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Biomedical subjects

R E Passingham

Publications and source records attributed to R E Passingham.

At least 19 recordsLinked to original sources

Motor practice and neurophysiological adaptation in the cerebellum: a positron tomography study.

We have used positron tomography (PET) to demonstrate that some parts of the motor system exhibit physiological adaptation during the repeated performance of a simple motor task, but others do not. In contrast to the primary sensori-motor cortex, the cerebellum exhibits a decrease in physiological activation (increases in regional blood flow during performance) with practice. A new application of factorial experimental design to PET activation studies was used to make these measurements in four normal males. This design allowed adaptation to be examined by testing for an interaction between regional cerebral blood flow (rCBF) increases brought about by a motor task and the number of trials (time). These findings are interpreted as the neurophysiological correlates of synaptic changes in the cerebellum associated with motor learning in man.

Adaptation, Physiological

Impaired mesial frontal and putamen activation in Parkinson's disease: a positron emission tomography study.

Selection of movement in normal subjects has been shown to involve the premotor, supplementary motor, anterior cingulate, posterior parietal, and dorsolateral prefrontal areas. In Parkinson's disease (PD), the primary pathological change is degeneration of the nigrostriatal dopaminergic projections, and this is associated with difficulty in initiating actions. We wished to investigate the effect of the nigral abnormality in PD on cortical activation during movement. Using C15O2 and positron emission tomography (PET), we studied regional cerebral blood flow in 6 patients with PD and 6 control subjects while they performed motor tasks. Subjects were scanned while at rest, while repeatedly moving a joystick forward, and while freely choosing which of four possible directions to move the joystick. Significant increases in regional cerebral blood flow were determined with covariance analysis. In normal subjects, compared to the rest condition, the free-choice task activated the left primary sensorimotor cortex, left premotor cortex, left putamen, right dorsolateral prefrontal cortex and supplementary motor area, anterior cingulate area, and parietal association areas bilaterally. In the patients with PD, for the free-choice task, compared with the rest condition, there was significant activation in the left sensorimotor and premotor cortices but there was impaired activation of the contralateral putamen, the anterior cingulate, supplementary motor area, and dorsolateral prefrontal cortex. Impaired activation of the medial frontal areas may account for the difficulties PD patients have in initiating movements.

Aged

Impaired activation of the supplementary motor area in Parkinson's disease is reversed when akinesia is treated with apomorphine.

Using positron emission tomography (PET) we previously showed that activation of the putamen, supplementary motor area, and cingulate cortex is impaired in patients with Parkinson's disease (PD) when they are off treatment and perform volitional motor tasks. Evidence suggests that these areas are involved in the generation of internally cued movements in normal subjects. We have now studied the effect of the dopamine agonist apomorphine on cerebral activation when used to treat the akinesia of PD. Regional cerebral blood flow was measured using C15O2 PET in PD patients at rest and when performing paced joystick movements with the right hand in one of four freely chosen directions. All patients used apomorphine regularly, and were studied before treatment, while still "off" but receiving a subcutaneous apomorphine infusion, and when switched "on" with apomorphine. Significant increases in regional cerebral blood flow were determined using statistical parametric mapping. Under resting conditions apomorphine had no effect on focal or global cerebral blood flow. Seven patients with PD performed the motor task adequately in the "off" and "on" states. This group of subjects demonstrated impaired activation of the supplementary motor area and contralateral putamen in the "off" state. Activation of the supplementary motor area significantly improved when the akinesia was reversed with apomorphine. We conclude that the concomitant improvement of supplementary motor area activation and motor function in apomorphine-treated patients with PD provides further evidence for the role of this structure in generating motor programs.

Adult

Control of arm movement after bilateral lesions of area 5 in the monkey (Macaca mulatta).

The effect of bilateral area 5 lesions on the analysis of proprioceptive information and the guidance of reaching movements was studied in three rhesus monkeys. In the first paradigm (Proprioceptive discrimination test) the monkeys were trained to discriminate between movements of a joystick to the right or left without visual control; they reported the direction of movement by touching or not touching a screen (go/no-go task). After area 5 had been removed, the monkeys were only mildly impaired on this test. It is concluded that such simple joint movement could be analysed in area 2, area 5 being concerned with more complex arm movements. In the second paradigm (Searching test) the monkey had to find a peanut on a board in the dark using proprioceptive information stored in memory during previous trials. After area 5 lesions, the number of correct reaches was not modified but the number of errors after an incorrect trial (correcting movement) was significantly increased. The data suggests that when visual input is not available, area 5 is involved in the guidance of arm movements on the basis of proprioceptive inputs.

Animals

Cortical areas and the selection of movement: a study with positron emission tomography.

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.

Adult

Regional cerebral blood flow during voluntary arm and hand movements in human subjects.

1. Regional cerebral blood flow (rCBF) was measured using positron emission tomography in six normal volunteers while at rest and while performing four different repetitive movements of the right arm. 2. The four movements were performed in random order and consisted of abduction of the index finger, making a fist, sequential thumb to digit opposition, and shoulder flexion. All the movements were done at the same rate, using an auditory cue and involved displacements through similar amounts of the physiological range at each joint. 3. Increases in rCBF were interpreted as evidence of local neural activation and all four movements were associated with significant increases in CBF in the contralateral sensorimotor and premotor areas and in the supplementary motor area (SMA). 4. The average increase in blood flow in the contralateral sensorimotor cortex was significantly greater for the shoulder movement (31%) than for the three other movements. The increases with finger opposition (21%) and fist-making (24%) were not significantly different, and both were significantly greater than with index finger movement (13%). These data indicate that neither "fractionation" nor distal movement per se cause selective activation of sensorimotor cortex. 5. Significantly greater increases in blood flow in both the contralateral premotor cortex and the SMA ("nonprimary motor areas") occurred with shoulder movement than with the other movements. Because this difference may be related to the significantly greater activation occurring concurrently in the sensorimotor cortex, this finding does not prove unequivocally a "selective" role of the nonprimary motor areas in proximal movement. 6. Neither of the two nonprimary motor areas showed selective activation when a simple sequence of finger movements was performed compared with repetitive contractions of the same fingers. 7. Shoulder movement alone was associated with significant increases in rCBF in the ipsilateral sensorimotor cortex (10%), the superior vermis of the cerebellum (19%), and Brodmann areas 5 and 40 in the contralateral hemisphere. 8. The average location of the center of excitation in the sensorimotor cortex and SMA differed for the four movements and was interpreted as evidence of within-limb somatotopy. The shoulder focus lay highest in the sensorimotor cortex and lowest in the SMA.

Adult

Prism adaptation and other tasks involving spatial abilities in patients with Parkinson's disease, patients with frontal lobe lesions and patients with unilateral temporal lobectomies.

Patients in the early stages of Parkinson's disease were compared with patients who had sustained damage specific to either the frontal or temporal lobes and normal controls on a delayed alternation task, a test of the left right orientation and a prism adaptation task. On the former two tasks age accounted for more of the variability in performance than did site of brain lesion. However, patients with frontal lobe, right temporal lobe or basal ganglia damage were significantly impaired on the adaptation task. The results are discussed with regard to "switching", "sequencing" and "internal guidance" of movement hypotheses.

Adult

Motor learning in monkeys (Macaca fascicularis) with lesions in motor thalamus.

The study examines the nature of the influence that the basal ganglia exert on frontal cortex via the motor nuclei of the thalamus. Twelve monkeys were trained to pull a handle given one colour cue and to turn it given another. Bilateral lesions were then placed in the ventral thalamus. Four monkeys with large anterior lesions including the VA nucleus and the anterior part of VLo were severely impaired at relearning the task. Monkeys with small lesions in VAmc or with lesions centred on VLo were not impaired. The analysis of the histology suggests that the impairment in the four monkeys did not result from involvement of the cerebellar relay through nucleus X. It is argued that the animals are not impaired because of faulty execution. This suggests that the basal ganglia have an influence on motor learning.

Animals

Sequence ability in parkinsonians, patients with frontal lobe lesions and patients who have undergone unilateral temporal lobectomies.

Patients in the early stages of Parkinson's disease were compared with patients who had sustained damage specific to either the frontal or temporal lobes and normal controls on a number of sequencing tests. These tests involved the reproduction of sequences of hand gestures, sequences tapped out on blocks, and sequences of digits. Only the groups with frontal lobe lesions or right temporal lobectomies were impaired on any of these tasks, though no group was impaired on all of the sequencing tasks.

Adolescent

The performance on learning tasks of patients in the early stages of Parkinson's disease.

It is known that in animals learning is disrupted by caudate lesions; but there has been no agreement about whether pathology in the basal ganglia causes a similar impairment in man. Nineteen patients in the early stages of Parkinson's disease were tested on two associative learning tasks and on the Wisconsin Card Sorting Task; and their performance was compared with that of patients with frontal or temporal lobe lesions. On the two associative learning tasks there was no overall difference between the Parkinsonian group and the controls. However, a minority of the Parkinsonian patients performed very poorly on these tasks; and it was noted that these tended to be the older patients.

Adult

Localisation in PET images: direct fitting of the intercommissural (AC-PC) line.

A technique is described for estimating the position of the intercommisural line (AC-PC line) directly from landmarks on positron emission tomographic (PET) images, namely the ventral aspects of the anterior and posterior corpus callosum, the thalamus, and occipital pole. The relationship of this estimate to the true AC-PC line, fitted through the centres of the anterior and posterior commissures, showed minimal vertical and angular displacement when measured on magnetic resonance imaging (MRI) scans. Using regression analysis, the ease and reliability of fitting to these points was found to be high. This directly derived AC-PC line estimate was validated in terms of the assumptions used in the method of Fox et al. The ratio of distance between the AC-PC line and a line passing through the base of the inion (GI line) to total brain height was 0.21, as predicted. The technique has been further validated by localizing focal activation of the sensorimotor cortex. The technique is discussed in terms of absolute limits to localization of structures in the brain using noninvasive tomographic techniques in general and PET in particular.

Brain

Premotor cortex and the retrieval of movement.

It is argued that the premotor cortex plays a crucial role in the retrieval of movement. Monkeys with bilateral lesions in premotor cortex were found to be impaired at selecting between two movements on the basis of visual cues. This was true whether the visual cue was present at the time of response or was no longer visible. Yet other monkeys with bilateral lesions in dorsal premotor cortex had little difficulty in remembering a movement if they had just been forced to make it a few seconds earlier. It is suggested that the premotor cortex is involved in the process of translation from a visual or auditory cue to an associated movement.

Animals

Neuronal activity of the supplementary motor area (SMA) during internally and externally triggered wrist movements.

The activity of neurones was recorded from the supplementary motor area (SMA) of monkeys while they were performing a discrete, arbitrary wrist movement. The cells responded similarly whether there was a triggering stimulus at the time of the movement or not. This experiment indicates that SMA neurones are active both in relation to externally triggered and internally initiated (voluntary) actions.

Animals

Premotor cortex and preparation for movement.

Many cells in premotor cortex change their activity while a monkey waits before responding. In the present experiment lesions were placed in premotor cortex in order to investigate the information carried by this neuronal activity. The monkeys were trained to make one of two movements depending on the colour of a cue. There were two conditions: in one they could respond when the cue was presented, in the other they had to wait three seconds before responding. The monkeys were then retested after the bilateral removal of premotor cortex. Animals with premotor lesions performed very poorly under both conditions. It is concluded that premotor cortex is concerned with retrieving the response that is appropriate given a particular cue.

Animals

Premotor cortex in the rat.

Donoghue and Wise (1982) identified an area AGm in the rat that they take to be a nonprimary motor area. In the present experiments, therefore, this area was removed bilaterally in rats. The animals were poor at relearning a visual conditional motor task but were able to learn spatial delayed alternation as rapidly as unoperated animals. Thus removing this area in rats has a similar effect to removing premotor cortex in monkeys. It is argued that this dorsomedial shoulder area should not be regarded as part of prefrontal cortex in the rat.

Animals

Two cortical systems for directing movement.

It is argued that the cortical premotor areas are concerned with the conditions for action. Actions are based both on facts about the outside world and about the actions of the animal itself. Observations on monkeys (Macaca fascicularis, Macaca mulatta) suggest that the arcuate premotor area directs actions on the basis of visual cues about the outside environment and that the supplementary motor area directs actions on the basis of proprioceptive cues concerning the animal's own actions.

Animals

Cues for movement in monkeys (Macaca mulatta) with lesions in premotor cortex.

It has been shown previously that after removal of premotor cortex, monkeys are poor at selecting movements on the basis of a visual contextual cue. In those experiments, the monkeys had to pull or turn a handle depending on the color of a cue presented in the foreground or background. In the present experiments, it is shown that animals with lesions that include premotor cortex can select movements correctly if the cue is given by information about the handle itself. In the first experiment, the cue was provided by the direction in which the monkey had last moved the handle; the monkeys had been required to squeeze a handle if they had been forced to squeeze it 5 s earlier, and they were required to turn it if they had been forced to turn it. In the second experiment, the cue was provided by the identity of the handle itself: When presented with a blue handle, they had to pull the handle; when presented with a yellow handle, they had to turn it. It is argued that the animals are impaired only when the task is a true conditional task.

Animals

Reorganization in the human brain as illustrated by the thalamus.

A comparison is made between the relative size of the various thalamic nuclei in man and other primates. Using data for non-human primates predictions are made as to the expected size of the nuclei for the human brain. Of the nuclear groupings five are of the size predicted but three are not. The lateral geniculate is proportionately smaller than predicted, but it is argued that this need not imply a radical change.

Animals