We have used positron emission tomography to study the functional anatomy of motor sequence learning. Subjects learned sequences of keypresses by trial and error using auditory feedback. They were scanned with eyes closed under three conditions: at rest, while performing a sequence that was practiced before scanning until overlearned, and while learning new sequences at the same rate of performance. Compared with rest, both sequence tasks activated the contralateral sensorimotor cortex to the same extent. Comparing new learning with performance of the prelearned sequence, differences in activation were identified in other areas. (1) Prefrontal cortex was only activated during new sequence learning. (2) Lateral premotor cortex was significantly more activated during new learning, whereas the supplementary motor area was more activated during performance of the prelearned sequence. (3) Activation of parietal association cortex was present during both motor tasks, but was significantly greater during new learning. (4) The putamen was equally activated by both conditions. (5) The cerebellum was activated by both conditions, but the activation was more extensive and greater in degree during new learning. There was an extensive decrease in the activity of prestriate cortex, inferotemporal cortex, and the hippocampus in both active conditions, when compared with rest. These decreases were significantly greater during new learning. We draw three main conclusions. (1) The cerebellum is involved in the process by which motor tasks become automatic, whereas the putamen is equally activated by sequence learning and retrieval, and may play a similar role in both. (2) When subjects learn new sequences of motor actions, prefrontal cortex is activated. This may reflect the need to generate new responses. (3) Reduced activity of areas concerned with visual processing, particularly during new learning, suggests that selective attention may involve depressing the activity of cells in modalities that are not engaged by the task.

Regional cerebral blood flow was measured in normal subjects with positron emission tomography (PET) while they performed five different motor tasks. In all tasks they had to moved a joystick on hearing a tone. In the control task they always pushed it forwards (fixed condition), and in four other experimental tasks the subjects had to select between four possible directions of movement. These four tasks differed in the basis for movement selection. A comparison was made between the regional blood flow for the four tasks involving movement selection and the fixed condition in which no selection was required. When selection of a movement was made, significant increases in regional cerebral blood flow were found in the premotor cortex, supplementary motor cortex, and superior parietal association cortex. A comparison was also made between the blood flow maps generated when subjects performed tasks based on internal or external cues. In the tasks with internal cues the subjects could prepare their movement before the trigger stimulus, whereas in the tasks with external cues they could not. There was greater activation in the supplementary motor cortex for the tasks with internal cues. Finally a comparison was made between each of the selection conditions and the fixed condition; the greatest and most widespread changes in regional activity were generated by the task on which the subjects themselves made a random selection between the four movements.

It is widely held that the prefrontal cortex is important for working memory. It has been suggested that the inferior convexity (IC) may play a special role in working memory for form and color (Wilson et al., 1993). We have therefore assessed the ability of monkeys with IC lesions to perform visual pattern association tasks and color-matching tasks, both with and without delay. In experiment 1, six monkeys were trained on a visual association task with delays of up to 2 sec. Conservative IC lesions that removed lateral area 47/12 in three animals had no effect on the task. Further experiments showed that these lesions had no effect on the postoperative new learning of a color-matching task with delays of up to 2 sec or versions of the visual association task involving delays of up to 8 sec. In experiment 2, larger lesions of both areas 47/12 and 45A were made in the three control animals. This lesion caused a profound deficit in the ability to relearn simultaneous color matching, but subsequent matching with delays of up to 8 sec was clearly unimpaired. We suggest that the IC may be more important for stimulus selection and attention as opposed to working memory.

Objective-To investigate whether micrographia in patients with Parkinson's disease is lessened either by giving visual targets or by continually reminding them that they should write with a normal amplitude. Methods-Eleven patients with Parkinson's disease (mean age 65.4 years) were compared with 14 control subjects (mean age 67.1 years). The subjects wrote with a stylus on a graphics tablet. There were three conditions: free writing, writing with dots to indicate the required size, and writing with continuous verbal reminders ("big"). Each condition was performed twice. Results-The patients wrote with a more normal amplitude when given either the visual cues or the auditory reminders. This improvement persisted when, shortly afterwards, the patients wrote freely without external cues. The increase in amplitude was achieved mainly by an increase in movement time rather than in peak velocity. Conclusion-Whereas the visual cues directly specified the required amplitude the auditory reminders did not. One effect of external cues is that they draw attention to the goal, and thus encourage the patients to write less automatically.