of "b" the force field was clockwise (CK) or counterclockwise (CCK). In each session, the monkeys performed in 3 subsequent behavioral conditions: BASELINE (no force), FORCE, and WASHOUT (no force). Each condition lasted for about 20 successful trials for each direction (about 160 trials total). Only one of the 2 force fields (CK or CCK) was used in each session.

Monkeys were exposed only to the nonperturbed reaching task during the training (4-6 mo), and the force fields were introduced only during the recording sessions. For monkey C, recording sessions with the 2 force fields were run in blocks (27 sessions with the CK force field, followed by 28 sessions with the CCK force field). Monkey F was tested on the CCK force field only (40 sessions). Sometimes, recording sessions began after the monkey had performed in nonperturbed conditions for 300 trials, allowing the time for the electrodes to settle, and for us to accurately define the spike thresholds. Each recording session lasted 1-2 h, after which we let the monkeys work as long as they continued. We ran no more than one session per day.

On separate control sessions we followed the same procedure, without ever introducing the perturbing force field. Thus in control sessions, the monkey performed in 3 arbitrarily divided conditions of about 160 successful trials each. Control sessions were intermixed with experimental sessions across days (16 control sessions in total).

Surgery and identification of the recording area

Aseptic stereotaxic surgery was performed to put a restraint device on the skull and a recording well (inner diameter: 28 mm and 19 mm for monkeys C and F, respectively). The chambers were centered on the midline, and in anterior coordinates A = 22 and A = 18 for monkeys C and F, respectively. The monkeys were given antibiotics and pain medications, and were allowed to fully rest for 1 wk after the surgery.

SMA was identified through electrical microstimulation (monkey C) and histology (monkey F). For microstimulation, we used a train of 20 biphasic pulse pairs (width = 0.1 ms, duration = 60 ms), at 330 Hz and 10-40 µA. Before the recordings, we extensively stimulated the left medial wall and obtained a map closely matching previous reports (Luppino et al. 1991). Monkey F was killed at the end of the experiment. We marked the recording sites with electrolytic lesions (cathodal current, 20 µA, 2 min). We then administered an overdose of pentobarbital sodium, and perfused the monkey transcardially with heparinized saline, followed by buffered formalin. The brain was marked with electrodes dipped in black ink, removed from the skull, photographed, sectioned (coronal plane, 28-µm sections), and Nisslstained. Recordings were located in the medial wall, caudal to the alignment with the genu of the arcuate sulcus (gAS). Microscopic inspection revealed that the recording region was poorly laminated, and lay within 6 mm rostral to tissue displaying a single line of giant pyramidal cells, thus identifying SMA (Matelli et al. 1991).

Recordings

For neuronal recordings, we used vinyl-coated tungsten electrodes (1-3 M impedance). We advanced electrodes by manually rotating a threaded rod carrying the electrode in a set-screw system, at an approximate depth resolution of 30 µm (300 µm/turn). Up to 8 electrodes were used in each session. Electrical signals acquired by the electrodes passed through a head stage (AI 401, Axon Instruments) and an amplifier (Cyberamp 380, Axon Instruments), and were filtered at a high and low cutoff of 10 kHz and 300 Hz, respectively. Data from each electrode were recorded and displayed using commercially available software (Experimenter's WorkBench 5.3, Data-Wave Technology). Electrical signals from each electrode were continuously sampled at a frequency of 20 kHz. Action potentials were detected by threshold crossing. Their waveforms (1.75-ms duration) were recorded on-line and saved to disk for subsequent analysis.

Data analysis: psychophysics

From each trajectory x(t) = [x(t), y(t)], we computed the speed profile s(t) = ||x(t)||. Thus s(t) was a vector of instantaneous speeds, sampled at 100 Hz. We defined the movement onset (mo) and movement end (me) with a threshold-crossing criterion on the speed (4 cm/s). We also defined the following positions. The initial position (IP) was the average hand position in the 50 ms preceding the mo. The movement position (MP) was the weighted average of the hand position during the 500 ms after the mo, with exponentially decaying weights and time constant = 50 ms. In formulaic expression

The final position (FP) was the average hand position from the me to the delivery of the reward. We defined the perpendicular displacement as the distance between the hand trajectory computed at peak speed and the line passing through IP and FP. We defined the initial angular deviation d as the angle between the line passing through IP and MP and the line passing through IP and FP and so that d > 0 when movements deviated in the direction of the external force.

Following Shadmehr and Mussa-Ivaldi (1994), we defined the correlation coefficient (CC) as the normalized covariance between the actual speed profile and an ideal speed profile. We first derived an ideal speed profile u(t) with an iterative process as a corrected average of BASELINE speed profiles and separately for each session and for each movement direction. Then we aligned for each trial the actual speed profile s(t) with the corresponding ideal speed profile u(t) at their peaks, and we computed the correlation coefficient CC(s, u) = cov (s, u)/[(s)(u)]. Hence, the values of the CC ranged between -1 and 1, and were close to 1 for actual speed profiles close to ideal.

To compare movements with similar kinematics, we disregarded for each condition the first 4 successful trials in each direction (32 successful trials in total). This arbitrary criterion was imposed for consistency with the previous work (Li et al. 2001; Padoa-Schioppa et al. 2002) and because it roughly corresponded to the initial adaptation phase. Loose time constraints were imposed on the reaction time (RT) during the experiments. In the analysis, we excluded anticipatory movements (RT < 200 ms) and outliers (RT > 400 ms). The remaining trials (>88%) were considered for further analysis.

Data analysis: neurons

The neuronal recordings were first subjected to a clustering analysis, to separate one or more individual neurons recorded from the same electrode from each other and from noise. Clustering was performed using commercially available software (Autocut 3, Data-Wave Technology), with a semimanual procedure. We visually inspected the waveforms after clustering, and often repeated the procedure one or more times. Only cells with convincingly consistent waveform (i.e., stable recordings) throughout the session were considered for further analysis.

We analyzed the activity of single neurons in 4 separate time windows. The center hold time (CH; 500 ms before cue), serving as a control time window; the delay time (DT; 500 ms before go); the movement time (MT; from 200 ms before mo to me); the target hold time (TH; 500 ms before rew). For each neuron and for each time window, we analyzed the spiking activity separately in the BASELINE, FORCE, and WASHOUT conditions. We averaged the activity across trials, and obtained a tuning curve for each condition. To characterize the tuning curves, we defined 3 parameters: the preferred direction (Pd), the average firing frequency (Avf), and the tuning width (Tw). The Pd of the neuron was defined as the direction of the vector average of the 8 vectors representing the activity recorded for the 8 movement directions. The Avf was defined as the average of the neuronal activity across the 8 directions. The Tw was defined as the angle over which the firing frequency was higher than half of the maximal activity across the 8 directions (maximum of the tuning curve). These parameters were defined for any given tuning curve, subject to the following preconditions. First, we considered tuning curves only with Avf values >1 Hz. Second, the Pd and Tw were defined for tuning curves displaying only a significantly unimodal distribution across directions (a directional tuning), as stated by the Rayleigh test (P < 0.01; Fisher 1993). Third, the Tw was defined only for strictly unimodal cells, for which the directions with firing frequency higher than half the maximum were continuous.

To analyze the changes of Pd over the entire population, we "flipped" the data recorded with the CK force field to obtain positive values when the Pd shifted in the direction of the external force.

Classification of cells

Significant changes across conditions for the 3 parameters Pd, Avf, and Tw were stated according to the method previously described in detail (Li et al. 2001). Briefly, given the 8-dimensional firing rate , the 8-dimensional SE (due to trial-by-trial variability in the activity of the cell) can be thought of as an error of measure for . We can expand each parameter p = P() at the first order in . Assuming that the 8 variables are Gaussian, p is also Gaussian and _p can be estimated as a linear combination of the 8 errors . For the analysis, we computed p and _p in each condition, and we compared the values of the parameter across conditions with a z-test (P < 0.001) using as an estimate of the variance.

Individual cells were classified separately for each parameter (Pd, Avf, and Tw) and for each time window (CH, DT, MT, and TH). For the sake of clarity, we illustrate the criteria of classification referring to the Pd. Cells that did not change their Pd across conditions (x-x-x) were designated "kinematic cells" because the desired kinematics remained unchanged throughout the session (see RESULTS). Cells that changed their Pd in the FORCE condition compared with BASELINE and returned to the original Pd in the WASHOUT (x-y-x) were designated "dynamic cells" because the dynamics of the movement were the same in the BASELINE and in the WASHOUT but different in the FORCE condition (where the monkeys compensate for the external force). Cells that changed their Pd in the FORCE compared with the BASELINE, and maintained in the WASHOUT their newly acquired Pd (x-y-y) were designated "memory cells" because they appeared to keep trace of the adaptation experience even after the monkey had returned to the nonperturbed conditions. More precisely, x-y-y cells were designated "memory I cells," as distinguished from "memory II cells," whose Pd did not change in the FORCE condition compared with BASELINE, but changed in the WASHOUT compared with the FORCE condition (x-x-y). Thus memory II cells were complementary to memory I cells. Finally, cells that changed their Pd in the FORCE condition and again in the WASHOUT (x-y-z) were designated "other" cells. The same criteria were applied for the Avf and the Tw.

For the statistical analysis of the population, we used conventional methods of linear (Avf) and circular (Pd and Tw) statistics (Fisher 1993).

Comparing the results of different classifications

SMA cells were classified for their changes across behavioral conditions separately for the 4 time windows and 3 parameters. One of the goals of the present study was to compare the results of classification across time windows (CH, DT, MT, and TH), and across parameters (Pd, Avf, and Tw). In addition, we wanted to compare the results recorded for experimental cells with those recorded for control cells. Finally, we wanted to compare the results recorded here for SMA with those recorded from M1 (Gandolfo et al. 2000; Li et al. 2001). We performed these comparisons using a Pearson's ² analysis (Freeman 1987), which we chose (over the likelihood ratio) because our contingency tables sometimes presented empty locations. For this same reason, we performed the comparison separately across populations, across time windows, and across parameters.

When comparing the classifications across time windows, we considered one parameter (e.g., the Avf) and 2 time windows (e.g., the DT and MT). We then addressed specific questions such as the following. Given that each given cell can be classified differently in the 2 time windows (e.g., "kinematic" in the DT and "dynamic" in the MT), are coincident classifications more frequent than would be expected if they occurred by chance? Having 5 possible classes (kinematic, dynamic, memory I, memory II, and other), we studied the 5 x 5 contingency table (5 DT classes x 5 MT classes) where the element n_ij is equal to the number of cells classified as "i" and "j" in the 2 time windows, respectively. We then computed the matrix

where

Pearson's ² is given by

In essence, the matrix element quantifies how "unlikely" is the value n_ij given all the other values n_lk, and ² quantifies how "unlikely" is the table n if the distribution across rows is independent of the distribution across columns (and vice versa). In our case, ² indicated whether the classifications in the DT and MT were at all interdependent, against the null hypothesis of homogeneity. To assess more specifically whether the 2 classifications coincided more frequently than expected by chance, we computed the trace

Because it is the sum of the diagonal elements of , Tr precisely quantifies how unlikely are coincident classifications.

When comparing the classifications across parameters, we considered one time window (e.g., the MT) and 2 parameters (e.g., the Pd and the Avf). We then addressed specific questions such as the following. Given that each given cell can be classified differently for the 2 parameters (e.g., "dynamic" for the Pd and "memory I" for the Avf), are coincident classifications more frequent than would be expected if they occurred by chance? Again, we studied the 5 x 5 contingency table, which we analyzed like before. In particular, we computed both .

A similar analysis was used when comparing the results for experimental and control cells. In this case, however, we collapsed cells of each group into 2 superclasses of "kinematic" and "nonkinematic" cells (nonkinematic cells included dynamics, memory I, memory II, and other cells). We obtained a 2 x 2 contingency table given by the 2 groups (experimental and control cells) and by the 2 superclasses (kinematics and nonkinematic cells). The value of Pearson's indicated whether there were any differences between groups against the null hypothesis of homogeneity. Because kinematic cells were generally more frequent between control cells, a significant deviation from homogeneity always indicated a higher proportion of nonkinematic cells in the group of experimental cells than would be expected by chance.

Electromyographic activity

In separate sessions, we recorded the electromyographic (EMG) activity of the muscles pectoralis, deltoid, biceps, triceps, and brachioradialis while the monkey performed in the task. We manually implanted Teflon-insulated wires in the shoulder and arm muscles. The EMG were recorded continuously, at the frequency of 1 kHz. In the analysis, we rectified and integrated the EMG over the same time windows used for the neurons. We obtained EMG's tuning curves, which we normalized and submitted to the same analysis used for neurons.

	RESULTS

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Psychophysics

The psychophysics of the task was previously described for humans (Shadmehr and Mussa-Ivaldi 1994) and monkeys (Gandolfo et al. 2000; Li et al. 2001). The present study confirms and further documents those results. Figure 1 illustrates the hand paths and speed profiles recorded in a representative session. In the absence of external perturbation, hand paths were roughly straight (Fig. 1A, BASELINE) and the speed profiles were close to bell-shaped (Fig. 1B, BASELINE). When we introduced a CK force field (FORCE condition), the hand paths were initially deviated and the speed profiles were also perturbed (Fig. 1, A and B, EARLY FORCE). As the monkey adapted to the perturbing force, however, the paths and the speed profiles gradually recovered (Fig. 1, A and B, LATE FORCE). When we removed the force field, the trajectories were initially deviated in a way that mirrored the deviation observed in the EARLY FORCE. This "aftereffect" could be observed both in the hand paths and in the speed profiles (Fig. 1, A and B, EARLY WASHOUT), before the monkey readapted to the nonperturbed conditions (Fig. 1, A and B, LATE WASHOUT).

View larger version (22K): [in this window] [in a new window]   FIG. 1. Psychophysics of motor adaptation: hand paths and speed profiles. A: hand paths. Hand paths are initially straight (LATE BASELINE), and become deviated when a CK force field is introduced (EARLY FORCE). As the monkey adapts to the perturbation, however, the trajectories gradually return straight (LATE FORCE) and become similar to that observed in the BASELINE (adaptation, or short-term learning). A transient aftereffect can be observed when the force is removed (EARLY WASHOUT), when hand trajectories deviate in a way that mirrors that observed in the EARLY FORCE. However, the monkey rapidly readapts to the nonperturbed conditions, and the trajectories return straight (LATE WASHOUT). B: speed profiles. Speed profiles for the first/last 5 trials in each movement direction are shown for each condition. Movement directions are1to8(top to bottom). Direction 1 is for rightward movements and direction number increases clockwise. Traces correspond to the hand trajectories illustrated in A, and the ideal speed profile is superimposed in red color. Dotted line indicates the threshold value of 4 cm/s. Unit bars on the bottom right represent 100 ms (x-axis) and 1 cm/s (y-axis).

View larger version (37K): [in this window] [in a new window]   FIG. 2. Psychophysics motor adaptation and motor learning: perpendicular displacement and correlation coefficient. A: perpendicular displacement, one session. Figure shows for each trial (x-axis, trial number) the values of the perpendicular displacement of the actual hand trajectory from the straight line passing through the initial location and the peripheral target computed at peak speed; the y-axis represents a normalized measure of distance, whereby the distance between the center location and the peripheral target equals 1. Each dot represents one trial, and positive values indicate a displacement in the direction of the external force. Displacement remains essentially constant and close to zero throughout the BASELINE (black color). In the CK FORCE (blue color) the displacement is initially greater than zero, and gradually return to values similar to that observed in the BASELINE as the monkey adapts. A clear aftereffect can be observed in the WASHOUT (green color), before the monkey readapts to the nonperturbed conditions. Solid lines are the result of linear fits. B: correlation coefficient, one session. For each trial, the correlation coefficient (CC) quantifies the similarity between actual speed profile and an ideal speed profile. The CC (y-axis) is plotted here against the trial number (x-axis). The CC ranges in values between -1 and 1, and is close to 1 when the speed profile is close to ideal. In the BASELINE, the CC has high values (CC about 0.98). When we introduce the CK FORCE, the CC drops sharply (CC <0.80). As the monkey adapts, the CC gradually recovers. When the force is then removed, we observe the aftereffect (CC about 0.93), before the monkey fully readapts. A statistical analysis indicated a significant difference between the CC recorded in the first 50 successful trials in the WASHOUT and the CC recorded in the last 50 successful trials in the BASELINE (P < 0.002, ANOVA). The values of the CC are smoothed in 10-trial bins. C: perpendicular displacement, all sessions. For each session, we computed the mean perpendicular displacement separately in the 3 conditions BASELINE (black triangles), FORCE (blue circles), and WASHOUT (green inverted triangles). The results are shown here for all the sessions and for the 2 monkeys. A clear effect of long-term learning can be observed because the mean perpendicular displacement in the FORCE gradually converged to the values observed in the BASELINE. D: correlation coefficient, all sessions. For each session, we averaged the CC over trials, separately in the 3 behavioral conditions (BASELINE, FORCE condition, WASHOUT). Two panels show the data for all the sessions and for the 2 monkeys. In each panel, the mean CC (y-axis) is plotted against the session number (x-axis), separately for the BASELINE (black triangles), the FORCE condition (blue circles), and the WASHOUT (green inverted triangles). For the BASELINE and the WASHOUT, the mean CC remained high throughout the recordings. For the FORCE condition, the mean CC increased over sessions (long-term learning). Note that the monkeys were still "learning" throughout the recording period.

Additional analysis indicates that other kinematic parameters remained essentially constant across conditions. Figure 3, A-C illustrates, for each session, the measures of average peak speed, average reaction time, and average movement time. Quantitative analysis with a 2-way ANOVA (factors: monkey, condition) provided the following results. With respect to the peak speed, the main factor of condition was not significant (F = 0.65, P > 0.5) and the interaction factor was not significant (F = 1.33, P > 0.2). With respect to the average reaction time, the main factor of condition was not significant (F = 0.01, P > 0.9) and the interaction factor was not significant (F = 0.6, P > 0.4). Finally, with respect to the average movement time, the main factor was not significant (F = 1.98, P > 0.1), although the interaction factor was significant (F = 12.65, P = 0).

View larger version (25K): [in this window] [in a new window]   FIG. 3. Psychophysics: other kinematic parameters. Figure shows for each of the sessions in which neurons were actually recorded (A) the average peak speed, (B) the average reaction time, and (C) the average movement time [from movement onset (mo) to movement end (me)]. Color and symbol conventions are the same as in Fig. 2, C and D. CK and CCK FORCE sessions are combined for monkey C (right panels).

In conclusion, behavioral results offered in principle an interpretative framework whereby neuronal activity that did not change across conditions could be associated with the (desired) kinematics and neuronal activity that changed across conditions could be associated with the dynamics (see also DISCUSSION). The association between activity changes and movement dynamics was further supported by the comparison of changes observed for the activity of neurons and changes observed for electromyographic activity of muscles following adaptation (see following text).

In the analysis of EMG and neuronal activity, we disregarded in each condition the first 4 successful trials in each movement direction. Thus we essentially compared the activity recorded during the LATE BASELINE, LATE FORCE, and LATE WASHOUT subconditions, corresponding to the 3 bottom panels of Fig. 1A. For the sake of brevity, we refer in the following to these 3 subconditions as BASELINE, FORCE, and WASHOUT conditions. However, the analysis never included the "EARLY" part, unless otherwise specified.

EMG activity

The choice of viscous, curl force fields F = BV offered two advantages. First, no perturbing force was ever present when the monkey held their hand still (V = 0). In particular, no external force was ever present— even in the FORCE condition— during the instructed delay (DT). Second, the curl force field imposed predictable and consistent changes onto the EMG activity of muscles during the movement time (MT). Specifically, by comparing the preferred direction (Pd) recorded in the FORCE condition with that recorded in the BASELINE, we observed a shift of Pd in the direction of the external force field.

Figure 4 illustrates the EMG activity of one representative muscle (triceps longhead). The 3 columns represent the 3 conditions (BASELINE, FORCE, and WASHOUT), and the 4 rows represent the 4 time windows (CH, DT, MT, and TH). In each panel, the muscle's tuning curve is plotted in blue in polar coordinates, and the preferred direction (Pd) is plotted in red. The Pd is defined only for directionally tuned EMG activity. It can be noticed that there is no directional activity in either the CH or the DT. With respect to the MT, the Pd of the muscle is oriented toward 21° in the BASELINE. In the FORCE condition— after adaptation to the CCK field—the Pd of the muscle shifts by 28° in the direction of the external force (the CCK direction). In the WASHOUT, the Pd of the muscle shifts back, essentially to that originally recorded in the BASELINE.

View larger version (32K): [in this window] [in a new window]   FIG. 4. Electromyographic (EMG) activity of the triceps-longhead muscle, recorded with the CCK force field. The tuning curve (blue) and the Pd (red) are plotted in polar coordinates, separately for the 4 time windows (CH, DT, MT, TH) and for the 3 conditions (BASELINE, FORCE condition, WASHOUT). The activity is normalized to the maximum across the 12 panels, and the Pd is defined only for directionally tuned activity. No directional EMG are present in either the CH (1st row) or the DT (2nd row). Considering the MT (3rd row) in the FORCE condition, the EMG activity modifies compared with the BASELINE, and the Pd shifts in the CCK direction (i.e., the direction of the external force). Shift of Pd in direction of the external force was consistent for all muscles and attributed to the vector sum between the force of the muscle and the external force. In the WASHOUT, the activity of the muscle returned to that observed in the BASELINE, and the Pd shifted back. With respect to the TH (4th row), we observed a more modest shift, which was not consistent for all the muscles. This suggests that the EMG activity in the TH was positional because viscous force fields (F = BV) equal zero when the hand is still (V = 0).

Neuronal database

We recorded the activity of 252 SMA cells in the adaptation task. In addition, we recorded the activity of 46 SMA cells in control sessions. Recordings were concentrated in the arm region of SMA (Fig. 5).

View larger version (14K): [in this window] [in a new window]   FIG. 5. Recording locations. A: microstimulation. Figure shows the results of microstimulation of the left medial wall of monkey C: x-axis indicates rostrocaudal position in stereotaxic coordinates; y-axis indicates depth of penetration (in mm). Somato-topic organization of SMA is clearly visible. B: recordings. Recordings were confined to the arm region of SMA (enlarged view here).

View larger version (56K): [in this window] [in a new window]   FIG. 6. Preferred directions (Pd). A: distribution of Pd. All SMA neurons are shown. Circular statistics indicated that the distribution of Pd around the clock was always homogeneous (minimal P > 0.04, Rayleigh test), except for the FORCE condition-MT time window (P < 0.002, Rayleigh test). B: comparing the Pd across time windows. Left panel: plot of the Pd recorded in the DT time window (x-axis) against the Pd recorded in the MT time window (y-axis). Each dot represents one cell. Note the broad correspondence between the Pd in the 2 time windows; the other 2 panels show the contrast between the Pd in the MT and that in the TH (center panel), and between the Pd in the DT and that in the TH (right panel).

View larger version (33K): [in this window] [in a new window]   FIG. 7. A field-specific cell. Left: raster plots obtained for the 3 conditions (columns), separately for each of the 8 movement directions. Each line represents one trial and each small black dot represents one spike. Trials are aligned at the mo (yellow circle) and ranked according to the duration of the movement. For each trial, the raster illustrates the activity from the beginning of the trial to the end of the trial. Other symbols indicate the beginning of trial (black right triangle), the presentation of the cue (red inverted triangle), the go signal (green diamond), the me (blue left triangle), and the reward (rew, magenta circle). All the trials with reaction time (RT) such that (200 ms) < RT < (400 ms) are shown. Right: tuning curve of the cell is plotted in blue in polar coordinates, separately for the 3 conditions and for the 4 time windows. Pd— defined only for directionally tuned activity—is plotted in red. Radial scale (9 Hz) is the same for all 12 panels, and is indicated in italics for the top left panel (CH, BASELINE). Activity of this cell was very scarce in the CH and DT, throughout the 3 conditions. Considering the MT (3rd row), low activity and no directional tuning is present in the BASELINE. In the FORCE condition, the activity increases and the cell becomes directionally tuned. In the WASHOUT, however, the activity of the cell returns to that observed in the BASELINE and the cell loses its directional tuning. These changes are dynamic in nature, given that the dynamics of the movement were the same in the BASELINE and in the WASHOUT, but different in the FORCE condition.

View larger version (30K): [in this window] [in a new window]   FIG. 8. A "tune-in" cell. Left: raster plots. All conventions are as in Fig. 7. Right: CH, DT, and TH activity of this cell remained scarce throughout the session. Considering the MT (3rd row), scarce activity is present in the BASELINE. However, after adaptation in the FORCE condition, the cell becomes sharply tuned. In the WASHOUT, after the monkey readapts to the nonperturbed conditions, the cell maintains the new directional tuning. Thus this cell maintains a memory of the newly acquired internal model for the dynamics. All conventions are as in Fig. 7.

View larger version (44K): [in this window] [in a new window]   FIG. 9. A kinematic cell (x-x-x). Left: raster plots. All conventions are as in Fig. 7. Right: considering either the DT (2nd row) or the MT (3rd row), the Pd of the cell remains essentially constant throughout the 3 conditions. We classified this cell as kinematic for its changes of Pd because the desired kinematics of the movement remained the same throughout. Note that— unlike the Pd—the Avf of the cell changed across conditions. Considering for instance the changes of Avf in the CH, the cell has memory I properties. All conventions are as in Fig. 7.

View larger version (43K): [in this window] [in a new window]   FIG. 10. A dynamic cell (x-y-x). Left: raster plots. All conventions are as in Fig. 7. Right: this cell was recorded with a CK force field. Cell is directionally tuned both in the DT and in the MT, in all 3 conditions. Considering the DT activity (2nd row), the Pd of the cell shifts in the FORCE condition compared with the BASELINE in the direction of the external force (CK direction). In the WASHOUT, the Pd of the cell shifts back to that observed in the BASELINE; thus we classified the cell as dynamic for its changes of Pd in the DT. Considering the MT activity (3rd row), the cell exhibits similar changes. Pd of the cell shifts in the CK direction in the FORCE condition, and shifts back in the WASHOUT essentially to that observed in the BASELINE; thus the cell was also classified as dynamic for its changes of Pd in the MT. Note that the shift of Pd is quantitatively more pronounced in the MT than in the DT, although qualitatively analogous in the 2 time windows. All conventions are as in Fig. 7.

View larger version (49K): [in this window] [in a new window]   FIG. 11. A memory I cell (x-y-y). Left: raster plots. All conventions are as in Fig. 7. Right: activity of this cell—recorded with a CCK force field—is directionally tuned in the DT, MT, and TH time windows. Cell is classified as memory I cell for its changes of Pd in all 3 time windows. Considering—for instance—the DT activity (2nd row), the activity of the cell modifies in the FORCE condition compared with the BASELINE and the Pd shifts in the CCK direction (the direction of the external force). In the WASHOUT, the activity of the cell and the Pd remain as observed in the FORCE condition. Because the cell appeared to maintain a trace of the adaptation experience, we classified it as a memory I cell. Considering the MT time window, we observe similar changes. Here again, the shift of Pd (and the overall changes) are quantitatively more pronounced in the MT than in the DT, but qualitatively analogous. This cell was also classified as a memory I cell for its changes of average firing rate (Avf), in both the MT and TH time windows. In contrast, the CH activity of the cell remained stable throughout the session. All conventions are as in Fig. 7.

View larger version (45K): [in this window] [in a new window]   FIG. 12. A memory II cell (x-x-y). Left: raster plots. All conventions are as in Fig. 7. Right: activity of this cell—recorded with a CCK force field—is directionally tuned in the MT throughout the 3 conditions. In the FORCE condition, the activity of the cell remained essentially unchanged compared with the BASELINE. In the WASHOUT, however, the activity modified, and the Pd shifted in the CK direction, that is the direction opposite to the previously experienced external force; thus the cell was classified as a memory II cell. All conventions are as in Fig. 7.

View larger version (41K): [in this window] [in a new window]   FIG. 13. A control cell. Left: raster plots. All conventions are as in Fig. 7. Right: this cell was recorded in a session where no perturbing force was ever introduced, and the monkey performed in BASELINE-like conditions throughout the session. Pd of the cell remained essentially unchanged throughout the 3 (arbitrarily defined) behavioral conditions, in the DT, MT, and TH time windows. Note, however, that the Avf of the cell increased over the course of the session. All conventions are as in Fig. 7.

The percentages of directionally tuned cells for the 3 behavioral conditions and in the 4 time windows are shown in Table 2. In total, 44-49% of cells (depending on the behavioral condition) were directionally tuned in the delay time (DT). These percentages increased in the movement time (MT), to 59-66%. In the target hold time (TH), 53-58% of cells were tuned.

Field-specific cells, tune-in cells, and tune-out cells

As the monkey adapted to the perturbing force, the activity of neurons in SMA changed. Some cells that were not tuned in the BASELINE became tuned in the FORCE condition after the adaptation, and lost their tuning again in the WASHOUT. Other cells that were originally tuned in the BASELINE lost their tuning in the FORCE condition, to regain it in the WASHOUT. These 2 types of cells were grouped in the class of "field-specific" cells. The changes observed in their directional tuning appeared dynamic in nature. Figure 7 illustrates one example of field-specific cell (MT activity). In total, field-specific cells accounted for 10% of SMA population (MT time window).

Another group of cells— designated "tune-in" cells—were initially not tuned in the BASELINE and acquired a directional tuning in the FORCE condition (Gandolfo et al. 2000). Unlike field-specific cells, however, tune-in cells maintained their newly acquired tuning in the WASHOUT, after the monkey had readapted to the nonperturbed conditions. Thus tune-in cells appeared to maintain a trace of the adaptation experience after readaptation in the WASHOUT. One example of tune-in cell is illustrated in Fig. 8. We also found a group of cells— designated "tune-out" cells—that were initially tuned in the BASELINE, lost their tuning in the FORCE condition, and failed to regain their tuning in the WASHOUT. Thus the changes observed for tune-in cells and tune-out cells appeared memory in nature. In total, tune-in cells and tune-out cells counted for 14 and for 8% of the population, respectively (analysis done on the MT activity).

Changes of preferred direction: delay time

Only cells that remained directionally tuned throughout the 3 conditions were analyzed and classified for their changes in the preferred direction (Pd). Cells were classified separately for the DT, MT, and TH time windows.

Figure 9 illustrates the activity of a kinematic cell, classified according to the changes of Pd. Considering the DT time window (2nd row), the Pd of the cell remains essentially constant throughout the session (x-x-x). Because the desired kinematics remained unchanged throughout the 3 conditions, this cell was classified as a kinematic cell.

Figure 10 illustrates the activity of a dynamic cell recorded with a CK force field, and classified according to the changes of Pd. The DT activity is shown in the 2nd row. In the FORCE condition, the Pd of the cell shifts in the direction of the external force (i.e., in the CK direction) compared with the BASELINE. In the WASHOUT, the Pd shifts in the opposite direc tion, back to that recorded in the BASELINE (x-y-x). Because the dynamics of the movement were the same in the BASELINE and in the WASHOUT, but different in the FORCE condition, this cell was classified as a dynamic cell.

Figure 11 illustrates the activity of a memory I cell recorded in SMA with a CCK force field, and classified according to the changes of Pd. Again, the DT activity is illustrated in the 2nd row. In the FORCE condition, the Pd of the cell shifts in the direction of the external force (i.e., the CCK direction) compared with the BASELINE. However, after readaptation in the WASHOUT, the Pd remained oriented in the newly acquired direction (x-y-y). Thus the cell appeared to maintain a trace of the previously adaptation experience. We therefore classified this cell as a memory I cell.

Considering the entire SMA population, a total of 68 cells could be classified according to their changes of Pd in the DT time window. The majority of these cells was classified as kinematic (51 cells, 75%). However, we also found dynamic cells (3 cells, 4%), memory I cells (9 cells, 13%), and memory II cells (5 cells, 7%). These percentages are summarized in Table 3a.

Changes of preferred direction: movement time

The classes of kinematic, dynamic, and memory I cells are illustrated for the DT time window in Figs. 9, 10, 11 (2nd rows). Similar classes of cells were also found for the MT time window, as illustrated in the same Figs. 9, 10, 11 (3rd rows). Considering the MT activity of the cell in Fig. 9 (3rd row), the Pd is essentially constant throughout the 3 conditions (x-x-x). Therefore the cell was classified as kinematic for the changes of Pd in the MT.

The cell in Fig. 10 was recorded with a CK force field. Considering the MT activity (3rd row), the Pd of the cell shifts in the direction of the external force in the FORCE condition compared with the BASELINE. In the WASHOUT, the Pd shifts back in the opposite direction, essentially to its original orientation (x-y-x). Therefore the cell was classified as dynamic for the changes of Pd in the MT.

The cell in Fig. 11 was recorded with a CCK force field. Again, considering the MT activity (3rd row), the Pd of the cell shifts in the direction of the external force in the FORCE condition compared with the BASELINE. In the WASHOUT, the cell maintains its newly acquired Pd (x-y-y). Thus this cell was classified as a memory I cell for the changes of Pd in the MT.

Figure 12 illustrates the activity of a memory II cell recorded in SMA with a CCK force field. In the DT (2nd row), the cell is not directionally tuned. Considering the MT time window (3rd row), the Pd is essentially unchanged in the FORCE condition compared with the BASELINE. In the WASHOUT, however, the Pd of the cell shifts in the direction opposite to the previously experienced force field, that is the CK direction (x-x-y). Thus this cell was classified as a memory II cell for the changes of Pd in the MT. Note that the shift of Pd of memory II cells seems to balance in the WASHOUT the shift of Pd of memory I cells (Li et al. 2001).

In total, we could classify 117 SMA cells according to their changes of Pd in the MT. Of these, 61 cells (52%) were kinematic, 20 cells (17%) were dynamic, 20 cells (17%) were memory I, 13<