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R E Passingham

Publications and source records attributed to R E Passingham.

At least 73 records · Page 4Linked to original sources

Parietal cortex and movement. I. Movement selection and reaching.

Recording studies in the parietal cortex have demonstrated single-unit activity in relation to sensory stimulation and during movement. We have performed three experiments to assess the effect of selective parietal lesions on sensory motor transformations. Animals were trained on two reaching tasks: reaching in the light to visual targets and reaching in the dark to targets defined by arm position. The third task assessed non-standard, non-spatial stimulus response mapping; in the conditional motor task animals were trained to either pull or turn a joystick on presentation of either a red or a blue square. We made two different lesions in the parietal cortex in two groups of monkeys. Three animals received bilateral lesions of areas 5, 7b and MIP, which have direct connections with the premotor and motor cortices. The three other animals subsequently received bilateral lesions in areas 7a, 7ab and LIP. Both groups were still able to select between movements arbitrarily associated with non-spatial cues in the conditional motor task. Removal of areas 7a, 7ab and LIP caused marked inaccuracy in reaching in the light to visual targets but had no effect on reaching in the dark. Removal of areas 5, 7b and MIP caused misreaching in the dark but had little effect on reaching in the light. The results suggest that the two divisions of the parietal cortex organize limb movements in distinct spatial coordinate systems. Area 7a/7ab/LIP is essential for spatial coordination of visual motor transformations. Area 5/7b/MIP is essential for the spatial coordination of arm movements in relation to proprioceptive and efference copy information. Neither part of the parietal lobe appears to be important for the non-standard, non-spatial transformations of response selection.

Animals↗

Parietal cortex and movement. II. Spatial representation.

Lesions in the two divisions of parietal cortex, 5/7b/MIP and 7a/LIP, produce dissociable reaching deficits. Monkeys with 5/7b/MIP removals were tested on reaching in the dark under two different conditions. All the reaches made on any day were from the same starting position to the same target position in the control condition. In the "transfer" condition, all the reaches were made to the same target position but consecutive reaches were made from different starting positions. The target could be represented as a constant pattern of joint and muscle positions in the control condition. The transfer condition required a representation of the starting position of the hand and/or a representation of the target in terms of its position in space. Removal of areas 5, 7b and MIP produced only a very mild impairment in the control condition and a severe impairment in the transfer condition. This suggests that 5/7b/MIP does not represent the limb in simple sensory or motor coordinates but in terms of its spatial position.

Animals↗

The left parietal cortex and motor attention.

The posterior parietal cortex, particularly in the right hemisphere, is crucially important for covert orienting; lesions impair the ability to disengage the focus of covert orienting attention from one potential saccade target to another (Posner, M. I. et al., Journal of Neuroscience, 1984, 4, 1863-1874). We have developed a task where precues allow subjects to covertly prepare subsequent cued hand movements, as opposed to an orienting or eye movement. We refer to this process as motor attention to distinguish it from orienting attention. Nine subjects with lesions that included the left parietal cortex and nine subjects with lesions including the right parietal cortex were compared with control subjects on the task. The left hemisphere subjects showed the same ability as controls to engage attention to a movement when they were forewarned by a valid precue. The left hemisphere subjects, however, were impaired in their ability to disengage the focus of motor attention from one movement to another when the precue was incorrect. The results support the existence of two distinct attentional systems allied to the orienting and limb motor systems. Damage to either system causes analogous problems in disengaging from one orienting/movement target to another. The left parietal cortex, particularly the supramarginal gyrus, is associated with motor attention. All the left hemisphere subjects had ideomotor apraxia and had particular problems performing sequences of movements. We suggest that the well documented left hemisphere and apraxic impairment in movement sequencing is the consequence of a difficulty in shifting the focus of motor attention from one movement in a sequence to the next.

Adult↗

Botulinum toxin does not reverse the cortical dysfunction associated with writer's cramp. A PET study.

Previous H2(15)O PET activation studies on patients with idiopathic torsion dystonia (ITD) have shown overactive striatum and frontal accessory areas and underactivity of the primary motor cortex and caudal supplementary motor area (SMA) during volitional movement. We have now examined activation of the motor system in healthy control subjects and patients with writer's cramp while they write a stereotyped word repetitively at a paced rate before and after treatment with botulinum toxin to see if these patients showed a similar pattern of abnormalities and whether they were reversible. As in ITD, our patients with writer's cramp showed impaired activation of the contralateral primary motor cortex, but enhanced activation of frontal association cortex. Botulinum-toxin treatment improved writing and increased activation in parietal cortex and caudal SMA. This may represent either a change in movement strategy or associated cortical reorganization secondary to deefferentation of alpha motor neurons. However, botulinum toxin failed to improve the impaired activation of the primary motor cortex. We conclude that, while botulinum toxin is clinically effective in writer's cramp, it does not reverse the associated dysfunction of primary motor and premotor cortex.

Adult↗

Evidence for lateral premotor and parietal overactivity in Parkinson's disease during sequential and bimanual movements. A PET study.

Patients with Parkinson's disease have great difficulty in performing sequential and bimanual movements. We used H2(15)O PET to study the regional cerebral blood flow associated with performance of sequential finger movements made unimanually and bimanually in a group of Parkinson's disease patients and a group of control volunteers. In controls, sequential finger movements led to activation of the contralateral motor cortex and inferior parietal cortex (Brodmann area 40), the lateral premotor cortex and bilateral supplementary motor area. No prefrontal activation was seen. Sequential finger movements in the Parkinson's disease group were associated with a similar pattern of activation but there was relative impairment of activation in the mesial frontal and prefrontal areas. A novel finding was the presence of relative overactivity in the lateral premotor and inferolateral parietal regions. We conclude that in Parkinson's disease there is a switch from the use of striato-mesial frontal to parietal-lateral premotor circuits in order to facilitate performance of complex finger movements.

Aged↗

Mirror movements in X-linked Kallmann's syndrome. II. A PET study.

To investigate the mechanism of mirror movements seen in X-linked Kallmann's syndrome, we measured changes of regional cerebral blood flow with H2 15O-PET. We studied six right-handed Kallmann male subjects and six matched, right-handed control subjects during an externally paced finger opposition task. The analyses were done both on a single subject and a group basis. The Kallmann group showed a strong primary motor cortex (M1) activation contralateral to the voluntarily moved hand, but there was also a significant degree of M1 activation ipsilateral to the voluntarily moved hand, i.e. contralateral to the mirroring hand. However, when comparing contralateral to ipsilateral M1 activation, the M1 activation contralateral to the voluntarily moved hand was significantly stronger. In the controls, significant increases in rCBF were seen in the contralateral M1 during voluntary movement of either hand; a small ipsilateral M1 activation was found in two out of six normal subjects when they moved their left hand. In a second experiment it was shown that, in two out of two Kallmann subjects, passive movements of the right hand resulted in left M1 activation that was similar to the activation in the left M1 when subjects made mirror movements with their right hand. This suggests, but does not prove, that the small but significant activation of the ipsilateral M1 in Kallmann's subjects may be due to sensory feedback from the involuntarily mirroring hand.

Adolescent↗

Relation between cognitive dysfunction and pseudobulbar palsy in amyotrophic lateral sclerosis.

OBJECTIVES: To examine the relation between cognitive dysfunction and pseudobulbar features in patients with amyotrophic lateral sclerosis (ALS). METHODS: The performance of two patient groups, ALS with pseudobulbar palsy (n = 24) and ALS without pseudobulbar palsy (n = 28), was compared with 28 healthy age matched controls on an extensive neuropsychological battery. Tests used were the national adult reading test, short form of the WAIS-R, recognition memory test, Kendrick object learning test, paired associate learning, Wisconsin card sorting test, verbal fluency, Stroop and negative priming tests, a random movement joystick test, and a computerised Tower of Hanoi test. RESULTS: Tests of executive function showed a pronounced deficit on written verbal fluency in both ALS groups in comparison to controls, which tended to be more prominent in patients with ALS with pseudobulbar palsy. The random movement joystick test (a non-verbal test of intrinsic movement generation) showed an impairment in the generation of random sequences in patients with pseudobulbar palsy only. The computerised Tower of Hanoi showed a subtle planning impairment (shorter planning times) in all the patients with ALS compared with controls on trials requiring more complex solutions. In addition the pseudobulbar patients displayed shorter planning times on complex trials, and tended to solve these trials less accurately. There was also evidence of a deficit for all patients with ALS in comparison with controls on total errors and number of categories achieved on the Wisconsin card sorting test and a strong tendency towards an impairment on a task of selective attention and cognitive inhibition (negative priming). A word recognition memory deficit was showed across both ALS groups. CONCLUSIONS: This study elicited cognitive deficits (involving predominantly executive processes, with some evidence of memory impairment) in patients with ALS and further strengthened the link between ALS and frontal lobe dysfunction, this being more prominent in patients with pseudobulbar palsy. However, cognitive impairments suggestive of extramotor cortical involvement were not exclusive to this subgroup.

Adult↗

Micrographia in Parkinson's disease: the effect of providing external cues.

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.

Aged↗

Anatomy of motor learning. I. Frontal cortex and attention to action.

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 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.

Adult↗

Anatomy of motor learning. II. Subcortical structures and learning by trial and error.

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 feedback to indicate success or failure, and so on learning occurred. 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 subject 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.

Acoustic Stimulation↗

Multiple nonprimary motor areas in the human cortex.

We measured the distribution of regional cerebral blood flow with positron emission tomography while three subjects moved their hand, shoulder, or leg. The images were coregistered with each individual's anatomic magnetic resonance scans. The data were analyzed for each individual to avoid intersubject averaging and so to preserve individual gyral anatomy. Instead of inspecting all pixels, we prospectively restricted the data analysis to particular areas of interest. These were defined on basis of the anatomic and physiological literature on nonhuman primates. By examining only a subset of areas, we strengthened the power of the statistical analysis and thereby increased the confidence in reporting single subject data. On the lateral convexity, motor related activity was found for all three subjects in the primary motor cortex, lateral premotor cortex, and an opercular area within the premotor cortex. In addition, there was activation of somatosensory cortex (SI), the supplementary somatosensory area (SII) in the Sylvian fissure, and parietal association areas (Brodmann areas 5 and 40). There was also activation in the insula. We suggest that the activation in the dorsal premotor cortex may correspond with dorsal premotor area (PMd) as described in the macaque brain. We propose three hypotheses as to the probable location of vental premotor area (PMv) in the human brain. On the medial surface, motor-related activity was found for all three subjects in the leg areas of the primary motor cortex and somatosensory cortex and also activity for the hand, shoulder, and leg in the supplementary motor area (SMA) on the dorsal medial convexity and in three areas in the cingulate sulcus. We suggest that the three cingulate areas may correspond with rostral cingulate premotor area, dorsal cingulate motor area (CMAd), and ventral cingulate motor area (CMAv) as identified in the macaque brain. Somatotopic mapping was demonstrated in the primary motor and primary somatosensory cortex. In all three subjects, the arm region lay anterior to the leg region in parietal area 5. Also in all three subjects, the arm region lay anterior to the leg region in the supplementary motor cortex.

Adult↗

Abnormal access of axial vibrotactile input to deafferented somatosensory cortex in human upper limb amputees.

We studied two human subjects with total deafferentation of one upper limb secondary to traumatic multiple cervical root avulsions. Both subjects developed a phantom limb and underwent elective amputation of the paralyzed, deafferentated limb. Psychophysical study revealed in each subject an area of skin in the pectoral region ipsilateral to the amputation where vibrotactile stimulation (VS) elicited referred sensations (RS) in the phantom limb. Positron emission tomography was then used to measure regional cerebral blood flow changes during VS of the pectoral region ipsilateral to the amputation with RS and during VS of a homologous part of the pectoral region adjacent to the intact arm without RS. A voxel-based correlation analysis was subsequently used to study functional connectivity. VS of the pectoral region adjacent to the intact arm was associated with activation of the dorsal part of the contralateral primary somatosensory cortex (S1) in a position consistent with the S1 trunk area. In contrast, VS of the pectoral region ipsilateral to the amputation with RS was associated with activation of the contralateral S1 that extended from the level of the trunk representation ventrally over distances of 20 and 12 mm, respectively, in the two subjects. The area of S1 activated during VS of the digits in a normal control subject was coextensive with the ventral S1 region abnormally activated during VS of the ectopic phantom representation in the two amputees, suggesting that the deafferented digit or hand/arm area had been activated by sensory input from the pectoral region. Correlation analysis showed an abnormal pattern of intrinsic connectivity within the deafferented S1 hand/arm area of both amputees. In one subject, the deafferented S1 was functionally connected with 3 times as many S1 voxels as the normally afferented S1. This abnormal functional connectivity extended in both the rostrocaudal and ventrodorsal dimensions. The results demonstrate that sensory input delivered to the axial body surface may gain access to the S1 hand/arm area in some humans who have suffered extensive deafferentation of this area. The findings are consistent with the hypothesis that deafferentation of an area of S1 may result in activation of previously dormant inputs from body surfaces represented in immediately adjacent parts of S1. The results also provide evidence that changes in functional connectivity between these adjacent areas of the cortex play a role in the somatotopic reorganization.

Adult↗

Attention to action.

The paper considers the question of why subjects are poor at performing two tasks simultaneously if both require attention. It is shown using positron emission tomography (PET) that during new learning of a motor sequence task the prefrontal and anterior cingulate cortex are extensively activated, but that they are no longer activated when a motor sequence has been practiced for an hour until it is automatic. It is also shown that early in motor learning there is interference if subjects are required to generate verbs at the same time, but that the interference is much less if they are required to do this late in motor learning. The prefrontal and anterior cingulate cortex are activated during verb generation. It is therefore suggested that the interference occurs centrally, and that it occurs in either prefrontal or anterior cingulate cortex.

Attention↗

The sensory guidance of movement: a comparison of the cerebellum and basal ganglia.

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.

Adult↗

The nucleus accumbens in monkeys (Macaca fascicularis): II. Emotion and motivation.

Changes in incentive and emotion have been demonstrated in monkeys with amygdala lesions and monkeys with cingulate and medial frontal lesions. The nucleus accumbens (NA) receives inputs from the amygdala, hippocampus and anterior cingulate cortex. In order to better understand the role of the NA and anterior cingulate cortex in processing emotional and motivational stimuli, studies were undertaken which compared the emotional and motivational behaviour of monkeys with NA lesions or anterior cingulate lesions with previous studies on amygdala-lesioned monkeys. A food preference task, a food vs. non-food discrimination task, and a approach-avoidance task were used with monkeys which received lesions of the NA or lesion of the anterior cingulate and medial frontal cortex. These tasks had previously been used to examine the emotional response of monkeys with amygdala lesions. In addition, the lesioned monkeys were tested on a frustration tasks and a button press acquisition-extinction task. Unlike amygdala-lesioned monkeys (Aggleton, J.P. and Passingham, R.E., J. Comp. Physiol. Psychol., 96 (1981) 961-977 and 96 (1982) 71-77), the NA-lesioned monkeys maintained normal food preferences, did not show signs of hyperorality in the food vs. non-food task, and performed normally on the approach-avoidance tasks. The NA-lesioned monkeys did, however, show an increase in activity, and violent and aggressive behaviour in response to stress in both the frustration task and the button press extinction task. In addition, the NA-lesioned monkeys performed normally during a button press acquisition task, but extinguished faster on a button press extinction task than the control monkeys. The anterior cingulate-lesioned monkeys were also found to exhibit an increased responsiveness to frustration. Results of the food preference, food vs. non-food discrimination, and approach-avoidance tasks were similar to those obtained with NA lesioned. These studies suggest that lesions of the NA or the anterior cingulate cortex result in substantial changes in emotional behavior, however, these changes do not mimic those found following lesions of the amygdala.

Animals↗

Associative learning in patients with cerebellar ataxia.

It has been claimed that patients with cerebellar pathology are impaired at associative learning. Patients with cerebellar ataxia (n = 7) were taught a visual-motor associative task. The task was chosen so as to allow comparisons with data currently being collected on the effects of cerebellar lesions on associative learning in monkeys. As a group the patients were as impaired at learning the task as a group of 8 patients with Huntington's disease. When each patient was individually matched with a control of the same age and IQ, some patients with cerebellar ataxia were found to be clearly impaired, but 2 were not. Of the 4 patients who were most clearly impaired, 2 had brainstem pathology and 2 did not. The relevance of these findings is discussed in relation to views concerning the functions of the cerebellum.

Adult↗