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Right-handed, healthy male participants (n = 16, age = 23.6 ± 3.2 years) were recruited and gave written consent. Participants lay in a supine position in a dimly lit sound-attenuated room, on the gurney of a GE 4096+ PET tomograph. A catheter was placed in the left cubital vein for injection of the radioisotope. Each man gripped the handle of a robot manipulandum with his right hand. The robot is a portable, light-weight, very low friction planar mechanism equipped with two pairs of optical position and velocity encoders, a force transducer at the handle, and brushless dc motors that deliver torques independently to each joint (8). Participants viewed a monitor that displayed a cursor corresponding to the handle's position. The task was to take the handle to a series of targets. Participants were instructed that they should reach for the displayed target and that their movement time should be within 500 ± 50 ms (targets were at 10 cm). A target randomly appeared in one of eight directions (Fig. 1 B). The target turned blue if a participant reached it too late, red if he reached it too soon, and "exploded" if the reach was in time. One second after a target was reached, the next target appeared. The experiment was approved by the Johns Hopkins University Joint Committee on Clinical Investigation.
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2O was administered [M. E. Raichle et al., J. Nucl. Med. 24, 790, (1983)]. Accumulated radioactivity in the 90 s after initiation of the scan was used as an index of rCBF. Scans were acquired at 10-min intervals. The motor task was initiated 1 min before administration of the bolus and continued until completion of the scan. Participants practiced in the field for 5 min between scans 6 and 7 and rested between all other scans. Arterial blood was not sampled. Blood flow data reported here are changes in units of flow relative to the mean of the flow acquired for the whole brain.
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Other measures of motor output, including total force, mechanical work, and integrated electromyogram, are correlated with movement length during learning of a force field.
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Images were realigned and normalized with SPM96 software [K. Friston et al., Hum. Brain Mapp. 2, 189 (1995)]. The scans from each participant were realigned with the first image used as a reference. AT1 weighted magnetic resonance image (MRI) was coregistered to the mean PET image for each participant and then stereotactically transformed to a standard MRI template in the Talairach and Tournoux space. The resulting transformation matrix was applied to the PET images. The normalized PET images were smoothed with an Isotropic Gaussian filter (ful width at half maximum of 12 mm). The normalized MRI scans were combined to generate a population-specific anatomic atlas. Based on a distance measure [R. P. Woods, S. R. Cherry, J. C. Mazziotta, J. Comput. Assist. Tomogr. 115, 565 (1992)] between the individual MRIs and the atlas, the median brain among the population of participants was labeled as typical. Smoothed, normalized PET data were analyzed with the use of SPM software with a multisubject block design, two replications per condition, and an analysis of covariance global normalization. Participant and global brain activity were two covariates of no interest, and the conditions of the task were the covariates of interest. The search volume was from z = -30 mm to z = 60 mm and did not allow a complete view of the cerebellum. In the parametric test, the contrasts represented the average movement length per condition. In the subtraction tests, the contrasts were -1 and 1 (or 1 and -1) for the conditions of interest. We considered as significant regions where voxel-level Z valrues exceeded 4.4 so that the corrected P < 0.05. We also considered as significant regions in the sensorimotor system that we had selected a priori, where voxel-level Z values exceeded 3.09. These regions were the primary sensorimotor, the premotor, and the supplementary motor areas, the striaturn, and the cerebellum.
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