Search

Cortical reactions to rare task-related stimuli have been studied with electrophysiological methods in the assessment of the P300 component as well as in functional imaging studies with regard to oddball tasks.While functional magnetic resonance imaging studies using auditory stimuli have to deal with interference between auditory stimuli and scanner noise, the aim of our study was to assess auditory target processing with the sparse imaging method. Single volumes of echo-planar imaging were acquired 4 s following the onset of the stimuli of interest. In keeping with previous studies, target stimuli activated the insula, superior temporal gyrus, cingulate gyrus, middle frontal gyrus, parietal cortex and the cerebellum. Our results encourage the application of the sparse imaging method in experiments on cognitive processing elicited by auditory stimulation in a silent environment. NeuroReport14:1597^1601 � c 2003 Lippincott Williams & Wilkins.

Jueptner, M., K. M. Stephan, C. D. Frith, D. J. Brooks, R.S.J. Frackowiak, and R. E. Passingham. Anatomy of motor learning. I. Frontal cortex and attention to action. J. Neurophysiol. 77: 1313–1324, 1997. We used positron emission tomography to study new learning and automatic performance in normal volunteers. Subjects learned sequences of eight finger movements by trial and error. In a previous experiment we showed that the prefrontal cortex was activated during new learning but not during automatic performance. The aim of the present experiment was to see what areas could be reactivated if the subjects performed the prelearned sequence but were required to pay attention to what they were doing. Scans were carried out under four conditions. In the first the subjects performed a prelearned sequence of eight key presses; this sequence was learned before scanning and was practiced until it had become overlearned, so that the subjects were able to perform it automatically. In the second condition the subjects learned a new sequence during scanning. In a third condition the subjects performed the prelearned sequence, but they were required to attend to what they were doing; they were instructed to think about the next movement. The fourth condition was a baseline condition. As in the earlier study, the dorsal prefrontal cortex and anterior cingulate area 32 were activated during new learning, but not during automatic performance. The left dorsal prefrontal cortex and the right anterior cingulate cortex were reactivated when subjects paid attention to the performance of the prelearned sequence compared with automatic performance of the same task. It is suggested that the critical feature was that the subjects were required to attend to the preparation of their responses. However, the dorsal prefrontal cortex and the anterior cingulate cortex were activated more when the subjects learned a new sequence than they were when subjects simply paid attention to a prelearned sequence. New learning differs from the attention condition in that the subjects generated moves, monitored the outcomes, and remembered the responses that had been successful. All these are nonroutine operations to which the subjects must attend. Further analysis is needed to specify which are the nonroutine operations that require the involvement of the dorsal prefrontal and anterior cingulate cortex.

We used positron emission tomography (PET) to localize a cerebellar timing function.Six healthy volunteers estimated time differences by comparing a test interval (defined by two tones) with a standard interval. In the timing condition, subjects lifted their right index finger if the test interval was shorter and their right middle finger if it was longer than the standard interval. In the control condition, the two intervals were identical and subjects had to alternate between lifting their index and middle fingers. We examined regional cerebral blood flow (rCBF) using the standard C 15 O 2 inhalation technique. Comparison of control and rest conditions revealed significant increases of rCBF during the control condition in the inferior parts of the ipsilateral cerebellar hemisphere, reflecting finger movements. Comparison of timing and control conditions showed additional activations of the cerebellar vermis and hemispheres bilaterally during the timing condition, reflecting the cerebellar timing process. We conclude that the cerebellum is involved in time-critical perception (``timing99). This nonmotor task can be separated from a motor task (finger movement). NEUROLOGY 1995;45: 1540-1545

In this article, the authors summarize results from imaging studies, analyzing the functional anatomy of motor sequence learning and timing. Emphasis is on the relationship between the cortical motor areas, the basal ganglia, and the cerebellum.

Event-related potential studies in man suggest a role for the supplementary motor area (SMA) in movement preparation, particularly when movements are internally generated. In a previous study combining PET with recording of movement-related cortical potentials, we found similar SMA activation and early pre-movement negativity during self-initiated and predictably paced index finger extensions. Early pre-movement negativity was absent when finger movements were paced by unpredictable cues. We postulated that preparation preceding self-initiated and predictably cued movements was responsible for equivalent levels of SMA activation in these two conditions. To test this, we have performed further studies on six normal volunteers with H2(15)O-PET. Twelve measurements of regional cerebral blood flow were made in each subject under three conditions: rest; self-initiated right index finger extension at a variable rate of once every 2-7 s; and finger extension triggered by pacing tones at unpredictable intervals (at a rate yoked to the self-initiated movements). Activation associated with these conditions was compared using analysis of covariance and t statistics. Compared with rest, unpredictably cued movements activated the contralateral primary sensorimotor cortex, caudal SMA and contralateral putamen. Self-initiated movements additionally activated rostral SMA, adjacent anterior cingulate cortex and bilateral dorsolateral prefrontal cortex (DLPFC). Direct comparison of the two motor tasks confirmed significantly greater activation of these areas and of caudal SMA in the self-initiated condition. These results, combined with our previous data, suggest that rostral SMA plays a primary role in movement preparation while caudal SMA is a motor executive area. In this experiment and in our earlier study, DLPFC was activated only during the self-initiated task, in which decisions were required about the timing of movements.

The performance of a motor task not only requires subjects to plan, prepare, and initiate but also to monitor how a movement is performed. We used positron emission tomography to examine to what extent the human cerebellum is involved in controlling motor output or sensory input from movements in normal subjects. In the first study, we compared the active performance of a motor task (flexion and extension of the right elbow) to the passive execution of the same movements. Passive movements were driven by a motor with the arm fixed in a guide hinge. Active movements (compared to rest) elicited increases of rCBF mainly in the ipsilateral neocerebellar hemisphere and vermis of the posterior lobe. During passive movements, almost identical parts of the cerebellar hemispheres and vermis were activated (compared to the rest condition). The direct comparison of active and passive movement conditions revealed a small activation of the neocerebellar hemisphere of the posterior lobe and cerebellar nuclei ipsilateral to the movement. Approximately 90% of cerebellar neuronal activity was related to sensory input. In the second study, we compared the execution of a free selection joystick movement task to a condition in which subjects simply imagined the movements. The execution of movements (compared to rest) was associated with increases of rCBF in the ipsilateral neocerebellar hemisphere and vermis of the posterior lobe. During movement imagination, a small part of the ipsilateral cerebellar hemisphere and vermis of the posterior lobe was activated (compared to rest). The increase of rCBF during movement imagination accounted for only 20% of the signal seen during movement execution. Our results indicate that the neocerebellum may be much more concerned with sensory information processing than has been considered previously.

CHANGES of cerebellar blood flow were studied in normal humans using positron emission tomography (PET). A motor driven peg marked pairs of lines on subjects' right hands at different velocities. Subjects had to decide whether the second line was marked slower or faster than the first. Estimation of velocity (compared with control, i.e. presentation of lines at constant velocity) led to increases of regional cerebral blood flow (rCBF) in the left cerebellar hemisphere and vermis. Presentation of lines at constant velocity (compared with rest) activated the right cerebellar hemisphere. We conclude that the cerebellum is involved in temporal information processing even in the absence of motor output. This process can be separated from mere presentation of somatosensory stimuli.

The energy metabolism of the adult human brain almost completely depends on glucose. The functional coupling of regional cerebral blood flow and local cerebral glucose metabolism has been established in a wide range of experiments using autoradiographic techniques in rats, cats, and monkeys as well as double-tracer techniques in humans. Glucose utilization in turn reflects neuronal activity and more specifically synaptic, mainly presynaptic, activity. The majority of glucose is needed for the maintenance of membrane potentials and restoration of ion gradients. PET as well as fMRI may be used to study changes in blood flow or flow-related phenomena in human subjects in vivo. Both techniques monitor changes of synaptic activity in a population of cells. These changes may be due to excitation or inhibition. More than 85% of cerebral glucose is used by neurons (mainly presynaptic axon terminals), while the remainder may at least partly account for metabolic processes in glial cells. Monitoring of regional cerebral blood flow with PET or fMRI thus mainly reflects neuronal and more specifically (pre-) synaptic activity.

We used positron emission tomography (PET) to compare the contribution of the cerebellum and basal ganglia to the sensory guidance of movement. In one condition the subjects used a computer mouse to draw a series of lines on a computer screen (DRAW). In the second condition the same lines were presented to the subjects, and they had to track the lines with a mouse pointer on the screen (COPY). In a third condition the subjects were again presented with the same lines, and they simply followed movements of the pointer with their eyes (EYES). In the fourth condition, the subjects fixated a central point, ignoring the sequence of presented lines (FIX). The pons and cerebellum were activated more during visually guided tracking than in freely generated drawing (COPY vs DRAW). The basal ganglia were activated equally in both DRAW and COPY. The prefrontal and inferior temporal cortex were activated more when subjects drew lines freely (DRAW) than when they copied them (COPY). We conclude that the cerebellum is specialized for using sensory information to correct movements, but that the basal ganglia are involved both in movements that are self-generated and in movements that are guided by external cues.

Jueptner, M., C. D. Frith, D. J. Brooks, R.S.J. Frackowiak, and R. E. Passingham. Anatomy of motor learning. II. Subcortical structures and learning by trial and error. J. Neurophysiol. 77: 1325–1337, 1997. We used positron emission tomography to study motor learning by trial and error. Subjects learned sequences of eight finger movements. Tones generated by a computer told the subjects whether any particular move was correct or incorrect. A control condition was used in which the subjects generated moves, but there was no feeback to indicate success or failure, and so no learning occured. In this condition (free selection) the subjects were required to make a finger movement on each trial and to vary the movements randomly over trials. The subjects had a free choice of which finger to move on any one trial. On this task there was no systematic change in responses over trials and no change in the response times. Two other conditions were included. In one the subjects repetitively moved the same finger on all trials and in a baseline condition the subjects heard the pacing tones and auditory feedback but made no movements. Comparing new learning with the free selection task, there was a small activation in the right prefrontal cortex. This may reflect the fact that in new learning, but not free selection, the subjects rehearse past moves and adapt their responses accordingly. The caudate nucleus was strongly activated during new learning. It is suggested that this activity may be related either to mental rehearsal or to reinforcement of the movements as a consequence of the outcomes. The putamen was activated anteriorly on the free selection task and more posteriorly when the subjects repetitively made the same movement. It is suggested that the differences in the location of the peak activation in the striatum may represent the operation of different corticostriatal loops. The cerebellar nuclei (bilaterally) and vermis were more active in the new learning condition than during the performance of the free selection task. There was no difference in the activation of the cerebellum when the free selection task was compared with repetitive performance of the same movement. We tentatively suggest that the basal ganglia may be involved in the specification of movement on the basis of memory of either the movements or the outcomes, but that the cerebellum may be more directly involved in changes in the parameters of movement execution.